Filamentation and inhibition of prokaryotic CTP synthase with ligands.

Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels.

The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder.

Introduction: Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms.

Methods: We compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as "amnestic" or "nonamnestic," based on the members' subjective reports concerning their forgetfulness.

Cerebrospinal fluid biomarker profiling of diverse pathophysiological domains in Alzheimer's disease.

Introduction: While Alzheimer's disease (AD) is defined by amyloid-β plaques and tau tangles in the brain, it is evident that many other pathophysiological processes such as inflammation, neurovascular dysfunction, oxidative stress, and metabolic derangements also contribute to the disease process and that varying contributions of these pathways may reflect the heterogeneity of AD. Here, we used a previously validated panel of cerebrospinal fluid (CSF) biomarkers to explore the degree to which different pathophysiological domains are dysregulated in AD and how they relate to each other.

Methods: Twenty-five CSF biomarkers were analyzed in individuals with a clinical diagnosis of AD verified by positive CSF AD biomarkers (AD, = 54) and cognitively unimpaired controls negative for CSF AD biomarkers (CU-N, = 26) using commercial single- and multi-plex immunoassays.

Krüppel-Like Factors Orchestrate Endothelial Gene Expression Through Redundant and Non-Redundant Enhancer Networks.

Background Proper function of endothelial cells is critical for vascular integrity and organismal survival. Studies over the past 2 decades have identified 2 members of the KLF (Krüppel-like factor) family of proteins, KLF2 and KLF4, as nodal regulators of endothelial function. Strikingly, inducible postnatal deletion of both KLF2 and KLF4 resulted in widespread vascular leak, coagulopathy, and rapid death.

Maternal overnutrition during critical developmental periods leads to different health adversities in the offspring: relevance of obesity, addiction and schizophrenia.

Maternal overnutrition during sensitive periods of early development increases the risk for obesity and neuropsychiatric disorders later in life. However, it still remains unclear during which phases of early development the offspring is more vulnerable. Here, we investigate the effects of maternal high-fat diet (MHFD) at different stages of pre- or postnatal development and characterize the behavioral, neurochemical and metabolic phenotypes.

Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells?

Low back pain (LBP) can significantly reduce the quality of life of patients, and has a considerable economic and social impact worldwide. It is commonly associated with disc degeneration, even though many people with degenerate discs are asymptomatic. Degenerate disc disease (DDD), is thus a common term for intervertebral disc (IVD) degeneration associated with LBP.

Data on triiodothyronine treated peroxisome proliferator-activated receptor-alpha-null mouse hearts using magnetic resonance imaging and magnetic resonance spectroscopy.

This data contain left ventricular end-diastolic volumes, end-systolic volumes, stroke volumes, ejection fractions, cardiac outputs, heart rates, phosphocreatine concentrations, adenosine 5'-triphosphate (ATP) concentrations, total creatine concentrations, citrate synthase activities and heart weights for wild-type and peroxisome proliferator-activated receptor-alpha-null mouse hearts without and with triiodothyronine treatment.

Pathogenic potential of antibodies to the GABA receptor.

GABA receptor (GABAR) autoantibodies have been detected in the serum of immunotherapy-responsive patients with autoimmune encephalitis. This study aimed to investigate the effect of immunoglobulin G (IgG) from a patient with GABAR antibodies on primary neuronal cultures and acute slices of entorhinal cortex. Primary hippocampal neuronal cultures were incubated with serum immunoglobulin from patients with GABAR or AMPA receptor (AMPAR) antibodies for up to 72 h to investigate their effect on receptor surface expression.

Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies.

We have developed a novel real-time quaking-induced conversion RT-QuIC-based assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results.

Deep Brain Stimulation in Three Related Cases of North Sea Progressive Myoclonic Epilepsy from South Africa.

We report on a white Afrikaans family from eastern South Africa with three members affected with North Sea progressive myoclonus epilepsy, resulting from a homozygous founder mutation (c.430G>T, p.Gly144Trp).

TRPV4 channels activity in bovine articular chondrocytes: regulation by obesity-associated mediators.

Turnover of the cartilage extracellular matrix depends exclusively on chondrocytes and varies in response to load and osmolarity fluctuations. Obesity can affect chondrocyte physiology; adipokines, insulin and proinflammatory cytokines levels are all altered in the obese and are related to matrix turnover impairments and thus to osteoarthritis. TRPV4, a mechanosensitive cation channel, is responsible for reacting to hypotonic variations.

UK Cardiology Training in Core Echocardiography Symposium Report: the good the bad and the ugly.

Training in core echocardiography skills within the UK has been the focus of considerable discussion following recent national surveys. This article reports the proceedings of a joint meeting held by the British Society of Echocardiography and British Junior Cardiologists' Association. It considers the current issues impacting on high-quality training and presents potential solutions for the future.

Targeting cardiac sympatho-vagal imbalance using gene transfer of nitric oxide synthase.

Heightened sympathetic excitation and diminished parasympathetic suppression of heart rate, cardiac contractility and vascular tone are all associated with cardiovascular diseases such as hypertension and ischemic heart disease. This phenotype often exists before these disease states have been established and is a strong correlate of mortality in the population. However, the causal role of the autonomic phenotype in the development and maintenance of hypertension and myocardial ischemia remains a subject of debate, as are the mechanisms responsible for regulating sympathovagal balance.

Periodic pattern formation in reaction-diffusion systems: an introduction for numerical simulation.

The aim of the present review is to provide a comprehensive explanation of Turing reaction-diffusion systems in sufficient detail to allow readers to perform numerical calculations themselves. The reaction-diffusion model is widely studied in the field of mathematical biology, serves as a powerful paradigm model for self-organization and is beginning to be applied to actual experimental systems in developmental biology. Despite the increase in current interest, the model is not well understood among experimental biologists, partly because appropriate introductory texts are lacking.

How to Make Drugs Orally Active: A Substrate Template for Peptide Transporter PepT1.

By building key structural features into hydrophilic drugs, they can be recognized by the PepT1 transporter system of the small intestine and rendered orally active. The model shown provides, for the first time, a 3D template for all known substrates of PepT1.