bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral autoregulation in pregnancies complicated by diabetes and overweight
Authors: van Veen Teelkien R , Panerai Ronney B , Haeri Sina , van den Berg Paul P , Zeeman Gerda G , Belfort Michael A 
Published: June 2015

Aim: The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulation in pregnancy. Methods: Cerebral autoregulation was evaluated in women with gestational diabetes, type 2 diabetes mellitus and/or overweight (body mass index ⩾ 25 kg m−2) and compared to a cohort of euglycaemic pregnant women. The autoregulation index was calculated using simultaneously recorded cerebral blood flow velocity in the middle cerebral artery and blood pressure. Autoregulation index values of 0 and 9 indicate absent and perfect autoregulation, respectively. Results: Autoregulation index in women with either diabetes ( n = 33, 6.6 ± 1.1) or overweight ( n = 21, 6.7 ± 0.6) was not significantly different to that in control patients ( n = 23, 6.6 ± 0.8, p = 0.96). Conclusion: Cerebral autoregulation is not impaired in pregnant women who have non-vasculopathic diabetes or overweight. This suggests that the increased risk of pre-eclampsia in diabetic and overweight women is not associated with early impaired cerebral autoregulation.
Effects of exercise training on HbA1c and VO2peak in patients with type 2 diabetes and coronary artery disease: A randomised clinical trial
Authors: Byrkjeland Rune , Njerve Ida U , Anderssen Sigmund , Arnesen Harald , Seljeflot Ingebjørg , Solheim Svein 
Published: June 2015

Objective: Few exercise trials have focused on patients with both type 2 diabetes and coronary artery disease. We investigated the effects of 1 year of exercise training on HbA1c and VO2peak in these patients. Methods: Patients with type 2 diabetes and coronary artery disease ( n = 137) were randomised to combined exercise training or control group. HbA1c was measured at the beginning and end of the study. Changes in VO2peak, and also ventilatory threshold and time to exhaustion, were assessed by cardiopulmonary exercise testing. Results: No differences in changes between the randomised groups were observed in HbA1c and VO2peak, whereas ventilatory threshold and time to exhaustion increased significantly in the exercise group compared with the controls ( p = 0.046 and p = 0.034). In patients without previous acute myocardial infarction and diabetes microvascular complications ( n = 46), the exercise group did improve HbA1c and VO2peak compared with the controls ( p = 0.052 and p = 0.035). Conclusion: No significant effects of exercise training on HbA1c or VO2peak were observed in patients with type 2 diabetes and coronary artery disease, although improvements were seen in patients without vascular complications beyond coronary artery disease, implying that the degree of vascular disease may influence exercise responses. Ventilatory threshold and time to exhaustion did increase significantly, indicating improved exercise performance despite the minor change in VO2peak.
Drag-reducing polymers increase exercise tolerance in an ischemic hind-limb rat model
Authors: Zhang Quan , Deng Yuanyan , Zhang Wenjing , Liu Yili , Zha Daogang 
Published: June 2015

Objective Drag-reducing polymers are long-chain, blood soluble macromolecules that can improve microcirculation in vivo. This study aimed to examine the effects of drag-reducing polymers on exercise tolerance in a rat model of hind-limb ischemia. Methods After adaptive running training, bilateral femoral artery ligation models were established in 64 Wistar rats. During an exhaustive exercise, polyethylene oxide or normal saline was intravenously injected to each group ( n = 32) at 4 mL/h for 10 min. The exhaustive exercise time was recorded, and lactic acid levels in gastrocnemius muscle and serum were measured. Serum levels of nitric oxide, creatine kinase and lactate dehydrogenase were measured as biomarkers of physical fatigue. Results Compared with saline-treated control group, rats in polyethylene oxide-treated group had longer exhaustive exercise time (774.7 ± 171.5 s vs. 687.6 ± 166.1 s, p = 0.043), and lower lactic acid level in gastrocnemius muscle ( p < 0.01) but no significant difference in serum lactic acid level between two groups was observed ( p > 0.05). Nitric oxide level was higher in polyethylene oxide group than in controls ( p < 0.05), but no significant differences in serum creatine kinase and lactate dehydrogenase levels between two groups were observed ( p > 0.05). Conclusion Drag-reducing polymers contribute to the enhancement of exercise endurance and exert anti-fatigue effect.
Repairing Osteochondral Defects of Critical Size Using Multiple Costal Grafts
Authors: Du Dajiang , Sugita Norihiko , Liu Zhen , Moriguchi Yu , Nakata Ken , Myoui Akira , Yoshikawa Hideki 
Published: June 2015

Objective: To investigate the feasibility of repairing osteochondral defects of critical size by performing mosaicplasty using multiple sliced costal cartilage grafts, which enables repair of extensively injured knees using grafts from a single rib. Design: Critical osteochondral defects were prepared on the femoral groove of skeletally mature Japanese white rabbits. Costal cartilage grafts from a single rib were harvested and sliced into multiple segments (approximately 3-5 mm in length). The defects were left untreated or repaired by performing mosaicplasty using costal cartilage grafts (with or without a longitudinal cut along the middle). At 4 and 12 weeks after transplantation, International Cartilage Repair Society macroscopic and histological grading was performed. Results: The macroscopic score and visual histological score were significantly higher in the repaired groups than in the untreated group at 4 and 12 weeks after surgery. Histological continuous integration between grafted costal cartilage and host bone was observed in both repaired groups. Conclusions: The findings suggest that costal cartilage might be a useful alternative source for chondral grafting. We were able to repair large osteochondral defects by performing mosaicplasty using multiple sliced costal cartilage grafts from a single rib.
PI3K Mediated Activation of GSK-3β Reduces At-Level Primary Afferent Growth Responses Associated with Excitotoxic Spinal Cord Injury Dysesthesias
Authors: Bareiss Sonja K , Dugan Elizabeth , Brewer Kori L 
Published: June 2015

Background Neuropathic pain and sensory abnormalities are a debilitating secondary consequence of spinal cord injury (SCI). Maladaptive structural plasticity is gaining recognition for its role in contributing to the development of post SCI pain syndromes. We previously demonstrated that excitotoxic induced SCI dysesthesias are associated with enhanced dorsal root ganglia (DRG) neuronal outgrowth. Although glycogen synthase kinase-3β (GSK-3β) is a known intracellular regulator neuronal growth, the potential contribution to primary afferent growth responses following SCI are undefined. We hypothesized that SCI triggers inhibition of GSK-3β signaling resulting in enhanced DRG growth responses, and that PI3K mediated activation of GSK-3β can prevent this growth and the development of at-level pain syndromes. Results Excitotoxic SCI using intraspinal quisqualic acid (QUIS) resulted in inhibition of GSK-3β in the superficial spinal cord dorsal horn and adjacent DRG. Double immunofluorescent staining showed that GSK-3βP was expressed in DRG neurons, especially small nociceptive, CGRP and IB4-positive neurons. Intrathecal administration of a potent PI3-kinase inhibitor (LY294002), a known GSK-3β activator, significantly decreased GSK-3βP expression levels in the dorsal horn. QUIS injection resulted in early (3 days) and sustained (14 days) DRG neurite outgrowth of small and subsequently large fibers that was reduced with short term (3 days) administration of LY294002. Furthermore, LY294002 treatment initiated on the date of injury, prevented the development of overgrooming, a spontaneous at-level pain related dysesthesia. Conclusions QUIS induced SCI resulted in inhibition of GSK-3β in primary afferents and enhanced at-level DRG intrinsic growth (neurite elongation and initiation). Early PI3K mediated activation of GSK-3β attenuated QUIS-induced DRG neurite outgrowth and prevented the development of at-level dysesthesias.
Middle-down electron capture dissociation and electron transfer dissociation for histone analysis
Authors: Moradian Annie , Franco Catarina , Sweredoski Michael J. , Hess Sonja 
Published: June 2015

Abstract
The post-translational modifications (PTMs) of histones play a major role in activating or silencing gene transcription. To gain better understanding of the interplay between the PTMs that occur on histones, they are extensively studied using mass spectrometry techniques. Due to the abundance of lysines and arginines, the typical trypsin digestion has been found less favorable and GluC-digests have been explored as an alternative to yield larger peptides amenable to middle-down approaches. In addition, the use of weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) and the use of electron-based fragmentation techniques were found to be advantageous for the in-depth characterization of histone variants containing multiple PTMs.
As a test model, we used histones from MEL (murine erythroleukemia) cells treated with butyric acid or DMSO. After acid extraction, histone pellets were dried and fractionated using a reversed-phase C3 column. For middle-down analysis, selected histone fractions were digested using GluC. The digested samples were separated on a WCX-HILIC capillary column packed in-house with PolyCAT A resin, coupled to a linear trap quadrupole Fourier transformation ion cyclotron resonance (LTQFT-ICR) instrument. Raw data was acquired on the LTQFT-ICR using electron capture dissociation (ECD). After deconvolution of the raw data, we generated heatmaps to illustrate differential maps between differentially treated histone samples. We also explored the innovative use of Skyline to quantify histone tails. In addition, we report some preliminary data using a synthetic histone peptide acquired on an Orbitrap Fusion using electron transfer dissociation (ETD). Both, ECD and ETD methods are capable of comprehensively analyzing complex histone variations not accessible with conventional techniques.
Critical illness-induced bone loss is related to deficient autophagy and histone hypomethylation
Authors: Owen Helen C , Vanhees Ineke , Gunst Jan , Van Cromphaut Sophie , Van den Berghe Greet 
Published: June 2015

Abstract

Background
Survivors of critical illness are at increased risk of fractures. This may be due to increased osteoclast formation during critical illness, leading to trabecular bone loss. Such bone loss has also been observed in Paget’s disease, and has been related to deficient autophagy. Deficient autophagy has also been documented in vital organs and skeletal muscle of critically ill patients. The objective of this study was to investigate whether deficient autophagy can be linked to critical illness-induced bone loss.

Methods
Osteoclasts grown in vitro and their precursor cells isolated from peripheral blood of critically ill patients and from matched healthy volunteers were analysed for the expression of autophagy genes (SQSTM1, Atg3 and Atg7), and proteins (p62, Atg–5, and microtubule-associated protein light chain 3–II (LC3–II)) and for autophagy and epigenetic signalling factors via PCR arrays and were treated with the autophagy inducer rapamycin. The effect of rapamycin was also investigated at the tissue level in an in vivo rabbit model of critical illness.

Results
Many more osteoclasts formed in vitro from the blood precursor cells isolated from critically ill patients, which accumulated p62, and displayed reduced expression of Atg5, Atg7, and LC3–II compared to healthy controls, suggesting deficient autophagy, whilst addition of rapamycin reduced osteoclast formation. PCR arrays revealed a down-regulation of histone methyltransferases coupled with an up-regulation of negative regulators of autophagy. Critically ill rabbits displayed a reduction in trabecular and cortical bone, which was rescued with rapamycin.

Conclusions
Deficient autophagy in osteoclasts and their blood precursor cells at least partially explained aberrant osteoclast formation during critical illness and was linked to global histone hypomethylation. Treatment with the autophagy activator Rapamycin reduced patient osteoclast formation in vitro and reduced the amount of bone loss in critically ill rabbits in vivo. These findings may help to develop novel therapeutic targets to prevent critical illness-induced bone loss.
Resveratrol increases F508del-CFTR dependent salivary secretion in cystic fibrosis mice
Authors: Dhooghe Barbara , Bouckaert Charlotte , Capron Arnaud , Wallemacq Pierre , Leal Teresinha , Noel Sabrina 
Published: June 2015

ABSTRACTCystic fibrosis (CF) is a fatal genetic disease associated with widespread exocrine gland dysfunction. Studies have suggested activating effects of resveratrol, a naturally-occurring polyphenol compound with antioxidant and anti-inflammatory properties, on CF transmembrane conductance regulator (CFTR) protein function. We assayed, in F508del-CFTR homozygous (CF) and in wild-type mice, the effect of resveratrol on salivary secretion in basal conditions, in response to inhibition by atropine (basal β-adrenergic-dependent component) and to stimulation by isoprenaline (CFTR-dependent component). Both components of the salivary secretion were smaller in CF mice than in controls. Two hours after intraperitoneal administration of resveratrol (50 mg/kg) dissolved in DMSO, the compound was detected in salivary glands. As in both CF and in wild-type mice, DMSO alone increased the response to isoprenaline in males but not in females, the effect of resveratrol was only measured in females. In wild-type mice, isoprenaline increased secretion by more than half. In CF mice, resveratrol rescued the response to isoprenaline, eliciting a 2.5-fold increase of β-adrenergic-stimulated secretion. We conclude that the salivary secretion assay is suitable to test DMSO-soluble CFTR modulators in female mice. We show that resveratrol applied in vivo to mice reaches salivary glands and increases β-adrenergic secretion. Immunolabelling of CFTR in human bronchial epithelial cells suggests that the effect is associated with increased CFTR protein expression. Our data support the view that resveratrol is beneficial for treating CF. The salivary secretion assay has a potential application to test efficacy of novel CF therapies.
SNAP23/25 and VAMP2 mediate exocytic event of transferrin receptor-containing recycling vesicles
Authors: Kubo Keiji , Kobayashi Minako , Nozaki Shohei , Yagi Chikako , Hatsuzawa Kiyotaka , Katoh Yohei , Shin Hye-Won , Takahashi Senye , Nakayama Kazuhisa 
Published: June 2015

ABSTRACT
We recently showed that Rab11 is involved not only in formation of recycling vesicles containing the transferrin (Tfn)–transferrin receptor (TfnR) complex at perinuclear recycling endosomes but also in tethering of recycling vesicles to the plasma membrane (PM) in concert with the exocyst tethering complex. We here aimed at identifying SNARE proteins responsible for fusion of Tfn–TfnR-containing recycling vesicles with the PM, downstream of the exocyst. We showed that exocyst subunits, Sec6 and Sec8, can interact with SNAP23 and SNAP25, both of which are PM-localizing Qbc-SNAREs, and that depletion of SNAP23 and/or SNAP25 in HeLa cells suppresses fusion of Tfn–TfnR-containing vesicles with the PM, leading to accumulation of the vesicles at the cell periphery. We also found that VAMP2, an R-SNARE, is colocalized with endocytosed Tfn on punctate endosomal structures, and that its depletion in HeLa cells suppresses recycling vesicle exocytosis. These observations indicate that fusion of recycling vesicles with the PM downstream of the exocyst is mediated by SNAP23/25 and VAMP2, and provide novel insight into non-neuronal roles of VAMP2 and SNAP25.
The galectin lattice at a glance
Authors: Nabi Ivan R. , Shankar Jay , Dennis James W. 
Published: June 2015

ABSTRACTGalectins are a family of widely expressed β-galactoside-binding lectins in metazoans. The 15 mammalian galectins have either one or two conserved carbohydrate recognition domains (CRDs), with galectin-3 being able to pentamerize; they form complexes that crosslink glycosylated ligands to form a dynamic lattice. The galectin lattice regulates the diffusion, compartmentalization and endocytosis of plasma membrane glycoproteins and glycolipids. The galectin lattice also regulates the selection, activation and arrest of T cells, receptor kinase signaling and the functionality of membrane receptors, including the glucagon receptor, glucose and amino acid transporters, cadherins and integrins. The affinity of transmembrane glycoproteins to the galectin lattice is proportional to the number and branching of their N-glycans; with branching being mediated by Golgi N-acetylglucosaminyltransferase-branching enzymes and the supply of UDP-GlcNAc through metabolite flux through the hexosamine biosynthesis pathway. The relative affinities of glycoproteins for the galectin lattice depend on the activities of the Golgi enzymes that generate the epitopes of their ligands and, thus, provide a means to analyze biological function of lectins and of the ‘glycome’ more broadly.
Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration
Authors: Schaefer Antje , Hordijk Peter L. 
Published: June 2015

ABSTRACT
The breaching of cellular and structural barriers by migrating cells is a driving factor in development, inflammation and tumor cell metastasis. One of the most extensively studied examples is the extravasation of activated leukocytes across the vascular endothelium, the inner lining of blood vessels. Each step of this leukocyte transendothelial migration (TEM) process is regulated by distinct endothelial adhesion receptors such as the intercellular adhesion molecule 1 (ICAM1). Adherent leukocytes exert force on these receptors, which sense mechanical cues and transform them into localized mechanosignaling in endothelial cells. In turn, the function of the mechanoreceptors is controlled by the stiffness of the endothelial cells and of the underlying substrate representing a positive-feedback loop. In this Commentary, we focus on the mechanotransduction in leukocytes and endothelial cells, which is induced in response to variations in substrate stiffness. Recent studies have described the first key proteins involved in these mechanosensitive events, allowing us to identify common regulatory mechanisms in both cell types. Finally, we discuss how endothelial cell stiffness controls the individual steps in the leukocyte TEM process. We identify endothelial cell stiffness as an important component, in addition to locally presented chemokines and adhesion receptors, which guides leukocytes to sites that permit TEM.
The Relationship Between Academic Achievement And Nonmarital Teenage Childbearing: Evidence from the Panel Study of Income Dynamics
Authors: Lou Cary , Thomas Adam 
Published: June 2015

CONTEXTFemales who do well in school are less likely than those who do poorly to experience a nonmarital teenage birth. However, little is known about which dimensions of academic achievement are the most strongly related to teenage childbearing, or about whether the relationship between achievement and childbearing varies according to the presence of other behavioral problems.METHODSIndividual‐level and family‐level data from the Panel Study of Income Dynamics, combined with information on contextual state‐level economic and policy measures, were used to study nonmarital childbearing between the ages of 16 and 19 among 701 females who turned 16 between 2000 and 2007. Multivariate logistic regression analyses examined the relationship between the probability of nonmarital teenage childbearing and age‐standardized scores on academic assessments of letter‐word identification, passage comprehension and applied problem‐solving ability.RESULTSScores on the passage comprehension and applied problem‐solving subtests were strongly associated with the probability of experiencing a nonmarital teenage birth among respondents who had relatively few behavioral problems. For this group, an increase of one standard deviation in the score on either assessment was associated with a reduction of about 50% in the risk of experiencing a nonmarital teenage birth. However, no evidence was found of an equivalent relationship among respondents with more pronounced behavioral problems or for the letter‐word identification assessment.CONCLUSIONSFuture research should continue to explore the possibility that improvements in academic achievement may help to reduce the rate of nonmarital teenage childbearing.
State Abortion Context and U.S. Women's Contraceptive Choices, 1995–2010
Authors: Jacobs Josephine , Stanfors Maria 
Published: June 2015

AbstractCONTEXTThe number of women in the United States exposed to restrictive abortion policies has increased substantially over the past decade. It is not well understood whether and how women adjust their contraceptive behavior when faced with restrictive abortion contexts.METHODSData from 14,523 women aged 15–44 were drawn from the 1995 and 2010 cycles of the National Survey of Family Growth. A difference‐in‐differences approach was employed to examine the relationship between state‐level changes in women's access to abortion and their contraceptive choices. Multinomial logistic regression analysis was used to determine the relative risk of using highly effective or less effective methods rather than no method for women exposed to varying levels of restrictive abortion contexts.RESULTSWomen who lived in a state where abortion access was low were more likely than women living in a state with greater access to use highly effective contraceptives rather than no method (relative risk ratio, 1.4). Similarly, women in states characterized by high abortion hostility (i.e., states with four or more types of restrictive policies in place) were more likely to use highly effective methods than were women in states with less hostility (1.3). The transition to a more restrictive abortion context was not associated with women's contraceptive behavior, perhaps because states that introduced restrictive abortion legislation between 1995 and 2010 already had significant limitations in place.CONCLUSIONTo prevent unwanted pregnancies, it is important to ensure access to highly effective contraceptive methods when access to abortions is limited.