bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hv1 proton channels differentially regulate the pH of neutrophil and macrophage phagosomes by sustaining the production of phagosomal ROS that inhibit the delivery of vacuolar ATPases
Authors: El Chemaly Antoun , Nunes Paula , Jimaja Wedali , Castelbou Cyril , Demaurex Nicolas 
Published: January 2014

ABSTRACTProduction of ROS and maintenance of an appropriate pH within the lumen of neutrophil and macrophage phagosomes are important for an effective immune response. Hv1 proton channels sustain ROS production at the plasma membrane, but their role in phagosomes is not known. Here, we tested whether Hv1 channels regulate the pHp and sustain phagosomal ROS production in neutrophils and macrophages. The presence of Hv1 channels on phagosomes of human neutrophils and mouse macrophages was confirmed by Western blot and immunostaining. Phagosomal ROS production, measured with OxyBurst-coupled targets, was reduced in neutrophils and macrophages isolated from Hv1-deficient mice. Ratiometric imaging of FITC-coupled targets showed that phagosomes acidified more slowly in Hv1-deficient macrophages and transiently alkalinized when the V-ATPase was inhibited. In WT neutrophils, 97% of phagosomes remained neutral 30 min after particle ingestion, whereas 37% of Hv1-deficient phagosomes were alkaline (pH&gt;8.3) and 14% acidic (pH&lt;6.3). The subpopulation of acidic phagosomes was eliminated by V-ATPase inhibition, whereas NOX inhibition caused a rapid acidification, independently of Hv1 expression. Finally, V-ATPase accumulation on phagosomes was inversely correlated to intraphagosomal ROS production in neutrophils. These data indicate that Hvcn1 ablation deregulates neutrophil pHp, leading to alkalinization in phagosomes with residual ROS production or to the early accumulation of V-ATPase on phagosomes that fail to mount an oxidative response. Hv1 channels therefore differentially regulate the pHp in neutrophils and macrophages, sustaining rapid acidification in macrophage phagosomes and maintaining a neutral pH in neutrophil phagosomes.
Cell adhesion and sorting in embryoid bodies derived from N- or E-cadherin deficient murine embryonic stem cells
Authors: Moore Robert , Tao Wensi , Meng Yue , Smith Elizabeth R. , Xu Xiang-Xi 
Published: January 2014

Summary
The primitive endoderm epithelial structure in mouse blastocysts forms following cell differentiation and subsequent sorting, and this two-step process can be reproduced in vitro using an embryoid body model. We found that in the chimeric embryoid bodies consisting of paired wildtype and E-cadherin null ES cells, the wildtype sorted to the center and were enveloped by the less adhesive E-cadherin null cells, in accord with Steinberg's hypothesis. However, wildtype and N-cadherin null ES cells intermixed and did not segregate, a situation that may be explained by Albert Harris' modified principle, which incorporates the unique properties of living cells. Furthermore, in chimeric embryoid bodies composed of N-cadherin and E-cadherin null ES cells, the two weakly interacting cell types segregated but did not envelop one another. Lastly, the most consistent and striking observation was that differentiated cells sorted to the surface and formed an enveloping layer, regardless of the relative cell adhesive affinity of any cell combination, supporting the hypothesis that the ability of the differentiated cells to establish apical polarity is the determining factor in surface sorting and positioning.
Bug22 influences cilium morphology and the post-translational modification of ciliary microtubules
Authors: Mendes Maia Teresa , Gogendeau Delphine , Pennetier Carole , Janke Carsten , Basto Renata 
Published: January 2014

Summary
Cilia and flagella are organelles essential for motility and sensing of environmental stimuli. Depending on the cell type, cilia acquire a defined set of functions and, accordingly, are built with an appropriate length and molecular composition. Several ciliary proteins display a high degree of conservation throughout evolution and mutations in ciliary genes are associated with various diseases such as ciliopathies and infertility. Here, we describe the role of the highly conserved ciliary protein, Bug22, in Drosophila. Previous studies in unicellular organisms have shown that Bug22 is required for proper cilia function, but its exact role in ciliogenesis has not been investigated yet. Null Bug22 mutant flies display cilia-associated phenotypes and nervous system defects. Furthermore, sperm differentiation is blocked at the individualization stage, due to impaired migration of the individualization machinery. Tubulin post-translational modifications (PTMs) such as polyglycylation, polyglutamylation or acetylation, are determinants of microtubule (MT) functions and stability in centrioles, cilia and neurons. We found defects in the timely incorporation of polyglycylation in sperm axonemal MTs of Bug22 mutants. In addition, we found that depletion of human Bug22 in RPE1 cells resulted in the appearance of longer cilia and reduced axonemal polyglutamylation. Our work identifies Bug22 as a protein that plays a conserved role in the regulation of PTMs of the ciliary axoneme.
LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition
Authors: Cuevas Eva P. , Moreno-Bueno Gema , Canesin Giacomo , Santos Vanesa , Portillo Francisco , Cano Amparo 
Published: January 2014

Summary
Lysyl-oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family that catalyzes the cross-linking of collagens or elastins in the extracellular matrix, thus regulating the tensile strength of tissues. However, many reports have suggested different intracellular roles for LOXL2, including the ability to regulate gene transcription and tumor progression. We previously reported that LOXL2 mediates epithelial-to-mesenchymal transition (EMT) by Snail1-dependent and independent mechanisms, related to E-cadherin silencing and downregulation of epidermal differentiation and cell polarity components, respectively. Whether or not the catalytic activity of LOXL2 is required to induce/sustain EMT is actually unknown. Here we show that LOXL2 catalytic inactive mutants collaborate with Snail1 in E-cadherin gene repression to trigger EMT and, in addition, promote FAK/Src pathway activation to support EMT. These findings reveal a non-conventional role of LOXL2 on regulating epithelial cell plasticity.
Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin 43 containing gap junctions in cardiac Myocytes
Authors: Zemljic-Harpf Alice E. , Godoy Joseph , Platoshyn Oleksandr , Asfaw Elizabeth K. , Busija Anna R. , Domenighetti Andrea A. , Ross Robert S. 
Published: January 2014

Vinculin (Vcl) links actin filaments to integrin and cadherin-based cellular junctions. Zonula occludens-1 (ZO-1) binds connexin-43 (Cx43), cadherin and actin. Vcl and ZO-1 anchor the actin cytoskeleton to the sarcolemma.
Since loss of Vcl from cardiomyocytes caused mal-distribution of Cx43 and predisposed cardiomyocyte-specific Vcl knockout mice with preserved heart function to arrhythmic sudden death, we hypothesized that Vcl and ZO-1 would interact and that loss of this interaction would destabilize gap junctions.

Results:
Vcl, Cx43 and ZO-1 colocalized at the intercalated disc (ICD). Loss of cardiomyocyte Vcl caused parallel loss of ZO-1 from ICDs. Vcl co-immunoprecipitated Cx43 and ZO-1, and directly bound ZO-1 in yeast two-hybrid studies. Vcl gene excision in neonatal mouse cardiomyocytes caused reduction of Vcl transcript and protein expression, leading to:
1) decreased protein expression of Cx43, ZO-1, talin, and β1D-integrin, 2) reduced PI3K activation, 3) increased activation of Akt, Erk1, and Erk2, and 4) cardiomyocyte necrosis.

Summary:
This is the first study showing a direct interaction between Vcl and ZO-1 and illustrates how Vcl plays a critical role in stabilizing gap junctions and myocyte integrity.
Comparative analysis of HLA II allele and genotype frequency distribution in patients with type 1 diabetes mellitus and autoimmune thyroiditis
Authors: Repina Ekaterina Alexandrovna , Atamanova Tatiana Mikhailovna , Zvereva Yana Stanislavovna , Tishina Yulia Vladimirovna , Prokof'ev Sergey Alexandrovich 
Published: January 2014

Aim. To compare HLA II allele and genotype frequency distribution in type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis (AIT) with that in isolated T1DM. Materials and Methods. A total of 92 T1DM patients were subdivided into two groups. The first group comprised 54 patients with established AIT comorbidity or elevation of anti-thyroid autoantibodies (ATA). Patients with isolated T1DM (ATA-negative) formed the second group. HLA-genotyping was performed by multiprimer PCR set for the three following genes: DRB1, DQA1 and DQВ1. Results. Prevalence of alleles DRB1*01, *03(017), *04, *07, *11 and genotypes 01/03, 01/04, 03/04 tends to be higher among patients with AIT comorbidity. The comorbidity group was also characterized by the trend towards higher prevalence of ?marker/marker? and ?marker/non-marker? combinations favouring the former variant. Conversely, ATA-negative patients exhibited trend for higher prevalence of ?non-marker/non-marker? combination. Conclusion. Statistically insignificant difference between HLA II alleles and genotypes in the two studied groups suggests that primary genetic factors are common in these two diseases. Plausibly, genes other than DRB1, DQA1 and DQВ1 determine the localization of the autoimmune process.
Analysis of the calcium-phosphorus metabolism and function of the parathyroid glands in patients with type 1 diabetes mellitus
Authors: Khantakova Ekaterina Alexandrovna , Khamnueva Larisa Yur'evna , Orlova Galina Mikhailovna 
Published: January 2014

Objective. To analyze the calcium-phosphorus metabolism in patients with diabetes mellitus (DM) type 1 depending on the functional state of the kidneys. Materials and Methods. The study involved 235 patients with type 1 diabetic (males). One hundred and thirty-four patients entered the group without diabetic nephropathy (DN) and 101 patients entered the group with DN. To study the phosphorous-calcium metabolism in patients with type 1 diabetes there were studied the following parameters in blood plasma: the level of intact parathyroid hormone (PTH), total calcium (Ca), ionized calcium (Ca2+), serum phosphorus (P), as well as calculated CaxP product. Results. In patients with type 1 diabetes in the progression of DN the increase of P was observed from stage 4 CKD and reduction of Ca ? from CKD stage 5. The increase of the level of PTH was observed from the stage of CKD 3, although isolated cases of secondary hyperparathyroidism were registered in patients with stage CKD 2. At the same time in a large group of the patients with type 1 diabetes there was observed level of PTH below the target values of the stages CKD 3, 4, 5. The deterioration of glycemic control in patients with type 1 diabetes is associated with decreased level of PTH. In patients with type 1 diabetes without DN and with DN there was observed inverse relationship between the level of glycated hemoglobin (HbA. 1c). Conclusion. In patients with type 1 diabetes the progression of DN leads to various disorders of phosphorus-calcium metabolism: reduction of Ca, higher level of P, alter the function of the parathyroid glands (secondary hyperparathyroidism and reduction of PTH below the target value). Deterioration of glycemic control in patients with type 1 diabetes is associated with a reduction of PTH.
Immunohystochemical study of the largest islets of human pancreas in aging and diabetes mellitus: perspectives for the transplantation
Authors: Proshchina Alexandra Evgen'evna , Krivova Yulia Sergeevna , Barabanov Valeriy Mikhaylovich , Savelyev Sergey Vyacheslavovich 
Published: January 2014

Aim. To study the distribution and cellular architecture of the largest human pancreatic islets (with a diameter of more than 200 micron) in aging and diabetes mellitus types 1 and 2. Materials and methods. Antibodies to insulin, glucagon, somastatin and nturon-specific enolase were applied. The autopsy samples of the pancreatic tissue of patients with diabetes mellitus type 1 (DMT1) and type 2 (DMT2) and 2 age groups (up to 50 years old (control) and after 50 (aging control)), not suffering from diseases of the pancreas and carbohydrate metabolism malfunction were investigated. Results. The number of islets with diameter more than 200 mkm compared to control group increased both in aging and diabetes groups. Their number reaches in some cases 15% (and higher in DM) of the total number of islets. These islets compared to the other are rich-vascularized. It was shown that glucagon and somatostatin-containing cells are found both on the periphery of the large islets, and inside them only in the immediate proximity of the capillaries. Insulin-containing cells form clusters, surrounded by the capillaries and the ?- and ?-cells, while the inner part of such clusters has no direct contact with the capillaries. In the large islets the number of glucagon-containing cells is often increased, and insulin-containing cells show signs of degradation. Conclusion. The largest of the pancreatic islets may be useless for the transplantation, because of the high content of glucagon-containing cells, the rich vascularization and, in some cases, the limited functionality of ?-cells.
Arrhythmogenic effects of hypoglycemia in children and adolescents with type 1 diabetes mellitus
Authors: Laptev Dmitriy Nikitich , Ryabykina Galina Vladimirovna 
Published: January 2014

Aim. To determine the effects of hypoglycemia on the duration of QT interval, heart rate variability (HRV) and frequency of arrhythmic events, as well as to closer investigate the factors associated with the development of various heart rhythm disorders in children and adolescents with type 1 diabetes mellitus (T1DM). Materials and methods. The study included 150 children and adolescents with T1DM at the age of 6?18 years. All participants underwent Holter monitoring and continuous glucose monitoring (CGM) for 24 hours. QTc and HRV parameters (SDNN, RMSSD, SVVR) were calculated automatically. Data was averaged for 5?-interval and juxtaposed with CGM. Patients identified with hypoglycemic events (blood glucose
Correlation between arterial wall stiffness, N-terminal prohormone of brain natriuretic peptide, functional and structural myocardial abnormalities in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy
Authors: Serhiyenko Viktoriya Alexandrovna , Serhiyenko Alexander Alexandrovich , Mankovsky Boris Nikitich 
Published: January 2014

Aim. To assess arterial wall stiffness, plasma levels of of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), as well as functional state and structure of the myocardium in patients with type 2 diabetes mellitus (T2DM) and cardiac autonomic neuropathy (CAN). Materials and Methods. The study involved a total of 65 patients with T2DM. 12 had no evidence of cardiovascular disease (CVD) or CAN, 14 were diagnosed with subclinical stage of CAN, 18 ? with functional stage, and 21 ? with organic stage. We measured aortic pulse wave velocity (PWV), aortic augmentation index (AIx), brachial artery AIx, ambulatory arterial stiffness index (AASI) and plasma levels of NT-proBNP. Clinical examination included ECG, Holter monitoring, ambulatory BP measurement and echocardiography. Results. Patients with isolated T2DM showed a trend for increased vascular wall stiffness. PWV was increased in patients with subclinical stage of CAN. Aortic and brachial AIx, PWV and AASI were elevated in patients with functional stage of CAN, PWV being significantly higher vs. subclinical CAN subgroup. Organic stage was characterized by pathologically increased values of all primary parameters; PWV and AASI were significantly higher compared with other groups. Development and progression of CAN was accompanied by an increase in NT-proBNP plasma levels. Concentration of NT-proBNP was in direct correlation with left ventricular mass (LVM) and PWV. PWV and LVM values also directly correlated between themselves. Conclusion. Development and progression of CAN in patients with T2DM is accompanied by an increase in vascular wall stiffness. The elevation of plasma NT-proBNP in patients with T2DM correlates with the development of CAN and is significantly and independently associated with an increase in LVM and PWV. Our data suggests the pathophysiological interconnection between metabolic, functional and structural myocardial abnormalities in patients with T2DM and CAN.
Clinical outcomes of lower limb peripheral vascular disease after endovascular intervention in patients with diabetes mellitus, critical limb ischemia and chronic kidney disease
Authors: Ayubova Natalya Leonidovna , Bondarenko Olga Nikolaevna , Galstyan Gagik Radikovich , Manchenko Oksana Vladimirovna , Dedov Ivan Ivanovich 
Published: January 2014

Aim. To assess the extent of the lower limb arterial calcification and to evaluate the long-term outcomes of percutaneous transluminal balloon angioplasty (PTBA) in patients with diabetes mellitus (DM), critical limb ischemia (CLI) and chronic kidney disease (CKD). Materials and Methods. 94 patients with CLI formed two groups (CKD-positive and CDK-negative). Quantitative assessment of tibial arterial calcification was performed with non-contrast CT. Outcomes of angioplasty were monitored during the 18?6 months of the follow-up period by means of duplex ultrasonography. Results. Long-term outcomes of PTBA were significantly worse in patients with CKD. Nevertheless, limb preservation and survival rates were relatively satisfactory in both groups (74% and 72%, respectively). Conclusion. PTBA in patients with DM, CLI and CKD presents a technical challenge. Despite that, in many cases the endovascular intervention allows avoiding high-level amputations and improves survival rates.
Efficacy and safety of glimepiride as initial treatment in Russian patients with type 2 diabetes mellitus
Authors: Ametov Alexander Sergeevich , Abaeva Fatima Totrazovna 
Published: January 2014

Aim. To investigate the efficacy and safety of glimepiride as initial mono-therapy in type 2 diabetes patients (T2DM). Materials and Methods. This is a multi-center, open-label prospective observational study. 245 treatment-naive T2DM patients, who had not achieved glycemic goals on lifestyle therapy during first 12 weeks after the diagnosis, were enrolled in this study. Anti-diabetes treatment was initiated with glimepiride and continued during the 6-month follow-up period. Prescription of the initial dose (1 mg per day) and further dose adjustments were carried out by the attending physician in accordance with the glimepiride data sheet. Dynamics of HbA1c, fasting plasma glucose (FPG), 2 h postprandial blood glucose (2hPPG), weight and waist circumference, as well as the incidence of hypoglycemia were the evaluated parameters. Results. The baseline HbA1c (mean: 7.9?0.5%; female: 7.8?0.4% ; male: 8.0?0.6%) was significantly reduced at week 12 (mean 7.2?0.6%, p
Impact of insulins glulisine and aspart on postprandial glycemia after a high-glycemic index meal in children with type 1 diabetes
Authors: Dżygało Katarzyna , Szypowska Agnieszka 
Published: January 2014

ObjectiveAccording to current knowledge, glulisine insulin (GLU) has a slightly faster onset of action than aspart (ASP) insulin. Therefore, GLU might lead to a better postprandial profile than ASP following the consumption of high-glycemic index (H-GI) meals. The aim of this study was to assess differences in the action of GLU and ASP after the consumption of a H-GI meal in type 1 diabetic children treated with insulin pumps.DesignFifty-six type 1 diabetic children of mean age 14.7±2.0 years were included in a randomized, double-blind, two-way crossover study. The subjects were allocated to one of two treatment orders: GLU–ASP and ASP–GLU. They were given a H-GI breakfast for two subsequent days.MethodsThe primary outcome was postprandial glycemia (PPG) based on continuous glucose monitoring system and self monitoring of blood glucose levels during 3 h of follow-up. The secondary outcomes were the frequency of hypoglycemia, glucose area under the curve, mean amplitude of glycemic excursion, and glycemic rise.ResultsThere were no significant differences between the groups with regard to PPG in the determined time intervals as well as with respect to the secondary outcomes. Between 60 and 120 min after food consumption in both study groups, blood glucose levels were close to or above 10.0 mmol/l. Glucose peaks were higher in the GLU–ASP group than in the ASP–GLU group (90 min:P=0.065; 120 min:P=0.052). Most of the episodes of hypoglycemia were observed after the second hour of follow-up.ConclusionsNo statistically significant difference was found between GLU and ASP with regard to PPG after the consumption of a H-GI breakfast. Neither GLU nor ASP stabilized the glycemic profile after the consumption of a H-GI meal.
Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in humans
Authors: Bak Monika J , Albrechtsen Nicolai Wewer , Pedersen Jens , Hartmann Bolette , Christensen Mikkel , Vilsbøll Tina , Knop Filip K , Deacon Carolyn F , Dragsted Lars O , Holst Jens J 
Published: January 2014

AimTo determine the specificity and sensitivity of assays carried out using commercially available kits for glucagon and/or oxyntomodulin measurements.MethodsTen different assay kits used for the measurement of either glucagon or oxyntomodulin concentrations were obtained. Solutions of synthetic glucagon (proglucagon (PG) residues 33–61), oxyntomodulin (PG residues 33–69) and glicentin (PG residues 1–69) were prepared and peptide concentrations were verified by quantitative amino acid analysis and a processing-independent in-house RIA. Peptides were added to the matrix (assay buffer) supplied with the kits (concentration range: 1.25–300 pmol/l) and to human plasma and recoveries were determined. Assays yielding meaningful results were analysed for precision and sensitivity by repeated analysis and ability to discriminate low concentrations.Results and conclusionThree assays were specific for glucagon (carried out using the Millipore (Billerica, MA, USA), Bio-Rad (Sundbyberg, Sweden), and ALPCO (Salem, NH, USA) and Yanaihara Institute (Shizuoka, Japan) kits), but none was specific for oxyntomodulin. The assay carried out using the Phoenix (Burlingame, CA, USA) glucagon kit measured the concentrations of all three peptides (total glucagon) equally. Sensitivity and precision were generally poor; the assay carried out using the Millipore RIA kit performed best with a sensitivity around 10 pmol/l. Assays carried out using the BlueGene (Shanghai, China), USCN LIFE (Wuhan, China) (oxyntomodulin and glucagon), MyBioSource (San Diego, CA, USA) and Phoenix oxyntomodulin kits yielded inconsistent results.