Ventral tegmental area dopaminergic lesion-induced depressive phenotype in the rat is reversed by deep brain stimulation of the medial forebrain bundle.

DBS of the medial forebrain bundle (MFB) has been investigated clinically in major depressive disorder patients with rapid and long-term reduction of symptoms. In the context of chronic bilateral high frequency deep brain stimulation (DBS) of the MFB, the current study looked at the impact of lesioning the ascending dopaminergic pathway at the level of the ventral tegmental area (VTA). Sprague-Dawley female rats were given bilateral injection of 6-OHDA into the VTA (VTA-lx group) or were left unlesioned (control group).

Zebrafish Database: Customizable, Free, and Open-Source Solution for Facility Management.

Zebrafish Database is a web-based customizable database solution, which can be easily adapted to serve both single laboratories and facilities housing thousands of zebrafish lines. The database allows the users to keep track of details regarding the various genomic features, zebrafish lines, zebrafish batches, and their respective locations. Advanced search and reporting options are available.

Chronic deep brain stimulation of the medial forebrain bundle reverses depressive-like behavior in a hemiparkinsonian rodent model.

Preclinical and clinical evidence suggests that depression might be associated with a dysfunction in the reward/motivation circuitry. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has been shown in a recent clinical trial to provide a prompt and consistent improvement of depressive symptoms in treatment-resistant patients. In order to better understand the underlying mechanisms of neuromodulation in the context of depression, the effects of chronic bilateral MFB-DBS were assessed in a combined rodent model of depression and Parkinson's disease.

Anks3 alters the sub-cellular localization of the Nek7 kinase.

Nephronophthisis (NPH) is an autosomal recessive cystic kidney disease, and a frequent cause of end-stage renal failure in children. To date, 17 NPH-associated gene products (NPHPs) have been identified. Most NPHPs participate in large multi-protein complexes that localize to the cilium and/or basal body; however, the precise composition of these complexes and their biological function remain largely unknown.

Autosomal dominant polycystic kidney disease: the changing face of clinical management.

Autosomal dominant polycystic kidney disease is the most common inherited kidney disease and accounts for 7-10% of all patients on renal replacement therapy worldwide. Although first reported 500 years ago, this disorder is still regarded as untreatable and its pathogenesis is poorly understood despite much study. During the past 40 years, however, remarkable advances have transformed our understanding of how the disease develops and have led to rapid changes in diagnosis, prognosis, and treatment, especially during the past decade.

Peripherin mutations cause a distinct form of recessive Leber congenital amaurosis and dominant phenotypes in asymptomatic parents heterozygous for the mutation.

Background: Dominant mutations in peripherin (PRPH2) are associated with a spectrum of retinal dystrophy phenotypes, many of which are adult onset and involve the macula. Recessive PRPH2 mutations cause retinal dystrophy associated with prominent maculopathy in adulthood; however, the presenting childhood phenotype has not been defined. We characterise this phenotype.

Interference of phosphatidylcholines with in-vitro cell proliferation - no flock without black sheep.

According to early experiments with natural extracts, phosphatidylcholines (PCs) are widely considered essentially non-toxic. In addition to these physiological mixed-chain PCs, many different synthetic diacyl-PCs are currently available, but they have never been systematically evaluated for any interference with cell proliferation. We thus investigated the cell proliferation of several cell lines in the presence of various liposomes consisting of a single PC component and cholesterol.

Rationale, design and objectives of ARegPKD, a European ARPKD registry study.

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood.

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents.

Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson's disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model.

Structure of the omalizumab Fab.

Omalizumab is a humanized anti-IgE antibody that inhibits the binding of IgE to its receptors on mast cells and basophils, thus blocking the IgE-mediated release of inflammatory mediators from these cells. Omalizumab binds to the Fc domains of IgE in proximity to the binding site of the high-affinity IgE receptor FcℇRI, but the epitope and the mechanisms and conformations governing the recognition remain unknown. In order to elucidate the molecular mechanism of its anti-IgE activity, the aim was to analyse the interaction of omalizumab with human IgE.

Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening.

This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible.

Anks3 interacts with nephronophthisis proteins and is required for normal renal development.

Nephronophthisis (NPH) is a heterogenetic autosomal recessive disorder associated with kidney cysts and multiple extrarenal manifestations. The disease-associated gene products (NPHPs) typically contain domains involved in protein-protein interactions, and appear to exert their tissue-specific functions in large protein complexes. Most NPHPs localize to the cilium and/or basal body; however, their precise molecular functions remain largely unknown.

An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification.

Frame-based stereotactic neurosurgery in children under the age of seven: Freiburg University's experience from 99 consecutive cases.

Introduction: Stereotactic frame-based procedures proved to be precise, safe and are of widespread use among adult patients. Regarding pediatric patients few data is available, therefore the use of the stereotactic frame remains controversial in this population. This motivated us to report our experience in stereotactic procedures in the youngest patients and review the literature concerning this subject.

Platelet dysfunction and acquired von Willebrand syndrome in patients with left ventricular assist devices.

Objectives: Unexplained bleeding events are a severe complication in patients with left ventricular assist devices (LVADs). Platelet dysfunction and acquired von Willebrand syndrome (AVWS) may contribute to bleeding tendencies. Yet, comprehensive data with respect to platelet function and AVWS in LVAD patients in terms of bleeding events are scarce.

AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics.

Autophagy maintains cellular homeostasis by degrading harmful or unnecessary intracellular components. How the autophagy response is induced rapidly and transiently remains largely unknown. We report that the E3 ubiquitin ligases Cullin-5 and Cullin-4 regulate the onset and termination of autophagy, respectively, by dynamically interacting with AMBRA1, a regulator of autophagy.

Electrical stimulation of the medial forebrain bundle in pre-clinical studies of psychiatric disorders.

Modulating neuronal activity by electrical stimulation has expanded from the realm of motor indications into the field of psychiatric disorders in the past 10 years. The medial forebrain bundle (MFB), with a seminal role in motor, reward orientated and affect regulation behaviors, and its afferent and efferent loci, have been targeted in several DBS trials in patients with psychiatric disorders. However, little is known about the consequences of modulating the MFB in affective disorders.

Oral hygiene-related self-efficacy as a predictor of oral hygiene behaviour: a prospective cohort study.

Aim: The aim of this study was to assess whether oral hygiene-related self-efficacy is correlated with current oral hygiene and might influence the outcome of oral hygiene instruction.

Materials And Methods: Hundred and twenty-six patients filled out questionnaires about oral hygiene-related self-efficacy, general self-efficacy, oral hygiene-related knowledge and demographic variables. Plaque and gingival inflammation were measured and an individual oral hygiene plan was conducted.

Definitions and outcome measures for mucous membrane pemphigoid: recommendations of an international panel of experts.

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses.

Transcriptional complexity in autosomal recessive polycystic kidney disease.

Background And Objectives: Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1 gene. The longest open reading frame comprises 66 exons encoding polyductin or fibrocystin, a type I transmembrane protein with 4074 amino acids. Functional investigations are considerably hampered by its large size and lack of expression in tissues that are usually available for analysis such as lymphocytes or fibroblasts.

Acetyl-coenzyme A: a metabolic master regulator of autophagy and longevity.

As the major lysosomal degradation pathway, autophagy represents the guardian of cellular homeostasis, removing damaged and potentially harmful material and replenishing energy reserves in conditions of starvation. Given its vast physiological importance, autophagy is crucially involved in the process of aging and associated pathologies. Although the regulation of autophagy strongly depends on nutrient availability, specific metabolites that modulate autophagic responses are poorly described.

Comparison of Von Willebrand factor (VWF) activity VWF:Ac with VWF ristocetin cofactor activity VWF:RCo.

Introduction: Ristocetin cofactor activity of Von Willebrand factor (VWF:RCo) and the ratio VWF:RCo to its antigen VWF:Ag are used as routine screening to estimate VWF function and to detect types of Von Willebrand disease (VWD) caused by loss of high molecular weight multimers. However, the VWF:RCo test is prone to analytic imprecisions due to various reasons. We compared an assay for VWF activity (VWF:Ac) with VWF:RCo putting emphasis on the ratios to VWF:Ag.