2,163 research outputs found
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From Neural Tube Formation Through the Differentiation of Spinal Cord Neurons: Ion Channels in Action During Neural Development.
Ion channels are expressed throughout nervous system development. The type and diversity of conductances and gating mechanisms vary at different developmental stages and with the progressive maturational status of neural cells. The variety of ion channels allows for distinct signaling mechanisms in developing neural cells that in turn regulate the needed cellular processes taking place during each developmental period. These include neural cell proliferation and neuronal differentiation, which are crucial for developmental events ranging from the earliest steps of morphogenesis of the neural tube through the establishment of neuronal circuits. Here, we compile studies assessing the ontogeny of ionic currents in the developing nervous system. We then review work demonstrating a role for ion channels in neural tube formation, to underscore the necessity of the signaling downstream ion channels even at the earliest stages of neural development. We discuss the function of ion channels in neural cell proliferation and neuronal differentiation and conclude with how the regulation of all these morphogenetic and cellular processes by electrical activity enables the appropriate development of the nervous system and the establishment of functional circuits adapted to respond to a changing environment
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Stable task information from an unstable neural population
Over days and weeks, neural activity representing an animalâs position and movement in sensorimotor cortex has been found to continually reconfigure or âdriftâ during repeated trials of learned tasks, with no obvious change in behavior. This challenges classical theories, which assume stable engrams underlie stable behavior. However, it is not known whether this drift occurs systematically, allowing downstream circuits to extract consistent information. Analyzing long-term calcium imaging recordings from posterior parietal cortex in mice (Mus musculus), we show that drift is systematically constrained far above chance, facilitating a linear weighted readout of behavioral variables. However, a significant component of drift continually degrades a fixed readout, implying that drift is not confined to a null coding space. We calculate the amount of plasticity required to compensate drift independently of any learning rule, and find that this is within physiologically achievable bounds. We demonstrate that a simple, biologically plausible local learning rule can achieve these bounds, accurately decoding behavior over many days
Minocycline as a re-purposed anti-Wolbachia macrofilaricide: superiority compared with doxycycline regimens in a murine infection model of human lymphatic filariasis
Lymphatic filariasis and onchocerciasis are parasitic helminth diseases, which cause severe morbidities such as elephantiasis, skin disease and blindness, presenting a major public health burden in endemic communities. The anti-Wolbachia consortium (A·WOL: http://www.a-wol.com/) has identified a number of registered antibiotics that target the endosymbiotic bacterium, Wolbachia, delivering macrofilaricidal activity. Here we use pharmacokinetics/pharmacodynamics (PK/PD) analysis to rationally develop an anti-Wolbachia chemotherapy by linking drug exposure to pharmacological effect. We compare the pharmacokinetics and anti-Wolbachia efficacy in a murine Brugia malayi model of minocycline versus doxycycline. Doxycycline exhibits superior PK in comparison to minocycline resulting in a 3-fold greater exposure in SCID mice. Monte-Carlo simulations confirmed that a bi-daily 25â40âmg/Kg regimen is bioequivalent to a clinically effective 100â200âmg/day dose for these tetracyclines. Pharmacodynamic studies showed that minocycline depletes Wolbachia more effectively than doxycycline (99.51% vs. 90.35%) after 28âday 25âmg/Kg bid regimens with a more potent block in microfilarial production. PK/PD analysis predicts that minocycline would be expected to be 1.7 fold more effective than doxycycline in man despite lower exposure in our infection models. Our findings warrant onward clinical investigations to examine the clinical efficacy of minocycline treatment regimens against lymphatic filariasis and onchocerciasis
Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas
SummaryBackgroundHematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease.MethodsThis study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition.ResultsThe frequencies of neutropenia (absolute neutrophil count â€1.3Ă109/l), anemia (hemoglobin â€10g/dl), and thrombocytopenia (platelets â€125Ă109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p<0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection.ConclusionsDifferences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings
Effect of head impacts on diffusivity measures in a cohort of collegiate contact sport athletes
Objective: To determine whether exposure to repetitive head impacts over a single season affects white matter diffusion measures in collegiate contact sport athletes.
Methods: A prospective cohort study at a Division I NCAA athletic program of 80 nonconcussed varsity football and ice hockey players who wore instrumented helmets that recorded the acceleration time history of the head following impact, and 79 nonâcontact sport athletes. Assessment occurred preseason and shortly after the season with diffusion tensor imaging and neurocognitive measures.
Results: There was a significant (p 5 0.011) athlete-group difference for mean diffusivity (MD) in the corpus callosum. Postseason fractional anisotropy (FA) differed (p 5 0.001) in the amygdala (0.238 vs 0.233). Measures of head impact exposure correlated with white matter diffusivity measures in several brain regions, including the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory.
Conclusion: This study suggests a relationship between head impact exposure, white matter diffusion measures, and cognition over the course of a single season, even in the absence of diagnosed concussion, in a cohort of college athletes. Further work is needed to assess whether such effects are short term or persisten
Lived experiences of palliative care among people living with HIV/AIDS: a qualitative study from Bihar, India.
OBJECTIVES: This study aimed to assess the lived experiences of palliative care among critically unwell people living with HIV/AIDS (PLHA), caregivers and relatives of deceased patients. It also aimed to understand the broader palliative care context in Bihar. DESIGN: This was an exploratory, qualitative study which used thematic analysis of semistructured, in-depth interviews as well as a focus group discussion. SETTING: All interviews took place in a secondary care hospital in Patna, Bihar which provides holistic care to critically unwell PLHA. PARTICIPANTS: We purposively selected 29 participants: 10 critically unwell PLHA, 5 caregivers of hospitalised patients, 7 relatives of deceased patients who were treated in the secondary care hospital and 7 key informants from community-based organisations. RESULTS: Critically ill PLHA emphasised the need for psychosocial counselling and opportunities for social interaction in the ward, as well as a preference for components of home-based palliative care, even though they were unfamiliar with actual terms such as 'palliative care' and 'end-of-life care'. Critically unwell PLHA generally expressed preference for separate, private inpatient areas for end-of-life care. Relatives of deceased patients stated that witnessing patients' deaths caused trauma for other PLHA. Caregivers and relatives of deceased patients felt there was inadequate time and space for grieving in the hospital. While both critically ill PLHA and relatives wished that poor prognosis be transparently disclosed to family members, many felt it should not be disclosed to the dying patients themselves. CONCLUSIONS: Despite expected high inpatient fatality rates, PLHA in Bihar lack access to palliative care services. PLHA receiving end-of-life care in hospitals should have a separate dedicated area, with adequate psychosocial counselling and activities to prevent social isolation. Healthcare providers should make concerted efforts to inquire, understand and adapt their messaging on prognosis and end-of-life care based on patients' preferences
Redefining neuromarketing as an integrated science of influence
Multiple transformative forces target marketing, many of which derive from new technologies that allow us to sample thinking in real time (i.e., brain imaging), or to look at large aggregations of decisions (i.e., big data). There has been an inclination to refer to the intersection of these technologies with the general topic of marketing as âneuromarketingâ. There has not been a serious effort to frame neuromarketing, which is the goal of this paper. Neuromarketing can be compared to neuroeconomics, wherein neuroeconomics is generally focused on how individuals make âchoicesâ, and represent distributions of choices. Neuromarketing, in contrast, focuses on how a distribution of choices can be shifted or âinfluencedâ, which can occur at multiple âscalesâ of behavior (e.g., individual, group, or market/society). Given influence can affect choice through many cognitive modalities, and not just that of valuation of choice options, a science of influence also implies a need to develop a model of cognitive function integrating attention, memory, and reward/aversion function. The paper concludes with a brief description of three domains of neuromarketing application for studying influence, and their caveats
Age-related striatal BOLD changes without changes in behavioral loss aversion
Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task
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