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32,593,212
|
Beneficial effects of DAAs on cardiac function and structure in hepatitis C patients with low-moderate liver fibrosis.
|
Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.
|
Journal of viral hepatitis
| 2,020
| 11
| 0
| 0
|
33,011,097
|
Estimates of Geriatric Delirium Frequency in Noncardiac Surgeries and Its Evaluation Across the Years: A Systematic Review and Meta-analysis.
|
Delirium is an acute neuropsychiatric syndrome associated with poor outcomes. Older adults undergoing surgery have a higher risk of manifesting perioperative delirium, particularly those having associated comorbidities. It remains unclear whether delirium frequency varies across surgical settings and if it has remained stable across the years. We conducted a systematic review to (1) determine the overall frequency of delirium in older people undergoing noncardiac surgery; (2) explore factors explaining the variability of the estimates; and (3) determine the changing of the estimates over the past 2 decades.
|
Journal of the American Medical Directors Association
| 2,021
| 3
| 0
| 0
|
31,064,428
|
Seeing for ourselves: Insights into the development of moral behaviour from models of visual perception and misperception.
|
Parallels from visual processing support Doris's cognitive architecture underlying moral agency. Unconscious visual processes change with conscious reflection. The sparse and partial representations of vision, its illusions, and hallucinations echo biases in moral reasoning and behaviour. Traditionally, unconscious moral processes are developed by teaching and reflection. Modern neuroscience could bypass reflection and directly influence unconscious processes, creating new dangers.
|
The Behavioral and brain sciences
| 2,018
| 1
| 0
| 0
|
24,862,419
|
Sudden worsening after subdural haematoma surgery: will there be a corpus callosum injury?
|
We report a case of mild encephalopathy with a reversible splenial lesion (MERS) which occurred after chronic subdural haematoma (CSDH) surgery. The patient was admitted to our hospital for drowsiness and marked asthenia. The cerebral CT scan revealed a CSDH and surgery allowed to improve the symptoms, but after several days we observed a sudden worsening. The patient developed left-sided myoclonic seizures followed by left hemiplegia and worsening drowsiness. Electrolytes imbalance and inflammatory causes were excluded. The CT scan showed a right cerebral swelling and the subsequent MRI revealed a single lesion in the splenium of the corpus callosum, hyperintense on diffusion-weighted images. After osmotic therapy the patient improved and on day 10 of admission the MRI showed a complete resolution of the lesion. This is the first report that described an association between CSDH and MERS. Possible aetiopathogenetic mechanisms are discussed.
|
BMJ case reports
| 2,014
| 5
| 0
| 0
|
32,544,613
|
Neural repetition suppression effects in the human hippocampus.
|
Neurons in the temporal lobe cortex exhibit reduced responses when a stimulus or a stimulus feature is repeated. This phenomenon, termed "repetition suppression", is the basis for many functional imaging studies that have used Blood Oxygenation Level Dependent (BOLD) activity differences between novel and repeated items as an index of neural selectivity in hippocampal subfields. However, it is not clear how hippocampal neural activity changes across repeated exposure to a stimulus. Here, we used direct intracranial electroencephalography (iEEG) recordings of hippocampal activity to examine whether neural activity in the human hippocampus is modulated across successive repetitions of an item. Time-frequency analyses revealed that high-frequency activity, which is thought to include gamma oscillations and possible correlates of multi-unit activity, declined monotonically across successive presentations of an item. In contrast, low-frequency oscillations in the alpha and beta bands monotonically increased across successive presentations of an object. These results provide support for the assumption that, at least under some circumstances, repetition suppression (as measured by declines in high-frequency activity) can be observed in the hippocampus, and these effects are accompanied by increases in low-frequency oscillations as well.
|
Neurobiology of learning and memory
| 2,020
| 9
| 0
| 0
|
32,652,198
|
Targeting apoptosis and autophagy following spinal cord injury: Therapeutic approaches to polyphenols and candidate phytochemicals.
|
Spinal cord injury (SCI) is a neurological disorder associated with the loss of sensory and motor function. Understanding the precise dysregulated signaling pathways, especially apoptosis and autophagy following SCI, is of vital importance in developing innovative therapeutic targets and treatments. The present study lies in the fact that it reveals the precise dysregulated signaling mediators of apoptotic and autophagic pathways following SCI and also examines the effects of polyphenols and other candidate phytochemicals. It provides new insights to develop new treatments for post-SCI complications. Accordingly, a comprehensive review was conducted using electronic databases including, Scopus, Web of Science, PubMed, and Medline, along with the authors' expertise in apoptosis and autophagy as well as their knowledge about the effects of polyphenols and other phytochemicals on SCI pathogenesis. The primary mechanical injury to spinal cord is followed by a secondary cascade of apoptosis and autophagy that play critical roles during SCI. In terms of pharmacological mechanisms, caspases, Bax/Bcl-2, TNF-α, and JAK/STAT in apoptosis along with LC3 and Beclin-1 in autophagy have shown a close interconnection with the inflammatory pathways mainly glutamatergic, PI3K/Akt/mTOR, ERK/MAPK, and other cross-linked mediators. Besides, apoptotic pathways have been shown to regulate autophagy mediators and vice versa. Prevailing evidence has highlighted the importance of modulating these signaling mediators/pathways by polyphenols and other candidate phytochemicals post-SCI. The present review provides dysregulated signaling mediators and therapeutic targets of apoptotic and autophagic pathways following SCI, focusing on the modulatory effects of polyphenols and other potential phytochemical candidates.
|
Pharmacological research
| 2,020
| 10
| 0
| 0
|
30,279,560
|
Correction: Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis.
|
This article was originally published under NPG's License to Publish, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the paper have been modified accordingly.
|
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
| 2,018
| 12
| 0
| 0
|
31,883,895
|
Enhancing biocompatibility and neuronal anti-inflammatory activity of polymyxin B through conjugation with gellan gum.
|
Polymyxins, as strong antibiotics with high liposaccharide deactivation abilities, are rarely used as neuronal anti-inflammatory agent because of their high cytotoxicity. In this study, polymyxin B (PMB) was conjugated with deacylated gellan gum for the sustained release of PMB to reduce its cytotoxicity at high concentration without affecting the antibacterial and liposaccharide binding activities. For the conjugate of original PMB/GN ratio of 1.0 (GPC), the conjugating rate was 96.40%, and the releasing ratio of PMB was 30.12% within 60 h. The FT-IR spectra of GPC indicated that the amino groups of PMB were covalently bonded with the COOH groups of gellan and other PMB molecules. Most GPCs were micelle shaped regardless of whether they were under dry conditions or in an aqueous solution. The inhibition zones of PMB against Escherichia coli and Pseudomonas aeruginosa were small, but the half maximal inhibitory concentration value against BV-2 cells increased from 15.63 μg/mL to 2000.00 μg/mL after conjugation. GPC can also effectively depress the liposaccharide-stimulated overexpression of cytotoxic nitric oxide by BV-2 cells. This study revealed the possibility of using polymyxins for neuronal anti-inflammation and that this gellan/PMB conjugate can potentially be applied to wound healing and implants.
|
International journal of biological macromolecules
| 2,020
| 3
| 0
| 0
|
30,026,395
|
Female Residents with Psychopathy in a High-Security Italian Hospital.
|
Before its closure on April 1, 2015, the Castiglione delle Stiviere was the only maximum-security hospital in Italy that admitted women. In this context, the investigators examined factors related to psychopathy that were thought to be gender specific. Several prior investigations have reported a significant correlation between psychopathy and borderline personality disorder, a disorder thought to represent the phenotypical expression of psychopathy in women. The purpose of this research was to identify psychopathological and phenotypical gender-specific factors that are associated with psychopathy in women. The data appear consistent with that found in the recent international literature and also highlight the different phenotypical manifestation of psychopathy in the two genders. Whereas in males psychopathy is associated with antisocial personality disorder, in females psychopathy is associated with borderline personality disorder.
|
The journal of the American Academy of Psychiatry and the Law
| 2,018
| 6
| 0
| 0
|
32,193,513
|
Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates.
|
The most common chemogenetic neuromodulatory system, designer receptors exclusively activated by designer drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is insensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug, particularly in experiments using nonhuman primates. We investigated working memory performance after injections of three DREADD actuators, clozapine, olanzapine, and deschloroclozapine, in four male rhesus monkeys tested in a spatial delayed response task before any DREADD transduction took place. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from vehicle in any of the four subjects. 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after 0.1 mg/kg olanzapine and two were impaired after 0.3 mg/kg deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs in the specific tasks under study to confirm that effects following DREADD receptor transduction are not owing to the actuator drug itself. They also suggest that off-target effects of DREADD actuators may limit translational applications of chemogenetic neuromodulation.
|
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
| 2,020
| 10
| 0
| 0
|
33,198,398
|
Zn, Cu, and Fe Concentrations in Dehydrated Herbs (Thyme, Rosemary, Cloves, Oregano, and Basil) and the Correlation with the Microbial Counts of
|
Zn, Cu, and Fe concentrations were measured in dehydrated herbs (thyme, rosemary, cloves, oregano, and basil) marketed in bulk or packaged in glass or polyethylene terephthalate (PET). Microbial counts of
|
Foods (Basel, Switzerland)
| 2,020
| 11
| 0
| 0
|
33,479,521
|
Solutes as controllers of endomembrane dynamics.
|
Membrane dynamics, such as those associated with intracellular traffic, require controlled deformation of the membrane. There is now evidence that the regulation of the luminal fluid composition — via solute fluxes — prominently impacts dynamic properties of endomembranes by modulating their tension. This has important consequences for the function of the endo-lysosomal system.
|
Nature reviews. Molecular cell biology
| 2,021
| 4
| 0
| 0
|
33,252,190
|
GRIN database: A unified and manually curated repertoire of GRIN variants.
|
Glutamatergic neurotransmission is crucial for brain development, wiring neuronal function, and synaptic plasticity mechanisms. Recent genetic studies showed the existence of autosomal dominant de novo GRIN gene variants associated with GRIN-related disorders (GRDs), a rare pediatric neurological disorder caused by N-methyl- d-aspartate receptor (NMDAR) dysfunction. Notwithstanding, GRIN variants identification is exponentially growing and their clinical, genetic, and functional annotations remain highly fragmented, representing a bottleneck in GRD patient's stratification. To shorten the gap between GRIN variant identification and patient stratification, we present the GRIN database (GRINdb), a publicly available, nonredundant, updated, and curated database gathering all available genetic, functional, and clinical data from more than 4000 GRIN variants. The manually curated GRINdb outputs on a web server, allowing query and retrieval of reported GRIN variants, and thus representing a fast and reliable bioinformatics resource for molecular clinical advice. Furthermore, the comprehensive mapping of GRIN variants' genetic and clinical information along NMDAR structure revealed important differences in GRIN variants' pathogenicity and clinical phenotypes, shedding light on GRIN-specific fingerprints. Overall, the GRINdb and web server is a resource for molecular stratification of GRIN variants, delivering clinical and investigational insights into GRDs. GRINdb is accessible at http://lmc.uab.es/grindb.
|
Human mutation
| 2,021
| 1
| 0
| 0
|
33,091,825
|
Brain-wide, scale-wide physiology underlying behavioral flexibility in zebrafish.
|
The brain is tasked with choosing actions that maximize an animal's chances of survival and reproduction. These choices must be flexible and informed by the current state of the environment, the needs of the body, and the outcomes of past actions. This information is physiologically encoded and processed across different brain regions on a wide range of spatial scales, from molecules in single synapses to networks of brain areas. Uncovering these spatially distributed neural interactions underlying behavior requires investigations that span a similar range of spatial scales. Larval zebrafish, given their small size, transparency, and ease of genetic access, are a good model organism for such investigations, allowing the use of modern microscopy, molecular biology, and computational techniques. These approaches are yielding new insights into the mechanistic basis of behavioral states, which we review here and compare to related studies in mammalian species.
|
Current opinion in neurobiology
| 2,020
| 10
| 0
| 0
|
32,776,088
|
Discoidin Domain Receptor 1 is a therapeutic target for neurodegenerative diseases.
|
The role of Discoidin Domain Receptors (DDRs) is poorly understood in neurodegeneration. DDRs are upregulated in Alzheimer's and Parkinson's disease (PD), and DDRs knockdown reduces neurotoxic protein levels. Here we show that potent and preferential DDR1 inhibitors reduce neurotoxic protein levels in vitro and in vivo. Partial or complete deletion or inhibition of DDR1 in a mouse model challenged with α-synuclein increases autophagy and reduces inflammation and neurotoxic proteins. Significant changes of cerebrospinal fluid microRNAs that control inflammation, neuronal injury, autophagy and vesicular transport genes are observed in PD with and without dementia and Lewy body dementia, but these changes are attenuated or reversed after treatment with the DDR1 inhibitor, nilotinib. Collectively, these data demonstrate that DDR1 regulates autophagy and reduces neurotoxic proteins and inflammation and is a therapeutic target in neurodegeneration.
|
Human molecular genetics
| 2,020
| 10
| 0
| 0
|
32,978,287
|
It Is All in the Right Amygdala: Increased Synaptic Plasticity and Perineuronal Nets in Male, But Not Female, Juvenile Rat Pups after Exposure to Early-Life Stress.
|
Early-life stress (ELS) is associated with increased vulnerability to mental disorders. The basolateral amygdala (BLA) plays a critical role in fear conditioning and is extremely sensitive to ELS. Using a naturalistic rodent model of ELS, the limited bedding paradigm (LB) between postnatal days 1-10, we previously documented that LB male, but not female preweaning rat pups display increased BLA neuron spine density paralleled with enhanced evoked synaptic responses and altered BLA functional connectivity. Since ELS effects are often sexually dimorphic and amygdala processes exhibit hemispheric asymmetry, we investigated changes in synaptic plasticity and neuronal excitability of BLA neurons
|
The Journal of neuroscience : the official journal of the Society for Neuroscience
| 2,020
| 10
| 0
| 0
|
32,522,471
|
Involvement of hippocampal agmatine in β
|
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by abnormal accumulation of extracellular β-amyloid (Aβ) plaques and neuronal damage. The present study investigated the effect of chronic intra-hippocampal agmatine administration on β-Amyloid (Aβ) induced memory impairment in mice. Aβ
|
Neurotoxicology
| 2,020
| 9
| 0
| 0
|
29,067,872
|
Selective neural sensitivity to familial threat in adolescents with weak family bonds.
|
Familial stressors, such as weak familial connectedness, are associated with the development of maladaptive threat processing, yet little is known regarding how weak familial bonds impinge on biological mechanisms of threat processing. The present study leveraged multivoxel pattern analysis of fMRI data to compare the neural encoding of familial and nonfamilial threatening and non-threatening stimuli in adolescents who endorsed varying levels of connectedness to their families. Adolescents (N = 22, Mage = 14.38 years) reporting lower family connectedness 1 year earlier showed elevated sensitivity to familial threat, but not to nonfamilial threat in a neural network associated with threat processing, comprising left and right amygdala, and right inferior and middle temporal gyri. Results suggest that a learning history about one's social environment may shape neural mechanisms of threat processing by sensitizing them to risk-relevant stimuli. Such findings advance our understanding of how familial stressors contribute to disordered threat processing in adolescence.
|
Social neuroscience
| 2,019
| 2
| 0
| 0
|
33,011,196
|
Effects of sub-concussion on neuropsychological performance and its potential mechanisms: A narrative review.
|
Concussion and mild traumatic brain injury (mTBI) are recognised as serious medical events that are relatively common in contact sports. Recently, the seemingly non-injurious phenomenon of sub-concussion has gained interest among neuroscience researchers and early studies are showing that there may be some acute and chronic effects on brain health and function with repeated sub-concussive events of the type seen in soccer, where players strike the ball with the head, and collision sports like the rugby codes. The aim of this narrative review is to describe sub-concussion and the current understanding of short and long term effects of repeated minor impacts that have been found to occur in human and animal models. Here, potential mechanisms for cognitive dysfunction following sub-concussion and recommend directions for future research are discussed. The Potential mechanisms of injuries resulting from sub-concussion such as changes in blood brain barrier integrity, neuroinflammation, cognitive impairment, and oxidative stress damage, among other changes in central nervous system function vary considerably making understanding of the underlying causative mechanism challenging for researchers. Some evidence suggests a link between impaired cerebrovascular function and cognitive impairment which poses a potential mechanism linking the two. It is hoped that this review helps guide researchers toward a potential direction of investigations.
|
Brain research bulletin
| 2,020
| 12
| 0
| 0
|
32,763,169
|
Anterior Cingulate Cortex Signals Attention in a Social Paradigm that Manipulates Reward and Shock.
|
The ability to recognize emotions in others and adapt one's behavior accordingly is critical for functioning in any social context. This ability is impaired in several psychiatric disorders, such as autism and psychopathy. Recent work has identified the anterior cingulate cortex (ACC) among other brain regions involved in this process. Neural recording studies have shown that neurons in ACC are modulated by reward or shock when delivered to a conspecific and when experienced first-hand. Because previous studies do not vary reward and shock within the same experiment, it has been unclear whether the observed activity reflects how much attention is being paid to outcomes delivered to a conspecific or the valence associated with those stimuli. To address this issue, we recorded from ACC as rats performed a Pavlovian task that predicted whether reward, shock, or nothing would be delivered to the rat being recorded from or a conspecific located in the opposite chamber. Consistent with previous reports, we found that the firing of ACC neurons was modulated by aversive stimuli delivered to the recording rat and their conspecific. Activity of some of these neurons genuinely reflected outcome identity (i.e., reward or shock); however, the population of neurons as a whole responded similarly for both reward and shock, as well as for cues that predicted their occurrence (i.e., reward > neutral and shock > neutral; attention). These results suggest that ACC can process information about outcomes (i.e., identity and recipient) in the service of promoting attention in some social contexts.
|
Current biology : CB
| 2,020
| 10
| 0
| 0
|
32,736,084
|
Neurofibromatosis 1 - Mutant microglia exhibit sexually-dimorphic cyclic AMP-dependent purinergic defects.
|
As critical regulators of brain homeostasis, microglia are influenced by numerous factors, including sex and genetic mutations. To study the impact of these factors on microglia biology, we employed genetically engineered mice that model Neurofibromatosis type 1 (NF1), a disorder characterized by clinically relevant sexually dimorphic differences. While microglia phagocytic activity was reduced in both male and female heterozygous Nf1 mutant (Nf1+/-) mice, purinergic control of phagocytosis was only affected in male Nf1+/- mice. ATP-induced P2Y-mediated membrane currents and P2RY12-dependent laser lesion-induced accumulation of microglial processes were also only impaired in male, but not female Nf1+/-, microglia. These defects resulted from Nf1+/- male-specific defects in cyclic AMP regulation, rather than from changes in purinergic receptor expression. Cyclic AMP elevation by phosphodiesterase blockade restored the male Nf1+/- microglia defects in P2Y-dependent membrane currents and process motility. Taken together, these data establish a sex-by-genotype interaction important to microglia function in the adult mouse brain.
|
Neurobiology of disease
| 2,020
| 10
| 0
| 0
|
32,593,131
|
Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma.
|
The humanized monoclonal antibody benralizumab targets the α subunit of the interleukin-5 (IL-5) receptor and the FcγRIIIa receptor expressed by natural killer cells. Through this dual mechanism of action, benralizumab neutralizes the pro-eosinophil functions of IL-5 and promotes eosinophil apoptosis.
|
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
| 2,020
| 9
| 0
| 0
|
24,304,777
|
Difficulty matters: unspecific attentional demands as a major determinant of performance highlighted by clinical studies.
|
The cognitive impairments shown by brain-damaged patients emphasize the role of task difficulty as a major determinant for performance. We discuss the proposal of Kurzban et al. in light of our findings on right-hemisphere-damaged patients, who show increasing awareness deficits for the contralesional hemispace when engaged with resource-consuming dual tasks. This phenomenon is readily explained by the assumption of unspecific depletable resources.
|
The Behavioral and brain sciences
| 2,013
| 12
| 0
| 0
|
30,001,511
|
Parallel Processing of Negative Feedback: E Unum Pluribus.
|
How do canonical computational elements interact to shape neural circuit function? In this issue of Neuron, Drinnenberg et al. (2018) show that parallel processing converts unitary negative feedback at the first synapse of the retina into diverse output signals to the brain.
|
Neuron
| 2,018
| 7
| 0
| 0
|
32,561,452
|
Remodeling microglia to a protective phenotype in Parkinson's disease?
|
Parkinson's disease (PD) is the most widespread movement disorder with a prevalence of 1 in 1000 individuals above 60 years of age. Until now, understanding the pathological mechanisms of PD to translate them into therapy has remained a high research priority. In this review, we highlight evidence describing the involvement of microglial dysfunction in PD. Thereafter, we provide current knowledge suggesting that the substantia nigra pars compacta and putamen, compared to other brain regions, show a reduced microglial density, as well as altered morphological and functional properties in homeostatic conditions, while presenting dystrophic features associated with aging. Further, we describe that this defective microglial programing emerges as early as the second postnatal week, persists until adulthood and impacts negatively on their transcriptional pattern and provision of local trophic support. We emphasize the role of α-synuclein oligomers as a major dysfunctional signal underlining microglial-mediated phenotypic switch and adaptive response contributing to neurodegeneration. Moreover, we explore available avenues should microglia be considered as target for neuroprotective or restorative strategies including preventing the aggregation of α-synuclein protofibrils formation. However, we provide a note of caution regarding the success of microglial-targeted PD strategies, using minocycline as an example. In conclusion, we discuss putative neuroprotective agents that were unsuccessful in previous trials but could be reconsidered by focusing on the stage of microglial-dependent pathogenic events during PD in suitable cohorts of patients.
|
Neuroscience letters
| 2,020
| 9
| 0
| 0
|
21,615,736
|
Study of the distribution of microvessels in normal and pathologic prostate using an information-based similarity analysis.
|
Categorizing biologic signals by analysis of symbolic sequences was employed in the study of prostate microvessels. The estimates of the volume fraction of the vessels immunostained to Factor-VIII was mapped to binary sequences. The distance between sequences was estimated by comparing the rank and frequency of repetitive elements. These measurements were applied to detect whether there are unique microvascular patterns for each individual, and to search for patterns describing prostate microvessels of different conditions. Normal prostate, benign prostate hyperplasia and prostate carcinoma groups were studied. All the specimens were immunostained to F-VIII and strips formed by adjacent quadrats were explored. At each point of the long axis of the strip, the V(V) F-VIII was calculated. These values were processed with the information-based similarity software to estimate the dissimilarity between two space series. The following comparisons were carried out: intrasubject versus intragroup distances; intragroup distances among the groups studied and intergroup distances. The distance defined between a vessels immunostained to Factor-VIII space series and its randomized surrogate was considered as an index of the nonrandomness of the space series. These indices were compared for all the groups. We conclude that (a) The information-based similarity analysis can be adapted to vessels immunostained to Factor-VIII space series from prostate microvessels. (b) There are no unique microvascular patterns associated with each individual. (c) There are characteristic patterns describing the microvessels from normal prostate, benign prostate hyperplasia and carcinoma. (d) This method is able to account for the differences between prostate cancer and both normal and benign prostate conditions, with respect to the microvessel patterns.
|
Journal of microscopy
| 2,011
| 9
| 0
| 0
|
27,279,159
|
[Multiple Sclerosis and Commensal Gut Flora].
|
Although a symbiotic relationship between commensal gut microbiota and host is widely appreciated, recent works have indicated that normal gut flora functions to prevent inflammatory bowel diseases and obesity in the host, indicating a more mutualistic relationship. Dysbiosis of the commensal flora may lead to development of these disorders. Studies using experimental auto immune encephalomyelitis (EAE), a rodent model for studying multiple sclerosis (MS), revealed that onset of MS may be triggered by dysbiosis in the gut. We recently revealed a significant reduction in certain clostridia strains, which probably function to induce regulatory T cells, in the gut microbiota of patients with MS. Results from this study should be consideved when designing strategies for the prevention and treatment of MS.
|
Brain and nerve = Shinkei kenkyu no shinpo
| 2,016
| 6
| 0
| 0
|
32,976,951
|
The endocannabinoid system in the amygdala and modulation of fear.
|
Posttraumatic stress disorder (PTSD) is a persistent, trauma induced psychiatric condition characterized by lifelong complex cognitive, emotional and behavioral phenotype. Although many individuals that experience trauma are able to gradually diminish their emotional responding to trauma-related stimuli over time, known as extinction learning, individuals suffering from PTSD are impaired in this capacity. An inability to decline this initially normal and adaptive fear response, can be confronted with exposure-based therapies, often in combination with pharmacological treatments. Due to the complexity of PTSD, currently available pharmacotherapeutics are inadequate in treating the deficient extinction observed in many PTSD patients. To develop novel therapeutics, researchers have exploited the conserved nature of fear and stress-associated behavioral responses and neurocircuits across species in an attempt to translate knowledge gained from preclinical studies into the clinic. There is growing evidence on the endocannabinoid modulation of fear and stress due to their 'on demand' synthesis and degradation. Involvement of the endocannabinoids in fear extinction makes the endocannabinoid system very attractive for finding effective therapeutics for trauma and stress related disorders. In this review, a brief introduction on neuroanatomy and circuitry of fear extinction will be provided as a model to study PTSD. Then, the endocannabinoid system will be discussed as an important component of extinction modulation. In this regard, anandamide degrading enzyme, fatty acid amide hydrolase (FAAH) will be exemplified as a target identified and validated strongly from preclinical to clinical translational studies of enhancing extinction.
|
Progress in neuro-psychopharmacology & biological psychiatry
| 2,021
| 3
| 0
| 0
|
33,070,094
|
The age-dependent associations of white matter hyperintensities and neurofilament light in early- and late-stage Alzheimer's disease.
|
Neurofilament light (NFL) is an emerging marker of axonal degeneration. This study investigated the relationship between white matter hyperintensities (WMHs) and plasma NFL in a large elderly cohort with, and without, cognitive impairment. We used the Alzheimer's Disease Neuroimaging Initiative and included 163 controls, 103 participants with a significant memory concern, 279 with early mild cognitive impairment (EMCI), 152 with late mild cognitive impairment (LMCI), and 130 with Alzheimer's disease, with 3T MRI and plasma NFL data. Multiple linear regression models examined the relationship between WMHs and NFL, with and without age adjustment. We used smoking status, history of hypertension, history of diabetes, and BMI as additional covariates to examine the effect of vascular risk. We found increases of between 20% and 41% in WMH volume per 1SD increase in NFL in significant memory concern, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer's disease groups (p < 0.02). Marked attenuation of the positive associations between WMHs and NFL were seen after age adjustment, suggesting that a significant proportion of the association between NFL and WMHs is age-related. No effect of vascular risk was observed. These results are supportive of a link between WMH and axonal degeneration in early to late disease stages, in an age-dependent, but vascular risk-independent manner.
|
Neurobiology of aging
| 2,021
| 1
| 0
| 0
|
33,289,879
|
The roles of ascending sensory signals and top-down central control in the entrainment of a locomotor CPG.
|
Previous authors have proposed two basic hypotheses about the factors that form the basis of locomotor rhythms in walking insects: sensory feedback only or sensory feedback together with rhythmic activity of small neural circuits called central pattern generators (CPGs). Here we focus on the latter. Following this concept, to generate functional outputs, locomotor control must feature both rhythm generation by CPGs at the level of individual joints and coordination of their rhythmic activities, so that all muscles are activated in an appropriate pattern. This work provides an in-depth analysis of an aspect of this coordination process based on an existing network model of stick insect locomotion. Specifically, we consider how the control system for a single joint in the stick insect leg may produce rhythmic output when subjected to ascending sensory signals from other joints in the leg. In this work, the core rhythm generating CPG component of the joint under study is represented by a classical half-center oscillator constrained by a basic set of experimental observations. While the dynamical features of this CPG, including phase transitions by escape and release, are well understood, we provide novel insights about how these transition mechanisms yield entrainment to the incoming sensory signal, how entrainment can be lost under variation of signal strength and period or other perturbations, how entrainment can be restored by modulation of tonic top-down drive levels, and how these factors impact the duty cycle of the motor output.
|
Biological cybernetics
| 2,020
| 12
| 0
| 0
|
31,704,493
|
A Standardized Anxiety Quotient in Elevated Open Platform Task Quantifies Rodent Anxiogenic Tendency with Improved Reliability and Sensitivity.
|
Sensitivity and reliability of animal behavioral assessment methods are critical for successful translation of in vitro findings to in vivo. Here we report a data transformation process in the elevated open platform task that generates a novel parameter, namely peak tolerance of fear (PTF) or its inversely correlated equivalent of anxiety quotient (AQ), to measure anxiogenic tendency in rodent. As compared to traditional parameters such as travel distance, time, or entries, PTF or AQ displays largely reduced data dispersion not only ingroup but also cross-study and cross-cohort, therefore representing a significant improvement of the methodology for rodent anxiety assessment.
|
Neuroscience
| 2,019
| 12
| 0
| 0
|
33,181,855
|
Multisystem inflammatory syndrome with refractory cardiogenic shock due to acute myocarditis and mononeuritis multiplex after SARS-CoV-2 infection in an adult.
|
A 22-year-old male with a typical history of pauci-symptomatic COVID-19 3 weeks earlier, confirmed by positive serology for SARS-CoV-2 (IgG), was admitted to the intensive care unit because of severe myocarditis with refractory cardiogenic shock that required extracorporeal life support. Due to a clinical presentation suggestive of Kawasaki-like disease with coronary aneurysm and severe systemic inflammation, intravenous immunoglobulins were administered in combination with tocilizumab. The initial clinical course was favourable with these treatments. However, the patient subsequently developed a severe mononeuritis multiplex leading to bilateral foot drop, which required intensive immunosuppressive therapy (corticosteroids, cyclophosphamide and rituximab). The clinical presentation meets the criteria for multisystem inflammatory syndrome associated with SARS-CoV-2, but includes very severe organ damages. Early recognition, a multidisciplinary approach and aggressive therapeutic intervention can lead to a favourable outcome.
|
Swiss medical weekly
| 2,020
| 11
| 0
| 0
|
30,048,622
|
hRPE cells derived from induced pluripotent stem cells are more sensitive to oxidative stress than ARPE-19 cells.
|
The ARPE-19 cell line is currently used as an in vitro model for retinal diseases such as age-related degeneration (AMD). However, several studies have pointed out morphological and genetic differences between ARPE-19 cells and human fetal or adult retinal pigment epithelial (hRPE) cells. This study aims to compare ARPE-19 cells to hRPE cells derived from human induced pluripotent stem cells (hiPSCs) in both normal and oxidative stress conditions induced by Fe-NTA treatment. Indeed, oxidative stress is an essential contributing factor in AMD. hiPSC obtained from peripheral venous blood samples or fibroblasts of individuals aged over 60 years were first reprogrammed to hiPSC and then differentiated into RPE cells. In contrast to ARPE-19 cells, hiPSC-RPE cells expressed β-galactosidase activity, suggesting that only the latter display signs of senescence. Treatment with 10 mM of FeNTA induced a higher reactive oxygen species (ROS) production and increased cell death in hiPSC-RPE cells compared to ARPE-19 cells. Moreover, morphological analysis and Annexin V and Propidium iodide (PI) test suggested a necrotic cell death pattern induced by treatment in hiPSC-RPE cells that is not observed in ARPE-19 cells. Taken as a whole, our findings suggest that hiPSC-RPE cells are more sensitive to oxidative stress than ARPE-19 cells.
|
Experimental eye research
| 2,018
| 12
| 0
| 0
|
32,985,459
|
Postnatal therapeutic approaches in genetic neurodevelopmental disorders.
|
Genetic neurodevelopmental disorders are characterized by abnormal neurophysiological and behavioral phenotypes, affecting individuals worldwide. While the subject has been heavily researched, current treatment options relate mostly to alleviating symptoms, rather than targeting the altered genome itself. In this review, we address the neurogenetic basis of neurodevelopmental disorders, genetic tools that are enabling precision research of these disorders in animal models, and postnatal gene-therapy approaches for neurodevelopmental disorders derived from preclinical studies in the laboratory.
|
Neural regeneration research
| 2,021
| 3
| 0
| 0
|
30,346,333
|
Efficacy and Safety of a Rapid Intravenous Injection of Ketamine 0.5 mg/kg in Treatment-Resistant Major Depression: An Open 4-Week Longitudinal Study.
|
Ketamine has been documented for its rapid antidepressant effects. However, optimal dose and delivery route have not yet been thoroughly investigated. The objectives of this study were to document the safety and test the antidepressant and antisuicidal effects of a single rapid 1-minute injection of ketamine 0.5 mg/kg in treatment-resistant depression (TRD).
|
Journal of clinical psychopharmacology
| 2,018
| 12
| 0
| 0
|
32,574,661
|
The role of sleep disturbances in depressive-like behavior with emphasis on α-ketoglutarate dehydrogenase activity in rats.
|
Sleep disorders may induce anxiety- and depressive-like behaviors. Furthermore, sleep disorders can alter the function of α-KGDH (α-ketoglutarate dehydrogenase), which is involved in the citric acid cycle. In this study, we evaluated the effect of two models of sleep deprivation (SD) including total SD (TSD) and partial SD (PSD), and two models of napping combined with each models of SD on rats' performance in Forced Swim Test (FST) and α-KGDH activity in both hemispheres of the amygdala. 64 male Wistar rats were used in this study. A modified water box was also used to induce SD. The results showed that, immobility was increased in 48-hour PSD group, indicating a possible depressive-like behavior. Swimming time was also increased following 48-hour TSD. However, climbing time was decreased in 48-hour PSD/TSD groups. Additionally, α-KGDH activity was increased in the left amygdala in 48-hour TSD and PSD groups. In conclusion, PSD may increase depressive-like behavior. TSD and PSD can decrease swimming time but increase climbing time, and these effects may be related to serotonergic and noradrenergic transmissions, respectively. Increase in α-KGDH activity in the left amygdala may be related to the brain's need for more energy during prolonged wakefulness. α-KGDH activity in the right amygdala was unaffected probably due to a decrease in alertness following SD.
|
Physiology & behavior
| 2,020
| 10
| 0
| 0
|
32,643,498
|
Buying-shopping disorder, emotion dysregulation, coping and materialism: a comparative approach with gambling patients and young people and adolescents.
|
The comorbidity between gambling disorder (GD) and buying-shopping disorder (BSD) has led to explore the core features that could be interacting between them. The main aim of this study was to examine the differences in both conditions considering emotion dysregulation, coping and materialism, as well as the relationship between these variables and their interaction with age and sex.
|
International journal of psychiatry in clinical practice
| 2,020
| 11
| 0
| 0
|
33,236,784
|
Connectome biomarkers of drug-resistant epilepsy.
|
Drug-resistant epilepsy (DRE) considerably affects patient health, cognition, and well-being, and disproportionally contributes to the overall burden of epilepsy. The most common DRE syndromes are temporal lobe epilepsy related to mesiotemporal sclerosis and extratemporal epilepsy related to cortical malformations. Both syndromes have been traditionally considered as "focal," and most patients benefit from brain surgery for long-term seizure control. However, increasing evidence indicates that many DRE patients also present with widespread structural and functional network disruptions. These anomalies have been suggested to relate to cognitive impairment and prognosis, highlighting their importance for patient management. The advent of multimodal neuroimaging and formal methods to quantify complex systems has offered unprecedented ability to profile structural and functional brain networks in DRE patients. Here, we performed a systematic review on existing DRE network biomarker candidates and their contribution to three key application areas: (1) modeling of cognitive impairments, (2) localization of the surgical target, and (3) prediction of clinical and cognitive outcomes after surgery. Although network biomarkers hold promise for a range of clinical applications, translation of neuroimaging biomarkers to the patient's bedside has been challenged by a lack of clinical and prospective studies. We therefore close by highlighting conceptual and methodological strategies to improve the evaluation and accessibility of network biomarkers, and ultimately guide clinically actionable decisions.
|
Epilepsia
| 2,021
| 1
| 0
| 0
|
33,156,956
|
Serotonin receptor 4 regulates hippocampal astrocyte morphology and function.
|
Astrocytes are an important component of the multipartite synapse and crucial for proper neuronal network function. Although small GTPases of the Rho family are powerful regulators of cellular morphology, the signaling modules of Rho-mediated pathways in astrocytes remain enigmatic. Here we demonstrated that the serotonin receptor 4 (5-HT
|
Glia
| 2,021
| 4
| 0
| 0
|
32,988,409
|
Combination of plasma amyloid beta
|
Blood-based biomarkers for Alzheimer's disease (AD) might facilitate identification of participants for clinical trials targeting amyloid beta (Abeta) accumulation, and aid in AD diagnostics. We examined the potential of plasma markers Abeta
|
Alzheimer's research & therapy
| 2,020
| 9
| 0
| 0
|
33,860,763
|
Synaptic learning rules for sequence learning.
|
Remembering the temporal order of a sequence of events is a task easily performed by humans in everyday life, but the underlying neuronal mechanisms are unclear. This problem is particularly intriguing as human behavior often proceeds on a time scale of seconds, which is in stark contrast to the much faster millisecond time-scale of neuronal processing in our brains. One long-held hypothesis in sequence learning suggests that a particular temporal fine-structure of neuronal activity - termed 'phase precession' - enables the compression of slow behavioral sequences down to the fast time scale of the induction of synaptic plasticity. Using mathematical analysis and computer simulations, we find that - for short enough synaptic learning windows - phase precession can improve temporal-order learning tremendously and that the asymmetric part of the synaptic learning window is essential for temporal-order learning. To test these predictions, we suggest experiments that selectively alter phase precession or the learning window and evaluate memory of temporal order.
|
eLife
| 2,021
| 4
| 0
| 0
|
29,888,997
|
Surgical treatment of bilateral glossopharyngeal neuralgia.
|
Glossopharyngeal neuralgia (GPN) is a condition characterised by sudden, severe pain in the distribution of the glossopharyngeal nerve. It can be triggered by talking, yawning, coughing and swallowing. Classically, patients experience a unilateral lancinating and excruciating pain described as electrical shock-like pain in the areas around the ear, tongue, or the mandibular angle. Uncommon manifestations include cardiac arrhythmias and syncope during pain episodes. Surgery is indicated in refractory cases. Bilateral GPN is rare, and definitive surgical treatment for bilateral GPN has not yet been reported. In this case report, a young woman with bilateral GPN who underwent staged surgery bilaterally is described. She did not develop life-threatening cardiac abnormalities postoperatively.
|
The International journal of neuroscience
| 2,018
| 12
| 0
| 0
|
29,735,372
|
Fornical Closed-Loop Stimulation for Alzheimer's Disease.
|
Pharmacological neuromodulation strategies have shown limited efficacy in treating memory deficits related to Alzheimer's disease (AD). Despite encouraging results from a few preclinical studies, clinical trials investigating open-loop deep brain stimulation (DBS) for AD have not been successful. Recent refinements in understanding the various phases of memory processes, animal studies investigating phase-specific modulation of hippocampal activity during memorization, and clinical studies using closed-loop DBS strategies to treat patients with movement disorders, all point to the need to investigate closed-loop fornical DBS strategies to better understand memory dynamics and potentially treat memory deficits in AD preclinical models.
|
Trends in neurosciences
| 2,018
| 7
| 0
| 0
|
33,450,392
|
Multiple genetic pathways regulating lifespan extension are neuroprotective in a G2019S LRRK2 nematode model of Parkinson's disease.
|
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of late-onset, familial Parkinson's disease (PD), and LRRK2 variants are associated with increased risk for sporadic PD. While advanced age represents the strongest risk factor for disease development, it remains unclear how different age-related pathways interact to regulate LRRK2-driven late-onset PD. In this study, we employ a C. elegans model expressing PD-linked G2019S LRRK2 to examine the interplay between age-related pathways and LRRK2-induced dopaminergic neurodegeneration. We find that multiple genetic pathways that regulate lifespan extension can provide robust neuroprotection against mutant LRRK2. However, the level of neuroprotection does not strictly correlate with the magnitude of lifespan extension, suggesting that lifespan can be experimentally dissociated from neuroprotection. Using tissue-specific RNAi, we demonstrate that lifespan-regulating pathways, including insulin/insulin-like growth factor-1 (IGF-1) signaling, target of rapamycin (TOR), and mitochondrial respiration, can be directly manipulated in neurons to mediate neuroprotection. We extend this finding for AGE-1/PI3K, where pan-neuronal versus dopaminergic neuronal restoration of AGE-1 reveals both cell-autonomous and non-cell-autonomous neuroprotective mechanisms downstream of insulin signaling. Our data demonstrate the importance of distinct lifespan-regulating pathways in the pathogenesis of LRRK2-linked PD, and suggest that extended longevity is broadly neuroprotective via the actions of these pathways at least in part within neurons. This study further highlights the complex interplay that occurs between cells and tissues during organismal aging and disease manifestation.
|
Neurobiology of disease
| 2,021
| 4
| 0
| 0
|
32,282,363
|
Maintaining Muscle Function Across the Lifespan: The State of Science.
|
Sarcopenia is a geriatric syndrome currently defined as pathological loss of muscle mass and function. Sarcopenia is not only a major contributor to loss of physical function in older adults but is also associated with increased risk of morbidity, mortality, and increased healthcare costs. As a complex and multifactorial syndrome, sarcopenia has been associated with numerous degenerative changes during the aging process, but there is building evidence for significant contributions to the development of sarcopenia from neurodegenerative changes in the peripheral nervous system. A variety of interventions have been investigated for the treatment of sarcopenia, but current management is primarily focused on nutrition and therapeutic exercise interventions. Great strides have been made to improve screening procedures and diagnostic criteria for sarcopenia, but continued optimization of diagnostic and screening strategies is needed to better identify individuals with sarcopenia or at risk of developing sarcopenia. Understanding and addressing the major drivers of sarcopenia pathogenesis will help develop therapeutics that can reduce the impact of sarcopenia on affected individuals and society.
|
American journal of physical medicine & rehabilitation
| 2,020
| 12
| 0
| 0
|
33,319,374
|
Murray Sidman and Patient H. M.: The role of behavior analysis in the emergence of collaborative modern neuroscience.
|
The intersection of the lives of 2 essential individuals in science, behavior analyst Murray Sidman (1923-2019), and Henry G. Molaison also known as Patient H.M. (1926-2008), warrants examination as it highlights the role of behavior analysis and other disciplines in the emergence of modern neuroscience and a collaborative approach to science. This paper describes the historical context and content of two publications by Sidman in which Molaison served as a research participant. The goal of the present paper is to emphasize this little-known facet of Sidman's rich career and to highlight the pioneering role of behavior analysis, and particularly the work of Murray Sidman, in the emergence of collaborative modern neuroscience.
|
Journal of the experimental analysis of behavior
| 2,021
| 1
| 0
| 0
|
28,196,698
|
[When and how prescribe antipsychotics?].
|
Antipsychotics are commonly prescribed in the general population since they have many indications. They can be used in acute care such as agitation or behavior disorders, or to treat more characterized psychiatric disorders like psychotic or mood disorders. Consequently, any practitioner will have to prescribe or renew a prescription of antipsychotics. These treatments require a benefit/risk balance assessment taking into account the specific context of each patient. Indeed, antipsychotics have many side effects, mainly neurological (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac. If these complications are poorly controlled, they could dramatically increase the morbidity and the mortality. Second-generation antipsychotics should be preferred to first-generation antipsychotics because of their better safety profile, especially in case of prolonged prescribing. Treatment monitoring, including effectiveness on the targeted symptoms, tolerance and observance, are major issues in the management of patients treated with antipsychotics.
|
La Revue de medecine interne
| 2,017
| 5
| 0
| 0
|
32,940,130
|
Proteoglycan 4 Reduces Neuroinflammation and Protects the Blood-Brain Barrier after Traumatic Brain Injury.
|
Neuroinflammation and dysfunction of the blood-brain barrier (BBB) are two prominent mechanisms of secondary injury in neurotrauma. It has been suggested that Toll-like receptors (TLRs) play important roles in initiating and propagating neuroinflammation resulting from traumatic brain injury (TBI), but potential beneficial effects of targeting these receptors in TBI have not been broadly studied. Here, we investigated the effect of targeting TLRs with proteoglycan 4 (PRG4) on post-traumatic neuroinflammation and BBB function. PRG4 is a mucinous glycoprotein with strong anti-inflammatory properties, exerting its biological effects by interfering with TLR2/4 signaling. In addition, PRG4 has the ability to inhibit activation of cluster of differentiation 44 (CD44), a cell-surface glycoprotein playing an important role in inflammation. Using the controlled cortical impact model of TBI in rats, we showed a rapid and prolonged upregulation of message for TLR2/4 and CD44 in the injured cortex. In the
|
Journal of neurotrauma
| 2,021
| 2
| 0
| 0
|
33,556,807
|
Wireless and battery-free platforms for collection of biosignals.
|
Recent progress in biosensors have quantitively expanded current capabilities in exploratory research tools, diagnostics and therapeutics. This rapid pace in sensor development has been accentuated by vast improvements in data analysis methods in the form of machine learning and artificial intelligence that, together, promise fantastic opportunities in chronic sensing of biosignals to enable preventative screening, automated diagnosis, and tools for personalized treatment strategies. At the same time, the importance of widely accessible personal monitoring has become evident by recent events such as the COVID-19 pandemic. Progress in fully integrated and chronic sensing solutions is therefore increasingly important. Chronic operation, however, is not truly possible with tethered approaches or bulky, battery-powered systems that require frequent user interaction. A solution for this integration challenge is offered by wireless and battery-free platforms that enable continuous collection of biosignals. This review summarizes current approaches to realize such device architectures and discusses their building blocks. Specifically, power supplies, wireless communication methods and compatible sensing modalities in the context of most prevalent implementations in target organ systems. Additionally, we highlight examples of current embodiments that quantitively expand sensing capabilities because of their use of wireless and battery-free architectures.
|
Biosensors & bioelectronics
| 2,021
| 4
| 0
| 0
|
27,255,704
|
Long Pauses in Cerebellar Interneurons in Anesthetized Animals.
|
Are long pauses in the firing of cerebellar interneurons (CINs) related to Purkinje cell (PC) pauses? If PC pauses affect the larger network, then we should find a close relationship between CIN pauses and those in PCs. We recorded activity of 241 cerebellar cortical neurons (206 CINs and 35 PCs) in three anesthetized cats. One fifth of the CINs and more than half of the PCs were identified as pausing. Pauses in CINs and PCs showed some differences: CIN mean pause length was shorter, and, after pauses, only CINs had sustained reduction in their firing rate (FR). Almost all pausing CINs fell into same cluster when we used different methods of clustering CINs by their spontaneous activity. The mean spontaneous firing rate of that cluster was approximately 53 Hz. We also examined cross-correlations in simultaneously recorded neurons. Of 39 cell pairs examined, 14 (35 %) had cross-correlations significantly different from those expected by chance. Almost half of the pairs with two CINs showed statistically significant negative correlations. In contrast, PC/CIN pairs did not often show significant effects in the cross-correlation (12/15 pairs). However, for both CIN/CIN and PC/CIN pairs, pauses in one unit tended to correspond to a reduction in the firing rate of the adjacent unit. In our view, our results support the possibility that previously reported PC bistability is part of a larger network response and not merely a biophysical property of PCs. Any functional role for PC bistability should probably be sought in the context of the broader network.
|
Cerebellum (London, England)
| 2,017
| 4
| 0
| 0
|
33,427,693
|
Impaired disengagement of attention from computer-related stimuli in Internet Gaming Disorder: Behavioral and electrophysiological evidence.
|
Attentional biases contribute to the maintenance of addictive behaviors. For the problematic use of online gaming - recognized as Internet Gaming Disorder (IGD) - first evidence points to a bias towards in-game stimuli. This study aimed to provide behavioral and electrophysiological evidence for a generalized bias towards computer-related stimuli, and to identify the specific attentional processes contributing to this bias: facilitated attention deployment, impaired disengagement or failed suppression.
|
Journal of behavioral addictions
| 2,021
| 1
| 0
| 0
|
33,137,472
|
Sharing voxelwise neuroimaging results from rhesus monkeys and other species with Neurovault.
|
Animal neuroimaging studies can provide unique insights into brain structure and function, and can be leveraged to bridge the gap between animal and human neuroscience. In part, this power comes from the ability to combine mechanistic interventions with brain-wide neuroimaging. Due to their phylogenetic proximity to humans, nonhuman primate neuroimaging holds particular promise. Because nonhuman primate neuroimaging studies are often underpowered, there is a great need to share data amongst translational researchers. Data sharing efforts have been limited, however, by the lack of standardized tools and repositories through which nonhuman neuroimaging data can easily be archived and accessed. Here, we provide an extension of the Neurovault framework to enable sharing of statistical maps and related voxelwise neuroimaging data from other species and template-spaces. Neurovault, which was previously limited to human neuroimaging data, now allows researchers to easily upload and share nonhuman primate neuroimaging results. This promises to facilitate open, integrative, cross-species science while affording researchers the increased statistical power provided by data aggregation. In addition, the Neurovault code-base now enables the addition of other species and template-spaces. Together, these advances promise to bring neuroimaging data sharing to research in other species, for supplemental data, location-based atlases, and data that would otherwise be relegated to a "file-drawer". As increasing numbers of researchers share their nonhuman neuroimaging data on Neurovault, this resource will enable novel, large-scale, cross-species comparisons that were previously impossible.
|
NeuroImage
| 2,021
| 1
| 0
| 0
|
33,127,445
|
Norepinephrine transporter antagonism prevents dopamine-dependent synaptic plasticity in the mouse dorsal hippocampus.
|
The rodent dorsal hippocampus is essential for episodic memory consolidation, a process heavily modulated by dopamine D1-like receptor (D1/5R) activation. It was previously thought that the ventral tegmental area provided the only supply of dopamine release to dorsal hippocampus, but several recent studies have established the locus coeruleus (LC) as the major source for CA1. Here we show that selective blockade of the norepinephrine transporter (NET) prevents dopamine-dependent, late long-term synaptic potentiation (LTP) in dorsal CA1, a neural correlate of memory formation that relies on LC-mediated activation of D1/5Rs. Since dopamine activation of D1/5Rs by vesicular release is expected to be enhanced by NET antagonism, our data identify NET reversal as a plausible mechanism for LC-mediated DA release. We also show that genetic deletion of LC NMDA receptors (NMDARs) blocks D1R-mediated LTP, suggesting the requirement of both a functional NET and presynaptic NMDARs for this release. As LC activity is highly correlated with attentional processes and memory, these experiments provide insight into how selective attention influences memory formation at the synaptic and circuit levels.
|
Neuroscience letters
| 2,021
| 1
| 0
| 0
|
28,880,735
|
2017 Midwest Zebrafish Meeting Report.
|
The 2017 Midwest Zebrafish meeting was held from June 16 to 18 at the University of Cincinnati, sponsored by the Cincinnati Children's Hospital Divisions of Developmental Biology, Molecular Cardiovascular Biology, and Gastroenterology, Hepatology, and Nutrition. The meeting, organized by Saulius Sumanas, Joshua Waxman, and Chunyue Yin, hosted >130 attendees from 16 different states. Scientific sessions were focused on morphogenesis, neural development, novel technologies, and disease models, with Steve Ekker, Stephen Potter, and Lila Solnica-Krezel presenting keynote talks. In this article, we highlight the results and emerging themes from the meeting.
|
Zebrafish
| 2,017
| 12
| 0
| 0
|
28,815,714
|
WILLIAM HAZLITT, OBSESSIVE LOVE, AND LIBER AMORIS.
|
William Hazlitt, a distinguished literary figure of the early nineteenth century and a forerunner of psychoanalytic insights, had a keen awareness of the impact of the imagination on assessing works of art. At forty-two, he became hopelessly involved in an obsessive love affair with a nineteen-year-old woman and could not extricate himself from the relationship. The affair followed the death of his father, a powerful influence on his life. Factors in his obsessive love included finding an object of idealization subject to his imaginative creation and narcissistically reexperiencing himself about to begin a new life.
|
The Psychoanalytic quarterly
| 2,017
| 7
| 0
| 0
|
32,898,679
|
A coordinate-based meta-analysis of music-evoked emotions.
|
Since the publication of the first neuroscience study investigating emotion with music about two decades ago, the number of functional neuroimaging studies published on this topic has increased each year. This research interest is in part due to the ubiquity of music across cultures, and to music's power to evoke a diverse range of intensely felt emotions. To support a better understanding of the brain correlates of music-evoked emotions this article reports a coordinate-based meta-analysis of neuroimaging studies (n = 47 studies with n = 944 subjects). The studies employed a range of diverse experimental approaches (e.g., using music to evoke joy, sadness, fear, tension, frissons, surprise, unpleasantness, or feelings of beauty). The results of an activation likelihood estimation (ALE) indicate large clusters in a range of structures, including amygdala, anterior hippocampus, auditory cortex, and numerous structures of the reward network (ventral and dorsal striatum, anterior cingulate cortex, orbitofrontal cortex, secondary somatosensory cortex). The results underline the rewarding nature of music, the role of the auditory cortex as an emotional hub, and the role of the hippocampus in attachment-related emotions and social bonding.
|
NeuroImage
| 2,020
| 12
| 0
| 0
|
33,004,691
|
IGF1, serum glucose, and retinopathy of prematurity in extremely preterm infants.
|
BACKGROUNDHyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood.METHODSIn 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum IGF1 levels were measured weekly. Mice with oxygen-induced retinopathy alone versus oxygen-induced retinopathy plus streptozotocin-induced hyperglycemia/hypoinsulinemia were assessed for glucose, insulin, IGF1, IGFBP1, and IGFBP3 in blood and liver. Recombinant human IGF1 was injected to assess the effect on glucose and retinopathy.RESULTSThe highest mean plasma glucose tertile of infants positively correlated with parenteral glucose intake [r(39) = 0.67, P < 0.0001]. IGF1 plasma levels were lower in the high tertile compared with those in low and intermediate tertiles at day 28 (P = 0.038 and P = 0.03). In high versus lower glucose tertiles, ROP was more prevalent (34 of 39 versus 19 of 39) and more severe (ROP stage 3 or higher; 71% versus 32%). In oxygen-induced retinopathy, hyperglycemia/hypoinsulinemia decreased liver IGF1 expression (P < 0.0001); rh-IGF1 treatment improved normal vascular regrowth (P = 0.027) and reduced neovascularization (P < 0.0001).CONCLUSIONIn extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased ROP severity. In a hyperglycemia retinopathy mouse model, decreased insulin signaling suppressed liver IGF1 production, lowered serum IGF1 levels, and increased neovascularization. IGF1 supplementation improved retinal revascularization and decreased pathological neovascularization. The data support IGF1 as a potential treatment for prevention of ROP.TRIAL REGISTRATIONClinicalTrials.gov NCT02760472 (Donna Mega).FUNDINGThis study has been supported by the Swedish Medical Research Council (14940, 4732, 20144-01-3, and 21144-01-3), a Swedish government grant (ALFGB2770), Lund medical faculty grants (ALFL, 11615 and 11601), the Skåne Council Foundation for Research and Development, the Linnéa and Josef Carlsson Foundation, the Knut and Alice Wallenberg Foundation, the NIH/National Eye Institute (EY022275, EY017017, EY017017-13S1, and P01 HD18655), European Commission FP7 project 305485 PREVENT-ROP, Deutsche Forschungsgemeinschaft (CA-1940/1-1), and Stiftelsen De Blindas Vänner.
|
JCI insight
| 2,020
| 10
| 0
| 0
|
22,151,206
|
Spinal Cord Stimulation for the Relief of Pain: Proceedings of a Symposium during the 4th International Congress of the International Neuromodulation Society, September 16-20, 1998, Lucerne, Switzerland.
|
Spinal cord stimulation has become an accepted technique used in the management of chronic neuropathic pain syndromes. However, a number of problematic questions remain unanswered. This introduction states some of these problems and concentrates on the problem of whether low back pain can be relieved by stimulation. This paper introduces subsequent contributions to this symposium, which offer some interesting new techniques, and attempts to answer some of the problems presented.
|
Neuromodulation : journal of the International Neuromodulation Society
| 1,999
| 7
| 0
| 0
|
33,012,287
|
Vitamin B6, vitamin B12 and methionine and risk of pancreatic cancer: a meta-analysis.
|
Nutrients involved in one-carbon metabolism may play a key role in pancreatic carcinogenesis. The aim of this study was to examine the association between pancreatic cancer risk and intake or blood levels of vitamins B6, B12 and methionine via meta-analysis.
|
Nutrition journal
| 2,020
| 10
| 0
| 0
|
33,037,649
|
The role of herpesvirus 6A and 6B in multiple sclerosis and epilepsy.
|
Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are two closely related viruses that can infect cells of the central nervous system (CNS). The similarities between these viruses have made it difficult to separate them on serological level. The broad term HHV-6 remains when referring to studies where the two species were not distinguished, and as such, the seroprevalence is over 90% in the adult population. HHV-6B has been detected in up to 100% of infants with the primary infection roseola infantum, but less is known about the primary infection of HHV-6A. Both viruses are neurotropic and have capacity to establish lifelong latency in cells of the central nervous system, with potential to reactivate and cause complications later in life. HHV-6A infection has been associated with an increased risk of multiple sclerosis (MS), whereas HHV-6B is indicated to be involved in pathogenesis of epilepsy. These two associations show how neurological diseases might be caused by viral infections, but as suggested here, through completely different molecular mechanisms, in an autoimmune disease, such as MS, by triggering an overreaction of the immune system and in epilepsy by hampering internal cellular functions when the immune system fails to eliminate the virus. Understanding the viral mechanisms of primary infection and reactivation and their spectrum of associated symptoms will aid our ability to diagnose, treat and prevent these severe and chronic diseases. This review explores the role of HHV-6A and HHV-6B specifically in MS and epilepsy, the evidence to date and the future directions of this field.
|
Scandinavian journal of immunology
| 2,020
| 12
| 0
| 0
|
33,034,252
|
Demographically adjusted trail making test norms in a Scandinavian sample from 41 to 84 years.
|
The trail making test (TMT) is one of the most widely used neuropsychological tests. TMT-A provides measures of visual scanning/visuomotor speed and TMT-B involves additional demands on executive functions. Derived scores TMT B-A and TMT B/A enhance measures of executive functioning. However, simple B-A subtraction may lead to false estimates of executive dysfunction in clinical samples. Norms for TMT have been published in several countries but are currently lacking for Scandinavia.
|
The Clinical neuropsychologist
| 2,020
| 12
| 0
| 0
|
29,736,808
|
Serial dependence promotes the stability of perceived emotional expression depending on face similarity.
|
Individuals can quickly and effortlessly recognize facial expressions, which is critical for social perception and emotion regulation. This sensitivity to even slight facial changes could result in unstable percepts of an individual's expression over time. The visual system must therefore balance accuracy with maintaining perceptual stability. However, previous research has focused on our sensitivity to changing expressions, and the mechanism behind expression stability remains an open question. Recent results demonstrate that perception of facial identity is systematically biased toward recently seen visual input. This positive perceptual pull, or serial dependence, may help stabilize perceived expression. To test this, observers judged random facial expression morphs ranging from happy to sad to angry. We found a pull in perceived expression toward previously seen expressions, but only when the 1-back and current face had similar identities. Our results are consistent with the existence of the continuity field for expression, a specialized mechanism that promotes the stability of emotion perception, which could help facilitate social interactions and emotion regulation.
|
Attention, perception & psychophysics
| 2,018
| 8
| 0
| 0
|
33,006,962
|
Non-equilibrium landscape and flux reveal the stability-flexibility-energy tradeoff in working memory.
|
Uncovering the underlying biophysical principles of emergent collective computational abilities, such as working memory, in neural circuits is one of the most essential concerns in modern neuroscience. Working memory system is often desired to be robust against noises. Such systems can be highly flexible for adapting environmental demands. How neural circuits reconfigure themselves according to the cognitive task requirement remains unclear. Previous studies explored the robustness and the flexibility in working memory by tracing individual dynamical trajectories in a limited time scale, where the accuracy of the results depends on the volume of the collected statistical data. Inspired by thermodynamics and statistical mechanics in physical systems, we developed a non-equilibrium landscape and flux framework for studying the neural network dynamics. Applying this approach to a biophysically based working memory model, we investigated how changes in the recurrent excitation mediated by slow NMDA receptors within a selective population and mutual inhibition mediated by GABAergic interneurons between populations affect the robustness against noises. This is realized through quantifying the underlying non-equilibrium potential landscape topography and the kinetics of state switching. We found that an optimal compromise for a working memory circuit between the robustness and the flexibility can be achieved through the emergence of an intermediate state between the working memory states. An optimal combination of both increased self-excitation and inhibition can enhance the flexibility to external signals without significantly reducing the robustness to the random fluctuations. Furthermore, we found that the enhanced performance in working memory is supported by larger energy consumption. Our approach can facilitate the design of new network structure for cognitive functions with the optimal balance between performance and cost. Our work also provides a new paradigm for exploring the underlying mechanisms of many cognitive functions based on non-equilibrium physics.
|
PLoS computational biology
| 2,020
| 10
| 0
| 0
|
32,548,630
|
Connections of the Human Orbitofrontal Cortex and Inferior Frontal Gyrus.
|
The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better its roles in emotion and its disorders. The medial OFC and ventromedial prefrontal cortex have direct connections with the pregenual and subgenual parts of the anterior cingulate cortex; all of which are reward-related areas. The lateral OFC (OFClat) and its closely connected right inferior frontal gyrus (rIFG) have direct connections with the supracallosal anterior cingulate cortex; all of which are punishment or nonreward-related areas. The OFClat and rIFG also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the OFClat and rIFG. Another key finding is that the ventromedial prefrontal cortex shares with the medial OFC especially strong outputs to the nucleus accumbens and olfactory tubercle, which comprise the ventral striatum, whereas the other regions have more widespread outputs to the striatum. Direct connections of the OFC and IFG were with especially the temporal pole part of the temporal lobe. The left IFG, which includes Broca's area, has direct connections with the left angular and supramarginal gyri.
|
Cerebral cortex (New York, N.Y. : 1991)
| 2,020
| 10
| 0
| 0
|
33,570,938
|
Structural Mechanism of ω-Currents in a Mutated Kv7.2 Voltage Sensor Domain from Molecular Dynamics Simulations.
|
Activation of voltage-gated ion channels is regulated by conformational changes of the voltage sensor domains (VSDs), four water- and ion-impermeable modules peripheral to the central, permeable pore domain. Anomalous currents, defined as ω-currents, have been recorded in response to mutations of residues on the VSD S4 helix and associated with ion fluxes through the VSDs. In humans, gene defects in the potassium channel Kv7.2 result in a broad range of epileptic disorders, from benign neonatal seizures to severe epileptic encephalopathies. Experimental evidence suggests that the R207Q mutation in S4, associated with peripheral nerve hyperexcitability, induces ω-currents at depolarized potentials, but the fine structural details are still elusive. In this work, we use atom-detailed molecular dynamics simulations and a refined model structure of the Kv7.2 VSD in the active conformation in a membrane/water environment to study the effect of R207Q and four additional mutations of proven clinical importance. Our results demonstrate that the R207Q mutant shows the most pronounced increase of hydration in the internal VSD cavity, a feature favoring the occurrence of ω-currents. Free energy and kinetics calculations of sodium permeation through the native and mutated VSD indicate as more favorable the formation of a cationic current in the latter. Overall, our simulations establish a mechanistic linkage between genetic variations and their physiological outcome, by providing a computational description that includes both thermodynamic and kinetic features of ion permeation associated with ω-currents.
|
Journal of chemical information and modeling
| 2,021
| 3
| 0
| 0
|
32,731,050
|
Peripheral blood expression levels of inflammasome complex components in two different focal epilepsy syndromes.
|
Although the role of inflammation in epilepsy pathogenesis has been extensively investigated, the inflammasome complex, a key component of neuroinflammation, has been understudied in epilepsy patients.
|
Journal of neuroimmunology
| 2,020
| 10
| 0
| 0
|
32,503,086
|
Association between liver fibrosis and cognition in a nationally representative sample of older adults.
|
Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults.
|
European journal of neurology
| 2,020
| 10
| 0
| 0
|
26,494,297
|
Identification of the neural crest-specific enhancer of Seraf gene in avian peripheral nervous system development.
|
In vertebrate embryos, trunk neural crest cells give rise to Schwann cells, along with other derivatives. In this study, to elucidate the molecular mechanisms for the Schwann cell specification, we aimed to identify enhancer elements responsible for the expression of the Seraf gene, the earliest marker for the Schwann cell precursors in the avian embryos. We first compared the genomic structure around the Seraf locus in various vertebrates, and found that, while mammals do not have a Seraf homolog, teleost fish species have it. However, the intergenic sequences around the Seraf locus are not conserved between zebrafish and chicken, consistent with the fact that fish Seraf expression is not Schwann cell precursor-specific. We thus compared the intergenic sequences around the Seraf locus among avian species, and identified a potential enhancer containing a cluster of Sox10-binding sites. Accordingly, the identified enhancer is activated in a neural crest-specific manner in transfected quail embryos. We also found that Sox10 activated the enhancer in cultured cells. Thus, our results revealed a new role of Sox10 in the earliest phase of the Schwann cell fate specification.
|
Biochemical and biophysical research communications
| 2,015
| 11
| 0
| 0
|
32,985,555
|
Gender differences in adolescent sleep neurophysiology: a high-density sleep EEG study.
|
During adolescence, differences between males and females in physiology, behavior and risk for psychopathology are accentuated. The goal of the current study was to examine gender differences in sleep neurophysiology using high-density sleep EEG in early adolescence. We examined gender differences in sleep EEG power and coherence across frequency bands for both NREM and REM sleep in a sample of 61 adolescents (31 girls and 30 boys; mean age = 12.48; SD = 1.34). In addition, sleep spindles were individually detected and characterized. Compared to boys, girls had significantly greater spindle activity, as reflected in higher NREM sigma power, spindle amplitude, spindle frequency and spindle density over widespread regions. Furthermore, power in higher frequency bands (16.2-44 Hz) was larger in girls than boys in a state independent manner. Oscillatory activity across frequency bands and sleep states was generally more coherent in females as compared to males, suggesting greater connectivity in females. An exception to this finding was the alpha band during NREM and REM sleep, where coherence was higher (NREM) or not different (REM) in boys compared to girls. Sleep spindles are generated through thalamocortical circuits, and thus, the greater spindle activity across regions in females may represent a stronger thalamocortical circuit in adolescent females as compared to males. Moreover, greater global connectivity in females may reflect functional brain differences with implications for cognition and mental health. Given the pronounced gender differences, our study highlights the importance of taking gender into account when designing and interpreting studies of sleep neurophysiology.
|
Scientific reports
| 2,020
| 9
| 0
| 0
|
29,743,387
|
SuHeXiang Essential Oil Inhalation Produces Antidepressant- and Anxiolytic-Like Effects in Adult Mice.
|
SuHeXiang (SHX) has been used to treat a wide range of diseases, including those related to the central nervous system. However, the effects of SHX on mood disorders are still elusive. This study aimed to investigate the effects of SHX essential oil on stress-induced depression of mice. In an acute stress-induced depression model, mice inhaled vehicle (1% Tween 80) for 10 min or 10% SHX for 10 or 30 min once daily for 12 continuous days. In the chronic mild stress (CMS)-induced depression model, mice were exposed to a 28-d CMS treatment. Tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and novelty suppressed feeding (NSF) test were conducted. In addition, serum levels of angiogenin (ANG), thrombopoietin (TPO), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA) assays. The results showed that in mice exposed to acute stress, repeated SHX inhalation exerted significant antidepressant and anxiolytic activities, and also reduced the serum levels of ANG, TPO, IL-6, and TNF-α. It also significantly reversed the depressive and anxiety-like behaviors, and reduced the serum levels of ANG and TPO in mice exposed to CMS. This is the first report to show that SHX inhalation could produce significant antidepressant and anxiolytic-like effects. These effects might be mediated by SHX ability to modulate the inflammatory response, and reduce dysfunction of vascular genesis and thrombosis. These results support further exploration for developing SHX inhalation as a novel therapeutic strategy for depression and stress-related disorders.
|
Biological & pharmaceutical bulletin
| 2,018
| 7
| 0
| 0
|
25,650,700
|
Signal attenuation as a rat model of obsessive compulsive disorder.
|
In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus which serves as a feedback cue. This feedback is later attenuated by repeated presentations of the stimulus without food (without the rat emitting the lever-press response). In the next stage, lever-pressing is assessed under extinction conditions (i.e., no food is delivered). At this stage rats display two types of lever-presses, those that are followed by an attempt to collect a reward, and those that are not. The latter are the measure of compulsive-like behavior in the model. A control procedure in which rats do not experience the attenuation of the feedback cue serves to distinguish between the effects of signal attenuation and of extinction. The signal attenuation model is a highly validated model of OCD and differentiates between compulsive-like behaviors and behaviors that are repetitive but not compulsive. In addition the measures collected during the procedure eliminate alternative explanations for differences between the groups being tested, and are quantitative, unbiased and unaffected by inter-experimenter variability. The major disadvantages of this model are the costly equipment, the fact that it requires some technical know-how and the fact that it is time-consuming compared to other models of OCD (11 days). The model may be used for detecting the anti- or pro-compulsive effects of pharmacological and non-pharmacological manipulations and for studying the neural substrate of compulsive behavior.
|
Journal of visualized experiments : JoVE
| 2,015
| 1
| 0
| 0
|
33,074,251
|
Revised and Neuroimaging-Compatible Versions of the Dual Task Screen.
|
Dual task paradigms simultaneously assess motor and cognitive abilities, and they can detect subtle, residual impairments in athletes with recent mild traumatic brain injury (mTBI). However, past dual task paradigms have focused solely on lower extremity skills and have relied on cumbersome, expensive laboratory equipment - thus limiting their practicality for everyday mTBI evaluation. Subsequently, we developed the Dual Task Screen (DTS), which takes <10 minutes to administer and score, uses low-cost portable equipment, and includes lower extremity (LE) and upper extremity (UE) subtasks. The purpose of this manuscript was twofold. First, we describe the administration protocol for the revised DTS, which we revised to address the limitations of the original DTS. Specifically, the revisions included additions of smart devices to acquire more detailed gait data and inclusion of single cognitive conditions to test for disrupted cognitive performance under dual task conditions. Importantly, the revised DTS is a measure intended for future clinical use, and we present representative results from three male athletes to illustrate the type of clinical data that can be acquired from the measure. Importantly, we have yet to evaluate the sensitivity and specificity of the revised DTS in athletes with mTBI, which is the next research initiative. The second purpose of this manuscript is to describe a neuroimaging-compatible version of the DTS. We developed this version so we could evaluate the neural underpinnings of single and dual task performance, for a better empirical understanding of the behavioral deficits associated with mTBI. Thus, this manuscript also describes the steps we took to enable simultaneous functional near-infrared spectroscopy (fNIRS) measurement during the DTS, along with how we acquired and completed first-level processing of the fNIRS data.
|
Journal of visualized experiments : JoVE
| 2,020
| 10
| 0
| 0
|
33,095,180
|
Therapist-Supported Online Interventions for Children and Young People With Tic Disorders: Lessons Learned From a Randomized Controlled Trial and Considerations for Future Practice.
|
In recent years, research into internet-based cognitive behavioral therapy (iCBT) has suggested that therapist-guided digital interventions have greater engagement, adherence, and effectiveness than self-directed digital therapies. While research has focused on the effectiveness of, and adherence to, these interventions, less attention has been paid to their implementation in practice and what aspects of the therapist role support success. An understanding of the key factors related to the therapist role and intervention delivery is required if these iCBTs are to be applied in routine clinical care and outcomes optimized. In light of the coronavirus disease 2019 (COVID-19) pandemic, there is greater emphasis on allowing patients access to remote therapies. We report the experiences and reflections of 4 therapists and their 2 supervisors in delivering an online, therapist-supported intervention in a randomized controlled trial for children and young people with tic disorders (the Online Remote Behavioural Intervention for Tics [ORBIT] trial). Themes discussed include the importance of training, supervision, creating support documents/manuals, and record keeping. Alongside this are communication strategies used by therapists to encourage patient adherence and treatment effectiveness. These include rapport building, treatment personalization, and suggestions for overcoming non-engagement. These reflections offer important considerations for the delivery of iCBTs as well as implications associated with the implementation of these interventions in existing services and future research studies. We share thoughts on where iCBTs may sit in a stepped care model, how services may deal with comorbid conditions, and the potential role of iCBTs in collecting clinical data.
|
JMIR mental health
| 2,020
| 10
| 0
| 0
|
33,863,377
|
Core Alzheimer's disease cerebrospinal fluid biomarker assays are not affected by aspiration or gravity drip extraction methods.
|
CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration.
|
Alzheimer's research & therapy
| 2,021
| 4
| 0
| 0
|
33,555,381
|
Emotional valence modulates arithmetic strategy execution in priming paradigm: an event-related potential study.
|
Combined with the prime paradigm, the present study aimed to explore the influence of emotion (anger, fear, happiness, and neutral) on performing multiplication estimation. Participants were asked to complete a two-digit multiplication estimation task using the down-up strategy (e.g., doing 20 × 80 = 1600 for 24 × 79). Behavioral results showed that the reaction time for completing multiplication estimation tasks under happy conditions was shorter than for those under anger and fear, and it was shorter under neutral than under fearful conditions. The ERP results showed that about 100 ms after multiplication estimation task onset, multiplication estimation execution in the context of happiness (vs. neutral) elicited smaller P1 amplitudes; about 170 ms after multiplication estimation task onset, the N170 amplitudes elicited by multiplication estimation strategy execution under different emotional priming conditions showed no significant differences. The above results showed that the impact of emotion priming demonstrates the occurrence of a dynamic process when participants use a specified strategy to complete the multiplication estimation task. The present study revealed that emotional valence modulated arithmetic strategy execution, suggesting the role of different emotions should be fully considered in similar study.
|
Experimental brain research
| 2,021
| 4
| 0
| 0
|
33,186,505
|
Bimodal Benefits Revealed by Categorical Perception of Lexical Tones in Mandarin-Speaking Kindergarteners With a Cochlear Implant and a Contralateral Hearing Aid.
|
Purpose Pitch reception poses challenges for individuals with cochlear implants (CIs), and adding a hearing aid (HA) in the nonimplanted ear is potentially beneficial. The current study used fine-scale synthetic speech stimuli to investigate the bimodal benefit for lexical tone categorization in Mandarin-speaking kindergarteners using a CI and an HA in opposite ears. Method The data were collected from 16 participants who were required to complete two classical tasks for speech categorical perception (CP) with CI + HA device condition and CI alone condition. Linear mixed-effects models were constructed to evaluate the identification and discrimination scores across different device conditions. Results The bimodal kindergarteners showed CP for the continuum varying from Mandarin Tone 1 and Tone 2. Moreover, the additional acoustic information from the contralateral HA contributes to improved lexical tone categorization, with a steeper slope, a higher discrimination score of between-category stimuli pair, and an improved peakedness score (i.e., an increased benefit magnitude for discriminations of between-category over within-category pairs) for the CI + HA condition than the CI alone condition. The bimodal kindergarteners with better residual hearing thresholds at 250 Hz level in the nonimplanted ear could perceive lexical tones more categorically. Conclusion The enhanced CP results with bimodal listening provide clear evidence for the clinical practice to fit a contralateral HA in the nonimplanted ear in kindergarteners with unilateral CIs with direct benefits from the low-frequency acoustic hearing.
|
Journal of speech, language, and hearing research : JSLHR
| 2,020
| 12
| 0
| 0
|
32,934,172
|
Stroke risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases.
|
To investigate the hypothesis that strokes occurring in patients with coronavirus disease 2019 (COVID-19) have distinctive features, we investigated stroke risk, clinical phenotypes, and outcomes in this population.
|
Neurology
| 2,020
| 12
| 0
| 0
|
32,810,357
|
Evaluation of a research awareness training programme to support research involvement of older people with dementia and their care partners.
|
Best-practice guidelines recommend that appropriate support be provided to public contributors to facilitate their involvement in research. One form of support is research awareness training. Older people with dementia and care partners were involved in four Research User Groups (RUGs) in the UK, France, Cyprus and Greece. We delivered research awareness training (RAT) to the RUGs. The aim of this study was to evaluate the acceptability and perceived outcomes of the training from the perspective of RUG members.
|
Health expectations : an international journal of public participation in health care and health policy
| 2,020
| 10
| 0
| 0
|
23,740,166
|
Neuronal synaptobrevin promotes longevity in Drosophila photoreceptors.
|
Neurons have unique challenges relative to other cell types. Unlike most other cells, neurons must remain healthy and functional throughout the lifespan of an animal. Premature neuronal loss underlies many age-related neurodegenerative diseases, including Alzheimer and Parkinson Diseases. Despite previous research aimed at understanding the mechanisms of age-related neurodegenerative diseases, little is known about the mechanisms that allow neurons to remain functional for the lifetime of a healthy animal. Understanding these cellular and biochemical processes is essential to promote healthful aging and reduce the severity of neurodegenerative disease. Here we discuss our recent identification of neuron-specific proteins that regulate endosome fusion events and the role of endosomes in maintaining healthy neurons.
|
Communicative & integrative biology
| 2,012
| 11
| 0
| 0
|
32,531,429
|
Sleep, inflammation, and perception of sad facial emotion: A laboratory-based study in older adults.
|
Facial emotion perception (FEP) is pivotal for discriminating salient emotional information. Accumulating data indicate that FEP responses, particularly to sad emotional stimuli, are impaired in depression. This study tests whether sleep disturbance and inflammation, two risk factors for depression, contribute to impaired FEP to sad emotional stimuli.
|
Brain, behavior, and immunity
| 2,020
| 10
| 0
| 0
|
18,608,762
|
The convenient synthesis and evaluation of the anticancer activities of new resveratrol derivatives.
|
In the present study we report the simple synthesis and antitumour activity of novel stilbene derivatives 13-22. The key synthetic strategies involved Wadsworth-Horner-Emmons condensation and coupling reactions in high yields. All compounds showed significant growth inhibition on human tumour cell lines, with the most potent compound (19) exhibiting an IC(50) of 5.7 microM-11.4 microM in vitro.
|
Journal of enzyme inhibition and medicinal chemistry
| 2,009
| 4
| 0
| 0
|
33,121,112
|
Efficacy and Safety of High-Dose Immunoglobulin-Based Regimen in Statin-Associated Autoimmune Myopathy: A Multi-Center and Multi-Disciplinary Retrospective Study.
|
Statin-associated autoimmune myopathy is a rare muscle disorder, characterized by autoantibodies against HMGCR. The anti-HMGCR myopathy persists after statin, and often requires immunosuppressive therapy. However, there is not a standardized therapeutic approach. The purpose of this study is to report the effectiveness of the immunosuppressive treatment employed in a multi-center and multi-disciplinary cohort of patients affected by anti-HMGCR myopathy, in which an immunoglobulin (IVIG)-based treatment strategy was applied. We collected 16 consecutive patients with a diagnosis of anti-HMGCR myopathy, between 2012 and 2019, and recorded data on clinical and laboratory presentation (i.e., muscle strength, serum CK levels, and anti-HMGCR antibody titer) and treatment strategies. Our results highlight the safety and efficacy of an induction therapy combining IVIG with GCs and/or methotrexate to achieve persistent remission of the disease and steroid-free maintenance. Under IVIG-based regimens, clinical improvement and CK normalization occurred in more than two thirds of patients by six months. Relapse rate was low (3/16) and 2/3 relapses occurred after treatment suspension. Nearly 90% of the patients who successfully discontinued GCs were treated with a triple immunosuppressive regimen. In conclusion, an IVIG-based regimen, which particularly includes high-dose immunoglobulin, GCs and methotrexate, can provide a fast remission achievement with GC saving.
|
Journal of clinical medicine
| 2,020
| 10
| 0
| 0
|
33,212,937
|
Clinical Reasoning for the Examination and Physical Therapy Treatment of Temporomandibular Disorders (TMD): A Narrative Literature Review.
|
The current narrative literature review aims to discuss clinical reasoning based on nociceptive pain mechanisms for determining the most appropriate assessment and therapeutic strategy and to identify/map the most updated scientific evidence in relation to physical therapy interventions for patients with temporomandibular disorders (TMDs). We will also propose an algorithm for clinical examination and treatment decisions and a pain model integrating current knowledge of pain neuroscience. The clinical examination of patients with TMDs should be based on nociceptive mechanisms and include the potential identification of the dominant, central, or peripheral sensitization driver. Additionally, the musculoskeletal drivers of these sensitization processes should be assessed with the aim of reproducing symptoms. Therapeutic strategies applied for managing TMDs can be grouped into tissue-based impairment treatments (bottom-up interventions) and strategies targeting the central nervous system (top-down interventions). Bottom-up strategies include joint-, soft tissue-, and nerve-targeting interventions, as well as needling therapies, whereas top-down strategies include exercises, grade motor imagery, and also pain neuroscience education. Evidence shows that the effectiveness of these interventions depends on the clinical reasoning applied, since not all strategies are equally effective for the different TMD subgroups. In fact, the presence or absence of a central sensitization driver could lead to different treatment outcomes. It seems that multimodal approaches are more effective and should be applied in patients with TMDs. The current paper also proposes a clinical decision algorithm integrating clinical diagnosis with nociceptive mechanisms for the application of the most appropriate treatment approach.
|
Journal of clinical medicine
| 2,020
| 11
| 0
| 0
|
24,524,919
|
Phlebographic study does not show differences between patients with MS and control subjects.
|
Hypothetical correlation between chronic cerebrospinal venous insufficiency and MS has gained the attention of patients and the scientific community. Studies performed by echo-color Doppler ultrasonography have shown different results, and it is necessary to use more objective diagnostic techniques. The aim of our study was to evaluate the presence of stenoses affecting azygos veins and internal jugular veins by use of venography in patients with MS.
|
AJNR. American journal of neuroradiology
| 2,014
| 6
| 0
| 0
|
33,190,164
|
Synergistic antidepressant- and anxiolytic-like effects of harmaline along with cinanserin in acute restraint stress-treated mice.
|
Acute restraint stress (ARS) is an experimental paradigm used for the induction of rodent models of stress-produced neuropsychiatric disorders, such as depression and anxiety. β-carbolines and serotonin (5-HT) systems are involved in the modulation of depression and anxiety behaviors.
|
Psychopharmacology
| 2,021
| 1
| 0
| 0
|
32,007,656
|
A method to compare prospective and historical cohorts to evaluate drug effects. Application to the analysis of early treatment effectiveness of intramuscular interferon-β1a in multiple sclerosis patients.
|
Disease modifying therapy have changed the natural evolution of multiple sclerosis (MS), with efficacy demonstrated in randomized clinical trials. Standard-of-care effectiveness is needed to complement clinical trial data and highlight outcomes in real-world practice, but comparing prospective patients with historical cohorts likely introduces biases. To address these potential biases, assigning a patient with a score that expresses his/her disease prognosis before starting a therapy may make it possible to evaluate the unbiased ability of the therapy to modify disease natural history. Thus, we aimed at analyzing the effectiveness of intramuscular interferon-β1a (im IFN-β1a) matching by BREMSO score (Bayesian Risk Estimate for Multiple Sclerosis at Onset) a prospective real-world cohort of treated patients with a historical cohort of untreated patients.
|
Multiple sclerosis and related disorders
| 2,020
| 5
| 0
| 0
|
33,025,410
|
Imaging the role of blood-brain barrier disruption in normal cognitive ageing.
|
To investigate whether blood-brain barrier (BBB) disruption is a potential mechanism of usual age-related cognitive decline, we conducted dynamic contrast-enhanced (DCE) MRI to measure BBB leakage in a healthy sample, and investigated the association with longitudinal cognitive decline. In a sample of neurologically and cognitively healthy, older individuals, BBB leakage rate in the white and grey matter and hippocampus was measured using DCE MRI with pharmacokinetic modelling. Regression analysis was performed to investigate whether the leakage rate was associated with decline in cognitive performance (memory encoding, memory retrieval, executive functioning and processing speed) over 12 years. White and grey matter BBB leakages were significantly associated with decline in memory retrieval. No significant relations were found between hippocampal BBB leakage and cognitive performance. BBB disruption already being associated with usual cognitive ageing, supports that this neurovascular alteration is a possible explanation for the cognitive decline inherent to the ageing process. More insight into BBB leakage during the normal ageing process could improve estimation and interpretation of leakage rate in pathological conditions. The current results might also stimulate the search for strategies to maintain BBB integrity and help increase the proportion people experiencing successful ageing. Netherlands Trial Register number: NL6358, date of registration: 2017-03-24.
|
GeroScience
| 2,020
| 12
| 0
| 0
|
32,535,350
|
Dysregulated translational control in brain disorders: from genes to behavior.
|
Control of protein synthesis (mRNA translation) is essential for proper brain development and function. Perturbations to the mechanisms governing mRNA translation have repeatedly been shown to constitute a neurodegenerative, neuropsychiatric, and neurodevelopmental disorder risk factor. Developing effective therapeutics for brain disorders will require a better understanding of the molecular mechanisms underlying the control of protein synthesis in brain function. Studies using transgenic animal models have been invaluable towards this end, providing exciting new insights into the genetic basis of brain disorders with hopeful prospects for new and effective treatment options.
|
Current opinion in genetics & development
| 2,020
| 12
| 0
| 0
|
31,883,788
|
In Vivo Imaging of the Coupling between Neuronal and CREB Activity in the Mouse Brain.
|
Sensory experiences cause long-term modifications of neuronal circuits by modulating activity-dependent transcription programs that are vital for regulation of long-term synaptic plasticity and memory. However, it has not been possible to precisely determine the interaction between neuronal activity patterns and transcription factor activity. Here we present a technique using two-photon fluorescence lifetime imaging (2pFLIM) with new FRET biosensors to chronically image in vivo signaling of CREB, an activity-dependent transcription factor important for synaptic plasticity, at single-cell resolution. Simultaneous imaging of the red-shifted CREB sensor and GCaMP permitted exploration of how experience shapes the interplay between CREB and neuronal activity in the neocortex of awake mice. Dark rearing increased the sensitivity of CREB activity to Ca
|
Neuron
| 2,020
| 3
| 0
| 0
|
27,248,691
|
The moral animal: virtue, vice, and human nature.
|
In Leo Tolstoy's famous novella, The Death of Ivan Ilyich, a rich and meaningful inner life is sacrificed in pursuit of material rewards and social status. How can we cultivate something intrinsic that transcends our worldly accomplishments? Assuming that a basic model or map of human nature is needed to navigate the road to the good life, what desires, tendencies, and aversions constitute our core nature? How has our evolutionary history shaped our moral impulses? Are we inherently good or fundamentally flawed? Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion with philosopher Christian Miller, neuroscientist Heather Berlin, and historian of science Michael Shermer to examine our moral ecology and its influence on our underlying assumptions about human nature.
|
Annals of the New York Academy of Sciences
| 2,016
| 11
| 0
| 0
|
33,078,279
|
Withaferin-A Treatment Alleviates TAR DNA-Binding Protein-43 Pathology and Improves Cognitive Function in a Mouse Model of FTLD.
|
Withaferin-A, an active withanolide derived from the medicinal herbal plant Withania somnifera induces autophagy, reduces TDP-43 proteinopathy, and improves cognitive function in transgenic mice expressing mutant TDP-43 modelling FTLD. TDP-43 is a nuclear DNA/RNA-binding protein with cellular functions in RNA transcription and splicing. Abnormal cytoplasmic aggregates of TDP-43 occur in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). To date, no effective treatment is available for TDP-43 proteinopathies. Here, we tested the effects of withaferin-A (WFA), an active withanolide extracted from the medicinal herbal plant Withania somnifera, in a transgenic mouse model of FTLD expressing a genomic fragment encoding mutant TDP-43
|
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
| 2,021
| 1
| 0
| 0
|
33,177,593
|
Concordance in detecting amyloid positivity between
|
We aimed to quantitatively and qualitatively assess whether there is a discrepancy in detecting amyloid beta (Aβ) positivity between 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) positron emission tomography (PET). We obtained paired FBB and FMM PET images from 107 participants. Three experts visually quantified the Aβ deposition as positive or negative. Quantitative assessment was performed using global cortical standardized uptake value ratio (SUVR) with the whole cerebellum as the reference region. Inter-rater agreement was excellent for FBB and FMM. The concordance rates between FBB and FMM were 94.4% (101/107) for visual assessment and 98.1% (105/107) for SUVR cut-off categorization. Both FBB and FMM showed high agreement rates between visual assessment and SUVR positive or negative categorization (93.5% in FBB and 91.2% in FMM). When the two ligands were compared based on SUVR cut-off categorization as standard of truth, although not statistically significant, the false-positive rate was higher in FMM (9.1%) than in FBB (1.8%) (p = 0.13). Our findings suggested that both FBB and FMM had excellent agreement when used to quantitatively and qualitatively evaluate Aβ deposits, thus, combining amyloid PET data associated with the use of different ligands from multi-centers is feasible.
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Scientific reports
| 2,020
| 11
| 0
| 0
|
34,709,323
|
Lead-DBS: an additional tool for stereotactic surgery.
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Use Lead-DBS software to analyze stereotactical surgical outcome of an operated population and demonstrate that small target deviations do not compromise the stimulation of desired structures, even with small amperages.
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Revista da Associacao Medica Brasileira (1992)
| 2,021
| 6
| 0
| 0
|
23,638,646
|
Paucisymptomatic Marchiafava-Bignami disease with relevant diffusion-weighted MRI lesions.
|
Marchiafava-Bignami disease (MBD) is a rare alcohol-associated disorder characterized by demyelization and necrosis of the corpus callosum. Diffusion-weighted (DW) MRI may reveal the lesions in patients showing serious clinical manifestations, high mortality rate and severe cognitive sequelae, though some cases with good outcome have been reported. We describe a case of a man with a history of chronic alcohol abuse associated with malabsorption; the man presented mild clinical signs on the first neurological exam, despite the presence of DW-MRI lesions, bilaterally involving entire corpus callosum, that are compatible with MBD diagnosis.
|
The International journal of neuroscience
| 2,013
| 10
| 0
| 0
|
32,981,023
|
A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View.
|
There is increasing evidence of neurological manifestations and complications in patients with coronavirus disease 19 (COVID-19). More than one-quarter of patients with COVID-19 developed various neurological symptoms, ranging from headache and dizziness to more serious medical conditions, such as seizures and stroke. The recent investigations introduced hyposmia as a potential early criterion of infection with COVID-19. Despite the high mortality and morbidity rate of COVID-19, its exact mechanism of action and pathogenesis is not well characterized. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could interact with angiotensin-converting enzyme 2 (ACE2) in the endothelial, neural, and glial cells. In the present study, we reviewed the most common neurological manifestations and complications that emerged after infection with the SARS-CoV-2 and discussed their possible relation to the expression and function of ACE2. Comprehensive and detailed studies are required to uncover how this virus invades the neural system as well as other critical organs.
|
Molecular neurobiology
| 2,021
| 2
| 0
| 0
|
33,021,017
|
Inhibitory control and set shifting describe different pathways from behavioral inhibition to socially anxious behavior.
|
Individuals with a behaviorally inhibited (BI) temperament are more likely to develop social anxiety. However, the mechanisms by which socially anxious behavior emerges from BI are unclear. Variation in different forms of top-down control, specifically executive functions (EF), may play distinct roles and characterize differential pathways to social anxiety. Here 291 children were assessed for BI in toddlerhood (ages 2 and 3), parent-reported inhibitory control and set shifting during middle childhood (age 7), and multidimensional assessment of socially anxious behavior completed during late childhood and early adolescence (ages 9 and 12). Structural equation modeling revealed that early variation in BI predicted the development of socially anxious behavior through either higher levels of parent-reported inhibitory control or lower levels of parent-reported set shifting. These data reinforce the notion that top-down control does not uniformly influence relations between temperament and socially anxious behavior. These data suggest novel approaches to thinking about the role of EFs and social anxiety outcomes as children approach adolescence.
|
Developmental science
| 2,021
| 1
| 0
| 0
|
33,065,234
|
Modulation of Corticospinal Excitability with Contralateral Arm Cycling.
|
This is the first study to examine the influence of activity in one limb on corticospinal excitability to the contralateral limb during a locomotor output. Corticospinal and spinal excitability to the biceps brachii of the ipsilateral arm were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of corticospinal axons, respectively. Responses were evoked during the mid-elbow extension position of arm cycling across three different cycling tasks: (1) bilateral arm cycling (BL), (2) unilateral, contralateral cycling with the ipsilateral arm moving passively (IP), and (3) unilateral, contralateral cycling with the ipsilateral arm at rest (IR). Each of these three tasks were performed at two cadences: 60 and 90 rpm. TMS-induced motor evoked potential (MEPs) amplitudes were significantly smaller during BL compared to the IP and IR conditions; however, MEP amplitudes were not significantly different between IP and IR. TMES-evoked cervicomedullary MEP (CMEPs) amplitudes followed a similar pattern of task-dependent modulation, with BL having the smallest CMEPs and IR having the largest. In line with our previous findings, MEP amplitudes increased and CMEP amplitudes decreased as the cadence increased from 60 to 90 rpm. We suggest that the higher corticospinal excitability to the ipsilateral limb during the IP and IR conditions was predominantly due to disinhibition at both the cortical and spinal levels.
|
Neuroscience
| 2,020
| 11
| 0
| 0
|
33,751,101
|
Analysis of Paralogons, Origin of the Vertebrate Karyotype, and Ancient Chromosomes Retained in Extant Species.
|
A manually curated set of ohnolog families has been assembled, for seven species of bony vertebrates, that includes 255 four-member families and 631 three-member families, encompassing over 2,900 ohnologs. Across species, the patterns of chromosomes upon which the ohnologs reside fall into 17 distinct categories. These 17 paralogons reflect the 17 ancestral chromosomes that existed in our chordate ancestor immediately prior to the two rounds of whole-genome duplication (2R-WGD) that occurred around 600 Ma. Within each paralogon, it has now been possible to assign those pairs of ohnologs that diverged from each other at the first round of duplication, through analysis of the molecular phylogeny of four-member families. Comparison with another recent analysis has identified four apparently incorrect assignments of pairings following 2R, along with several omissions, in that study. By comparison of the patterns between paralogons, it has also been possible to identify nine chromosomal fusions that occurred between 1R and 2R, and three chromosomal fusions that occurred after 2R, that generated an ancestral bony-vertebrate karyotype comprising 47 chromosomes. At least 27 of those ancestral bony-vertebrate chromosomes can, in some extant species, be shown not to have undergone any fusion or fission events. Such chromosomes are here termed "archeochromosomes," and have each survived essentially unchanged in their content of genes for some 400 Myr. Their utility lies in their potential for tracking the various fusion and fission events that have occurred in different lineages throughout the expansion of bony vertebrates.
|
Genome biology and evolution
| 2,021
| 4
| 0
| 0
|
28,095,674
|
The "Century of Biology" and the Evolving Role of Medicinal Chemists in Neuroscience.
|
Society expects that the wave of contemporary new discoveries in biological sciences will soon lead to novel treatments for human diseases, including many devastating brain disorders. Historically, medicinal chemists have contributed to drug discovery teams in ways that synergize with those from their partner sciences, and help transform new knowledge into the ultimate tangible asset: a new drug. The optimal balance of resources and the right strategy to minimize the risk of late clinical failure may differ for different therapeutic indications. Recent progress in the oncology and neuroscience therapeutic areas is compared and contrasted, in particular looking at the biological target space and functional attributes of recently FDA-approved drugs and those in the late clinical pipeline. Medicinal chemists are poised to have major influence in neuroscience drug research, and examples of areas of potential impact are presented, together with a discussion of the soft skills they bring to their project teams and why they have been so impactful.
|
ACS chemical neuroscience
| 2,017
| 1
| 0
| 0
|
32,795,558
|
Processing Ambiguous Morphemes in Chinese Compound Word Recognition: Behavioral and ERP Evidence.
|
This study examined the processing of ambiguous morphemes in Chinese word recognition with a masked priming lexical decision task. Both behavioral and event-related potential (ERP) were recorded. All targets were bimorphemic compound words that contained ambiguous morphemes as the first morphemes. The ambiguous morphemes either took the dominant or subordinate interpretation, depending on the second morphemes. The prime words contained the same ambiguous morphemes in the dominant interpretation, the subordinate interpretation, or were unrelated to the targets. Analyses on response times revealed significant facilitative priming whenever primes and targets shared morphemes, but the strength of facilitation was stronger when the morpheme meanings were consistent. A similar pattern was found in the analyses of N400 (300-500 ms after target onset) amplitudes. However, in the earlier N250 time window (200-300 ms after target onset), only the dominant targets, but not the subordinate ones, were primed by the morpheme-sharing primes. More importantly, the strength of facilitation was similar between the dominant and subordinate primes. These results have two implications to the processing of ambiguous morphemes during Chinese compound word recognition. First, the morpheme meanings could be activated rapidly. Second, the more frequently used dominant meanings could be activated more easily than the less frequently used subordinate meanings.
|
Neuroscience
| 2,020
| 10
| 0
| 0
|
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