Choline and trimethylamine (TMA) are small molecules that play central roles in biological processes throughout all kingdoms of life. These ubiquitous metabolites are linked through a single biochemical transformation, the conversion of choline to TMA by anaerobic microorganisms. This metabolic activity, which contributes to methanogenesis and human disease, has been ...

P-TEFb, a cellular kinase composed of Cyclin T1 and CDK9, is essential for processive HIV-1 transcription. P-TEFb activity is dependent on phosphorylation of Thr186 in the CDK9 T loop. In resting CD4(+) T cells which are nonpermissive for HIV-1 replication, the levels of Cyclin T1 and T-loop-phosphorylated CDK9 are very ...

Nonstructural protein 5B (NS5B) is essential for hepatitis C virus (HCV) replication as it carries the viral RNA-dependent RNA polymerase enzymatic activity. HCV replication occurs in a membrane-associated multiprotein complex in which HCV NS5A and host cyclophilin A (CypA) have been shown to be present together with the viral polymerase. ...

Recent discussions within the neuroimaging community have highlighted the problematic presence of selection bias in experimental design. Although initially centering on the selection of voxels during the course of fMRI studies, we demonstrate how this bias can potentially corrupt voxel-based analyses. For such studies, template-based registration plays a critical role ...

We synthesized di-substituted liquid crystalline polyacetylene (di-LCPA) derivatives bearing 4-nonyloxy phenyl groups with lyotropic and thermotropic LC behavior. The poly(diphenylacetylene) (PDPA) main chain structure of the di-LCPAs and the chirality induced with either chiral moieties or chiral dopants allow the formation of a highly ordered lyotropic N*-LC phase. Circular dichroism ...

Tight control over the segregation of endoderm, mesoderm, and ectoderm is essential for normal embryonic development of all species, yet how neighboring embryonic blastomeres can contribute to different germ layers has never been fully explained. We postulated that microRNAs, which fine-tune many biological processes, might modulate the response of embryonic ...

The diameter of collagen fibrils in connective tissues, such as tendons and ligaments is known to decrease upon injury or with age, leading to inferior biomechanical properties and poor healing capacity. This study tests the hypotheses that scaffold fiber diameter modulates the response of human tendon fibroblasts, and that diameter-dependent ...

STAT5a/b species are well known as transcription factors that regulate nuclear gene expression. In a novel line of research in human pulmonary arterial endothelial cells (HPAECs), we previously observed that STAT5a associated with the Golgi apparatus and that siRNA-mediated knockdown of STAT5a/b led to the rapid development of a dramatic ...

Background: Biodegradable polymer drug eluting stents (BP-DES) have been developed to overcome the limitations of first generation durable polymer DES (DP-DES) but the clinical results of different BP-DES are not consistent. We performed a meta-analysis to compare the outcomes of BP-DES and DP-DES in the treatment of coronary artery disease ...

Background:Depression is an important health issue amongst older adults. Internet-delivered cognitive behaviour therapy (iCBT) may help to reduce barriers and improve access to treatment, but few studies have examined its use with older adults. The present study evaluated the efficacy, acceptability and feasibility of a brief iCBT program, the Managing ...

The development of the nervous system is under the strict control of a number of signal transduction pathways, often interconnected. Among them, the phosphoinositide (PI) pathway and the related phospholipase C (PI-PLC) family of enzymes have been attracting much attention. Besides their well-known role in the regulation of intracellular calcium ...

Kindlin-2 is a novel focal adhesion gene mediating the cell-extracellular matrix (ECM) adhesion. Tumor-associated macrophages (TAMs) play an important role in linking chronic inflammation to cancer progression. Both kindlin-2 and TAMs have been found to promote the invasion of gastric cancer cells in our previous studies. However, the correlation between ...

The effects of vitamin D supplementation in healthy prepubertal children on physiologic outcomes have not been investigated. The objective was to evaluate the effects of supplementation with 1000 IU vitamin D(3)/d on calcium absorption. In a double-blind, placebo-controlled trial, we randomly assigned 64 children to 1000 IU vitamin D(3)/d (n ...

Regulatory T cells play important roles in cancer development and progression by limiting the generation of innate and adaptive anti-tumor immunity. We hypothesized that in addition to natural CD4(+)CD25(+) regulatory T cells (Tregs) and myeloid-derived suppressor cells, tumor Ag-specific Tregs interfere with the detection of anti-tumor immunity after immunotherapy. Using ...

RNA viruses in insects are targets of an RNA interference (RNAi)-based antiviral immune response, in which viral replication intermediates or viral dsRNA genomes are processed by Dicer-2 (Dcr-2) into viral small interfering RNAs (vsiRNAs). Whether dsDNA virus infections are controlled by the RNAi pathway remains to be determined. Here, we ...

ABSTRACT: BACKGROUND: Antipsychotic drugs are considered a trigger factor for autonomic dysregulation, which has been shown to predict potentially fatal arrhythmias in schizophrenia. However, the dose-dependent effect of antipsychotic drugs and other psychotropic drugs on autonomic nervous system (ANS) activity remain unclear. The purpose of this study was to investigate ...

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hyperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the ...

The G protein-coupled chemokine receptor CXCR3 plays a role in numerous inflammatory events. The endogenous ligands for the chemokine receptors are peptides, but in this study we disclose small-molecule ligands that are able to activate CXCR3. A class of biaryl-type compounds that is assembled by convenient synthetic routes is described ...

The nuclear receptor constitutive androstane receptor (CAR) is a key regulator for drug metabolism in liver. Human CAR (hCAR) transcripts are subjected to alternative splicing. Some hCAR splicing variants (SVs) have been shown to encode functional proteins by reporter assays. However, in vivo research on the activity of these hCAR ...

ABSTRACT: BACKGROUND: Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse. METHODS: ...

[Fe(ebtz)(2)(C(2)H(5)CN)(2)](ClO(4))(2) was prepared in the reaction of 1,2-di(tetrazol-2-yl)ethane (ebtz) with Fe(ClO(4))(2)·6H(2)O in propionitrile. The compound crystallizes as a one-dimensional (1D) network, where bridging of neighboring iron(II) ions by two ebtz ligand molecules results in formation of a [Fe(ebtz)(2)](∞) polymeric skeleton. The 1D chains are assembled into supramolecular layers with axially ...

ABSTRACT: BACKGROUND: The evidence on the effect of acupuncture or counseling for depression is not conclusive yet is sufficient to warrant further research. Our aim is to conduct a full-scale RCT to determine the clinical and cost effectiveness of acupuncture and counseling compared to usual care alone. We will explore ...

An overview of methods developed for chemical analysis of single cells over the last two years is presented. Many biological systems contain an ensemble of cells with heterogeneous chemistry; therefore it is important to analyze them on an individual basis in order to elucidate the role each cell plays in ...

The extracellular space, or cell microenvironment, choreographs cell behavior through myriad controlled signals, and aberrant cues can result in dysfunction and disease. For functional studies of human cell biology or expansion and delivery of cells for therapeutic purposes, scientists must decipher this intricate map of microenvironment biology and develop ways ...

Although first described almost half a century ago, parastomal varices are not easily recognised as a cause of stomal bleeding even though they occur in up to 5 % of all people who have a stoma. The main challenges associated with this condition are diagnosis and management. For that reason, the ...

The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic drugs. We used gene-targeted Sglt2 knockout (Sglt2(-/-)) mice to elucidate the contribution of SGLT2 to blood glucose control, glomerular hyperfiltration, kidney growth, and markers of renal growth and injury ...

Selective serotonin reuptake inhibitors are the most widely prescribed drugs targeting the CNS with acute and chronic effects in cognitive, emotional and behavioral processes. This suggests that microcircuits of the human cerebral cortex are powerfully modulated by selective serotonin reuptake inhibitors, however, direct measurements of serotonergic regulation on human synaptic ...

Triple-transgenic mice (3xTgAD) overexpressing Swedish-mutated β-amyloid precursor protein (βAPP(swe)), P310L-Tau (Tau(P301L)), and physiological levels of M146V-presenilin-1 (PS1(M146V)) display extracellular amyloid-β peptides (Aβ) deposits and Tau tangles. More disputed is the observation that these mice accumulate intraneuronal Aβ that has been linked to synaptic dysfunction and cognitive deficits. Here, we provide ...

BACKGROUND: Hypoxia plays an important role in many biological/pathological processes. In particular, hypoxia is associated with cardiac ischemia which, while initially inducing a protective response, will ultimately lead to the death of cardiomyocytes and loss of tissue, severely impacting cardiac functionality. While myocardial damage/loss remains an insurmountable problem for adult ...

OBJECTIVE: We report the clinical characteristics of the largest series of nontraumatic spinal cord injury in novice surfers (surfers' myelopathy). METHODS: A retrospective review of the electronic medical record was performed in patients with nontraumatic spinal cord injury associated with surfing identified upon admission to the largest tertiary referral hospital ...

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells in cancer patients and tumor-bearing mice that potently inhibits T cell responses. During tumor progression, MDSCs accumulate in several organs, including the tumor tissue. So far, tumor-infiltrating MDSC subpopulations remain poorly explored. In this study, we performed global gene ...

Using retrospective (n=200) and prospective (n=150) nasopharyngeal specimens, we evaluated the Nanosphere Verigene RV+ and the Focus Diagnostics Simplexa Flu A/B & RSV tests. Overall, the RV+ demonstrated a sensitivity/specificity of 96.6%/100% for influenza A, 100%/99.7% for influenza B, and 100%/100% for RSV, while the Simplexa test sensitivity/specificity was 82.8%/99.7%, ...

ABSTRACT: In the previous issue of Critical Care, Maslove and colleagues studied circulating neutrophil transcriptional expression to discover and validate a molecular subclassification of adult patients with sepsis. The authors divided patients into small derivation (n = 55) and validation (n = 71) cohorts. Their complex methodology included partitioning around ...

The Epstein-Barr virus (EBV) is an important human pathogen that is associated with multiple cancers. The major oncoprotein of the virus, latent membrane protein 1 (LMP1), is essential for EBV B-cell immortalization and is sufficient to transform rodent fibroblasts. This viral transmembrane protein activates multiple cellular signaling pathways by engaging ...

Both entry and cell-to-cell spread of herpes simplex virus (HSV) involve a cascade of cooperative interactions among the essential glycoproteins D, B, and H/L (gD, gB, and gH/gL, respectively) initiated by the binding of gD to a cognate HSV entry receptor. We previously reported that a variant (D285N/A549T) of glycoprotein ...

An oligodeoxynucleotide (ODN) containing a 2',2'-difluorinated analogue of a C4'-oxidized abasic site (C4'-OAS) was designed for the amine modification of biomolecules that interact with nucleic acids. In contrast to the parent C4'-OAS, which yielded amine-modified products accompanied by DNA strand scission, the ODN containing the difluoro C4'-OAS efficiently yielded products ...

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease that is frequently caused by a de novo point mutation at position 1824 in LMNA. This mutation activates a cryptic splice donor site in exon 11, and leads to an in-frame deletion within the prelamin A mRNA and the production of ...

The immune adherence (IA) between the porcine erythrocytes and the opsonized Escherichia coli carried green fluorescent protein gene (GFP-E.coli) were detected by the fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with an attempt to verify the existence of IA between the porcine erythrocytes and complemented-opsonized microbes. ...

Two reference measurement procedures are presented here that allow the determination of the iron saturation in human transferrin, based on different molecular properties. The results, directly derived from the number of ions bound to the protein molecule, are traceable to the SI. Up to now, the iron saturation has only ...

Background:A randomised, double-blind, placebo-controlled study evaluated lipid- and glucose-lowering effects of colesevelam in patients with prediabetes and primary hyperlipidaemia. We report the effect of colesevelam on lipoprotein particle concentration and particle size (determined by nuclear magnetic resonance spectroscopy) in these patients.Methods:Adults with prediabetes (World Health Organization criteria), low-density lipoprotein cholesterol ...

A rising conciousness within both the medical community and in the public has been created by the current levels of radiation exposure from increased use of computed tomography. The concern has prompted the need for more data collection and analysis of hospital and imaging center exam doses. This has spurred ...

This population-based matched cohort analysis explored the effects of bisphosphonate treatment on acute myocardial infarction (AMI). We found that patients who received bisphosphonate therapy had a lower risk of AMI during a 2-year follow-up period (hazard ratio (HR) = 0.35). Our data support that bisphosphonates may provide protective effects against cardiovascular events. ...

Polymer-ceramic composites obtained as the result of a mineralization process hold great promise for the future of tissue engineering. Simulated body fluids (SBFs) are widely used for the mineralization of polymer scaffolds. In this work an exhaustive study with the aim of optimizing the mineralization process on a poly(L-lactic acid) ...

PURPOSE: To perform a literature review of the spectrum of complications associated with UAE relative to surgery and compare the risk of reintervention as well as minor, major, and overall complications. MATERIALS AND METHODS: Literature review was conducted in PubMed, MEDLINE, Cochrane, and CINAHL databases, and meta-analysis was performed. RESULTS: ...

ABSTRACT: INTRODUCTION: Despite the benefits of endocrine therapies such as tamoxifen and aromatase inhibitors in treating estrogen receptor alpha (ERalpha)-positive breast cancer, many tumors eventually become resistant. The molecular mechanisms governing resistance remain largely unknown. Pigment epithelium-derived factor (PEDF) is a multifunctional secreted glycoprotein that displays broad anti-tumor activity based ...

μ-Opioid receptors (MORs) in the ventral tegmental area (VTA) are pivotally involved in addictive behavior. While MORs are typically activated by opioids, they can also become constitutively active in the absence of any agonist. In the current study, we present evidence that MOR constitutive activity is highly relevant in the ...

To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression ...

Objective: To investigate the relation between fetal heart defects and maternal serum placental growth factor (PlGF), a marker of placental angiogenesis, because animal models demonstrated an association between angiogenesis and abnormal heart development. Methods: Maternal serum PLGF, pregnancy associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (PI) at 11-13 ...

Acute pulmonary thromboembolism (PE) is a cardiovascular emergency associated with significant morbidity and a 5-35 % mortality for untreated pulmonary embolism. If promptly diagnosed and treated, the mortality rate can be significantly reduced. Diagnosis of acute PE continues to be a clinical challenge, with diagnostic imaging playing an important role. This ...

Most cardiac ryanodine receptor (RyR2) mutations associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) are postulated to cause a distinctive form of Ca(2+) release dysfunction. Considering the spread distribution of CPVT mutations, we hypothesized that dysfunctional heterogeneity also was feasible. To determine the molecular and cellular mechanisms by which a novel ...