bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anaplasma phagocytophilum strains from voles and shrews exhibit specific ankA gene sequences
Authors: Majazki Juliana , Wüppenhorst Nicole , Hartelt Kathrin , Birtles Richard , von Loewenich Friederike D 
Published: November 2013

Abstract

Background

Anaplasma phagocytophilum is a Gram-negative bacterium that replicates obligate intracellularly in neutrophils. It is transmitted by Ixodes spp. ticks and causes acute febrile disease in humans, dogs, horses, cats, and livestock. Because A. phagocytophilum is not transmitted transovarially in Ixodes spp., it is thought to depend on reservoir hosts to complete its life cycle. In Europe, A. phagocytophilum was detected in roe deer, red deer, wild boars, and small mammals. In contrast to roe deer, red deer and wild boars have been considered as reservoir hosts for granulocytic anaplasmosis in humans, dogs, and horses according to groESL- and ankA-based genotyping. A. phagocytophilum variants infecting small mammals in Europe have not been characterized extensively to date.

Results
We amplified the total ankA open reading frames of 27 strains from voles and shrews. The analysis revealed that they harboured A. phagocytophilum strains that belonged to a distinct newly described ankA gene cluster. Further, we provide evidence that the heterogeneity of ankA gene sequences might have arisen via recombination.

Conclusions
Based on ankA-based genotyping voles and shrews are unlikely reservoir hosts for granulocytic anaplasmosis in humans, dogs, horses, and livestock in Europe.
B cells tell scleroderma fibroblasts to produce collagen
Authors: Daoussis Dimitrios , Liossis Stamatis-Nick C 
Published: November 2013

AbstractIn fibrosis fibroblasts are activated and overproduce collagen in a process with unknown drivers and equally unknown brakes that recently implicated a novel and surprising player, the B cell. B cells may be crucially involved in fibrosis in several ways: B cells may produce autoantibodies that can directly stimulate fibroblasts; B cells can produce profibrotic cytokines such as IL-6 or transforming growth factor beta; and, finally, B cells could directly stimulate fibroblasts by a contact-dependent mechanism. Recent experimental evidence suggests that B cells can enhance collagen production by fibroblasts, by a contact-dependent mechanism, and therefore are profibrotic ex vivo. These data strengthen the rationale of pursuing B-cell targeting therapies in systemic sclerosis.
Lower Expression of the TWIK-Related Acid-Sensitive K+ Channel 2 (TASK-2) Gene Is a Hallmark of Aldosterone-Producing Adenoma Causing Human Primary Aldosteronism
Authors: Lenzini Livia , Caroccia Brasilina , Campos Abril González , Fassina Ambrogio , Belloni Anna S. , Seccia Teresa M. , Kuppusamy Maniselvan , Ferraro Silvia , Skander Ghizlane , Bader Michael , Rainey William E. , Rossi Gian Paolo 
Published: November 2013

Context:The molecular mechanisms of primary aldosteronism, a common cause of human hypertension, are unknown, but alterations of K+ channels can play a key role.Objective:The objective of the study was to investigate the following: 1) the expression of the Twik-related acid-sensitive K+ channels (TASK) in aldosterone producing adenomas (APAs); 2) the role of TASK-2 in aldosterone synthesis; and 3) the determinants of TASK-2-blunted expression in APAs.Design:We analyzed the transcriptome and the microRNA profiles of 32 consecutive APAs and investigated the protein expression and localization of TASK-2 in APA and adrenocortical cell lines (H295R and HAC15) using immunoblotting and confocal microscopy. The functional effect of TASK-2 blunted activity caused by a dominant-negative mutation on steroidogenic enzymes, and aldosterone production was also assessed. TASK-2 regulation by selected microRNA was studied by a luciferase assay.Results:TASK-2 was consistently less expressed at the transcript and protein levels in APAs than in the normal human adrenal cortex. H295R cell transfection with a TASK-2 dominant-negative mutant construct significantly increased the aldosterone production by 153% and the gene expression of aldosterone synthase (CYP11B2, gene expression fold change 3.1 vs control, P &lt; .05) and the steroidogenic acute regulatory protein (gene expression fold change 1.8 vs control, P &lt; .05). Two microRNAs, hsa-miR-23 and hsa-miR-34, were found to decrease the TASK-2 expression by binding to the 3′ untranslated region of the TASK-2 gene.Conclusions:The TASK-2 channel lower expression represents a hallmark of APA and is associated with a higher expression of hsa-miR-23 and hsa-miR-34. The ensuing blunted TASK-2 activity increased the production of aldosterone in vitro and the expression of steroidogenic acute regulatory protein and CYP11B2. Hence, the lower expression of TASK-2 channel in APA cells can explain high aldosterone secretion in human primary aldosteronism despite the suppression of angiotensin II, hypertension, and hypokalemia.
Pyroglutamylated RF-amide Peptide (QRFP) Gene Is Regulated by Metabolic Endotoxemia
Authors: Jossart Christian , Mulumba Mukandila , Granata Riccarda , Gallo Davide , Ghigo Ezio , Marleau Sylvie , Servant Marc J. , Ong Huy 
Published: November 2013

AbstractPyroglutamylated RF-amide peptide (QRFP) is involved in the regulation of food intake, thermogenesis, adipogenesis, and lipolysis. The expression of QRFP in adipose tissue is reduced in diet-induced obesity, a mouse model in which plasma concentrations of endotoxins are slightly elevated. The present study investigated the role of metabolic endotoxemia (ME) on QRFP gene regulation. Our results uncovered the expression of QRFP in murine macrophages and cell lines. This expression has been found to be decreased in mice with ME. Low doses of lipopolysaccharide (LPS) transiently down-regulated QRFP by 59% in RAW264.7 macrophages but not in 3T3-L1 adipocytes. The effect of LPS on QRFP expression in macrophages was dependent on the inhibitor of kB kinase and TIR-domain-containing adapter-inducing interferon (IFN)-β (TRIF) but not myeloid differentiation primary response gene 88. IFN-β was induced by ME in macrophages. IFN-β sustainably reduced QRFP expression in macrophages (64%) and adipocytes (49%). IFN-γ down-regulated QRFP (74%) in macrophages only. Both IFNs inhibited QRFP secretion from macrophages. LPS-stimulated macrophage-conditioned medium reduced QRFP expression in adipocytes, an effect blocked by IFN-β neutralizing antibody. The effect of IFN-β on QRFP expression was dependent on phosphoinositide 3-kinase, p38 MAPK, and histone deacetylases. The effect of IFN-γ was dependent on MAPK/ERK kinase 1/2 and histone deacetylases. Macrophage-conditioned medium containing increased amounts of QRFP preserved adipogenesis in adipocytes. In conclusion, LPS induces IFN-β release from macrophages, which reduces QRFP expression in both macrophages and adipocytes in an autocrine/paracrine-dependent manner, suggesting QRFP as a potential biomarker in ME.
Both Estrogen Receptor α and β Stimulate Pituitary GH Gene Expression
Authors: Avtanski Dimiter , Novaira Horacio J. , Wu Sheng , Romero Christopher J. , Kineman Rhonda , Luque Raul M. , Wondisford Fredric , Radovick Sally 
Published: November 2013

Abstract
Although sex steroids have been implicated in the control of mammalian growth, their direct effect on GH synthesis is less clear. The aim of this study was to establish whether estradiol (E2) directly affects GH synthesis in somatotrophs. Somatotroph GH3 and MtT/S cells were used as in vitro models. At physiological doses of E2 stimulation, GH mRNA levels were increased and the ER antagonist ICI 182,780 completely abolished this effect. Estrogen receptor (ER) α– and ERβ-selective agonists, propylpyrazole triol (PPT), and 2,3-bis(4-hydroxyphenyl) propionitrile (DPN), respectively, augmented GH mRNA expression and secretion, whereas E2 and PPT, but not DPN increased prolactin (PRL) mRNA levels. E2, PPT, and DPN stimulated expression of the pituitary transcription factor Pou1f1 and increased its binding to the GH promoter. In vivo evidence of E2 effects on GH synthesis was obtained from the generation of the somatotroph-specific ERα knockout (sERα-KO) mouse model. Basal pituitary GH, PRL, POU1F1, and ERα mRNA expression levels were lower in sERα-KO mice compared with those in controls; whereas ERβ mRNA levels remained unchanged. E2 and DPN stimulated pituitary GH mRNA expression and serum GH levels in control and sERα-KO ovariectomized mice; however, serum GH levels were unchanged in PPT-treated ovariectomized sERα-KO mice. In these animal models, PRL mRNA levels increased after either E2 or PPT, but an increase was not seen after DPN treatment. Thus, we propose a mechanism by which estrogen directly regulates somatotroph GH synthesis at a pretranslational level. In contrast to the predominant effect of ERα in the lactotroph, these results support a role for both ERα and ERβ in the transcriptional control of Gh in the somatotroph and illustrate important differences in ER isoform specificity in the anterior pituitary gland.
GATA Factors Promote ER Integrity and β-Cell Survival and Contribute to Type 1 Diabetes Risk
Authors: Sartori Daniel J. , Wilbur Christopher J. , Long Simon Y. , Rankin Matthew M. , Li Changhong , Bradfield Jonathan P. , Hakonarson Hakon , Grant Struan F. A. , Pu William T. , Kushner Jake A. 
Published: November 2013

Abstract
Pancreatic β-cell survival remains poorly understood despite decades of research. GATA transcription factors broadly regulate embryogenesis and influence survival of several cell types, but their role in adult β-cells remains undefined. To investigate the role of GATA factors in adult β-cells, we derived β-cell-inducible Gata4- and Gata6-knockout mice, along with whole-body inducible Gata4 knockouts. β-Cell Gata4 deletion modestly increased the proportion of dying β-cells in situ with ultrastructural abnormalities suggesting endoplasmic reticulum (ER) stress. Notably, glucose homeostasis was not grossly altered in Gata4- and Gata6-knockout mice, suggesting that GATA factors do not have essential roles in β-cells. Several ER stress signals were up-regulated in Gata4 and Gata6 knockouts, most notably CHOP, a known regulator of ER stress-induced apoptosis. However, ER stress signals were not elevated to levels observed after acute thapsigargin administration, suggesting that GATA deficiency only caused mild ER stress. Simultaneous deletion of Gata4 and CHOP partially restored β-cell survival. In contrast, whole-body inducible Gata4 knockouts displayed no evidence of ER stress in other GATA4-enriched tissues, such as heart. Indeed, distinct GATA transcriptional targets were differentially expressed in islets compared with heart. Such β-cell-specific findings prompted study of a large meta-analysis dataset to investigate single nucleotide polymorphisms harbored within the human GATA4 locus, revealing several variants significantly associated with type 1 diabetes mellitus. We conclude that GATA factors have important but nonessential roles to promote ER integrity and β-cell survival in a tissue-specific manner and that GATA factors likely contribute to type 1 diabetes mellitus pathogenesis.
Minireview: Dynamic Structures of Nuclear Hormone Receptors: New Promises and Challenges
Authors: Simons S. Stoney , Edwards Dean P. , Kumar Raj 
Published: November 2013

Abstract
Therapeutic targeting of nuclear receptors (NRs) is presently restricted due to 2 constraints: 1) a limited knowledge of the structural dynamics of intact receptor when complexed to DNA and coregulatory proteins; and 2) the inability to more selectively modulate NR actions at specific organ/gene targets. A major obstacle has been the current lack of understanding about the function and structure of the intrinsically disordered N-terminal domain that contains a major regulatory transcriptional activation function (AF1). Current studies of both mechanism of action and small molecule-selective receptor modulators for clinical uses target the structured pocket of the ligand-binding domain to modulate coregulatory protein interactions with the other activation function AF2. However, these approaches overlook AF1 activity. Recent studies have shown that highly flexible intrinsically disordered regions of transcription factors, including that of the N-terminal domain AF1 of NRs, not only are critical for several aspects of NR action but also can be exploited as drug targets, thereby opening unique opportunities for endocrine-based therapies. In this review article, we discuss the role of structural flexibilities in the allosteric modulation of NR activity and future perspectives for therapeutic interventions.
Lectures on discipline &#34;Motivation and stimultion of labour activity&#34;
Authors: Митрофанова  , Mitrofanova Elena 
Published: November 2013

Given article opens a series of the publications shining prospects
of development of educative and methodical maintenance (textbooks,
abstracts of lectures and so forth) preparations of bachelors and masters
in a direction «Human resource management». The author brings to attention
of readers the abstract of lectures on discipline «Motivation and
stimulation of labor activity» under the program of preparation of bachelors.
Comparison of restricted mean survival times between treatments based on a stratified Cox model
Authors: Zhang Xu 
Published: November 2013

Abstract
Causal inference in survival analysis has been centered on treatment effect assessment with adjustment of covariates. The direct adjustment method is usually employed to find the survival function of a treatment. A Cox model that stratifies the cumulative hazard by treatment is an ideal choice for performing direct adjustment because the treatment effects are allowed to vary over time. A SAS macro was developed to implement comparison of direct adjusted survivals between treatments at a selected time point. The restricted mean survival time can be derived from a direct adjusted survival function. This statistic summarizes the survival outcome of a treatment. Comparison of restricted means provides assessment of treatment effect over a time interval. The first aim of this article was to provide an overview of the restricted mean survival time. The second aim was to introduce a SAS macro that computes the restricted mean survival times from direct adjusted survivals based on a stratified Cox model. Data preparation and macro invocation are illustrated in an analysis of survival data involving three types of stem cell transplants.
Digital endocasts of the cranial surface generated by the 3D vision system
Authors: Skrzat Janusz , Sioma Andrzej 
Published: November 2013

Abstract
This article demonstrates a technique of generating digital endocasts of the cranial interior using the three-dimensional (3D) vision system. Obtained digital endocasts reflected the shape and size of the brain, pattern of dural vascularization, position, and interlocking of the cranial sutures. Hence, some minor anatomical structures (granulations faveole, digital impressions) were recorded by the 3D vision system and were revealed on the digital endocasts.
The identification and the elimination of clashes in the structure of an early-stage intermediate in the protein folding process
Authors: Baster Zbigniew 
Published: November 2013

Abstract
The model (under consideration) to simulate the protein folding process assumes two steps: early stage (ES) and late stage (LS). The first is assumed to define the preliminary structure, which when applied to an optimization procedure, may produce the proper structure of the protein. However, the ES model produces the structures with clashes. This work demonstrates the possible solution to remove clashes before proceeding to the LS. Additionally, the presented solution describes mathematically the precession phenomenon, which might be useful in other fields of studies aside from protein folding such as medical imaging, quantum physics, and astronomy.
Forensic voice comparison by means of artificial neural networks
Authors: Sałapa Kinga , Trawińska Agata , Roterman-Konieczna Irena 
Published: November 2013

Abstract
This article examines the effectiveness of artificial neural networks (ANNs) as forensic voice comparison techniques. This study specifically considers feed-forward multilayer perceptron (MLP) and radial basic function (RBF) network models. Formant frequencies of Polish vowel e (stressed or unstressed) in selected contexts were used as predictors. This has already been confirmed in an earlier investigation that determined that dynamic formant frequencies of vowels are powerful elements in distinguishing the voice. It has been concluded that neural networks might assist in distinguishing speakers from the others with very good accuracy, reaching 100%. MLP models should be given preference. The results of the investigation have shown the influence of vowel e triads on the effectiveness of correct classification rates. In addition, the authors have determined that the accuracy of classification is greater when based on a single context than for similar input data aggregated over several different contexts.
Cimetidine Reduces Alveolar Bone Loss in Induced Periodontitis in Rat Molars
Authors: Longhini Renata , Aparecida de Oliveira Priscila , Sasso‐Cerri Estela , Cerri Paulo Sérgio 
Published: November 2013

Background: There is evidence that histamine released during inflammation plays a role in bone metabolism via the H2 receptor, stimulating bone resorption. The purpose of this study is to evaluate whether cimetidine, a histamine H2‐receptor antagonist, interferes with the initiation and progression of induced periodontal disease in rat molars.Methods: Forty male rats received 100 mg/kg body weight of cimetidine (cimetidine group [CimG]) or saline solution (sham group [SG]). Periodontal disease was induced in the maxillary left first molars (PDSG and PDCimG); maxillary right molars were used as non‐ligature controls. After 7, 15, 30, and 50 days, maxillary fragments were embedded in paraffin. The sections were stained with Masson trichrome and hematoxylin and eosin and subjected to the tartrate‐resistant acid phosphatase (TRAP) method. The distances between the cemento‐enamel junction (CEJ) and alveolar process (AP) crest, as well as between the CEJ and junctional epithelium (JE) level, were measured; the number of inflammatory cells was computed. Receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) immunohistochemistry was carried out, and the RANKL/OPG ratio was calculated.Results: In PDSG and PDCimG, a significant increase (P ≤0.05) was observed in CEJ‐AP and CEJ‐JE distances. However, the increases in both distances were significantly less in PDCimG compared with PDSG at 15, 30, and 50 days. Numerous TRAP‐positive osteoclasts were found in the PDSG and PDCimG. In PDCimG, the volume density of inflammatory cells and the RANKL/OPG ratio were significantly lower (P ≤0.05) than in PDSG.Conclusions: Cimetidine exerts a beneficial effect on periodontal disease in rats, decreasing the RANKL/OPG ratio in gingival connective tissue and reducing alveolar bone resorption.
Cu(II) removal enhancement from aqueous solutions using ion-imprinted membrane technique
Authors: Zarghami Soheil , Kazemimoghadam Mansoor , Mohammadi Toraj 
Published: November 2013

AbstractIn this study, Cu(II)-ion-imprinted membrane adsorbents were prepared via cross-linking of blended chitosan/poly(vinyl alcohol) using glutaraldehyde as cross-linker and copper ions as template. The ability of IIMs to adsorb copper ions from aqueous solutions was assessed using a batch of experiments under different conditions by changing cross-linking density (0.05 mass %, 0.1 mass %, and 0.2 mass %), template content (0.2 mass %, 0.5 mass %, and 0.9 mass %), initial analyte concentration (50 mg L−1, 100 mg L−1, and 150 mg L−1), and adsorbent concentration (0.5 g L−1, 1.0 g L−1, and 2.0 g L−1). The Taguchi method was used to plan a minimum number of experiments. The following optimal levels were thus determined for the four factors: cross-linking density: 0.1 mass %; template content: 0.5 mass %; initial analyte concentration: 150 mg L−1; and adsorbent concentration: 0.3 g L−1.
Modelling Late Weichselian evolution of the Eurasian ice sheets forced by surface meltwater-enhanced basal sliding
Authors: Clason C.C. , Applegate P.J. , Holmlund P. 
Published: November 2013

AbstractWe simulated the Late Weichselian extent and dynamics of the Eurasian ice sheets using the shallow-ice approximation ice-sheet model SICOPOLIS. Our simulated Last Glacial Maximum ice-sheet extents closely resemble geomorphological reconstructions, and areas of modelled fast flow are consistent with the known locations of palaeo-ice streams. Motivated by documented velocity response to increased meltwater inputs on Greenland, we tested the sensitivity of the simulated ice sheet to the surface meltwater effect (SME) through a simple parameterization relating basal sliding to local surface melt rate and ice thickness. Model runs including the SME produce significantly reduced ice volume during deglaciation, with maximum ice surface velocities much greater than in similar runs that neglect the SME. We find that the simple treatment of the SME is not applicable across the whole ice sheet; however, our results highlight the importance of the SME for dynamic response to increased melting. The southwest sector of the Scandinavian ice sheet is most sensitive to the SME, with fast flow in the Baltic ice stream region shutting off by 15 ka BP when the SME is turned on, coincident with a retreat of the ice-margin position into the Gulf of Bothnia.
Assessing ice-cliff backwasting and its contribution to total ablation of debris-covered Miage glacier, Mont Blanc massif, Italy
Authors: Reid T.D. , Brock B.W. 
Published: November 2013

AbstractContinuous surface debris cover strongly reduces the ablation of glaciers, but high melt rates may occur at ice cliffs that are too steep to hold debris. This study assesses the contribution of ice-cliff backwasting to total ablation of Miage glacier, Mont Blanc massif, Italy, in 2010 and 2011, based on field measurements, physical melt models and mapping of ice cliffs using a high-resolution (1 m) digital elevation model (DEM). Short-term model calculations closely match the measured melt rates. A model sensitivity analysis indicates that the effects of cliff slope and albedo are more important for ablation than enhanced longwave incidence from sun-warmed debris or reduced turbulent fluxes at sheltered cliff bases. Analysis of the DEM indicates that ice cliffs account for at most 1.3% of the 1 m pixels in the glacier’s debris-covered zone, but application of a distributed model indicates that ice cliffs account for ~7.4% of total ablation. We conclude that ice cliffs make an important contribution to the ablation of debris-covered glaciers, even when their spatial extent is very small.