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Goebbels S, Wieser GL, Pieper A, Spitzer S, Weege B, Yan K, Edgar JM, Yagensky O, Wichert SP, Agarwal A, Karram K, Renier N, Tessier-Lavigne M, Rossner MJ, Karadottir RT, Nave KA
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A neuronal PI(3,4,5)P-3-dependent program of oligodendrocyte precursor recruitment and myelination (opens in new window)

NATURE NEUROSCIENCE 2017 JAN; 20(1):10-15
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The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1-mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligodendrocyte progenitor cells, oligodendrocyte differentiation and de novo myelination of parallel fibers. Thus, a neuronal program dependent on the phosphoinositide P1(3,4,5)P-3 is sufficient to trigger all steps of myelination.
Butelman ER, Kreek MJ
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Medications for substance use disorders (SUD): emerging approaches (opens in new window)

EXPERT OPINION ON EMERGING DRUGS 2017; 22(4):301-315
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Introduction: Substance use disorders are a group of chronic relapsing disorders of the brain, which have massive public health and societal impact. In some disorders (e.g., heroin/prescription opioid addictions) approved medications have a major long-term benefit. For other substances (e.g., cocaine, amphetamines and cannabis) there are no approved medications, and for alcohol there are approved treatments, which are not in wide usage. Approved treatments for tobacco use disorders are available, and novel medications are also under study. Areas covered: Medication-based approaches which are in advanced preclinical stages, or which have reached proof-of concept clinical laboratory studies, as well as clinical trials. Expert opinion: Current challenges involve optimizing translation between preclinical and clinical development, and between clinical laboratory studies to therapeutic clinical trials. Comorbidities including depression or anxiety are challenges for study design and analysis. Improved pharmacogenomics, biomarker and phenotyping approaches are areas of interest. Pharmacological mechanisms currently under investigation include modulation of glutamatergic, GABA, vasopressin and.-receptor function, as well as inhibition of monoamine re-uptake. Other factors that affect potential market size for emerging medications include stigma, availability of treatment settings, adoption by clinicians, and the prevalence of persons with SUD who are not actively treatment-seeking.
McEwen BS, Milner TA
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Understanding the Broad Influence of Sex Hormones and Sex Differences in the Brain (opens in new window)

JOURNAL OF NEUROSCIENCE RESEARCH 2017 JAN-FEB; 95(1-2):24-39
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Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects on gene expression induce spine synapses, up-or downregulate and alter the distribution of neurotransmitter receptors, and regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, which influence functions not previously regarded as subject to such differences, indicate that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. (C) 2016 Wiley Periodicals, Inc.
Paller AS, Renert-Yuval Y, Suprun M, Esaki H, Oliva M, Huynh TN, Ungar B, Kunjravia N, Friedland R, Peng XY, Zheng XZ, Estrada YD, Krueger JG, Choate KA, Suarez-Farinas M, Guttman-Yassky E
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An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis (opens in new window)

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2017 JAN; 139(1):152-165
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Background: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-basedtherapy is largely lacking because the underlying molecular basis is poorly understood. Objective: We sought to characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. Methods: We analyzed biopsy specimens from 21 genotyped patients with ichthyosis (congenital ichthyosiform erythroderma, n = 6; lamellar ichthyosis, n = 7; epidermolytic ichthyosis, n = 5; and Netherton syndrome, n = 3) using immunohistochemistry and RT-PCR and compared them with specimens from healthy control subjects, patients with atopic dermatitis (AD), and patients with psoriasis. Clinical measures included the Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); transepidermal water loss; and pruritus. Results: Ichthyosis samples showed increased epidermal hyperplasia (increased thickness and keratin 16 expression) and Tcell and dendritic cell infiltrates. Increases of general inflammatory (IL-2), innate (IL-1 beta), and some TH1/interferon (IFN-gamma) markers in patients with ichthyosis were comparable with those in patients with psoriasis or AD. TNF-alpha levels in patients with ichthyosis were increased only in those with Netherton syndrome but were much lower than in patientswith psoriasis and those withAD. Expression of TH2 cytokines (IL-13 and IL-31) was similar to that seen in control subjects. The striking induction of IL-17-related genes or markers synergistically induced by IL-17 and TNF-alpha (IL-17A/C, IL-19, CXCL1, PI3, CCL20, and IL36G; P <.05) in patients with ichthyosis was similar to that seen in patients with psoriasis. IASI and IASI-E scores strongly correlated with IL-17A (r = 0.74, P <.001) and IL-17/TNF-synergistic/additive gene expression. These markers also significantly correlated with transepidermal water loss, suggesting a link between the barrier defect and inflammation in patients with ichthyosis. Conclusion: Our data associate a shared TH17/IL-23 immune fingerprint with the major orphan forms of ichthyosis and raise the possibility of IL-17-targeting strategies.
Bournazos S, Ravetch JV
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Anti-retroviral antibody FcR-mediated effector functions (opens in new window)

IMMUNOLOGICAL REVIEWS 2017 JAN; 275(1):285-295
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The antiviral activity of antibodies reflects the bifunctional properties of these molecules. While the Fab domains mediate highly specific antigenic recognition to block virus entry, the Fc domain interacts with diverse types of Fc receptors (FcRs) expressed on the surface of effector leukocytes to induce the activation of distinct immunomodulatory pathways. Fc-FcR interactions are tightly regulated to control IgG-mediated inflammation and immunity and are largely determined by the structural heterogeneity of the IgG Fc domain, stemming from differences in the primary amino acid sequence of the various subclasses, as well as the structure and composition of the Fc-associated N-linked glycan. Engagement of specific FcR types on effector leukocytes has diverse consequences that affect several aspects of innate and adaptive immunity. In this review, we provide an overview of the complexity of FcR-mediated pathways, discussing their role in the in vivo protective activity of anti-HIV-1 antibodies. We focus on recent studies on broadly neutralizing anti-HIV-1 antibodies that revealed that Fc-FcR interactions are required to achieve full therapeutic activity through clearance of IgG-opsonized virions and elimination of HIV-infected cells. Manipulation of Fc-FcR interactions to specifically activate distinct FcR-mediated pathways has the potential to affect downstream effector responses, influencing thereby the in vivo protective activity of anti-HIV-1 antibodies; a strategy that has already been successfully applied to other IgG-based therapeutics, substantially improving their clinical efficacy.
Xu M, Kolding J, Cohen JE
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Taylor's power law and fixed-precision sampling: application to abundance of fish sampled by gillnets in an African lake (opens in new window)

CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENCES 2017 JAN; 74(1):87-100
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Taylor's power law (TPL) describes the variance of population abundance as a power-law function of the mean abundance for a single or a group of species. Using consistently sampled long-term (1958-2001) multimesh capture data of Lake Kariba in Africa, we showed that TPL robustly described the relationship between the temporal mean and the temporal variance of the captured fish assemblage abundance (regardless of species), separately when abundance was measured by numbers of individuals and by aggregate weight. The strong correlation between the mean of abundance and the variance of abundance was not altered after adding other abiotic or biotic variables into the TPL model. We analytically connected the parameters of TPL when abundance was measured separately by the aggregate weight and by the aggregate number, using a weight-number scaling relationship. We utilized TPL to find the number of samples required for fixed-precision sampling and compared the number of samples when sampling was performed with a single gillnet mesh size and with multiple mesh sizes. These results facilitate optimizing the sampling design to estimate fish assemblage abundance with specified precision, as needed in stock management and conservation.
Muesing MA, Mohammed KD, Luo Y
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Deciphering the HIV-host interactome: overcoming the bottleneck of previous approaches (opens in new window)

FUTURE VIROLOGY 2017 JAN; 12(1):5-7
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Cercek A, Holt PR
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The care of the colorectal cancer survivor (opens in new window)

CURRENT OPINION IN GASTROENTEROLOGY 2017 JAN; 33(1):26-33
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Purpose of reviewThe gastroenterology literature emphasizes factors that increase colorectal cancer (CRC) incidence but presents little about management after initial CRC treatments. The purpose of this review is to describe the remarkably increasing numbers of CRC survivors in whom surveillance guidelines are often not followed and patient care is fragmented. The gastroenterologist can play an important role in this care to improve prognosis and overall health.Recent findingsExisting surveillance recommendations by specialty societies for CRC survivors are fairly consistent but implementation occurs in less than half. The gastroenterologist can help to coordinate care to ensure appropriate surveillance and also can help to diagnose and treat chemotherapy and radiotherapy complications in survivors which can affect the quality of life long after the initial treatment. The gastroenterologist also can focus on host factors, including management of obesity, exercise programs, and the diet and can introduce potential chemopreventive agents such as nonsteroidal anti-inflammatory drugs when positive prospective studies are forthcoming. Interested gastroenterologists also have a role in participating in such prospective studies.SummaryThe gastroenterologist should enhance her/his role for coordinated management of CRC survivors to improve patient surveillance care, to treat posttherapy complications and encourage preventive measures to improve prognosis and quality of life.
Hite RK, Tao X, MacKinnon R
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Structural basis for gating the high-conductance Ca2+-activated K+ channel (opens in new window)

NATURE 2017 JAN 5; 541(7635):52-57
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The precise control of an ion channel gate by environmental stimuli is crucial for the fulfilment of its biological role. The gate in Slo1 K+ channels is regulated by two separate stimuli, intracellular Ca2+ concentration and membrane voltage. Slo1 is thus central to understanding the relationship between intracellular Ca2+ and membrane excitability. Here we present the Slo1 structure from Aplysia californica in the absence of Ca2+ and compare it with the Ca2+-bound channel. We show that Ca2+ binding at two unique binding sites per subunit stabilizes an expanded conformation of the Ca2+ sensor gating ring. These conformational changes are propagated from the gating ring to the pore through covalent linkers and through protein interfaces formed between the gating ring and the voltage sensors. The gating ring and the voltage sensors are directly connected through these interfaces, which allow membrane voltage to regulate gating of the pore by influencing the Ca2+ sensors.
Bahadoran M, Moradpour H, Ali J, Poznanski RR
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A survey of the new proposal about the photon momentum (opens in new window)

OPTIK 2017; 139(?):6-8
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Based on the energy conservation law, a new formula for the photon momentum was proposed in 11 I. In this work, some defects of this new proposal are discussed. It is shown that this new proposal can lead to negative energy of photons. In addition, the group velocity of massive particles exceeds the light velocity which violates the causality principle. Finally, we show that the momentum conservation law combined with the conventional formula for the photon momentum can predict a rational velocity for the velocity of the relativistic scattered particles which revalidate the conventional formula for the photon momentum. (C) 2017 Elsevier GmbH. All rights reserved.