Lipid-Composition-Mediated Forces Can Stabilize Tubular Assemblies of I-BAR Proteins.

Collective action by inverse-Bin/Amphiphysin/Rvs (I-BAR) domains drive micron-scale membrane remodeling. The macroscopic curvature sensing and generation behavior of I-BAR domains is well characterized, and computational models have suggested various mechanisms on simplified membrane systems, but there remain missing connections between the complex environment of the cell and the models proposed thus far. Here, we show a connection between the role of protein curvature and lipid clustering in the relaxation of large membrane deformations.

Somato-Dendritic Regulation of Raphe Serotonin Neurons; A Key to Antidepressant Action.

Several lines of evidence implicate serotonin (5-hydroxytryptamine, 5-HT)in regulating personality traits and mood control. Serotonergic neurons are classically thought to be tonic regular-firing, "clock-like" neurons. Neurotransmission by serotonin is tightly regulated by the serotonin transporter (SERT) and by autoreceptors (serotonin receptors expressed by serotonin neurons) through negative feedback inhibition at the cell bodies and dendrites (5-HT receptors) of the dorsal raphe nuclei or at the axon terminals (5-HT receptors).

JUNO, the receptor of sperm IZUMO1, is expressed by the human oocyte and is essential for human fertilisation.

Study Question: Is JUNO protein present at the surface membrane of human oocytes and involved in the fertilisation process?

Summary Answer: JUNO protein is expressed on the plasma membrane of human oocytes and its inhibition by a monoclonal antibody completely blocks gamete fusion.

What Is Known Already: Fusion of gamete membranes is the culminating event of the fertilisation process, but its molecular mechanisms are poorly understood. Until now, three molecules have been shown to be essential: CD9 tetraspanin in the oocyte, Izumo1 protein on the sperm and Juno, its corresponding receptor on the oocyte.

Post-traumatic massive hand lymphedema fully cured by vascularized lymph node flap transfer.

Post-traumatic localized hand lymphedema is a rare situation and its diagnosis may be difficult, causing lack of care leading to failure of care. Our case study is of two young women with massive post-traumatic hand lymphedema who were treated for algodystrophy for 2 years, and whose bandages and physiotherapy were unsuccessful. Major social and psychological consequences due to difficulty with diagnosis and management resulting in inappropriate tests and therapeutic treatment were prescribed due to these issues.

Plasma copeptin and chronic kidney disease risk in 3 European cohorts from the general population.

Background: The prevalence of chronic kidney disease (CKD) is increasing worldwide. The identification of factors contributing to its progression is important for designing preventive measures. Previous studies have suggested that chronically high vasopressin is deleterious to renal function.

Angiotropism and extravascular migratory metastasis in cutaneous and uveal melanoma progression in a zebrafish model.

Cutaneous melanoma is a highly aggressive cancer with a propensity for distant metastasis to various organs. In contrast, melanoma arising in pigmented uveal layers of the eye metastasizes mostly in the liver. The mechanisms of these metastases, which are ultimately resistant to therapy, are still unclear.

Structural Basis for a Bimodal Allosteric Mechanism of General Anesthetic Modulation in Pentameric Ligand-Gated Ion Channels.

Ion channel modulation by general anesthetics is a vital pharmacological process with implications for receptor biophysics and drug development. Functional studies have implicated conserved sites of both potentiation and inhibition in pentameric ligand-gated ion channels, but a detailed structural mechanism for these bimodal effects is lacking. The prokaryotic model protein GLIC recapitulates anesthetic modulation of human ion channels, and it is accessible to structure determination in both apparent open and closed states.

In Vitro Models to Analyze the Migration of MGE-Derived Interneurons.

In the developing brain, MGE-derived interneuron precursors migrate tangentially long distances to reach the cortex in which they later establish connections with the principal cortical cells to control the activity of adult cortical circuits. Interneuron precursors exhibit complex morphologies and migratory properties, which are difficult to study in the heterogeneous and uncontrolled in vivo environment. Here, we describe two in vitro models in which the migration environment of interneuron precursors is significantly simplified and where their migration can be observed for one to 3 days.

Substitutions of the S4DIV R2 residue (R1451) in Na1.4 lead to complex forms of paramyotonia congenita and periodic paralyses.

Mutations in Na1.4, the skeletal muscle voltage-gated Na channel, underlie several skeletal muscle channelopathies. We report here the functional characterization of two substitutions targeting the R1451 residue and resulting in 3 distinct clinical phenotypes.

The structure of the mental lexicon: What primary progressive aphasias reveal.

Like recursive syntax, a structured mental lexicon is specific to the human species but its internal organization remains unclear. It is thought to contain information about the semantic, syntactic (e.g.

Conserved rules in embryonic development of cortical interneurons.

This review will focus on early aspects of cortical interneurons (cIN) development from specification to migration and final positioning in the human cerebral cortex. These mechanisms have been largely studied in the mouse model, which provides unique possibilities of genetic analysis, essential to dissect the molecular and cellular events involved in cortical development. An important goal here is to discuss the conservation and the potential divergence of these mechanisms, with a particular interest for the situation in the human embryo.

PD-L1 Expression and CD8 T-cell Infiltrate are Associated with Clinical Progression in Patients with Node-positive Prostate Cancer.

Prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy are at higher risk of tumor recurrence and receive immediate androgen deprivation therapy (ADT). While approximately 30% of these patients do not experience recurrence, others experience disease recurrence despite ADT, and currently no biomarkers can accurately identify them. We analyzed tumors from 51 patients with node-positive prostate cancer using immunohistochemistry to investigate whether expression of the immune checkpoint ligand PD-L1 by tumor cells or the density of CD8 or CD20 cells are associated with clinical progression.

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers.

The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care.

Paraglaciecola hydrolytica sp. nov., a bacterium with hydrolytic activity against multiple seaweed-derived polysaccharides.

A novel bacterial strain, S66T, was isolated from eelgrass collected on the coastline of Zealand, Denmark. Polyphasic analyses involving phenotypic, phylogenetic and genomic methods were used to characterize strain S66T. The strain was Gram-reaction-negative, rod-shaped, aerobic, and displayed growth at 10-25 °C (optimum 20-25 °C) and at pH 7-9 (optimum pH 7.

Aortic involvement in relapsing polychondritis.

Objective: To assess prevalence of aortic involvement in relapsing polychondritis (RP) patients; to evaluate clinical features and long-term outcome of RP patients exhibiting aortitis, aortic ectasia and/or aneurysm.

Methods: One hundred and seventy-two RP patients underwent aortic computed tomography (CT)-scan; they were seen in 3 medical centers.

Results: Eleven patients (6.

Outpatient Appendectomy in an Emergency Outpatient Surgery Unit 24 h a Day: An Intention-to-Treat Analysis of 194 Patients.

Objective: To evaluate the feasibility and outcomes of patients operated on for uncomplicated acute appendicitis (UAA) in our 24-h emergency outpatient surgery unit.

Methods: This was a prospective observational study with intention-to-treat (ITT) analysis. From 12/2013 to 03/2015, all consecutive patients admitted for acute appendicitis (AA) were prospectively screened.

Modulating Portal Hemodynamics With Vascular Ring Allows Efficient Regeneration After Partial Hepatectomy in a Porcine Model.

Objective: To investigate safety and efficacy of temporary portal hemodynamics modulation with a novel percutaneously adjustable vascular ring (MID-AVR) onto a porcine model of 75% hepatectomy.

Background: Postoperative liver failure is a leading cause of mortality after major hepatectomy. Portal flow modulation is an increasingly accepted concept to prevent postoperative liver failure.

Spectral consensus strategy for accurate reconstruction of large biological networks.

Background: The last decades witnessed an explosion of large-scale biological datasets whose analyses require the continuous development of innovative algorithms. Many of these high-dimensional datasets are related to large biological networks with few or no experimentally proven interactions. A striking example lies in the recent gut bacterial studies that provided researchers with a plethora of information sources.

Autoimmune cytopenias associated with inflammatory bowel diseases: Insights from a multicenter retrospective cohort.

Introduction: Autoimmune cytopenias (AIC) including autoimmune hemolytic anemia (AIHA) and immunologic thrombocytopenia (ITP) are rare immunologic disorders, scarcely reported in inflammatory bowel diseases (IBD). We conducted a multicentric retrospective study, including a case-control analysis, that aimed to describe the characteristics and outcomes of patients affected by AIC and IBD.

Method: Forty cases were recruited from 4 IBD centers and 2 AIC tertiary centers.

Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A.

Statin therapy and low-density lipoprotein cholesterol reduction in HIV-infected individuals after acute coronary syndrome: Results from the PACS-HIV lipids substudy.

Unlabelled: Knowledge about lipid interventions in secondary prevention in HIV-infected individuals is limited; studies are sparse.

Methods: A prospective observational multicenter study enrolled 282 patients on statin 1 month after first acute coronary syndrome (ACS) (95 HIV-infected individuals, 187 HIV-uninfected). Data on fasting lipids (total cholesterol [TC], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], non-HDL-C, triglycerides, TC/HDL-C ratio) were collected over 3 years.

Cytogenetics and outcome of allogeneic transplantation in first remission of acute myeloid leukemia: the French pediatric experience.

We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced.

Looking closer at acute respiratory distress syndrome: the role of advanced imaging techniques.

Purpose Of Review: Advanced imaging techniques have provided invaluable insights in understanding of acute respiratory distress syndrome (ARDS) and the effect of therapeutic strategies, thanks to the possibility of gaining regional information and moving from simple 'anatomical' information to in-vivo functional imaging.

Recent Findings: Computed tomography (CT) led to the understanding of several ARDS mechanisms and interaction with mechanical ventilation. It is nowadays frequently part of routine diagnostic workup, often leading to treatment changes.

Long-term outcome of basilar stenosis in Erdheim-Chester disease: A case report.

Background: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis. This inflammatory myeloid neoplasm is frequently complicated by neurological symptoms, but stroke is an exceptional manifestation of this disease.

Methods: We report the case of a 59-year-old woman who presented a vertebrobasilar stroke secondary to infiltration and severe stenosis of the basilar artery, improved after interferon-alpha therapy.