Hydrogen-bond dynamics at the bio-water interface in hydrated proteins: a molecular-dynamics study.

Water is fundamental to the biochemistry of enzymes. It is well known that without a minimum amount of water, enzymes are not biologically active. Bare minimal solvation for biological function corresponds to about a single layer of water covering enzymes' surfaces.

Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans.

Background: All living cells display a rapid molecular response to adverse environmental conditions, and the heat shock protein family reflects one such example. Hence, failing to activate heat shock proteins can impair the cellular response. In the present study, we evaluated whether the loss of different isoforms of heat shock protein (hsp) genes in Caenorhabditis elegans would affect their vulnerability to Manganese (Mn) toxicity.

HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes.

Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC.

Elastic Scattering Spectroscopy (ESS): an Instrument-Concept for Dynamics of Complex (Bio-) Systems From Elastic Neutron Scattering.

A new type of neutron-scattering spectroscopy is presented that is designed specifically to measure dynamics in bio-systems that are difficult to obtain in any other way. The temporal information is largely model-free and is analogous to relaxation processes measured with dielectric spectroscopy, but provides additional spacial and geometric aspects of the underlying dynamics. Numerical simulations of the basic instrument design show the neutron beam can be highly focussed, giving efficiency gains that enable the use of small samples.

Comparative liver accumulation of dioxin-like compounds in sheep and cattle: Possible role of AhR-mediated xenobiotic metabolizing enzymes.

PCDDs, PCDFs, and PCBs are persistent organic pollutants (POPs) that accumulate in animal products and may pose serious health problems. Those able to bind the aryl hydrocarbon receptor (AhR), eliciting a plethora of toxic responses, are defined dioxin-like (DL) compounds, while the remainders are called non-DL (NDL). An EFSA opinion has highlighted the tendency of ovine liver to specifically accumulate DL-compounds to a greater extent than any other farmed ruminant species.

Heavy metals and essential elements in Italian cereals.

Crops intended for human nutrition and food production containing different essential trace elements, such as copper and zinc, could be contaminated by toxic metals like cadmium and lead. The interrelationship between micronutrients and contaminant trace elements in different cereals was investigated in North-western Italy, where both agricultural and industrial activities are present. Elemental concentrations in sampled cereals were assessed by inductively coupled plasma mass spectrometry (ICP-MS).

The Hippo transducers TAZ/YAP and their target CTGF in male breast cancer.

Male breast cancer (MBC) is a rare disease and its biology is poorly understood. Deregulated Hippo pathway promotes oncogenic functions in female breast cancer. We herein investigated the expression of the Hippo transducers TAZ/YAP and their target CTGF in MBC.

Rhythmic modulation of visual contrast discrimination triggered by action.

Recent evidence suggests that ongoing brain oscillations may be instrumental in binding and integrating multisensory signals. In this experiment, we investigated the temporal dynamics of visual-motor integration processes. We show that action modulates sensitivity to visual contrast discrimination in a rhythmic fashion at frequencies of about 5 Hz (in the theta range), for up to 1 s after execution of action.

Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial.

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m(2) intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m(2) and cyclophosphamide, 600 mg/m(2) , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery.

Dynamics of the erythropoiesis stimulating agent resistance index in incident hemodiafiltration and high-flux hemodialysis patients.

Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period.

Anti-Yo Antibodies in Children With ADHD: First Results About Serum Cytokines.

We investigated whether ADHD children who are positive to Purkinje cell antibodies display pro-inflammatory activity associated with high cytokine serum levels. Fifty-eight ADHD outpatients were compared with 36 healthy, age- and sex-matched children. Forty-five of the ADHD children were positive to anti-Yo antibodies, whereas 34 of the control children were negative.

Association between maternal serum high mobility group box 1 levels and pregnancy complicated by gestational diabetes mellitus.

Background And Aims: Gestational diabetes mellitus (GDM), is characterized by chronic, low-grade subclinical inflammation with altered production of cytokines and mediators. Recently, a new protein acting as a "danger signal", high mobility group box 1 (HMGB1), that migrates quickly during electrophoresis, has been identified. The aim of our study was to analyze serum levels of HMGB1 in pregnant women, with or without GDM, in the third trimester of pregnancy to evaluate correlation with insulin resistance and other risk factors for GDM.

Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

Background: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series.

Methods: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes.

Adipose-derived mesenchymal stromal (stem) cells differentiate to osteoblast and chondroblast lineages upon incubation with conditioned media from dental pulp stem cell-derived osteoblasts and auricle cartilage chondrocytes.

The potential of adipose-derived mesenchymal stromal (stem) cells (ADSCs) to differentiate into either osteoblasts or chondrocytes is controversial. In this study we investigated the multicapacity potential of ADSCs to differentiate towards adipocyte, osteoblast, and chondrocyte lineages when cells are seeded onto plastic in comparison with incubation with conditioned media (CM) obtained from differentiated cell types.ADSCs, obtained from liposuctions, were characterized for mesenchymal and hematopoietic markers by cytofluorimetry.

Topographic expression of the Hippo transducers TAZ and YAP in triple-negative breast cancer treated with neoadjuvant chemotherapy.

Background: The Hippo signaling acts as a tumor-suppressor pathway that negatively regulates TAZ and YAP. Increasing evidence supports the activation of TAZ and YAP in breast cancer. Moreover, the Hippo pathway is involved in the biology of non-neoplastic cells residing in the tumor microenvironment.

Oxidative stress related to chlorpyrifos exposure in rainbow trout: Acute and medium term effects on genetic biomarkers.

Organophosphates (OPs) are derivatives of phosphoric acid widely used in agriculture as pesticides. Chlorpyrifos (CPF) is an OP that is extremely toxic to aquatic organisms. Rainbow trout (Oncorhynchus mykiss) is considered as a sentinel model species for ecotoxicology assessment in freshwater ecosystems.

Dioxins, DL-PCB and NDL-PCB accumulation profiles in livers from sheep and cattle reared in North-western Italy.

Products of animal origin represent the main route of human exposure to dioxins and dioxin-like PCBs (DL-compounds). Recently, concerns have been raised about ovine products, particularly the liver, in which relatively high levels of DL-compounds have been reported. We surveyed ovine and bovine livers in areas with no known sources of dioxin or DL-PCB contamination, in order to assess accumulation patterns for both DL-compounds and non-DL (NDL-) PCBs.

ΔNp63 regulates IL-33 and IL-31 signaling in atopic dermatitis.

Atopic dermatitis (AD) is the most common inflammatory skin disease with no well-delineated cause or effective cure. Here we show that the p53 family member p63, specifically the ΔNp63, isoform has a key role in driving keratinocyte activation in AD. We find that overexpression of ΔNp63 in transgenic mouse epidermis results in a severe skin phenotype that shares many of the key clinical, histological and molecular features associated with human AD.

Dissociable saccadic suppression of pupillary and perceptual responses to light.

We measured pupillary constrictions in response to full-screen flashes of variable luminance, occurring either at the onset of a saccadic eye movement or well before/after it. A large fraction of perisaccadic flashes were undetectable to the subjects, consistent with saccadic suppression of visual sensitivity. Likewise, pupillary responses to perisaccadic flashes were strongly suppressed.

Perinatal outcome in a Caucasian population with gestational diabetes and preexisting diabetes first diagnosed in pregnancy.

Aim: Our objective was to compare, in a Caucasian population, the perinatal outcomes of pregnancies complicated by pregestational diabetes diagnosed in the first-trimester of pregnancy with those of pregnancies complicated by gestational diabetes.

Methods: A retrospective evaluation of maternal and neonatal outcomes was performed for all consecutive pregnancies complicated by gestational or pregestational diabetes that happened between 2005 and 2011. Pregestational diabetes was diagnosed for the first time in pregnancy if the first-trimester fasting glycaemia was ≥126 mg/dL.

Functions of vasopressin and oxytocin in bone mass regulation.

Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr(-/-) mice have osteopenia, and Avpr1α(-/-) mice display a high bone mass phenotype.

Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial.

Objective: To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women.

Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m(2)). The primary outcome was the incidence of GDM.

Longitudinal Changes in Body Composition in Patients After Initiation of Hemodialysis Therapy: Results From an International Cohort.

Objective: In patients with advanced kidney disease, metabolic and nutritional derangements induced by uremia interact and reinforce each other in a deleterious vicious circle. Literature addressing the effect of dialysis initiation on changes in body composition (BC) is limited and contradictory. The aim of this study was to evaluate changes in BC in a large international cohort of incident hemodialysis patients.

Predictive significance of DNA damage and repair biomarkers in triple-negative breast cancer patients treated with neoadjuvant chemotherapy: An exploratory analysis.

Response of cancer cells to chemotherapy-induced DNA damage is regulated by the ATM-Chk2 and ATR-Chk1 pathways. We investigated the association between phosphorylated H2AX (γ-H2AX), a marker of DNA double-strand breaks that trigger the ATM-Chk2 cascade, and phosphorylated Chk1 (pChk1), with pathological complete response (pCR) in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy. γ-H2AX and pChk1 were retrospectively assessed by immunohistochemistry in a series of pretreatment biopsies related to 66 patients.