bluuebunny/crossref_metadata_2025_split huggingface dataset:
PPARD rs2016520 polymorphism affects repaglinide response in Chinese Han patients with type 2 diabetes mellitus
Authors: Song Jin‐Fang , Wang Tao , Zhu Jing , Zhou Xue‐Yan , Lu Qian , Guo Hao , Zhang Fan , Wang Yan , Li Wei , Wang Dan‐Dan , Cui Ya‐Wen , Lv Dong‐Mei , Yin Xiao‐Xing 
Published: October 2014

SummaryRepaglinide is a short‐acting insulin secretagogue, which often results in considerable interindividual variability in therapeutic efficacy when widely used in a clinical setting. Among various reasons under discussion is genetic polymorphism, especially the genes related to insulin secretion and resistance. Recent studies have described the importance of PPARD in regulating the secretion and resistance of insulin. However, little is known about the impacts of PPARD genetic polymorphism on the efficacy of repaglinide. Therefore, the current study was designed to investigate the associations of PPARD rs2016520 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. A total of 338 T2DM patients and 200 healthy subjects were genotyped for PPARD rs2016520 polymorphism by polymerase chain reaction–restriction fragment length polymorphism assay. A total of 84 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take repaglinide for 8 weeks. Then the pharmacodynamic parameters of repaglinide and biochemical indicators were determined before and after repaglinide treatment. No significant difference was found in either allelic frequency (P = 0.298) or genotype distribution (P = 0.151) of PPARD rs2016520 between T2DM patients and healthy subjects. However, T2DM patients carrying genotype TC showed a significantly lower increase in postprandial serum insulin (mU/L) than those with wild‐type TT (P < 0.05). These findings suggest that PPARD rs2016520 polymorphism might influence the therapeutic effect of repaglinide rather than T2DM susceptibility in Chinese Han T2DM patients.
Novel mouse model of left ventricular pressure overload and infarction causing predictable ventricular remodelling and progression to heart failure
Authors: Weinheimer Carla J , Lai Ling , Kelly Daniel P , Kovacs Attila 
Published: October 2014

SummaryMouse surgical models are important tools for evaluating mechanisms of human cardiac disease. The clinically relevant comorbidities of hypertension and ischaemia have not been explored in mice. We have developed a surgical approach that combines transverse aortic constriction and distal left anterior coronary ligation (MI) to produce a gradual and predictable progression of adverse left ventricular (LV) remodelling that leads to heart failure (HF). Mice received either sham, MI alone, transverse aortic constriction alone or HF surgery. Infarct size and LV remodelling were evaluated by serial 2‐D echocardiograms. Transverse aortic constriction gradients were measured by the Doppler velocity–time integral ratio between constricted and proximal aortic velocities. At 4 weeks, hearts were weighed and analysed for histology and brain natriuretic peptide, a molecular marker of HF. Echocardiographic analysis of segmental wall motion scores showed similarly small apical infarct sizes in the MI and HF groups at day 1 postsurgery. MI alone showed little change in infarct size over 4 weeks (0.26 ± 0.02 to 0.27 ± 0.04, P = 0.77); however, HF mice showed infarct expansion (0.25 ± 0.06 to 0.39 ± 0.09, P < 0.05). HF mice also showed LV remodelling with increases in LV volumes (1 day = 36.5 ± 5.2 mL, 28 days = 89.1 ± 16.0 mL) versus no significant changes in the other groups. Furthermore, systolic function progressively deteriorated in the HF group only (ejection fraction, 1 day = 55.6 ± 3.6%, 28 days = 17.6 ± 4.1%, P < 0.05) with an increase of brain natriuretic peptide by 3.5‐fold. This surgical model of pressure overload in the setting of a small infarction causes progressive deterioration of cardiac structural and functional properties, and provides a clinically relevant tool to study adverse LV remodelling and heart failure.
Transplantation of human umbilical mesenchymal stem cells attenuates dextran sulfate sodium‐induced colitis in mice
Authors: Lin Yan , Lin Lianjie , Wang Qiushi , Jin Yu , Zhang Ying , Cao Yong , Zheng Changqing 
Published: October 2014

SummaryUlcerative colitis is a major form of inflammatory bowel disease and increases the risk of the development of colorectal carcinoma. The anti‐inflammatory and immunomodulatory properties of mesenchymal stem cells (MSC) make them promising tools for treating immune‐mediated and inflammatory diseases. However, the lack of robust technique for harvesting and expanding of MSC has hampered the use of bone marrow and umbilical cord blood derived MSC in clinical applications. In the present study, we investigated the intestinal protective effects of Wharton's jelly‐derived umbilical MSC (UMSC) on dextran sulfate sodium‐induced colitis in mice. The severity of colitis in mice was assessed using bodyweight loss, stool consistency, rectal bleeding, colon shortening and haematological parameters. Colonic myeloperoxidase and pro‐inflammatory cytokines levels were also measured. Furthermore, the expression of cyclooxygenase 2 and inducible nitric oxide synthase in the colon were detected. In addition, intestinal permeability and tight junction proteins expressions in the colon were examined as well. The results showed that Wharton's jelly‐derived UMSC significantly diminished the severity of colitis, reduced histolopathological score, and decreased myeloperoxidase activity and cytokines levels. Furthermore, the UMSC markedly decreased the expression of cyclooxygenase 2and inducible nitric oxide synthase in the colon. In addition, transplantation of UMSC reduced intestinal permeability and upregulated the expression of tight junction proteins. These results show that the anti‐inflammation and regulation of tight junction proteins by Wharton's jelly‐derived UMSC ameliorates colitis.
Hypertonic saline releases the attached small intestinal cystic fibrosis mucus
Authors: Ermund Anna , Meiss Lauren N , Scholte Bob J , Hansson Gunnar C 
Published: October 2014

SummaryHypertonic saline inhalation has become a cornerstone in the treatment of cystic fibrosis (CF), but its effect on CF mucus is still not understood. In CF, mucus stagnates in the airways, causing mucus plugging, and forming a substrate for bacterial invasion. Using horizontal Ussing‐type chambers to allow easy access to the tissue, we have recently shown that the small intestinal mucus of CF mice is attached to the epithelium and not freely movable as opposed to normal mucus, thus pointing to a similarity between the CF mucus in the ileum and airways. In the same type of system, we investigated how hypertonic saline affects mucus thickness, attachment and penetrability to fluorescent beads the size of bacteria in ileal explants from the cystic fibrosis transmembrane conductance regulator mutant (ΔF508) mouse, in order to characterize how this common therapy affects mucus properties. Hypertonic saline (1.75–5%) detached the mucus from the epithelium, but the mucus remained impenetrable to beads the size of bacteria. This approach might be used to test other mucolytic interventions in CF.
On the early origins of the Germanic preterite presents
Authors: Randall William , Jones Howard 
Published: October 2014

AbstractWe deal with the origins of the Germanic preterite presents within the Proto‐Indo‐European (PIE) verb system, highlighting the problems encountered when linking these verbs to existing PIE categories. We argue for the existence of a PIE ‘derived stative’ verb category formed by adding stative inflections to eventive (aorist) roots. Morphologically this category resembles the PIE perfect, but it is unreduplicated; semantically, it denotes a pure state, not a resultant state. This category may be the origin of most of the fifteen Germanic preterite presents. The derived stative category may also be seen as the missing link between the PIE root stative and the PIE perfect.
A guide to statistical analysis in microbial ecology: a community-focused, living review of multivariate data analyses
Authors: Buttigieg Pier Luigi , Ramette Alban 
Published: October 2014

Abstract
The application of multivariate statistical analyses has become a consistent feature in microbial ecology. However, many microbial ecologists are still in the process of developing a deep understanding of these methods and appreciating their limitations. As a consequence, staying abreast of progress and debate in this arena poses an additional challenge to many microbial ecologists. To address these issues, we present the GUide to STatistical Analysis in Microbial Ecology (GUSTA ME): a dynamic, web-based resource providing accessible descriptions of numerous multivariate techniques relevant to microbial ecologists. A combination of interactive elements allows users to discover and navigate between methods relevant to their needs and examine how they have been used by others in the field. We have designed GUSTA ME to become a community-led and -curated service, which we hope will provide a common reference and forum to discuss and disseminate analytical techniques relevant to the microbial ecology community.
Explorations in Australian Legal Geography: The Evolution of Lease Tenures as Policy Instruments
Authors: HOLMES JOHN 
Published: October 2014

AbstractIn their programmatic statement towards an Australian perspective on legal geography, Bartel et al. acknowledge that ‘it is perhaps in the institution of property and the regulation of land use that law has its most obvious overlap with geography … in a settler society such as Australia'. Given this statement, it is surprising that the seven co‐authors fail to acknowledge the formidable contributions already made by Australian geographers within a highly relevant, substantial research agenda, namely the evolution of lease tenures as policy instruments in shaping rural land settlement and rural society. The earliest contributions on lease tenures were made by an eminent group of historical geographers enquiring into the evolution of a distinctive, adaptable portfolio of Australian land tenures and other resource rights in response to the challenges of frontier squatter settlement and the subsequent policy agenda in pursuit of closer settlement. Their successors have focused on the contemporary relevance of lease tenures as potentially adaptable instruments towards sustainability and coexistence. Geographers have also acted as consultants, policy advisers, advocates, and expert witnesses through consultancy reports, discussion papers, newspaper articles, and news reports. There is a strong case to be made that, together with Aboriginal land rights and native title, these two research agendas have provided the most substantial and coherent scholarly contributions to Australian legal geography. This deficiency in the review of Australian research may well be an outcome from a comparable deficiency in theorising property rights within the subdiscipline internationally. If Australian legal geography is to fulfil its potential, greater recognition needs to be given to foundational Australian contributions to this subdiscipline and to property rights theory in the matter of natural resources, notably land.
The potential drivers in forming avian biodiversity hotspots in the East Himalaya Mountains of Southwest China
Authors: LEI Fumin , QU Yanhua , SONG Gang , ALSTRÖM Per , FJELDSÅ Jon 
Published: October 2014

AbstractLittle has been published to describe or interpret Asian biodiversity hotspots, including those in the East Himalayan Mountains of Southwest China (HMSC), thus making necessary a review of the current knowledge. The Pliocene and Pleistocene geological and glacial histories of the Asian continent differ from those of Europe and North America, suggesting different mechanisms of speciation and extinction, and, thus, different responses to climate changes during the Quaternary glaciations. This short review summarizes potential drivers in shaping and maintaining high species richness and endemism of birds in the HMSC. The geographical location at the junction of different biogeographical realms, the wide range of habitats and climates along the extensive elevational range, the complex topography and the distinct geological history of this region have probably contributed to the evolution of an exceptionally species‐rich and endemic‐rich, specialized montane avian fauna. The Mountain systems in the HMSC may have provided refugia where species survived during the glacial periods and barriers for preventing species dispersal after the glacial periods. More studies are required to further test this refugia hypothesis by comparing more cold‐tolerent and warm‐tolerent species.
Concentrations of Volatile 4‐Alkyl‐Branched Fatty Acids in Sheep and Goat Milk and Dairy Products
Authors: Kaffarnik Stefanie , Kayademir Yasemin , Heid Carolina , Vetter Walter 
Published: October 2014

AbstractGoat and sheep milk and dairy products thereof are characterized by a strong and unique flavor. In this context, the volatile minor fatty acid 4‐ethyloctanoic acid plays a prominent role along with 4‐methyloctanoic acid when both are present in free form. Using a novel GC/MS method in the selected ion‐monitoring mode, previously developed for sheep subcutaneous adipose tissue, we were able to analyze the total concentrations of these flavor‐relevant minor fatty acids as methyl esters in goat and sheep milk as well as in their products. Differences between the concentrations and ratios of 4‐methyloctanoic acid and 4‐ethyloctanoic acid in goat milk (n = 4), goat cheese (n = 4), sheep milk (n = 2), and sheep cheese (n = 4) were observed. Goat milk and cheese resulted in higher concentrations for both fatty acids (190 to 480 μg/g milk fat) and smaller 4‐Me‐8:0 to 4‐Et‐8:0 ratios (1.4 to 2.7) compared to sheep milk and cheese (78 to 220 μg/g milk fat; 4‐Me‐8:0 to 4‐Et‐8:0 ratio: 15 to 42). In all samples, the concentration of 4‐Me‐8:0 exceeded the one of 4‐Et‐8:0. However, due to its lower flavor threshold value the contribution of 4‐Et‐8:0 to the flavor was generally >76%. The calculated flavor values were >1400 for goat milk and cheeses and >200 for sheep milk and cheeses. In goat milk and its products, only a proportion of <0.1% 4‐alkyl‐branched fatty acids present in free form in the goat milk and <0.5% in the sheep samples would be sufficient to generate the characteristic goaty flavor. Parameters that promote or prevent the release of 4‐Me‐8:0, and especially 4‐Et‐8:0, will be decisive for the flavor in the resulting dairy product.
Exercise training prevents the attenuation of anesthetic pre‐conditioning‐mediated cardioprotection in diet‐induced obese rats
Authors: LI L. , MENG F. , LI N. , ZHANG L. , WANG J. , WANG H. , LI D. , ZHANG X. , DONG P. , CHEN Y. 
Published: October 2014

BackgroundObesity abolishes anesthetic pre‐conditioning‐induced cardioprotection due to impaired reactive oxygen species (ROS)‐mediated adenosine monophosphate‐activated protein kinase (AMPK) pathway, a consequence of increased basal myocardial oxidative stress. Exercise training has been shown to attenuate obesity‐related oxidative stress.ObjectiveThis study tests whether exercise training could normalize ROS‐mediated AMPK pathway and prevent the attenuation of anesthetic pre‐conditioning‐induced cardioprotection in obesity.MethodsMale Sprague–Dawley rats were divided into lean rats fed with control diet and obese rats fed with high‐fat diet. After 4 weeks of feeding, lean and obese rats were assigned to sedentary conditions or treadmill exercise for 8 weeks.ResultsThere was no difference in infarct size between lean sedentary and obese sedentary rats after 25 min of myocardial ischemia followed by 120 min reperfusion. In lean rats, sevoflurane equally reduced infarct size in lean sedentary and lean exercise‐trained rats. Molecular studies revealed that AMPK activity, endothelial nitric oxide synthase, and superoxide production measured at the end of ischemia in lean rats were increased in response to sevoflurane. In obese rats, sevoflurane increased the above molecular parameters and reduced infarct size in obese exercise‐trained rats but not in obese sedentary rats. Additional study showed that obese exercise‐trained rats had decreased basal oxidative stress than obese sedentary rats.ConclusionThe results indicate that exercise training can prevent the attenuation of anesthetic cardioprotection in obesity. Preventing the attenuation of this strategy may be associated with reduced basal oxidative stress and normalized ROS‐mediated AMPK pathway, but the causal relationship remains to be determined.
Influence of diabetes mellitus on mortality in breast cancer patients
Authors: Zhou Yunhai , Zhang Xiang , Gu Chen , Xia Jiazeng 
Published: October 2014

AbstractBackgroundBreast cancer is one of the most common malignant tumours among women worldwide. Besides, diabetes mellitus is also a major health problem in developed countries. This study explores the association between diabetes mellitus and breast cancer patients' survival outcomes.MethodsA systematic literature search in Embase (http://www.embase.com) and MEDLINE (http://www.ncbi.nlm.nih.gov/pubmed) was conducted from January 1960 to April 2014 and systematically identified clinical studies that evaluated the association between breast cancer mortality and diabetes mellitus. Clinical studies investigating the association between diabetes mellitus and breast cancer patients' survival outcomes were included.ResultsTwenty publications were chosen for the meta‐analysis, of which 16 studies had all‐cause mortality data and 12 studies had breast cancer mortality data. Published from 2001 to 2013, all 20 studies followed a total of 2 645 249 patients including more than 207 832 diabetic patients. Pre‐existing diabetes mellitus was associated with a 37% increased risk for all‐cause mortality in women with breast cancer (hazard ratio (HR) = 1.37; 95% confidence interval (CI): 1.34–1.41; P = 0.02). Diabetes mellitus was associated with a 17% increased risk for breast cancer mortality in women with breast cancer (HR = 1.17; 95% CI: 1.11–1.22; P < 0.01).ConclusionsWomen with diabetes mellitus are at higher risk of breast cancer‐specific and all‐cause mortality after initial breast cancer diagnosis.
The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double‐blind, placebo‐controlled, phase 3 trials
Authors: Chang L. , Lembo A. J. , Lavins B. J. , Shiff S. J. , Hao X. , Chickering J. G. , Jia X. D. , Currie M. G. , Kurtz C. B. , Johnston J. M. 
Published: October 2014

SummaryBackgroundFew clinical trials in chronic idiopathic constipation (CIC) patients have evaluated abdominal symptom severity and whether CIC patients with abdominal symptoms respond similarly to patients with limited abdominal symptoms.AimsTo examine abdominal symptom severity and relationships between symptoms and global measures at baseline; compare linaclotide's effect on symptoms in subpopulations with more or less abdominal pain; and assess relationships between symptom improvement and global measures in these two subpopulations.MethodsIn two phase 3 trials, patients meeting modified Rome II CIC criteria were assigned to linaclotide 145 μg, 290 μg, or placebo once daily. Patients rated abdominal and bowel symptoms daily during 2‐week pre‐treatment and 12‐week treatment periods. Linaclotide's effect on symptoms and global measures [constipation severity, health‐related quality of life (HRQOL), treatment satisfaction] and their inter‐relationships were assessed in post hoc analyses of abdominal pain subpopulations.ResultsOf 1271 CIC patients, 23%, 32%, and 43% reported moderate‐to‐severe abdominal pain, discomfort, and bloating, respectively, during baseline. In more‐severe abdominal pain patients, abdominal symptoms were more strongly correlated than bowel symptoms with global measures, but in less‐severe abdominal pain patients, abdominal and bowel symptoms were similarly correlated with global measures, at baseline and post‐treatment. Linaclotide significantly improved all symptoms and global measures in both subpopulations.ConclusionsWhen abdominal pain is present in CIC, abdominal and not bowel symptoms may drive patient assessments of constipation severity, HRQOL, and treatment satisfaction. Linaclotide (145 μg and 290 μg) is an effective treatment for both abdominal and bowel symptoms, even in CIC patients with more severe abdominal pain at baseline. (Clinicaltrials.gov: NCT00765882, NCT00730015).
Preparation and characterization of anti‐tissue factor single‐chain variable fragment antibody for cancer diagnosis
Authors: Sato Ryuta , Obonai Toshifumi , Tsumura Ryo , Tsumoto Kouhei , Koga Yoshikatsu , Yasunaga Masahiro , Matsumura Yasuhiro 
Published: October 2014

Tissue factor (TF), which serves as the initiator of the extrinsic blood coagulation cascade, has been found to be overexpressed in various solid tumors, especially brain tumors, pancreatic cancer, and gastric cancer. Overexpression of TF is considered to contribute to the high incidence of thrombotic complications and poor prognosis in patients with such cancers. Therefore, detection or targeting of TF may be a promising approach for the diagnosis and treatment of solid tumors that are known to overexpress the protein. Here, we used the recombinant DNA technology to develop an anti‐TF single‐chain Fv (scFv) of small size and high affinity for its target. The biochemical characteristics of the anti‐TF scFv were evaluated using surface plasmon resonance (SPR) sensing and flow cytometry. The data obtained showed that the affinity of the anti‐TF scFv was 2.04 × 10−8 (KD), and that the protein showed significant binding to the cancer cells. Then, Alexa 647‐labeled anti‐TF scFv and anti‐TF IgG were administered to mice bearing chemically induced spontaneous tumors. The maximum tumor to background ratios of anti‐TF scFv and anti‐TF IgG were obtained 3 and 24 h after the injections, respectively. This study indicates anti‐TF scFv may be suitable as an imaging probe for the diagnosis of solid tumors.
Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of activeMycobacterium tuberculosisinfection
Authors: Feruglio S L , Tonby K , Kvale D , Dyrhol-Riise A M 
Published: October 2014

SummaryBiomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4+ T regulatory cells (Tregs) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN-γ and single IFN-γ-producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2+ cells increased over time for both CD4+ and CD8+ T cells. The Treg subsets CD25highCD127low, CD25highCD147++ and CD25highCD127lowCD161+ expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25highCD127lowCD39+ Tregs remained unchanged. The fraction of CD25highCD127low Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4+ and CD8+ T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further.