bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative splicing of the human gene SYBL1 modulates protein domain architecture of longin VAMP7/TI-VAMP, showing both non-SNARE and synaptobrevin-like isoforms
Authors: Vacca Marcella , Albania Lara , Ragione Floriana Della , Carpi Andrea , Rossi Valeria , Strazzullo Maria , De Franceschi Nicola , Rossetto Ornella , Filippini Francesco , D'Esposito Maurizio 
Published: May 2011

AbstractBackgroundThe control of intracellular vesicle trafficking is an ideal target to weigh the role of alternative splicing in shaping genomes to make cells. Alternative splicing has been reported for several SolubleN-ethylmaleimide-sensitive factor Attachment protein REceptors of the vesicle (v-SNAREs) or of the target membrane (t-SNARES), which are crucial to intracellular membrane fusion and protein and lipid traffic in Eukaryotes. However, splicing has not yet been investigated in Longins, i.e. the most widespread v-SNAREs. Longins are essential in Eukaryotes and prototyped by VAMP7, Sec22b and Ykt6, sharing a conserved N-terminal Longin domain which regulates membrane fusion and subcellular targeting. Human VAMP7/TI-VAMP, encoded by gene SYBL1, is involved in multiple cell pathways, including control of neurite outgrowth.ResultsAlternative splicing of SYBL1 by exon skipping events results in the production of a number of VAMP7 isoforms. In-frame or frameshift coding sequence modifications modulate domain architecture of VAMP7 isoforms, which can lack whole domains or domain fragments and show variant or extra domains. Intriguingly, two main types of VAMP7 isoforms either share the inhibitory Longin domain and lack the fusion-promoting SNARE motif, or vice versa. Expression analysis in different tissues and cell lines, quantitative real time RT-PCR and confocal microscopy analysis of fluorescent protein-tagged isoforms demonstrate that VAMP7 variants have different tissue specificities and subcellular localizations. Moreover, design and use of isoform-specific antibodies provided preliminary evidence for the existence of splice variants at the protein level.ConclusionsPrevious evidence on VAMP7 suggests inhibitory functions for the Longin domain and fusion/growth promoting activity for the Δ-longin molecule. Thus, non-SNARE isoforms with Longin domain and non-longin SNARE isoforms might have somehow opposite regulatory functions. When considering splice variants as "natural mutants", evidence on modulation of subcellular localization by variation in domain combination can shed further light on targeting determinants. Although further work will be needed to characterize identified variants, our data might open the route to unravel novel molecular partners and mechanisms, accounting for the multiplicity of functions carried out by the different members of the Longin proteins family.
Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target
Authors: Collison Adam , Herbert Cristan , Siegle Jessica S , Mattes Joerg , Foster Paul S , Kumar Rakesh K 
Published: May 2011

Abstract

Background
The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Relatively little is known, however, about the role of miRNAs in inflammatory and immunologically-driven disorders. In a mouse model, we have previously shown that miRNAs are potentially important therapeutic targets in allergic asthma, because inhibition of miR-126, one of a small subset of miRNAs upregulated in the airway wall, effectively suppressed Th2-driven airway inflammation and other features of asthma. In the present study, we extended investigation of the therapeutic potential of miRNA inhibition to our well-established model of chronic asthma.

Methods
Female BALB/c mice were systemically sensitised with ovalbumin (OVA) and chronically challenged with low mass concentrations of aerosolised OVA for up to 6 weeks. Airway tissue was obtained by blunt dissection and RNA was isolated for miRNA profiling. On the basis of the results obtained, animals were subsequently treated with either an antagomir to miR-126 (ant-miR-126) or a scrambled control antagomir once weekly during the 6 weeks of chronic challenge, and the effects on airway inflammation and remodelling were assessed using established morphometric techniques.

Results
Compared to naïve mice, there was selective upregulation of a modest number of miRNAs, notably miR-126, in the airway wall tissue of chronically challenged animals. The relative increase was maximal after 2 weeks of inhalational challenge and subsequently declined to baseline levels. Compared to treatment with the scrambled control, ant-miR-126 significantly reduced recruitment of intraepithelial eosinophils, but had no effect on the chronic inflammatory response, or on changes of airway remodelling.

Conclusions
In this model of chronic asthma, there was an initial increase in expression of a small number of miRNAs in the airway wall, notably miR-126. However, this later declined to baseline levels, suggesting that sustained changes in miRNA may not be essential for perpetuation of chronic asthma. Moreover, inhibition of miR-126 by administration of an antagomir suppressed eosinophil recruitment into the airways but had no effect on chronic inflammation in the airway wall, or on changes of remodelling, suggesting that multiple miRNAs are likely to regulate the development of these lesions.
Multi tyrosine kinase inhibitor dasatinib as novel cause of severe pre-capillary pulmonary hypertension?
Authors: Hennigs Jan K , Keller Gunhild , Baumann Hans Jörg , Honecker Friedemann , Kluge Stefan , Bokemeyer Carsten , Brümmendorf Tim H , Klose Hans 
Published: May 2011

Abstract

Background
Pulmonary hypertension (PH) is a life-threatening disease with poor prognosis. Encouraging efforts have been made to target the main vasoproliferative aspects of the disease. Promising emerging therapeutics are tyrosine kinase inhibitors such as imatinib.

Case presentation
Here, we discuss the relevance of previously published cases and add another well-characterised patient who developed pre-capillary PH under long-term therapy with the multi-tyrosine kinase inhibitor dasatinib approved for therapy of chronic myeloic leukaemia (CML) and Philadelphia chromosome positive acute lymphocytic leukaemia (mean time of all patients on dasatinib: 26 months). Hence, we discuss the possibility of dasatinib itself causing PH after long-term therapy and turn specialist's attention to this possible severe side effect.
At present, the true incidence of dasatinib-associated PH remains illusive and systematic data regarding haemodynamics are missing.

Conclusion
We therefore recommend systematic screening of dasatinib-treated patients for pulmonary hypertension and subsequent collection of haemodynamic data.
Screening of soy protein-derived hypotriglyceridemic di-peptides in vitro and in vivo
Authors: Inoue Nao , Nagao Koji , Sakata Kotaro , Yamano Naomi , Gunawardena Pathma Elgoda Ranawakage , Han Seo-Young , Matsui Toshiro , Nakamori Toshihiro , Furuta Hitoshi , Takamatsu Kiyoharu , Yanagita Teruyoshi 
Published: May 2011

Abstract

Background
Soy protein and soy peptides have attracted considerable attention because of their potentially beneficial biological properties, including antihypertensive, anticarcinogenic, and hypolipidemic effects. Although soy protein isolate contains several bioactive peptides that have distinct physiological activities in lipid metabolism, it is not clear which peptide sequences are responsible for the triglyceride (TG)-lowering effects. In the present study, we investigated the effects of soy protein-derived peptides on lipid metabolism, especially TG metabolism, in HepG2 cells and obese Otsuka Long-Evans Tokushima fatty (OLETF) rats.

Results
In the first experiment, we found that soy crude peptide (SCP)-LD3, which was prepared by hydrolyze of soy protein isolate with endo-type protease, showed hypolipidemic effects in HepG2 cells and OLETF rats. In the second experiment, we found that hydrophilic fraction, separated from SCP-LD3 with hydrophobic synthetic absorbent, revealed lipid-lowering effects in HepG2 cells and OLETF rats. In the third experiment, we found that Fraction-C (Frc-C) peptides, fractionated from hydrophilic peptides by gel permeation chromatography-high performance liquid chromatography, significantly reduced TG synthesis and apolipoprotein B (apoB) secretion in HepG2 cells. In the fourth experiment, we found that the fraction with 0.1% trifluoroacetic acid, isolated from Frc-C peptides by octadecylsilyl column chromatography, showed hypolipidemic effects in HepG2 cells. In the final experiment, we found that 3 di-peptides, Lys-Ala, Val-Lys, and Ser-Tyr, reduced TG synthesis, and Ser-Tyr additionally reduced apoB secretion in HepG2 cells.

Conclusion
Novel active peptides with TG-lowering effects from soy protein have been isolated.
Differences and similarities of postprandial lipemia in rodents and humans
Authors: Panzoldo Natalia B , Urban Aline , Parra Eliane S , Oliveira Rogério , Zago Vanessa S , da Silva Lívia R , de Faria Eliana C 
Published: May 2011

Abstract

Background
The rat has been a mainstay of physiological and metabolic research, and more recently mice. This study aimed at characterizing the postprandial triglyceride profile of two members of the Muridae family: the Wistar rats (Rattus norvegicus albinus) and C57BL/6 mice (Mus musculus) plus comparing them to the profile obtained in humans.

Methods
Thirty-one male and twelve female Wistar rats, ten C57BL/6 male and nine female mice received a liquid meal containing fat (17%), protein (4%) and carbohydrates (4%), providing 2 g fat/Kg. Thirty-one men and twenty-nine women received a standardized liquid meal containing fat (25%), dextromaltose (55%), protein (14%), and vitamins and minerals (6%), and providing 40 g of fat per square meter of body surface. Serial blood samples were collected at 2, 4, 6, 8 and 10 h after the ingestion in rats, at 1, 2, 3, 4, 5 and 6 h in mice and in humans at 2, 4, 6 and 8 h. Wilcoxon and Mann-Whitney tests were used.

Results/Discussion
The triglyceride responses were evaluated after the oral fat loads. Fasting and postprandial triglyceridemia were determined sequentially in blood sample. AUC, AUIC, AR, RR and late peaks were determined.

Conclusions
Rats are prone to respond in a pro-atherogenic manner. The responses in mice were closer to the ones in healthy men. This study presents striking differences in postprandial triglycerides patterns between rats and mice not correlated to baseline triglycerides, the animal baseline body weight or fat load in all animal groups.
LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells
Authors: Kaufmann Larissa , Marinescu Gabriela , Nazarenko Irina , Thiele Wilko , Oberle Carolin , Sleeman Jonathan , Blattner Christine 
Published: May 2011

AbstractBackgroundThe incidence of cancer in patients with neurological diseases, who have been treated with LiCl, is below average. LiCl is a well-established inhibitor of Glycogen synthase kinase-3, a kinase that controls several cellular processes, among which is the degradation of the tumour suppressor protein p53. We therefore wondered whether LiCl induces p53-dependent cell death in cancer cell lines and experimental tumours.ResultsHere we show that LiCl induces apoptosis of tumour cells bothin vitroandin vivo. Cell death was accompanied by cleavage of PARP and Caspases-3, -8 and -10. LiCl-induced cell death was not dependent on p53, but was augmented by its presence. Treatment of tumour cells with LiCl strongly increased TNF-α and FasL expression. Inhibition of TNF-α induction using siRNA or inhibition of FasL binding to its receptor by the Nok-1 antibody potently reduced LiCl-dependent cleavage of Caspase-3 and increased cell survival. Treatment of xenografted rats with LiCl strongly reduced tumour growth.ConclusionsInduction of cell death by LiCl supports the notion that GSK-3 may represent a promising target for cancer therapy. LiCl-induced cell death is largely independent of p53 and mediated by the release of TNF-α and FasL.Key words: LiCl, TNF-α, FasL, apoptosis, GSK-3, FasL
Mutation of the elongin C binding domain of human respiratory syncytial virus non-structural protein 1 (NS1) results in degradation of NS1 and attenuation of the virus
Authors: Straub Claire P , Lau Wei-Har , Preston Faith M , Headlam Madeleine J , Gorman Jeffery J , Collins Peter L , Spann Kirsten M 
Published: May 2011

Abstract

Background
Human respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in the paediatic population, immunocompromised individuals and the elderly worldwide. However, despite global efforts over the past several decades there are no commercially available vaccines. RSV encodes 2 non-structural proteins, NS1 and NS2, that are type I interferon antagonists. RSV restricts type I interferon signaling and the expression of antiviral genes by degrading STAT2. It has been proposed that NS1 binds to elongin C to form a ubiquitin ligase (E3) complex that targets STAT2 for ubiquitination and proteosomal degradation.

Results
Here, we have engineered a live recombinant RSV in which the 3 consensus amino acids of the NS1 elongin C binding domain have been replaced with alanine (NS1F-ELCmut). Mutation of this region of NS1 resulted in attenuation of RSV replication in A549 cells to levels similar to that observed when the NS1 gene is completely deleted (ΔNS1). This mutation also resulted in moderate attenuation in Vero cells. Attenuation was correlated to intracellular degradation of the mutated NS1 protein. Time course analysis showed that mutant NS1 protein accumulated in cytoplasmic bodies that contained the lysosomal marker LAMP1. However lack of cleavage of LC3 suggested that autophagy was not involved. Induction of IFN-β mRNA expression also was observed in association with the degradation of NS1 protein and attenuation of viral growth.

Conclusions
These results indicate that the elongin C binding region of NS1 is crucial for survival of the protein and that disruption of this region results in the degradation of NS1 and restriction of RSV replication.
Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy
Authors: Oksuz Didem C , Prestwich Robin J , Carey Brendan , Wilson Stuart , Senocak Mustafa S , Choudhury Ananya , Dyker Karen , Coyle Catherine , Sen Mehmet 
Published: May 2011

Abstract

Background
To establish recurrence patterns among locally advanced head and neck non-nasopharyngeal squamous cell carcinoma (HNSCC) patients treated with radical (chemo-) radiotherapy and to correlate the sites of loco-regional recurrence with radiotherapy doses and target volumes

Method
151 locally advanced HNSCC patients were treated between 2004-2005 using radical three-dimensional conformal radiotherapy. Patients with prior surgery to the primary tumour site were excluded. The sites of locoregional relapses were correlated with radiotherapy plans by the radiologist and a planning dosimetrist.

Results
Median age was 59 years (range:34-89). 35 patients had stage III disease, 116 patients had stage IV A/B. 36 patients were treated with radiotherapy alone, 42 with induction chemotherapy, 63 with induction and concomitant chemoradiotherapy and 10 concomitant chemoradiotherapy. Median follow-up was 38 months (range 3-62). 3-year cause specific survival was 66.8%. 125 of 151 (82.8%) achieved a complete response to treatment. Amongst these 125 there were 20 local-regional recurrence, comprising 8 local, 5 regional and 7 simultaneous local and regional; synchronous distant metastases occurred in 7 of the 20. 9 patients developed distant metastases in the absence of locoregional failure. For the 14 local recurrences with planning data available, 12 were in-field, 1 was marginal, and 1 was out-of-field. Of the 11 regional failures with planning data available, 7 were in-field, 1 was marginal and 3 were out-of-field recurrences.

Conclusion
The majority of failures following non-surgical treatment for locally advanced HNSCC were loco-regional, within the radiotherapy target volume. Improving locoregional control remains a high priority.
Delayed endovascular treatment of descending aorta stent graft collapse in a patient treated for post- traumatic aortic rupture: a case report
Authors: Nano Giovanni , Mazzaccaro Daniela , Malacrida Giovanni , Occhiuto Maria Teresa , Stegher Silvia , Tealdi Domenico G 
Published: May 2011

Abstract

Background
We report a case of delayed endovascular correction of graft collapse occurred after emergent Thoracic Endovascular Aortic Repair (TEVAR) for traumatic aortic isthmus rupture.

Case presentation
In 7th post-operative day after emergent TEVAR for traumatic aortic isthmus rupture (Gore TAG® 28-150), a partial collapse of the endoprosthesis at the descending tract occurred, with no signs of visceral ischemia. Considering patient's clinical conditions, the graft collapse wasn't treated at that time. When general conditions allowed reintervention, the patient refused any new treatment, so he was discharged.
Four months later the patient complainted for severe gluteal and sural claudication, erectile disfunction and abdominal angina; endovascular correction was performed. At 18 months the graft was still patent.

Discussion and Conclusion
Graft collapse after TEVAR is a rare event, which should be detected and treated as soon as possible. Delayed correction of this complication can be lethal due to the risk of visceral ischemia and limbs loss.
Insurance type and sepsis-associated hospitalizations and sepsis-associated mortality among US adults: A retrospective cohort study
Authors: O'Brien James M , Lu Bo , Ali Naeem A , Levine Deborah A , Aberegg Scott K , Lemeshow Stanley 
Published: May 2011

Abstract
Introduction
Socio-demographic and clinical factors associated with increased sepsis risk, including older age, non-white race and specific co-morbidities, are more common among patients with Medicare or Medicaid or no health insurance. We hypothesized that patients with Medicare and/or Medicaid or without health insurance have a higher risk of sepsis-associated hospitalization or sepsis-associated death than those with private health insurance.

Methods
We performed a retrospective cohort study of records from the 2003 Nationwide Inpatient Sample. We stratified the study cohort by Medicare age-qualification (18 to 64 and 65+ years old). We examined the association between insurance category and sepsis diagnosis and death among admissions involving sepsis. We used validated diagnostic codes to determine the presence of sepsis, co-morbidities and organ dysfunction and to provide risk-adjustment.

Results
Among patients 18 to 64 years old, those with Medicaid (adjusted odds ratio (AOR) 1.50), Medicare (AOR 1.96), Medicaid + Medicare (AOR 2.22) and the uninsured (AOR 1.18) had significantly higher risk-adjusted odds of a sepsis-associated admission than those with private insurance (all P < 0.0001). Those with Medicaid (AOR 1.17, P < 0.001) and those without insurance (AOR 1.45, P < 0.001) also had significantly higher adjusted odds of sepsis-associated hospital mortality than those with private insurance. Among those 65+ years old, those with Medicaid (AOR 1.43), Medicare alone (AOR 1.13) or Medicaid + Medicare (AOR 1.62) had significantly higher risk-adjusted odds of sepsis-associated admission than those with private insurance and Medicare (all P < 0.0001). Among sepsis patients 65+, uninsured patients had significantly higher risk-adjusted odds (AOR 1.45, P = 0.0048) and those with Medicare alone had significantly lower risk-adjusted odds (AOR 0.92, P = 0.0072) of hospital mortality than those with private insurance and Medicare. Lack of health insurance remained associated with sepsis-associated mortality after stratification of hospitals into quartiles based on rates of sepsis-associated admissions or mortality in both age strata.

Conclusions
Risks of sepsis-associated hospitalization and sepsis-associated death vary by insurance. These increased risks were not fully explained by the available socio-demographic factors, co-morbidities or hospital rates of sepsis-related admissions or deaths.
Nodal Status and Clinical Outcomes in a Large Cohort of Patients With Triple-Negative Breast Cancer
Authors: Hernandez-Aya Leonel F. , Chavez-MacGregor Mariana , Lei Xiudong , Meric-Bernstam Funda , Buchholz Thomas A. , Hsu Limin , Sahin Aysegul A. , Do Kim-Anh , Valero Vicente , Hortobagyi Gabriel N. , Gonzalez-Angulo Ana Maria 
Published: May 2011

Purpose To evaluate the clinical outcomes and relationship between tumor size, lymph node status, and prognosis in a large cohort of patients with confirmed triple receptor–negative breast cancer (TNBC). Patients and Methods We reviewed 1,711 patients with TNBC diagnosed between 1980 and 2009. Patients were categorized by tumor size and nodal status. Kaplan-Meier product limit method was used to calculate overall survival (OS) and relapse-free survival (RFS). A Sidak adjustment was used for multiple group comparisons. Cox proportional hazards models were fit to determine the association of tumor size and nodal status with survival outcomes after adjustment for other patient and disease characteristics. Results Median age was 48 years (range, 21 to 87 years). At a median follow-up of 53 months (range, 0.7 to 317 months), there were 614 deaths and 747 recurrences. The 5-year OS was 80% for node-negative patients (N0), 65% for one to three positive lymph nodes (N1), 48% for four to nine positive lymph nodes (N2), and 44% for ≥ 10 positive lymph nodes (N3; P < .0001). The 5-year RFS rates were 67% for N0, 52% for N1, 36% for N2, and 33% for N3 (P < .0001). Pairwise comparison by nodal status showed that when comparing N0 with node-positive disease, there was a significant difference in OS and RFS (P < .001 all comparisons). However, when comparing N1 with N2 and N3 disease regardless of tumor size, there were no significant differences in OS or RFS. Conclusion In patients with TNBC, once there is evidence of lymph node metastasis, the prognosis may not be affected by the number of positive lymph nodes.
Mechanical Behavior of Aluminum Alloys During Small Punch Test
Authors: Sanders Matthew , Di Bella Frank , Liang Hong 
Published: May 2011

Abstract
Small Punch Tests (SPTs) were conducted in order to determine material properties and understand their mechanical behavior. Equations were derived to calculate the yield strength, ultimate tensile strength, modulus of elasticity, and hardness of five aluminum alloys. A greater understanding of the mechanisms of the SPT and how specimens behave during testing is also discussed. It was found that the 2024-T3 and 7075-T651 aluminum alloys were shown to have the highest maximum small punch force before failure. The relationship between the SPT parameters and the yield strength, tensile strength, elastic modulus, and hardness is shown to be linear. The empirical equation developed here is suitable for aluminum alloys.
Introduction
Authors: Blatt Martin 
Published: May 2011

Abstract
These four essays critique Ken Burns's PBS documentary series The National Parks: America's Best Idea. Burns has over the last several decades established himself as the central producer of PBS multi-part documentaries, addressing such topics as the Civil War, baseball, jazz, and World War II. National Park Service (NPS) leadership recognized the promotional opportunities for the NPS and aligned themselves closely with Burns and PBS. Critical discussion in the essays focuses in three areas: the treatment of Native Americans; the reverential treatment of “nature” in the national parks, and the distorted focus on the natural park in the West as the embodiment of the National Park system.