bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Key Role for Matrix Metalloproteinases and Neutral Sphingomyelinase-2 in Transplant Vasculopathy Triggered by Anti-HLA Antibody
Authors: Galvani Sylvain , Trayssac Magali , Augé Nathalie , Thiers Jean-Claude , Calise Denis , Krell Hans-Willi , Sallusto Federico , Kamar Nassim , Rostaing Lionel , Thomsen Mogens , Nègre-Salvayre Anne , Salvayre Robert 
Published: November 2011

Background—
Outcomes for organ transplantation are constantly improving because of advances in organ preservation, surgical techniques, immune clinical monitoring, and immunosuppressive treatment preventing acute transplant rejection. However, chronic rejection including transplant vasculopathy still limits long-term patient survival. Transplant vasculopathy is characterized by progressive neointimal hyperplasia leading to arterial stenosis and ischemic failure of the allograft. This work sought to decipher the manner in which the humoral immune response, mimicked by W6/32 anti-HLA antibody, contributes to transplant vasculopathy.

Methods and Results—
Studies were performed in vitro on cultured human smooth muscle cells, ex vivo on human arterial segments, and in vivo in a model consisting of human arterial segments grafted into severe combined immunodeficiency/beige mice injected weekly with anti-HLA antibodies. We report that anti-HLA antibodies are mitogenic for smooth muscle cells through a signaling mechanism implicating matrix metalloproteinases (MMPs) (membrane type 1 MMP and MMP2) and neutral sphingomyelinase-2. This mitogenic signaling and subsequent DNA synthesis are blocked in smooth muscle cells silenced for MMP2 or for neutral sphingomyelinase-2 by small interfering RNAs, in smooth muscle cells transfected with a vector coding for a dominant-negative form of membrane type 1 MMP, and after treatment by pharmacological inhibitors of MMPs (Ro28-2653) or neutral sphingomyelinase-2 (GW4869). In vivo, Ro28-2653 and GW4869 reduced the intimal thickening induced by anti-HLA antibodies in human mesenteric arteries grafted into severe combined immunodeficiency/beige mice.

Conclusions—
These data highlight a crucial role for MMP2 and neutral sphingomyelinase-2 in vasculopathy triggered by a humoral immune response and open new perspectives for preventing transplant vasculopathy with the use of MMP and neutral sphingomyelinase inhibitors, in addition to conventional immunosuppression.
Absence of SOCS3 in the Cardiomyocyte Increases Mortality in a gp130-Dependent Manner Accompanied by Contractile Dysfunction and Ventricular Arrhythmias
Authors: Yajima Toshitaka , Murofushi Yoshiteru , Zhou Hanbing , Park Stanley , Housman Jonathan , Zhong Zhao-Hua , Nakamura Michinari , Machida Mitsuyo , Hwang Kyung-Kuk , Gu Yusu , Dalton Nancy D. , Yajima Tomoko , Yasukawa Hideo , Peterson Kirk L. , Knowlton Kirk U. 
Published: November 2011

Background—
Suppressor of cytokine signaling-3 (SOCS3) is a key negative-feedback regulator of the gp130 receptor that provides crucial signaling for cardiac hypertrophy and survival; however, an in vivo role of SOCS3 regulation on cardiac gp130 signaling remains obscure.

Methods and Results—

We generated cardiac-specific SOCS3 knockout (SOCS3 cKO) mice. These mice showed increased activation of gp130 downstream signaling targets (STAT3, ERK1/2, AKT, and p38) from 15 weeks of age and developed cardiac dysfunction from approximately 25 weeks of age with signs of heart failure. Surprisingly, SOCS3 cKO failing hearts had minimal histological abnormalities with intact myofibril ultrastructure. In addition, Ca
2+
transients were significantly increased in SOCS3 cKO failing hearts compared with wild-type hearts. We also found that Ser23/24 residues of troponin I were hypophosphorylated in SOCS3 cKO hearts before the manifestation of cardiac dysfunction. These data suggested the presence of abnormalities in myofilament Ca
2+
sensitivity in SOCS3 cKO mice. In addition to the contractile dysfunction, we found various ventricular arrhythmias in SOCS3 cKO nonfailing hearts accompanied by a sarcoplasmic reticulum Ca
2+
overload. To determine the contribution of gp130 signaling to the cardiac phenotype that occurs with SOCS3 deficiency, we generated cardiac-specific gp130 and SOCS3 double KO mice. Double KO mice lived significantly longer and had different histological abnormalities when compared with SOCS3 cKO mice, thus demonstrating the importance of gp130 signaling in the SOCS3 cKO cardiac phenotype.

Conclusions—
Our results demonstrate an important role of SOCS3 regulation on cardiac gp130 signaling in the pathogenesis of contractile dysfunction and ventricular arrhythmias.
The Initiation of Modern “Soft Snowball” and “Hard Snowball” Climates in CCSM3. Part II: Climate Dynamic Feedbacks
Authors: Yang Jun , Peltier W. Richard , Hu Yongyun 
Published: November 2011

Abstract
This study investigates the climate dynamic feedbacks during a transition from the present climate to the extremely cold climate of a “Snowball Earth” using the Community Climate System Model, version 3 (CCSM3). With the land–sea distribution fixed to modern, it is found that by reducing solar luminosity and/or carbon dioxide concentration: 1) the amount of atmospheric water vapor and its attendant greenhouse effect decrease with the logarithm of sea ice cover, thereby promoting the expansion of sea ice; 2) over the sea ice, the cloud radiative feedback is positive, thus enhancing sea ice advance; over the ocean, the cloud radiative feedback is first negative and then becomes positive as sea ice enters the tropics; and 3) the strength of the atmospheric Hadley cell and the wind-driven ocean circulation increases significantly in the Southern Hemisphere, inhibiting the expansion of sea ice into the tropics. Meanwhile, the North Atlantic Deep Water cell disappears and the Antarctic Bottom Water cell strengthens and expands to occupy almost the entire Atlantic basin. In the experiment with 6% less solar radiation and 70 ppmv CO2 compared to the control experiment with 100% solar radiation and 355 ppmv CO2 near the ice edge (28°S latitude), the changes of solar radiation, CO2 forcing, water vapor greenhouse effect, longwave cloud forcing at the top of the model, and atmospheric and oceanic energy transport are −22.4, −6.2, −54.4, +6.2, and +16.3 W m−2, respectively. Therefore, the major controlling factors in producing global ice cover are ice albedo feedback (Yang et al., Part I) and water vapor feedback.
Organization of Flash-Flood-Producing Precipitation in the Northeast United States
Authors: Jessup Stephen M. , Colucci Stephen J. 
Published: November 2011

Abstract
Heavy precipitation and flash flooding have been extensively studied in the central United States, but less so in the Northeast. This study examines 187 warm-season flash flood events identified in Storm Data to better understand the structure of the precipitation systems that cause flash flooding in the Northeast. Based on the organization and movement of these systems on radar, the events are classified into one of four categories—back-building, linear, multiple, and other/size—and then further classified into subtypes for each category. Eight of these subtypes were not previously recognized in the literature. The back-building events were the most common, followed by the multiple, other/size, and linear types. The linear event types appear to produce flash flooding less commonly in the Northeast than in other regions. In general, the subtypes producing the highest precipitation estimates are those whose structures are most conducive to a long duration of sustained moderate to heavy rainfall. The event types were found to differ from those in the central United States in that the events were more often found to be more disorganized in the Northeast. One event type in particular, back-building with merging features, while not more disorganized than the previously recognized event types, offers promise for improved forecasting because its radar signature makes the duration of sustained heavy precipitation potentially easier to predict.
Listening to indigenous health workers
Authors: Walker David , Tennant Marc , Short Stephanie D 
Published: November 2011

Objective: This research was undertaken to explore factors operating at the level of the clinic and the community which influence the development of the oral health role of Indigenous Health Workers. The research is a significant aspect of a wider study of the disconnect between the strong national policy support for the development of the oral health role of Indigenous Health Workers and the limited development of the role. Design: Semi-structured interviews were conducted with Indigenous Health Workers to explore their perceptions of the priority of the development of an oral health role and to identify facilitators and barriers to sustainable role development. Setting: The study was conducted in three remote Indigenous communities and two regional centres of the Cape York region in far north Australia. Method: Interviews were conducted with 21 Indigenous Health Workers through five group interviews and eight individual interviews. Results: The findings highlight the high priority given by Indigenous Health Workers to the development of their oral health role while also identifying significant barriers to the sustainable development of this role. Conclusion: The identification of barriers to role development operating at the level of the clinic and the community helps to explain the disconnect between policy and practice in the development of the oral health role of these community health personnel.
The Otolaryngologist’s Cost in Treating Facial Trauma
Authors: McCusker Scott B. , Schmalbach Cecelia E. 
Published: November 2011

Objectives(1) To define practice patterns and perceptions of junior otolaryngologists treating maxillofacial/neck trauma. (2) To identify manners in which the American Academy of Otolaryngology—Head and Neck Surgery (AAO‐HNS) can meet future trauma needs.Study DesignCross‐sectional survey.SettingAcademic and private otolaryngology practices.MethodsA 26‐question survey was designed to identify demographics, practice patterns, perceptions, and areas for improvement in maxillofacial/neck trauma care. It was distributed anonymously to AAO‐HNS members completing residency from 2005 to 2009. Analysis included descriptive statistics and χ2 comparisons.ResultsOf 1343 otolaryngologists, 444 (33%) responded. A total of 85% of responding physicians treat maxillofacial/neck trauma, and 64% identify trauma as an ideal part of their practice. Sense of duty (54%), institutional requirements (33%), and enjoyment (32%) are the most common reasons for treating trauma. Major deterrents include patient noncompliance (60%) and lifestyle limitations (47%). Five respondents (3.1%) have been involved in a trauma‐related lawsuit. While insufficient reimbursement is a major deterrent to treating trauma (52%), only 36% would increase their volume if reimbursement improved. Increased educational opportunities represent the most common request to the AAO‐HNS (59%), followed by AAO‐HNS focus on improved reimbursement and tort reform (28%).ConclusionMost junior otolaryngologists treat maxillofacial/neck trauma on a monthly basis. A total of 64% identify trauma as a component of their ideal practice. They report being well to very well trained in all facets of trauma, with the exception of vascular and laryngotracheal injuries; but they desire additional education, such as courses and panels. Universal concerns include inadequate reimbursement, limited pool of treating physicians, and lack of practice guidelines.
Anti-inflammatory and antioxidant effects of infliximab in a rat model of intestinal ischemia/reperfusion injury
Authors: Pergel Ahmet , Kanter Mehmet , Yucel Ahmet Fikret , Aydin Ibrahim , Erboga Mustafa , Guzel Ahmet 
Published: November 2011

The aim of this study was to investigate the possible protective effects of infliximab on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group comprised 10 animals. Sham group animals underwent laparotomy without I/R injury. I/R groups after undergoing laparotomy, 1 hour of superior mesenteric artery ligation occurred, which was followed by 1 hour of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered intravenously. All animals were killed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no biochemical and histopathological changes have been reported regarding intestinal I/R injury in rats due to infliximab treatment. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased reduced superoxide dismutase and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Infliximab treatment significantly attenuated the severity of intestinal I/R injury, inhibiting I/R-induced apoptosis, and cell proliferation. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects on the experimental intestinal I/R model of rats.
Fatigue-Related Gene Networks Identified in CD14+ Cells Isolated From HIV-Infected Patients—Part II
Authors: Voss Joachim G. , Dobra Adrian , Morse Caryn , Kovacs Joseph A. , Raju Raghavan , Danner Robert L. , Munson Peter J. , Logan Carolea , Rangel Zoila , Adelsberger Joseph W. , McLaughlin Mary , Adams Larry D. , Dalakas Marinos C. 
Published: November 2011

Purpose: In limited samples of valuable biological tissues, univariate ranking methods of microarray analyses often fail to show significant differences among expression profiles. In order to allow for hypothesis generation, novel statistical modeling systems can be greatly beneficial. The authors applied new statistical approaches to solve the issue of limited experimental data to generate new hypotheses in CD14+ cells of patients with HIV-related fatigue (HRF) and healthy controls. Methodology: We compared gene expression profiles of CD14+ cells of nucleoside reverse transcriptase inhibitor (NRTI)-treated HIV patients with low versus high fatigue to healthy controls ( n = 5 each). With novel Bayesian modeling procedures, the authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. Sparse association and liquid association networks further elucidated the possible biological pathways in which these genes are involved. Relevance for nursing practice: Genetic networks developed in a comprehensive Bayesian framework from small sample sizes allow nursing researchers to design future research approaches to address such issues as HRF. Implication for practice: The findings from this pilot study may take us one step closer to the development of useful biomarker targets for fatigue status. Specific and reliable tests are needed to diagnosis, monitor and treat fatigue and mitochondrial dysfunction.
Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis
Authors: Simpson Steve , Taylor Bruce , Dwyer Dominic E , Taylor Janette , Blizzard Leigh , Ponsonby Anne-Louise , Pittas Fotini , Dwyer Terence , van der Mei Ingrid 
Published: November 2011

Background: Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however. Methods: Prospective cohort of 198 persons with clinically definite MS, followed 2002–5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein–Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed-effects linear regression. Results: For the 145 persons with relapsing–remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend ( p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males. Discussion: These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing–remitting MS clinical course.
BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells
Authors: Jämsä Anne , Belda Oscar , Edlund Michael , Lindström Erik 
Published: November 2011

Abstract

Background
Accumulation of amyloid β-peptide (Aβ) in the plaques is one of the major pathological features in Alzheimer's disease (AD). Sequential cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE-1) and γ-secretase results in the formation of Aβ peptides. Preventing Aβ formation is believed to attenuate AD progression and BACE-1 and γ-secretase are thus attractive targets for AD drug development.

Methods
Combining BACE-1 and γ-secretase inhibition on Aβ secretion from human neuroblastoma SH-SY5Y cells was evaluated in this study. Secreted Aβ40 and Aβ42 levels were measured from SH-SY5Y cells stably transfected with APPwt or APPswe genes. A selective BACE inhibitor and the γ-secretase inhibitor LY450139 (semagacestat) were used to inhibit respective secretase.

Results
LY450139 increased Aβ40 and Aβ42 secretion from SH-SY5Y APPwt cells at low concentrations (by 60% at 3 nM) followed by subsequent inhibition at higher concentrations (IC50 90 nM). Washout studies showed that the Aβ increase evoked by 3 nM LY450139 was not due to enhanced cleavage following substrate accumulation but rather to activation of Aβ formation. By contrast, LY450139 inhibited Aβ formation from SH-SY5Y APPswe in a monophasic manner (IC50 18 nM). The BACE inhibitor per se inhibited Aβ secretion from both SH-SY5Y APPwt and SH-SY5Y APPswe cells with IC50s ranging between 7 - 18 nM and also prevented the increased Aβ secretion evoked by 3 nM LY450139. Combining the BACE inhibitor with higher inhibitory concentrations of LY450139 failed to demonstrate any clear additive or synergistic effects.

Conclusion
BACE-1 inhibition attenuates the Aβ increase evoked by LY450139 while not providing any obvious synergistic effects on LY450139-mediated inhibition.
Chipster: user-friendly analysis software for microarray and other high-throughput data
Authors: Kallio M Aleksi , Tuimala Jarno T , Hupponen Taavi , Klemelä Petri , Gentile Massimiliano , Scheinin Ilari , Koski Mikko , Käki Janne , Korpelainen Eija I 
Published: November 2011

AbstractBackgroundThe growth of high-throughput technologies such as microarrays and next generation sequencing has been accompanied by active research in data analysis methodology, producing new analysis methods at a rapid pace. While most of the newly developed methods are freely available, their use requires substantial computational skills. In order to enable non-programming biologists to benefit from the method development in a timely manner, we have created the Chipster software.ResultsChipster (http://chipster.csc.fi/) brings a powerful collection of data analysis methods within the reach of bioscientists via its intuitive graphical user interface. Users can analyze and integrate different data types such as gene expression, miRNA and aCGH. The analysis functionality is complemented with rich interactive visualizations, allowing users to select datapoints and create new gene lists based on these selections. Importantly, users can save the performed analysis steps as reusable, automatic workflows, which can also be shared with other users. Being a versatile and easily extendable platform, Chipster can be used for microarray, proteomics and sequencing data. In this article we describe its comprehensive collection of analysis and visualization tools for microarray data using three case studies.ConclusionsChipster is a user-friendly analysis software for high-throughput data. Its intuitive graphical user interface enables biologists to access a powerful collection of data analysis and integration tools, and to visualize data interactively. Users can collaborate by sharing analysis sessions and workflows. Chipster is open source, and the server installation package is freely available.
Cis-regulatory functions of overlapping HIF-1alpha/E-box/AP-1-like sequences of CD164
Authors: Tang Jingqun , Luo Zhaohui , Zhou Guangqian , Song Chao , Yu Fenglei , Xiang Juanjuan , Li Gang 
Published: November 2011

Abstract

Background
CD164 (also known as MGC-24v or endolyn) is a sialomucin which has been suggested to participate in regulating the proliferation, cell adhesion and differentiation of hematopoietic stem and progenitor cells. CD164 is also involved in the development of cancer. The functions of cis-regulatory elements of CD164 remain relatively unknown.

Methods
In this study, we investigated the function of cis-regulatory elements within the promoter of CD164. We fused the 5'-flanking region of CD164 to a luciferase reporter vector. The minimal promoter region was confirmed by luciferase reporter assay. Using in silico analysis, we found the presence of one HIF-1alpha (HIF-1A) motif (5_-RCGTG-3_) overlapping E-box (CACGTG) and two AP-1-like binding sites (CGCTGTCCC, GTCTGTTG), one of which is also overlapped with HIF-1alpha sequence. Dual-luciferase assay was performed to examine the transcriptional activity of AP-1 and HIF-1alpha of CD164 promoter. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to measure CD164 expression. Chromatin Immunoprecipitation was used to confirm the binding of HIF-1alpha and CD164.

Results
Co-transfection of c-jun, HIF-1alpha and minimal promoter region construct demonstrated that c-jun and HIF-1alpha bound the CD164 promoter and promoted CD164 expression. Hypoxia treatment also led to the up-regulation of CD164 expression. The mutation of overlapping sequences resulted in the reduced expression of CD164 induced by HIF-1alpha. Chromatin Immunoprecipitation demonstrated that the HIF-1alpha bound the minimal promoter region.

Conclusions
Determination of the optimal promoter region and transcription factors governing CD164 expression is useful in understanding CD164 functions. These results suggest that cis-regulatory elements of CD164 overlapping HIF-1alpha/E-box/AP-1-like sequences may play important regulatory roles.