bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome analysis of long non‐coding RNAs of the nucleus accumbens in cocaine‐conditioned mice
Authors: Bu Qian , Hu Zhengtao , Chen Feng , Zhu Ruiming , Deng Yi , Shao Xue , Li Yan , Zhao Jinxuan , Li Hongyu , Zhang Baolai , Lv Lei , Yan Guangyan , Zhao Yinglan , Cen Xiaobo 
Published: September 2012

AbstractCocaine dependence involves in the brain's reward circuit as well as nucleus accumbens (NAc), a key region of the mesolimbic dopamine pathway. Many studies have documented altered expression of genes and identified transcription factor networks and epigenetic processes that are fundamental to cocaine addiction. However, all these investigations have focused on mRNA of encoding genes, which may not always reflect the involvement of long non‐coding RNAs (lncRNAs), which has been implied in a broad range of biological processes and complex diseases including brain development and neuropathological process. To explore the potential involvement of lncRNAs in drug addiction, which is viewed as a form of aberrant neuroplasticity, we used a custom‐designed microarray to examine the expression profiles of mRNAs and lncRNAs in brain NAc of cocaine‐conditioned mice and identified 764 mRNAs, and 603 lncRNAs were differentially expressed. Candidate lncRNAs were identified for further genomic context characterization as sense‐overlap, antisense‐overlap, intergenic, bidirection, and ultra‐conserved region encoding lncRNAs. We found that 410 candidate lncRNAs which have been reported to act in cis or trans to their targeted loci, providing 48 pair mRNA‐lncRNAs. These results suggest that the modification of mRNAs expression by cocaine may be associated with the actions of lncRNAs. Taken together, our results show that cocaine can cause the genome‐wide alterations of lncRNAs expressed in NAc, and some of these modified RNA transcripts may to play a role in cocaine‐induced neural plasticity and addiction.
A comprehensive study on long‐term injury to nigral dopaminergic neurons following intracerebroventricular injection of lipopolysaccharide in rats
Authors: Zhou Yan , Zhang Yanxin , Li Junquan , Lv Fengyue , Zhao Yongmei , Duan Deyi , Xu Qunyuan 
Published: September 2012

AbstractParkinson's disease (PD) is characterized by selective and progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Lipopolysaccharide (LPS) can induce chronic inflammation and has been widely used to study the pathogenesis of PD. In this study, a single intracerebroventricular injection of LPS was used to induce neurotoxic effects on dopaminergic neurons in Sprague–Dawley rats. The long‐term neurotoxic effects of LPS were evaluated at different time points. Microglia were activated in the hippocampus and striatum at 4 weeks, and in the SN at 24 weeks. Astrocytes were activated in the hippocampus and nigrostriatal system at 2 and 24 weeks. The expression of brain‐derived neurotrophic factor in the SN increased at 4 weeks and decreased after 12 weeks, and tyrosine hydroxylase‐positive neurons in the SN were shown to have an atrophic appearance, with cell loss evident after 24 weeks. Phospho‐α‐synuclein expression, a reflection of parkinsonian pathogenesis, increased at 12 weeks, and peaked at 24 weeks. Abnormal motor behavior appeared at 16 weeks and lasted up to 48 weeks. These results indicate that microglia are activated for several months after a single, low dose injection of LPS, which eventually results in progressive and selective damage to dopaminergic neurons in the SN.
The distribution and expression of S100A8 and S100A9 in gingival epithelium of mice
Authors: Nishii K. , Usui M. , Yamamoto G. , Yajima S. , Tsukamoto Y. , Tanaka J. , Tachikawa T. , Yamamoto M. 
Published: September 2012

Objective and BackgroundGingival epithelium protects against bacterial infection by producing antimicrobial peptides such as calprotectin. Calprotectin consists of proteins S100A8 and S100A9. Although in vitro assay has shown that neutrophils and gingival epithelial cells express calprotectin, the expression of S100A8 and S100A9 and colocalization of both S100 proteins in gingival tissue in vivo are not fully understood. The aim of this study was to investigate the distribution of S100A8 and S100A9 expression in gingival epithelium of mice in the presence and absence of infection.Materials and MethodsA quantitative analysis of S100A8 and S100A9 mRNA in junctional epithelium (JE) and oral gingival epithelium (OGE) of both germ‐free mice and conventional mice was performed using laser microdissection and real‐time polymerase chain reaction (PCR). Confirmation of S100A8 and S100A9 mRNA expression in the JE was conducted by fluorescent immunohistochemistry.ResultsReal‐time PCR analysis indicated that S100A8 and S100A9 expressions were mainly detected in JE and only slightly or not detected in OGE. Levels of both S100A8 and S100A9 mRNA expression in JE of conventional mice were significantly higher than those in JE of germ‐free mice. Additionally, fluorescent immunohistochemistry showed that S100A8 expression was observed in the JE of both conventional and germ‐free mice, whereas S100A9 was expressed in the JE of conventional but not germ‐free mice.ConclusionS100A8 protein is expressed in JE cells of mice in the presence and in the absence of infection with oral bacteria. S100A9 expression in JE cells in the presence of microflora is significantly increased compared with the absence of microflora, which suggests that S100A9 expression may be induced by infection of microflora. The production of calprotectin in gingival epithelial cells may be mediated through S100A9 induction by bacterial infection.
New secreted toxins and immunity proteins encoded within the Type VI secretion system gene cluster of Serratia marcescens
Authors: English Grant , Trunk Katharina , Rao Vincenzo A. , Srikannathasan Velupillai , Hunter William N. , Coulthurst Sarah J. 
Published: September 2012

SummaryProtein secretion systems are critical to bacterial virulence and interactions with other organisms. The Type VI secretion system (T6SS) is found in many bacterial species and is used to target either eukaryotic cells or competitor bacteria. However, T6SS‐secreted proteins have proven surprisingly elusive. Here, we identified two secreted substrates of the antibacterial T6SS from the opportunistic human pathogen, Serratia marcescens. Ssp1 and Ssp2, both encoded within the T6SS gene cluster, were confirmed as antibacterial toxins delivered by the T6SS. Four related proteins encoded around the Ssp proteins (‘Rap’ proteins) included two specifically conferring self‐resistance (‘immunity’) against T6SS‐dependent Ssp1 or Ssp2 toxicity. Biochemical characterization revealed specific, tight binding between cognate Ssp–Rap pairs, forming complexes of 2:2 stoichiometry. The atomic structures of two Rap proteins were solved, revealing a novel helical fold, dependent on a structural disulphide bond, a structural feature consistent with their functional localization. Homologues of the Serratia Ssp and Rap proteins are found encoded together within other T6SS gene clusters, thus they represent founder members of new families of T6SS‐secreted and cognate immunity proteins. We suggest that Ssp proteins are the original substrates of the S. marcescens T6SS, before horizontal acquisition of other T6SS‐secreted toxins. Molecular insight has been provided into how pathogens utilize antibacterial T6SSs to overcome competitors and succeed in polymicrobial niches.
Vitamin D: a clinical perspective
Authors: Halpern Allan C. 
Published: September 2012

SummaryVitamin D has been the focus of considerable recent scientific study and media attention because of a growing appreciation of its potential importance in extra‐skeletal health. This ‘Perspective’ presents data supporting the viewpoint that physicians should not routinely test vitamin D levels in the general population but should routinely endorse vitamin D supplementation at levels recommended by the Institute of Medicine. It further reasons that it is unadvisable to recommend intentional limited sun exposure as a source of vitamin D.
Novel seed coat lignins in the Cactaceae: structure, distribution and implications for the evolution of lignin diversity
Authors: Chen Fang , Tobimatsu Yuki , Jackson Lisa , Nakashima Jin , Ralph John , Dixon Richard A. 
Published: September 2012

SummaryWe have recently described a hitherto unsuspected catechyl lignin polymer (C‐lignin) in the seed coats of Vanilla orchid and in cacti of one genus, Melocactus (Chen et al., Proc. Natl. Acad. Sci. USA. 2012, 109, 1772‐1777.). We have now determined the lignin types in the seed coats of 130 different cactus species. Lignin in the vegetative tissues of cacti is of the normal guaiacyl/syringyl (G/S) type, but members of most genera within the subfamily Cactoidae possess seed coat lignin of the novel C‐type only, which we show is a homopolymer formed by endwise β–O–4‐coupling of caffeyl alcohol monomers onto the growing polymer resulting in benzodioxane units. However, the species examined within the genera Coryphantha, Cumarinia, Escobaria and Mammillaria (Cactoideae) mostly had normal G/S lignin in their seeds, as did all six species in the subfamily Opuntioidae that were examined. Seed coat lignin composition is still evolving in the Cactaceae, as seeds of one Mammillaria species (M. lasiacantha) possess only C‐lignin, three Escobaria species (E. dasyacantha, E. lloydii and E. zilziana) contain an unusual lignin composed of 5‐hydroxyguaiacyl units, the first report of such a polymer that occurs naturally in plants, and seeds of some species contain no lignin at all. We discuss the implications of these findings for the mechanisms that underlie the biosynthesis of these newly discovered lignin types.
Development of prognostic tools in pulmonary arterial hypertension: Lessons from modern day registries
Authors: Gomberg-Maitland Mardi , Frost Adaani , Frantz Robert , Humbert Marc , McGoon Michael , Benza Raymond 
Published: September 2012

SummaryPulmonary arterial hypertension (PAH) is characterised by increased pressure in the pulmonary arteries leading to right-sided ventricular failure, and death. Identification of factors that affect patient survival is important to improve patient management and outcomes. The first registry to evaluate survival and develop a prognostic model was the National Institutes of Health (NIH) registry in 1981. Importantly this prognostic model is based on data collected prior to availability of PAH-targeted therapies and does not reflect survival rates for treated patients. Since the 1980s, however, four modern registries of PAH now exist which compensate for the NIH equations shortcomings and include the French National registry, Pulmonary Hypertension Connection registry, the Mayo registry, and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). The similarities and difference in these registries are highlighted in this review and although similar in many respects, the four registries vary in patient population, including the numbers of newly and previously diagnosed patients, as well as the era of observation, period of survival, and timing of assessment of potential predictive factors. Despite this, the predictive factors identified in each registry and described in detail within the body of this manuscript share surprising homology in that disease aetiology, patient gender and factors reflective of right heart failure are integral in depicting survival. Future modifications of modern prognostic equations should be an ongoing goal of the PAH community in order to provide increased accuracy with identification of novel risk factors and prediction of disease course.
Maternal chromosome 4 heterodisomy/isodisomy and Bβ chain Trp323X mutation resulting in severe hypodysfibrinogenaemia
Authors: Xi Xiaodong , Ding Qiulan , Ouyang Qi , Wang Xuefeng , Shen Yiping , Wang Hongli 
Published: September 2012

SummaryWe report a rare case of congenital hypodysfibrinogenaemia due to maternal uniparental disomy of chromosome 4 (mat UPD 4) and a maternally inherited novel nonsense mutation Trp323X in the fibrinogen Bβ chain (FGB) gene. Western blot analysis of patient's plasma revealed an abnormal fibrinogen which consisted of truncated Bβ chain and normal Aα and γ chains. Patient's clinical history and laboratory evidence are presented. Microsatellite genotyping analysis revealed a mixed nature of heterodisomy and isodisomy along chromosome 4. High density SNP genotyping array analysis further confirmed the mat UPD 4 and defined two segments of chromosome 4 (4pter-p15.33 and 4q31.21–4q32.3) as maternal isodisomy (iUPD4) and the remaining regions as maternal heterodisomy (hUPD4), with the FGB gene carrying the mutation resided in the iUPD4 region on the long (q) arm. It was predicted that the segmental nature of iUPD and hUPD was caused by three recombination events at positions around 167.96 cM, 145.51 cM and 14.40 cM on chromosome 4 followed by a meiosis I non-disjunction. This case is clinically and molecularly unique and offers an opportunity for understanding novel mechanisms of congenital hypodysfibrinogenaemia associated with complex UPD and fibrinogen secretion.
Exercise training in intermittent claudication: Effects on antioxidant genes, inflammatory mediators and proangiogenic progenitor cells
Authors: Nowobilski Roman , Kusinska Katarzyna , Bukowska-Strakova Karolina , Nizankowski Rafal , Nowak Witold , Mika Piotr , Jozkowicz Alicja , Szczeklik Andrzej , Dulak Jozef 
Published: September 2012

SummaryExercise training remains a therapy of choice in intermittent claudication (IC). However, too exhaustive exercise may cause ischaemic injury and inflammatory response. We tested the impact of three-month treadmill training and single treadmill exercise on antioxidant gene expressions, cytokine concentrations and number of marrow-derived proangiogenic progenitor cells (PPC) in the blood of IC patients. Blood samples of 12 patients were collected before and after training, before and 1, 3 and 6 hours after the single exercise. PPCs were analysed with flow cytometry, cytokine concentrations were checked with Milliplex MAP, while expression of mRNAs and miRNAs was evaluated with qRT-PCR. Treadmill training improved pain-free walking time (from 144 ± 44 seconds [s] to 311 ± 134 s, p=0.02) and maximum walking time (from 578 ± 293 s to 859 ± 423 s, p=0.01) in IC patients. Before, but not after training, the single treadmill exercise increased the number of circulating CD45dimCD34+CD133-KDR+ PPCs (p=0.048), decreased expression of HMOX1 (p=0.04) in circulating leukocytes, reduced tumour necrosis factor-α (p=0.03) and tended to elevate myeloperoxidase (p=0.06) concentrations in plasma. In contrast, total plasminogen activator inhibitor-1 was decreased by single exercise only after, but not before training (p=0.02). Both before and after training the single exercise decreased monocyte chemoattractant protein (MCP)-1 (p=0.006 and p=0.03) concentration and increased SOD1 (p=0.001 and p=0.01) expression. Patients after training had also less interleukin-6 (p=0.03), but more MCP-1 (p=0.04) in the blood. In conclusion, treadmill training improves walking performance of IC patients, attenuates the single exercise-induced changes in gene expressions or PPC mobilisation, but may also lead to higher production of some proinflammatory cytokines.
Increased prevalence of hypertension in haemophilia patients
Authors: van de Putte Dietje E. , Fischer Kathelijn , Makris Michael , Tait R. , Collins Peter W. , Meijer Karina , Roosendaal Goris , Chowdary Pratima , Schutgens Roger E. G. , Mauser-Bunschoten Eveline P. 
Published: September 2012

SummaryAn increased prevalence of hypertension is reported in haemophilia patients, but data from large, unbiased studies are lacking. The aim of our study was to cross-sectionally assess the prevalence of hypertension in a large cohort of 701 haemophilia patients. Blood pressure (BP) measurements performed in 386 Dutch and 315 UK haemophilia patients aged 30 years or older were analysed and compared with the general age-matched male population. Mean values of up to three BP measurements were used when available. Hypertension was defined as BP over 140/90 mmHg and/or the use of antihypertensive medication. A total of 49% of patients had severe haemophilia. Mean age was 49.8 years. The prevalence of hypertension was significantly higher in haemophilia patients (49%, 95% confidence interval [CI] 45–53) than in the general population (40%, 95% CI 37–43). The prevalence of hypertension was higher in patients with severe haemophilia than in those with non-severe disease, but similar across haemophilia types and in Dutch and UK patients. Multiple BP measurements were available for 70%.The prevalence of hypertension was similar in patients with multiple BP measurements and the complete cohort. Hypertension was not significantly associated with renal function, a history of renal bleeding or with infection with hepatitis C or HIV, but it was associated with overweight/obesity and age. In conclusion, the prevalence of hypertension is higher in haemophilia patients than in the general population. The cause of this increased prevalence is unknown. Blood pressure measurements should be part of standard care in haemophilia patients aged 30 years or older.
Lipid levels do not influence the risk of venous thromboembolism
Authors: Mahmoodi Bakhtawar , Gansevoort Ron , Muntinghe Friso , Dullaart Robin , Kluin-Nelemans Hanneke , Veeger Nic , van Schouwenburg Inge , Meijer Karina 
Published: September 2012

SummaryStudies on the association between lipid profile and venous thromboembolism (VTE) are inconsistent. This could be caused by classical lipoproteins being inferior to apolipoproteins as markers for VTE risk. Therefore, we examined whether apolipoproteins are more strongly related to VTE than lipoproteins. For this analysis we used the PREVEND prospective community based observational cohort study. Levels of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (TC), high-density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL), triglycerides (TG), lipoprotein(a), ApoB/ApoA1 and TC/HDL ratio were assessed. Subjects with VTE were identified using databases of the national registries of hospital discharge diagnoses, death certificates, and the regional anticoagulation clinic. Out of 7,627 subjects, 110 developed VTE during a median follow-up of 10.5 years. In both univariate and multivariable analyses no significant associations between apolipoproteins and overall VTE were observed. Of the classical lipoproteins, TC, non-HDL, LDL, TG, and TC/HDL ratio were significantly associated with overall VTE in univariate analysis. Significant associations were no longer present in multivariable analysis. TGL and LDL were significantly associated with unprovoked VTE in univariate analysis. After adjustment for age and sex this significance was lost. No significant associations between (apo-) lipoproteins and provoked VTE were found. We conclude that apolipoproteins are not better in predicting VTE risk than the classical lipoproteins. Our population-based cohort study does not show an association between both apolipoproteins and the classical lipoproteins and VTE risk.
Atheroprotective mechanisms of shear stress-regulated microRNAs
Authors: Boon Reinier A. , Hergenreider Eduard , Dimmeler Stefanie 
Published: September 2012

SummaryMicroRNAs (miRs) are small non-coding RNAs that control gene expression by inhibiting translation or inducing degradation of targeted mRNA. miRs play a crucial role in vascular homeostasis but also during pathophysiological processes. Functionally active endothelial cells maintain homeostasis of the vasculature and protect against cardiovascular disease. The mechanical activation of endothelial cells by laminar shear stress provides a potent atheroprotective effect and reduces endothelial inflammation and cell cycle progression. Laminar shear stress induces profound changes in gene expression and recently was shown to regulate various miRs. The down-regulation of miR-92a by shear stress enhances the expression of the endothelial nitric oxide synthase, whereas the up-regulation of miR-19a contributes to the shear stress-induced inhibition of cell proliferation. In addition, members of the miR-23–27–24 cluster are increased and specifically miR-23b blocks cell cycle progression, whereas miR-27b was shown to reduce endothelial cell repulsive signals. Finally, increased miR-10 expression in atheroprotected regions reduced the inflammatory response of endothelial cells and increased endothelial miR-143/145 levels improved smooth muscle cells functions. Together, the regulation of miRs by shear stress contributes to the anti-inflammatory, cell cycle inhibitory and vasculoprotective effects in endothelial cells.
The Impact of Foot Insole on the Energy Consumption of Flat-Footed Individuals During Walking
Authors: Karimi Mohammad Taghi , Fereshtehnejad Niloofar , Pool Fatemeh 
Published: September 2012

Background. The human foot contains one of the most variable structures of the body, which is the medial longitudinal arch. Decrease in the height of this arch results in a flat foot. Although there is some evidence regarding the influence of flat foot on gait performance of flat-footed individuals, there is no strong evidence to support the theory that being flat-footed has an effect on energy consumption. Therefore, the aim of this study was to find the relationship between flat foot and energy consumption. Method. Two groups of normal and flat-footed participants were recruited in this research project. They were selected from the staff and students of Isfahan University of Medical Sciences. The foot indexes of both groups were obtained using the footprint method with help of Solid worker software. The physiological cost index (PCI) of the participants was measured by the use of a heart rate monitoring system (Polar Electro, Finland). The differences between the PCIs of both groups of participants was determined using a t test. In addition, the influence of using an insole was evaluated using a paired t test. Result. The energy consumption of flat-footed individuals differed significantly from that of normal individuals (the PCIs of normal and flat-footed individuals were 0.357 and 0.368 beats/m, respectively). Using a foot insole improved the performance of the flat-footed individuals during walking. Conclusion. The PCI of flat-footed individuals is more than that of normal participants as a result of misalignment of foot structure. Moreover, using a foot insole improved foot alignment and decreased energy consumption. Levels of Evidence: Therapeutic, Level III: comparative case series