bluuebunny/crossref_metadata_2025_split huggingface dataset:
Newly developed TGF-β2 knock down transgenic mouse lines express TGF-β2 differently and its distribution in multiple tissues varies
Authors: XiYang Yan-Bin , Wang Fang , Qian Bao-Jiang , You Ling , Lu Bing-Tuan , Zhang Wei , Quan Xiong-Zhi , Ge Wen-Ping , Liu Su , Zhang Lian-Feng , Wang Ting-Hua 
Published: August 2013

Abstract

Background
Transforming growth factor-betas (TGF-βs), including beta2 (TGF-β2), constitute a superfamily of multifunctional cytokines with important implications in morphogenesis, cell differentiation and tissue remodeling. TGF-β2 is thought to play important roles in multiple developmental processes and neuron survival. However, before we carried out these investigations, a TGF-β2 gene down-regulated transgenic animal model was needed. In the present study, expressional silencing TGF-β2 was achieved by select predesigning interference short hairpin RNAs (shRNAs) targeting mouse TGF-β2 genes.

Results
Four homozygous transgenic offspring were generated by genetic manipulation and the protein expressions of TGF-β2 were detected in different tissues of these mice. The transgenic mice were designated as Founder 66, Founder 16, Founder 53 and Founder 41. The rates of TGF-β2 down-expression in different transgenic mice were evaluated. The present study showed that different TGF-β2 expressions were detected in multiple tissues and protein levels of TGF-β2 decreased at different rates relative to that of wild type mice. The expressions of TGF-β2 proteins in transgenic mice (Founder 66) reduced most by 52%.

Conclusions
The present study generated transgenic mice with TGF-β2 down-regulated, which established mice model for systemic exploring the possible roles of TGF-β2 in vivo in different pathology conditions.
ERK-associated changes in E2F4 phosphorylation, localization and transcriptional activity during mitogenic stimulation in human intestinal epithelial crypt cells
Authors: Paquin Marie-Christine , Cagnol Sébastien , Carrier Julie C , Leblanc Caroline , Rivard Nathalie 
Published: August 2013

Abstract

Background
The transcription factor E2F4 controls proliferation of normal and cancerous intestinal epithelial cells. E2F4 localization in normal human intestinal epithelial cells (HIEC) is cell cycle-dependent, being cytoplasmic in quiescent differentiated cells but nuclear in proliferative cells. However, the intracellular signaling mechanisms regulating such E2F4 localization remain unknown.

Results
Treatment of quiescent HIEC with serum induced ERK1/2 activation, E2F4 phosphorylation, E2F4 nuclear translocation and G1/S phase transition while inhibition of MEK/ERK signaling by U0126 prevented these events. Stimulation of HIEC with epidermal growth factor (EGF) also led to the activation of ERK1/2 but, in contrast to serum or lysophosphatidic acid (LPA), EGF failed to induce E2F4 phosphorylation, E2F4 nuclear translocation and G1/S phase transition. Furthermore, Akt and GSK3β phosphorylation levels were markedly enhanced in serum- or LPA-stimulated HIEC but not by EGF. Importantly, E2F4 phosphorylation, E2F4 nuclear translocation and G1/S phase transition were all observed in response to EGF when GSK3 activity was concomitantly inhibited by SB216763. Finally, E2F4 was found to be overexpressed, phosphorylated and nuclear localized in epithelial cells from human colorectal adenomas exhibiting mutations in APC and KRAS or BRAF genes, known to deregulate GSK3/β-catenin and MEK/ERK signaling, respectively.

Conclusions
The present results indicate that MEK/ERK activation and GSK3 inhibition are both required for E2F4 phosphorylation as well as its nuclear translocation and S phase entry in HIEC. This finding suggests that dysregulated E2F4 nuclear localization may be an instigating event leading to hyperproliferation and hence, of tumor initiation and promotion in the colon and rectum.
Three-stage biochemical selection: cloning of prototype class IIS/IIC/IIG restriction endonuclease-methyltransferase TsoI from the thermophile Thermus scotoductus
Authors: Skowron Piotr M , Vitkute Jolanta , Ramanauskaite Danute , Mitkaite Goda , Jezewska-Frackowiak Joanna , Zebrowska Joanna , Zylicz-Stachula Agnieszka , Lubys Arvydas 
Published: August 2013

Abstract

Background
In continuing our research into the new family of bifunctional restriction endonucleases (REases), we describe the cloning of the tsoIRM gene. Currently, the family includes six thermostable enzymes: TaqII, Tth111II, TthHB27I, TspGWI, TspDTI, TsoI, isolated from various Thermus sp. and two thermolabile enzymes: RpaI and CchII, isolated from mesophilic bacteria Rhodopseudomonas palustris and Chlorobium chlorochromatii, respectively. The enzymes have several properties in common. They are large proteins (molecular size app. 120 kDa), coded by fused genes, with the REase and methyltransferase (MTase) in a single polypeptide, where both activities are affected by S-adenosylmethionine (SAM). They recognize similar asymmetric cognate sites and cleave at a distance of 11/9 nt from the recognition site. Thus far, we have cloned and characterised TaqII, Tth111II, TthHB27I, TspGWI and TspDTI.

Results
TsoI REase, which originate from thermophilic Thermus scotoductus RFL4 (T. scotoductus), was cloned in Escherichia coli (E. coli) using two rounds of biochemical selection of the T. scotoductus genomic library for the TsoI methylation phenotype. DNA sequencing of restriction-resistant clones revealed the common open reading frame (ORF) of 3348 bp, coding for a large polypeptide of 1116 aminoacid (aa) residues, which exhibited a high level of similarity to Tth111II (50% identity, 60% similarity). The ORF was PCR-amplified, subcloned into a pET21 derivative under the control of a T7 promoter and was subjected to the third round of biochemical selection in order to isolate error-free clones. Induction experiments resulted in synthesis of an app. 125 kDa protein, exhibiting TsoI-specific DNA cleavage. Also, the wild-type (wt) protein was purified and reaction optima were determined.

Conclusions
Previously we identified and cloned the Thermus family RM genes using a specially developed method based on partial proteolysis of thermostable REases. In the case of TsoI the classic biochemical selection method was successful, probably because of the substantially lower optimal reaction temperature of TsoI (app. 10-15°C). That allowed for sufficient MTase activity in vivo in recombinant E. coli. Interestingly, TsoI originates from bacteria with a high optimum growth temperature of 67°C, which indicates that not all bacterial enzymes match an organism’s thermophilic nature, and yet remain functional cell components. Besides basic research advances, the cloning and characterisation of the new prototype REase from the Thermus sp. family enzymes is also of practical importance in gene manipulation technology, as it extends the range of available DNA cleavage specificities.
Common rs7138803 variant of FAIM2 and obesity in Han Chinese
Authors: Li Cong , Qiu Xueping , Yang Na , Gao Jiajia , Rong Yuan , Xiong Chenling , Zheng Fang 
Published: August 2013

Abstract

Background
Obesity causes severe healthcare problem worldwide leading to numerous diseases, such as cardiovascular diseases and diabetes mellitus. Previous Genome-Wide Association Study (GWAS) identified an association between a single nucleotide polymorphism (SNP) rs7138803, on chromosome 12q13 and obesity in European Caucasians. Since the genetic architecture governing the obesity may vary among different populations, we investigate the variant rs7138803 in Chinese population to find out whether it is associated with obesity.

Methods
A population-based cohort association study was carried out using the High Resolution Melt (HRM) method with 1851 participants. The association between rs7138803 genotypes and body mass index (BMI) was modeled with a general linear model, and a case–control study for the association between rs7138803 genotypes and obesity was performed using Pearson’s χ2 test. There was no indication of a deviation from Hardy-Weinberg equilibrium (HWE p value = 0.51) in our sample.

Results
No association was detected between SNP rs7138803 and BMI in our Chinese Han population with a P value of 0.51. SNP rs7138803 was found to be not associated with common forms of obesity after adjusting for age and sex in the Chinese population. SNP rs7138803 was not associated with other obesity related traits, including T2DM, hypertension, lipid profiles, and ischemic stroke.

Conclusion
Our data suggest that the rs7138803 exerts no significant effect on obesity in Chinese Han population. Larger cohorts may be more appropriate to detect an effect of this SNP on common obesity.
Screening for phenotype selective activity in multidrug resistant cells identifies a novel tubulin active agent insensitive to common forms of cancer drug resistance
Authors: Fryknäs Mårten , Gullbo Joachim , Wang Xin , Rickardson Linda , Jarvius Malin , Wickström Malin , Hassan Saadia , Andersson Claes , Gustafsson Mats , Westman Gunnar , Nygren Peter , Linder Stig , Larsson Rolf 
Published: August 2013

AbstractBackgroundDrug resistance is a common cause of treatment failure in cancer patients and encompasses a multitude of different mechanisms. The aim of the present study was to identify drugs effective on multidrug resistant cells.MethodsThe RPMI 8226 myeloma cell line and its multidrug resistant subline 8226/Dox40 was screened for cytotoxicity in response to 3,000 chemically diverse compounds using a fluorometric cytotoxicity assay (FMCA). Follow-up profiling was subsequently performed using various cellular and biochemical assays.ResultsOne compound, designated VLX40, demonstrated a higher activity against 8226/Dox40 cells compared to its parental counterpart. VLX40 induced delayed cell death with apoptotic features. Mechanistic exploration was performed using gene expression analysis of drug exposed tumor cells to generate a drug-specific signature. Strong connections to tubulin inhibitors and microtubule cytoskeleton were retrieved. The mechanistic hypothesis of VLX40 acting as a tubulin inhibitor was confirmed by direct measurements of interaction with tubulin polymerization using a biochemical assay and supported by demonstration of G2/M cell cycle arrest. When tested against a broad panel of primary cultures of patient tumor cells (PCPTC) representing different forms of leukemia and solid tumors, VLX40 displayed high activity against both myeloid and lymphoid leukemias in contrast to the reference compound vincristine to which myeloid blast cells are often insensitive. Significantin vivoactivity was confirmed in myeloid U-937 cells implanted subcutaneously in mice using the hollow fiber model.ConclusionsThe results indicate that VLX40 may be a useful prototype for development of novel tubulin active agents that are insensitive to common mechanisms of cancer drug resistance.
Local therapies for inflammatory eye disease in translation: past, present and future
Authors: Tempest-Roe Shenzhen , Joshi Lavnish , Dick Andrew D , Taylor Simon RJ 
Published: August 2013

Abstract
Despite their side-effects and the advent of systemic immunosuppressives and biologics, the use of corticosteroids remains in the management of patients with uveitis, particularly when inflammation is associated with systemic disease or when bilateral ocular disease is present. The use of topical corticosteroids as local therapy for anterior uveitis is well-established, but periocular injections of corticosteroid can also be used to control mild or moderate intraocular inflammation. More recently, intraocular corticosteroids such as triamcinolone and steroid-loaded vitreal inserts and implants have been found to be effective, including in refractory cases. Additional benefits are noted when ocular inflammation is unilateral or asymmetric, when local therapy may preclude the need to increase the systemic medication.
Implants in particular have gained prominence with evidence of efficacy including both dexamethasone and fluocinolone loaded devices. However, an appealing avenue of research lies in the development of non-corticosteroid drugs in order to avoid the side-effects that limit the appeal of injected corticosteroids. Several existing drugs are being assessed, including anti-VEGF compounds such as ranibizumab and bevacizumab, anti-tumour necrosis factor alpha antibodies such as infliximab, as well as older cytotoxic medications such as methotrexate and cyclosporine, with varying degrees of success. Intravitreal sirolimus is currently undergoing phase 3 trials in uveitis and other inflammatory pathways have also been proposed as suitable therapeutic targets. Furthermore, the advent of biotechnology is seeing advances in generation of new therapeutic molecules such as high affinity binding peptides or modified high affinity or bivalent single chain Fab fragments, offering higher specificity and possibility of topical delivery.
Triangulating perspectives on functional neuroimaging for disorders of mental health
Authors: Anderson James A , Mizgalewicz Ania , Illes Judy 
Published: August 2013

Abstract

Background
Functional neuroimaging is being used in clinical psychiatry today despite the vigorous objections of many in the research community over issues of readiness. To date, a systematic examination of the perspectives of key stakeholders involved in this debate has not yet been attempted. To this fill this gap, we interviewed investigators who conduct functional neuroimaging studies involving adults with mood disorders, schizophrenia, obsessive compulsive disorder, and/or attention deficit hyperactivity disorder, providers who offer clinical neuroimaging services in the open marketplace, and consumers of these services, in order to understand perspectives underlying different views and practices.

Methods
Semi-structured interviews were conducted over the telephone. Verbal consent was obtained and all interviews were audio recorded. Interviews of investigators and service providers followed the same interview guide. A separate set of questions was developed for consumers. All interviews were transcribed and made software ready. We applied the qualitative methodology of constant comparison to analyze the data, whereby two researchers independently analyzed the results into textual themes. Coding discrepancies were discussed until consensus was achieved.

Results
Investigators, service providers, and consumers held many common perspectives about the potential or actual risks and benefits of functional neuroimaging for mental illness. However, we also found striking divergences. Service providers focused on the challenges posed by the persistence of symptoms based diagnostic categories, whereas the limitations of the science in this area was the challenge noted most frequently by investigators. The majority of consumers stated that their expectations were met.

Conclusion
Our findings point toward a fundamental tension between academic investigators on the one hand, and commercial service providers and their customers on the other. This scenario poses dangers to the communities directly involved, and to public trust in science and medicine more generally. We conclude with recommendations for work that needs to be done to minimize tensions and maximize the potential of neurotechnology through concerted efforts to respect its limitations while leveraging the strengths, investments, and hopes of each stakeholder group.
L1 Norm based common spatial patterns decomposition for scalp EEG BCI
Authors: Li Peiyang , Xu Peng , Zhang Rui , Guo Lanjin , Yao Dezhong 
Published: August 2013

Abstract

Background
Brain computer interfaces (BCI) is one of the most popular branches in biomedical engineering. It aims at constructing a communication between the disabled persons and the auxiliary equipments in order to improve the patients’ life. In motor imagery (MI) based BCI, one of the popular feature extraction strategies is Common Spatial Patterns (CSP). In practical BCI situation, scalp EEG inevitably has the outlier and artifacts introduced by ocular, head motion or the loose contact of electrodes in scalp EEG recordings. Because outlier and artifacts are usually observed with large amplitude, when CSP is solved in view of L2 norm, the effect of outlier and artifacts will be exaggerated due to the imposing of square to outliers, which will finally influence the MI based BCI performance. While, L1 norm will lower the outlier effects as proved in other application fields like EEG inverse problem, face recognition, etc.

Methods
In this paper, we present a new CSP implementation using the L1 norm technique, instead of the L2 norm, to solve the eigen problem for spatial filter estimation with aim to improve the robustness of CSP to outliers. To evaluate the performance of our method, we applied our method as well as the standard CSP and the regularized CSP with Tikhonov regularization (TR-CSP), on both the peer BCI dataset with simulated outliers and the dataset from the MI BCI system developed in our group. The McNemar test is used to investigate whether the difference among the three CSPs is of statistical significance.

Results
The results of both the simulation and real BCI datasets consistently reveal that the proposed method has much higher classification accuracies than the conventional CSP and the TR-CSP.

Conclusions
By combining L1 norm based Eigen decomposition into Common Spatial Patterns, the proposed approach can effectively improve the robustness of BCI system to EEG outliers and thus be potential for the actual MI BCI application, where outliers are inevitably introduced into EEG recordings.
Enhancing performance of a miniaturized surface plasmon resonance sensor in the reflectance detection mode using a waveguide-coupled bimetallic chip
Authors: Lee Yeon Kyung , Jang Dae Ho , Lee Kyeong-Seok , Kim Won Mok , Sohn Young-Soo 
Published: August 2013

Abstract
The characteristics of a waveguide-coupled bimetallic (WcBiM) chip in a miniaturized surface plasmon resonance (SPR) sensor and its detection capability for a low molecular weight biomolecule were investigated. The configuration of the WcBiM chip was gold (Au)/waveguide (ZnS-SiO2)/silver (Ag). In the intensity measurement mode, the sensitivity could be improved by reducing the full width at half maximum (FWHM) of the reflectance curve. The FWHM of the WcBiM chip is narrower than that of the Au chip, which suggests that the slope of the reflectance curve for the WcBiM chip is steeper. In order to generate enhanced resolution, the reflectance should be monitored at the specific angle where the slope is the steepest in the reflectance curve. For the detection of biotin that is a low molecular weight biomolecule, streptavidin was formed on the SPR sensor chip surface. The response of the SPR to biotin at various concentrations was then acquired. The sensitivities of the WcBiM chip and the Au chip were 0.0052%/(ng/ml) and 0.0021%/(ng/ml), respectively. The limit of detection of the biotin concentration for both the WcBiM and Au chips was calculated. The values were 2.87 ng/ml for the WcBiM chip and 16.63 ng/ml for the Au chip. Enhancement of the sensitivity in the intensity detection mode was achieved using the WcBiM chip compared with the Au chip. Therefore, sufficient sensitivity for the detection of a disease-related biomarker is attainable with the WcBiM chip in the intensity measurement mode using a miniaturized SPR sensor.
The iterative methods for solving nonlinear matrix equation "Equation missing"
Authors: Vaezzadeh Sarah , Vaezpour Seyyed Mansour , Saadati Reza , Park Choonkil 
Published: August 2013

AbstractIn this paper, we study the matrix equationX+A⋆X−1A+B⋆X−1B=Q, whereAandBare square matrices, andQis a positive definite matrix, and propose the iterative methods for finding positive definite solutions of the matrix equation. Also, general convergence results for the basic fixed point iteration for these equations are given. Some numerical examples are presented to show the usefulness of the iterations.MSC:65F10, 65F30, 65H10, 15A24.
Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines
Authors: Dashdorj Amarjargal , KR Jyothi , Lim Sangbin , Jo Ara , Nguyen Minh Nam , Ha Joohun , Yoon Kyung-Sik , Kim Hyo Jong , Park Jae-Hoon , Murphy Michael P , Kim Sung Soo 
Published: August 2013

Abstract

Background
MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation.

Methods
Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed.

Results
Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells.

Conclusion
Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease.
The distinct expression patterns of claudin-2, -6, and −11 between human gastric neoplasms and adjacent non-neoplastic tissues
Authors: Lin Zhe , Zhang Xiaowei , Liu Zhijing , Liu Qihui , Wang Liping , Lu Yan , Liu Yuanyuan , Wang Min , Yang Minlan , Jin Xiangshu , Quan Chengshi 
Published: August 2013

AbstractBackgroundCancers have a multifactorial etiology a part of which is genetic. Recent data indicate that expression of the tight junction claudin proteins is involved in the etiology and progression of cancer.MethodsTo explore the correlations of the tight junction proteins claudin-2,-6, and −11 in the pathogenesis and clinical behavior of gastric cancer, 40 gastric cancer tissues and 28 samples of non-neoplastic tissues adjacent to the tumors were examined for expression of claudin-2,-6, and −11 by streptavidin-perosidase immunohistochemical staining method.ResultsThe positive expression rates of claudin-2 in gastric cancer tissues and adjacent tissues were 25% and 68% respectively (P < 0.001). The positive expression rates of claudin-6 in gastric cancer tissues and adjacent tissues were 55% and 79% respectively (P = 0.045 < 0.05). In contrast, the positive expression rates of claudin-11 in gastric cancer tissues and gastric cancer adjacent tissues were 80% and 46% (P = 0.004 < 0.01). Thus in our study, the expression of claudin-2, and claudin-6 was down regulated in gastric cancer tissue while the expression of claudin-11 was up regulated. Correlations between claudin expression and clinical behavior were not observed.ConclusionOur study provides the first evidence that claudin-2,-6, and −11 protein expression varies between human gastric cancers and adjacent non-neoplastic tissues.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/5470513569630744