bluuebunny/crossref_metadata_2025_split huggingface dataset:
TAK1 kinase signaling regulates embryonic angiogenesis by modulating endothelial cell survival and migration
Authors: Morioka Sho , Inagaki Maiko , Komatsu Yoshihiro , Mishina Yuji , Matsumoto Kunihiro , Ninomiya-Tsuji Jun 
Published: September 2012

Abstract
TGF-β activated kinase 1 (TAK1) is a mediator of various cytokine signaling pathways. Germline deficiency of Tak1 causes multiple abnormalities, including dilated blood vessels at midgestation. However, the mechanisms by which TAK1 regulates vessel formation have not been elucidated. TAK1 binding proteins 1 and 2 (TAB1 and TAB2) are activators of TAK1, but their roles in embryonic TAK1 signaling have not been determined. In the present study, we characterized mouse embryos harboring endothelial-specific deletions of Tak1, Tab1, or Tab2 and found that endothelial TAK1 and TAB2, but not TAB1, were critically involved in vascular formation. TAK1 deficiency in endothelial cells caused increased cell death and vessel regression at embryonic day 10.5 (E10.5). Deletion of TNF signaling largely rescued endothelial cell death in TAK1-deficient embryos at E10.5. However, embryos deficient in both TAK1 and TNF signaling still exhibited dilated capillary networks at E12.5. TAB2 deficiency caused reduced TAK1 activity, resulting in abnormal capillary blood vessels, similar to the compound deficiency of TAK1 and TNF signaling. Ablation of either TAK1 or TAB2 impaired cell migration and tube formation. Our results show that endothelial TAK1 signaling is important for 2 biologic processes in angiogenesis: inhibiting TNF-dependent endothelial cell death and promoting TNF-independent angiogenic cell migration.
Excess F-actin mechanically impedes mitosis leading to cytokinesis failure in X-linked neutropenia by exceeding Aurora B kinase error correction capacity
Authors: Moulding Dale A. , Moeendarbary Emad , Valon Leo , Record Julien , Charras Guillaume T. , Thrasher Adrian J. 
Published: September 2012

AbstractThe constitutively active mutant of the Wiskott-Aldrich Syndrome protein (CA-WASp) is the cause of X-linked neutropenia and is linked with genomic instability and myelodysplasia. CA-WASp generates abnormally high levels of cytoplasmic F-actin through dysregulated activation of the Arp2/3 complex leading to defects in cell division. As WASp has no reported role in cell division, we hypothesized that alteration of cell mechanics because of increased F-actin may indirectly disrupt dynamic events during mitosis. Inhibition of the Arp2/3 complex revealed that excess cytoplasmic F-actin caused increased cellular viscosity, slowed all phases of mitosis, and perturbed mitotic mechanics. Comparison of chromosome velocity to the cytoplasmic viscosity revealed that cells compensated for increased viscosity by up-regulating force applied to chromosomes and increased the density of microtubules at kinetochores. Mitotic abnormalities were because of overload of the aurora signaling pathway as subcritical inhibition of Aurora in CA-WASp cells caused increased cytokinesis failure, while overexpression reduced defects. These findings demonstrate that changes in cell mechanics can cause significant mitotic abnormalities leading to genomic instability, and highlight the importance of mechanical sensors such as Aurora B in maintaining the fidelity of hematopoietic cell division.
Prothrombin activation in blood coagulation: the erythrocyte contribution to thrombin generation
Authors: Whelihan Matthew F. , Zachary Vicentios , Orfeo Thomas , Mann Kenneth G. 
Published: September 2012

AbstractProthrombin activation can proceed through the intermediates meizothrombin or prethrombin-2. To assess the contributions that these 2 intermediates make to prothrombin activation in tissue factor (Tf)–activated blood, immunoassays were developed that measure the meizothrombin antithrombin (mTAT) and α-thrombin antithrombin (αTAT) complexes. We determined that Tf-activated blood produced both αTAT and mTAT. The presence of mTAT suggested that nonplatelet surfaces were contributing to approximately 35% of prothrombin activation. Corn trypsin inhibitor–treated blood was fractionated to yield red blood cells (RBCs), platelet-rich plasma (PRP), platelet-poor plasma (PPP), and buffy coat. Compared with blood, PRP reconstituted with PPP to a physiologic platelet concentration showed a 2-fold prolongation in the initiation phase and a marked decrease in the rate and extent of αTAT formation. Only the addition of RBCs to PRP was capable of normalizing αTAT generation. FACS on glycophorin A–positive cells showed that approximately 0.6% of the RBC population expresses phosphatidylserine and binds prothrombinase (FITC Xa·factor Va). These data indicate that RBCs participate in thrombin generation in Tf-activated blood, producing a membrane that supports prothrombin activation through the meizothrombin pathway.
IL-36 signaling amplifies Th1 responses by enhancing proliferation and Th1 polarization of naive CD4+ T cells
Authors: Vigne Solenne , Palmer Gaby , Martin Praxedis , Lamacchia Céline , Strebel Deborah , Rodriguez Emiliana , Olleros Maria L. , Vesin Dominique , Garcia Irene , Ronchi Francesca , Sallusto Federica , Sims John E. , Gabay Cem 
Published: September 2012

AbstractThe interleukin-1 (IL-1) superfamily of cytokines comprises a set of pivotal mediators of inflammation. Among them, the action of IL-36 cytokines in immune responses has remained elusive. In a recent study, we demonstrated a direct effect of IL-36 on immune cells. Here we show that, among T cells, the IL-36 receptor is predominantly expressed on naive CD4+ T cells and that IL-36 cytokines act directly on naive T cells by enhancing both cell proliferation and IL-2 secretion. IL-36β acts in synergy with IL-12 to promote Th1 polarization and IL-36 signaling is also involved in mediating Th1 immune responses to Bacillus Calmette-Guerin infection in vivo. Our findings point toward a critical function of IL-36 in the priming of Th1 cell responses in vitro, and in adaptive immunity in a model of mycobacterial infection in vivo.
Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation
Authors: Smith Stephanie A. , Choi Sharon H. , Collins Julie N. R. , Travers Richard J. , Cooley Brian C. , Morrissey James H. 
Published: September 2012

AbstractInorganic polyphosphates are linear polymers of orthophosphate that modulate blood clotting and inflammation. Polyphosphate accumulates in infectious microorganisms and is secreted by activated platelets; long-chain polyphosphate in particular is an extremely potent initiator of the contact pathway, a limb of the clotting cascade important for thrombosis but dispensable for hemostasis. Polyphosphate inhibitors therefore might act as novel antithrombotic/anti-inflammatory agents with reduced bleeding side effects. Antipolyphosphate antibodies are unlikely because of polyphosphate's ubiquity and simple structure; and although phosphatases such as alkaline phosphatase can digest polyphosphate, they take time and may degrade other biologically active molecules. We now identify a panel of polyphosphate inhibitors, including cationic proteins, polymers, and small molecules, and report their effectiveness in vitro and in vivo. We also compare their effectiveness against the procoagulant activity of RNA. Polyphosphate inhibitors were antithrombotic in mouse models of venous and arterial thrombosis and blocked the inflammatory effect of polyphosphate injected intradermally in mice. This study provides proof of principle for polyphosphate inhibitors as antithrombotic/anti-inflammatory agents in vitro and in vivo, with a novel mode of action compared with conventional anticoagulants.
A tissue-specific chromatin loop activates the erythroid ankyrin-1 promoter
Authors: Yocum Ashley O. , Steiner Laurie A. , Seidel Nancy E. , Cline Amanda P. , Rout Emily D. , Lin Jolinta Y. , Wong Clara , Garrett Lisa J. , Gallagher Patrick G. , Bodine David M. 
Published: September 2012

Abstract
The human ankyrin-1 gene (ANK1) contains 3 tissue-specific alternative promoters. We have shown previously that the erythroid-specific ankyrin 1 (ANK1E) core promoter contains a 5′ DNase I hypersensitive site (HS) with barrier insulator function that prevents gene silencing in vitro and in vivo. Mutations in the ANK1E barrier region lead to decreased ANK1 mRNA levels and hereditary spherocytosis. In this report, we demonstrate a second ANK1E regulatory element located in an adjacent pair of DNase I HS located 5.6 kb 3′ of the ANK1E promoter at the 3′ boundary of an erythroid-specific DNase I–sensitive chromatin domain. The 3′ regulatory element exhibits enhancer activity in vitro and in transgenic mice, and it has the histone modifications associated with an enhancer element. One of the ANK1E 3′HS contains an NF-E2 binding site that is required for enhancer function. We show that a chromatin loop brings the 3′ enhancer and NF-E2 into proximity with the 5′ barrier region including the ANK1E core promoter. These observations demonstrate a model for the tissue-specific activation of alternative promoters that may be applicable to the ∼ 30% of mammalian genes with alternative promoters that exhibit distinct expression patterns.
Alterations of microbiota in urine from women with interstitial cystitis
Authors: Siddiqui Huma , Lagesen Karin , Nederbragt Alexander J , Jeansson Stig L , Jakobsen Kjetill S 
Published: September 2012

Abstract

Background
Interstitial Cystitis (IC) is a chronic inflammatory condition of the bladder with unknown etiology. The aim of this study was to characterize the microbial community present in the urine from IC female patients by 454 high throughput sequencing of the 16S variable regions V1V2 and V6. The taxonomical composition, richness and diversity of the IC microbiota were determined and compared to the microbial profile of asymptomatic healthy female (HF) urine.

Results
The composition and distribution of bacterial sequences differed between the urine microbiota of IC patients and HFs. Reduced sequence richness and diversity were found in IC patient urine, and a significant difference in the community structure of IC urine in relation to HF urine was observed. More than 90% of the IC sequence reads were identified as belonging to the bacterial genus Lactobacillus, a marked increase compared to 60% in HF urine.

Conclusion
The 16S rDNA sequence data demonstrates a shift in the composition of the bacterial community in IC urine. The reduced microbial diversity and richness is accompanied by a higher abundance of the bacterial genus Lactobacillus, compared to HF urine. This study demonstrates that high throughput sequencing analysis of urine microbiota in IC patients is a powerful tool towards a better understanding of this enigmatic disease.
Internet-based psychoeducation for bipolar disorder: a qualitative analysis of feasibility, acceptability and impact
Authors: Poole Ria , Simpson Sharon A , Smith Daniel J 
Published: September 2012

Abstract

Background
In a recent exploratory randomised trial we found that a novel, internet-based psychoeducation programme for bipolar disorder (Beating Bipolar) was relatively easy to deliver and had a modest effect on psychological quality of life. We sought to explore the experiences of participants with respect to feasibility, acceptability and impact of Beating Bipolar.

Methods
Participants were invited to take part in a semi-structured interview. Thematic analysis techniques were employed; to explore and describe participants’ experiences, the data were analysed for emerging themes which were identified and coded.

Results
The programme was feasible to deliver and acceptable to participants where they felt comfortable using a computer. It was found to impact upon insight into illness, health behaviour, personal routines and positive attitudes towards medication. Many participants regarded the programme as likely to be most beneficial for those recently diagnosed.

Conclusions
An online psychoeducation package for bipolar disorder, such as Beating Bipolar, is feasible and acceptable to patients, has a positive impact on self-management behaviours and may be particularly suited to early intervention. Alternative (non-internet) formats should also be made available to patients.
Development of a diagnostic method for neosporosis in cattle using recombinant Neospora caninum proteins
Authors: Dong Jinhua , Otsuki Takahiro , Kato Tatsuya , Park Enoch Y 
Published: September 2012

AbstractBackgroundNeosporosis is an infectious disease primarily of cattle and dogs, caused by intracellular parasite,Neospora caninum. Neosporosis appears to be a major cause of abortion in dairy cattle worldwide and causes to huge economic loss to dairy industry.ResultsRecombinant surface associated antigen 1 (NcSAG1), NcSAG1 related sequence 2 (NcSRS2) and the dense granule antigen 2 (NcGRA2) ofN. caninumwere expressed either in silkworm or inEscherichia coliand purified. The purified recombinant proteins bound to theN. caninum-specific antibodies in serum samples from infected cattle as revealed by an enzyme-linked immunosorbent assay (ELISA). By co-immobilizing these recombinant proteins, a novel indirect ELISA was developed for detection of neosporosis. With the use of 32 serum samples, comprising 12 positive serum samples and 20 negative serum samples, the sensitivity and specificity of the assay were found to be 91.7 and 100%, respectively. Seventy-two serum samples from dairy farms were also tested and one was diagnosed with neosporasis with both this method and a commercial assay.ConclusionsA diagnostic method employing recombinant proteins ofN. caninumwas developed. The method showed high sensitivity and specificity. Diagnostic test with field serum samples suggested its applicability to the practical diagnosis of neosporosis.
The German adaptation of the Cambridge pulmonary hypertension outcome review (CAMPHOR)
Authors: Cima Katharina , Twiss James , Speich Rudolf , McKenna Stephen P , Grünig Ekkehard , Kähler Christian M , Ehlken Nicola , Treder Ursula , Crawford Sigrid R , Huber Lars C , Ulrich Silvia 
Published: September 2012

Abstract

Background
Individuals with precapillary pulmonary hypertension (PH) experience severely impaired quality of life. A disease-specific outcome measure for PH, the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was developed and validated in the UK and subsequently adapted for use in additional countries. The aim of this study was to translate and assess the reliability and validity of the CAMPHOR for German-speaking populations.

Methods
Three main adaptation stages involved; translation (employing bilingual and lay panels), cognitive debriefing interviews with patients and validation (assessment of the adaptation’s psychometric properties). The psychometric evaluation included 107 patients with precapillary PH (60 females; age mean (standard deviation) 60 (15) years) from 3 centres in Austria, Germany and Switzerland.

Results
No major problems were found with the translation process with most items easily rendered into acceptable German. Participants in the cognitive debriefing interviews found the questionnaires relevant, comprehensive and easy to complete. Psychometric analyses showed that the adaptation was successful. The three CAMPHOR scales (symptoms, activity limitations and quality of life) had excellent test-retest reliability correlations (Symptoms = 0.91; Activity limitations = 0.91; QoL = 0.90) and internal consistency (Symptoms = 0.94; Activity limitations = 0.93; QoL = 0.94). Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the CAMPHOR scales. The CAMPHOR adaptation also showed known group validity in its ability to distinguish between participants based on perceived general health, perceived disease severity, oxygen use and NYHA classification.

Conclusions
The CAMPHOR has been shown to be valid and reliable in the German population and is recommend for use in clinical practice.
A 21-day Daniel fast with or without krill oil supplementation improves anthropometric parameters and the cardiometabolic profile in men and women
Authors: Trepanowski John F , Kabir Mohammad M , Alleman Rick J , Bloomer Richard J 
Published: September 2012

Abstract

Background
The Daniel Fast is a vegan diet that prohibits the consumption of animal products, refined foods, white flour, preservatives, additives, sweeteners, flavorings, caffeine, and alcohol. Following this dietary plan for 21 days has been demonstrated to improve blood pressure, LDL-C, and certain markers of oxidative stress, but it has also been shown to lower HDL-C. Krill oil supplementation has been shown to increase HDL-C.

Methods
We investigated the effects of following a Daniel Fast dietary plan with either krill oil supplementation (2 g/day) or placebo supplementation (coconut oil; 2 g/day) for 21 days. The subjects in this study (12 men and 27 women) were heterogeneous with respect to body mass index (BMI) (normal weight, overweight, and obese), blood lipids (normolipidemic and hyperlipidemic), blood glucose (normal fasting glucose, impaired fasting glucose, and type 2 diabetic), and blood pressure (normotensive and hypertensive).

Results
Krill oil supplementation had no effect on any outcome measure (all p > 0.05), and so the data from the krill oil group and the placebo group were collapsed and analyzed to examine the effects of following a 21-day Daniel Fast. Significant reductions were observed in LDL-C (100.6 ± 4.3 mg/dL vs. 80.0 ± 3.7 mg/dL), the LDL:HDL ratio (2.0 ± 0.1 vs. 1.7 ± 0.1), fasting blood glucose (101.4 ± 7.5 mg/dL vs. 91.7 ± 3.4 mg/dL), fasting blood insulin (7.92 ± 0.80 μU/mL vs. 5.76 ± 0.59 μU/mL), homeostasis model assessment of insulin resistance (HOMA-IR) (2.06 ± 0.30 vs. 1.40 ± 0.21), systolic BP (110.7 ± 2.2 mm Hg vs. 105.5 ± 1.7 mm Hg), and body weight (74.1 ± 2.4 kg vs. 71.5 ± 2.3 kg) (all p < 0.05).

Conclusion
Following a Daniel Fast dietary plan improves a variety of cardiometabolic parameters in a wide range of individuals in as little as 21 days, and these improvements are unaffected by krill oil supplementation.

Trial registration
Clinicaltrial.govNCT01378767
Cervicothoracic spinal cord and pontomedullary injury secondary to high-voltage electrocution: a case report
Authors: Johl Harpreet K , Olshansky Adel , Beydoun Said R , Rison Richard A 
Published: September 2012

Abstract

Introduction
High-voltage electrical injuries are uncommonly reported and may predispose to both immediate and delayed neurologic complications.

Case presentation
We report the case of a 43-year-old Caucasian man who experienced a high-voltage electrocution injury resulting in ischemic myelopathy and secondary paraparesis.

Conclusion
High-voltage electrocution injuries are a serious problem with potential for both immediate and delayed neurologic sequelae. The existing literature regarding effective treatment of neurologic complications is limited. Long-term follow-up and multidisciplinary management of these patients is required.
Giant hydatid cyst of the liver with a retroperitoneal growth: a case report
Authors: Ettorre Giuseppe Maria , Vennarecci Giovanni , Santoro Roberto , Laurenzi Andrea , Ceribelli Cecilia , Di Cintio Antonio , Rizzi Elisa Busi , Antonini Mario 
Published: September 2012

Abstract

Introduction
Hydatid disease is a helminthic anthropozoonosis with worldwide distribution due to the close associations among sheep, dogs, and humans. It can occur almost anywhere in the body with a variety of imaging features, which may change according to the growth stage, associated complications, and affected tissues. A definitive diagnosis requires a combination of imaging, serologic and immunologic studies. Ultrasonography, computed tomography and magnetic resonance imaging are highly accurate in detecting a hepatic hydatid cyst. However, hepatic hydatid cysts in an unusual location and/or of an unusual dimension, with atypical imaging findings, may complicate the differential diagnosis. Surgical treatment remains the best treatment.

Case presentation
We describe an unusual case of a giant hydatid cyst, with exophytic growth from the right lobe of the liver of a 55-year-old Egyptian man. The cyst was strongly adhered to his ipsilateral kidney, which was displaced in a downwards and anterior direction, close to his abdominal wall, simulating a retroperitoneal origin. This atypical growth raised doubts about the most appropriate surgical approach. Magnetic resonance imaging easily clarified the origin of the cyst as our patient’s liver, allowing accurate surgical planning.

Conclusion
Rarely, hydatid cysts can reach an extremely large size without any additional symptoms. Giant cysts need radical therapy because they might lead to perforation and anaphylaxis in some patients. Magnetic resonance imaging is very useful in the study of hydatid disease because of its capacity to allow a large field of view, multiplanar acquisition, and high contrast resolution. In some unusual hepatic presentations, magnetic resonance imaging can be used to determine the correct anatomical relationships.
Identification of genes with a correlation between copy number and expression in gastric cancer
Authors: Cheng Lei , Wang Ping , Yang Sheng , Yang Yanqing , Zhang Qing , Zhang Wen , Xiao Huasheng , Gao Hengjun , Zhang Qinghua 
Published: September 2012

Abstract

Background
To elucidate gene expression associated with copy number changes, we performed a genome-wide copy number and expression microarray analysis of 25 pairs of gastric tissues.

Methods
We applied laser capture microdissection (LCM) to obtain samples for microarray experiments and profiled DNA copy number and gene expression using 244K CGH Microarray and Human Exon 1.0 ST Microarray.

Results
Obviously, gain at 8q was detected at the highest frequency (70%) and 20q at the second (63%). We also identified molecular genetic divergences for different TNM-stages or histological subtypes of gastric cancers. Interestingly, the C20orf11 amplification and gain at 20q13.33 almost separated moderately differentiated (MD) gastric cancers from poorly differentiated (PD) type. A set of 163 genes showing the correlations between gene copy number and expression was selected and the identified genes were able to discriminate matched adjacent noncancerous samples from gastric cancer samples in an unsupervised two-way hierarchical clustering. Quantitative RT-PCR analysis for 4 genes (C20orf11, XPO5, PUF60, and PLOD3) of the 163 genes validated the microarray results. Notably, some candidate genes (MCM4 and YWHAZ) and its adjacent genes such as PRKDC, UBE2V2, ANKRD46, ZNF706, and GRHL2, were concordantly deregulated by genomic aberrations.

Conclusions
Taken together, our results reveal diverse chromosomal region alterations for different TNM-stages or histological subtypes of gastric cancers, which is helpful in researching clinicopathological classification, and highlight several interesting genes as potential biomarkers for gastric cancer.