Cortisol secretion in obesity revisited: lower basal serum and salivary cortisol with diminished cortisol response to the low dose ACTH challenge.

Context: Some clinical resemblance may exist between obesity, particularly abdominal obesity, and Cushing's syndrome. This has stimulated ongoing interest in the role of cortisol's secretion pattern, control and metabolism in obesity.

Goals: To investigate whether basal and stimulated levels of cortisol differ between healthy people with obesity and individuals with normal weight Design: Total, free, and salivary cortisol were tested at baseline state and after 1 g ACTH stimulation in 60 healthy subjects with obesity and 54 healthy lean controls.

Detecting Impending Stroke From Cognitive Traits Evident in Internet Searches: Analysis of Archival Data.

Background: Cerebrovascular disease is a leading cause of mortality and disability. Common risk assessment tools for stroke are based on the Framingham equation, which relies on traditional cardiovascular risk factors to predict an acute event in the near decade. However, no tools are currently available to predict a near/impending stroke, which might alert patients at risk to seek immediate preventive action (eg, anticoagulants for atrial fibrillation, control of hypertension).

Improving blood glucose level predictability using machine learning.

This study was designed to improve blood glucose level predictability and future hypoglycemic and hyperglycemic event alerts through a novel patient-specific supervised-machine-learning (SML) analysis of glucose level based on a continuous-glucose-monitoring system (CGM) that needs no human intervention, and minimises false-positive alerts. The CGM data over 7 to 50 non-consecutive days from 11 type-1 diabetic patients aged 18 to 39 with a mean HbA1C of 7.5% ± 1.

Pancreatic Beta-Cell Proliferation Induced by Estradiol-17β is Foxo1 Dependent.

Estradiol-17β (E2) and the Foxo1 transcription factor have each been implicated in the regulation of β-cell proliferation. Interaction between Foxo1and estrogen receptor alpha (ERα), effecting cell cycle, has been demonstrated in breast cancer cells, but has not been studied thus far in β-cells. Using human islets and the INS1-E β-cell line, this study investigated the contribution of Foxo1 to E2-mediated β-cell replication.

The Proatherogenic Effect of Chronic Nitric Oxide Synthesis Inhibition in ApoE-Null Mice Is Dependent on the Presence of PPAR α.

Inhibition of endothelial nitric oxide synthase (eNOS) accelerates atherosclerosis in ApoE-null mice by impairing the balance between angiotensin II (AII) and NO. Our previous data suggested a role for PPAR α in the deleterious effect of the renin-angiotensin system (RAS). We tested the hypothesis that ApoE-null mice lacking PPAR α (DKO mice) would be resistant to the proatherogenic effect of NOS inhibition.

Induction of polyploidy by nuclear fusion mechanism upon decreased expression of the nuclear envelope protein LAP2β in the human osteosarcoma cell line U2OS.

Background: Polyploidy has been recognized for many years as an important hallmark of cancer cells. Polyploid cells can arise through cell fusion, endoreplication and abortive cell cycle. The inner nuclear membrane protein LAP2β plays key roles in nuclear envelope breakdown and reassembly during mitosis, initiation of replication and transcriptional repression.

FreeStyle Mini blood glucose results are accurate and suitable for use in glycemic clamp protocols.

Objective: We assessed the accuracy of the FreeStyle Mini (FSM) meter for use in glycemic clamp and meal protocols in comparison with the HemoCue Glucose 201 DM Analyzer (HemoCue) and the YSI 2300 STAT Glucose Oxidase Analyzer (YSI).

Methods: Seven volunteers with type 2 diabetes mellitus, 35-69 years old, underwent a frequently sampled meal test and a graded hyperglycemic test, on two separate days, with one of the volunteers undergoing each test twice. Samples for glucose measurements were obtained from arterialized venous blood.

LAP2zeta binds BAF and suppresses LAP2beta-mediated transcriptional repression.

Proteins of the nuclear envelope have been implicated as participating in gene silencing. BAF, a DNA- and LEM domain-binding protein, has been suggested to link chromatin to the nuclear envelope. We have previously shown that LAP2beta, a LEM-domain inner nuclear membrane protein, represses transcription through binding to HDAC3 and induction of histone H4 deacetylation.

Gene silencing at the nuclear periphery.

The nuclear envelope (NE) is composed of inner and outer nuclear membranes (INM and ONM, respectively), nuclear pore complexes and an underlying mesh like supportive structure--the lamina. It has long been known that heterochromatin clusters at the nuclear periphery adjacent to the nuclear lamina, hinting that proteins of the lamina may participate in regulation of gene expression. Recent studies on the molecular mechanisms involved show that proteins of the nuclear envelope participate in regulation of transcription on several levels, from direct binding to transcription factors to induction of epigenetic histone modifications.

Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes.

Extensive research in recent years has broadened the functions of nuclear envelope proteins beyond simply stabilizing the nucleus architecture. Particularly, integral nuclear membrane proteins, such as the alternative spliced isoforms of lamina-associated polypeptide 2 (LAP2), have been shown to be important for the initiation of replication and repression of transcription. The latter is regulated by epigenetic changes, induced by the binding of LAP2beta to histone deacetylase-3 (HDAC3), resulting in histone H4 deacetylation.

BCL6 is regulated by p53 through a response element frequently disrupted in B-cell non-Hodgkin lymphoma.

The BCL6 transcriptional repressor mediates survival, proliferation, and differentiation blockade of B cells during the germinal-center reaction and is frequently misregulated in B-cell non-Hodgkin lymphoma (BNHL). The p53 tumor-suppressor gene is central to tumorigenesis. Microarray analysis identified BCL6 as a primary target of p53.

The nuclear-envelope protein and transcriptional repressor LAP2beta interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation.

Nuclear-envelope proteins have been implicated in diverse and fundamental cell functions, among them transcriptional regulation. Gene expression at the territory of the nuclear periphery is known to be repressed by epigenetic modifications such as histone deacetylation and methylation. However, the mechanism by which nuclear-envelope proteins are involved in such modifications is still obscure.

Nuclear envelopathies--raising the nuclear veil.

The nuclear envelope separates the chromosomes from cytoplasm in eukaryotic cells and consists of three main domains: inner and outer nuclear membranes and nuclear pore complexes. The inner nuclear membrane maintains close associations with the underlying chromatin and nuclear lamina. For many years, the nuclear envelope was thought to function mainly as an architectural stabilizer of the nucleus, participating in assembly and disassembly processes during mitosis.

Microarray studies of prognostic stratification and transformation of follicular lymphomas.

Follicular lymphoma (FL) is a common, indolent malignancy with a natural history of transformation to the more aggressive form of diffuse large B-cell lymphoma (DLBCL) in 25-60% of cases. In order to understand the pathogenesis of lymphoma genesis and evolution, the molecular changes characteristic of FL and transformed DLBCL are being studied. The most common abnormality associated with FL is the t(14;18)(q32;q21) chromosomal translocation, but many more molecular aberrations have been found in patient subgroups.