bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility to scrapie and disease phenotype in sheep: cross-PRNP genotype experimental transmissions with natural sources
Authors: González Lorenzo , Jeffrey Martin , Dagleish Mark P , Goldmann Wilfred , Sisó Sílvia , Eaton Samantha L , Martin Stuart , Finlayson Jeanie , Stewart Paula , Steele Philip , Pang Yvonne , Hamilton Scott , Reid Hugh W , Chianini Francesca 
Published: July 2012

Abstract
It has long been established that the sheep Prnp genotype influences the susceptibility to scrapie, and some studies suggest that it can also determine several aspects of the disease phenotype. Other studies, however, indicate that the source of infection may also play a role in such phenotype. To address this question an experiment was set up in which either of two different natural scrapie sources, AAS from AA136 Suffolk and VVC from VV136 Cheviot sheep, were inoculated into AA136, VA136 and VV136 sheep recipients (n = 52). The immunohistochemical (IHC) profile of disease-associated PrP (PrPd) accumulation in the brain of recipient sheep was highly consistent upon codon 136 homologous and semi-homologous transmission, but could be either similar to or different from those of the inoculum donors. In contrast, the IHC profiles were highly variable upon heterologous transmission (VVC to AA136 and AAS to VV136). Furthermore, sheep of the same Prnp genotype could exhibit different survival times and PrPd profiles depending on the source of infection, and a correlation was observed between IHC and Western blot profiles. It was found that additional polymorphisms at codons 112 or 141 of AA136 recipients resulted in a delayed appearance of clinical disease or even in protection from infection. The results of this study strongly suggest that the scrapie phenotype in sheep results from a complex interaction between source, donor and recipient factors, and that the Prnp genotype of the recipient sheep does not explain the variability observed upon codon 136 heterologous transmissions, arguing for other genetic factors to be involved.
Protein genes in repetitive sequence—antifreeze glycoproteins in Atlantic cod genome
Authors: Zhuang Xuan , Yang Chun , Fevolden Svein-Erik , Cheng C-H Christina 
Published: July 2012

Abstract

Background
Highly repetitive sequences are the bane of genome sequence assembly, and the short read lengths produced by current next generation sequencing technologies further exacerbates this obstacle. An adopted practice is to exclude repetitive sequences in genome data assembly, as the majority of repeats lack protein-coding genes. However, this could result in the exclusion of important genotypes in newly sequenced non-model species. The absence of the antifreeze glycoproteins (AFGP) gene family in the recently sequenced Atlantic cod genome serves as an example.

Results
The Atlantic cod (Gadus morhua) genome was assembled entirely from Roche 454 short reads, demonstrating the feasibility of this approach. However, a well-known major adaptive trait, the AFGP, essential for survival in frigid Arctic marine habitats was absent in the annotated genome. To assess whether this resulted from population difference, we performed Southern blot analysis of genomic DNA from multiple individuals from the North East Arctic cod population that the sequenced cod belonged, and verified that the AFGP genotype is indeed present. We searched the raw assemblies of the Atlantic cod using our G. morhua AFGP gene, and located partial AFGP coding sequences in two sequence scaffolds. We found these two scaffolds constitute a partial genomic AFGP locus through comparative sequence analyses with our newly assembled genomic AFGP locus of the related polar cod, Boreogadus saida. By examining the sequence assembly and annotation methodologies used for the Atlantic cod genome, we deduced the primary cause of the absence of the AFGP gene family from the annotated genome was the removal of all repetitive Roche 454 short reads before sequence assembly, which would exclude most of the highly repetitive AFGP coding sequences. Secondarily, the model teleost genomes used in projection annotation of the Atlantic cod genome have no antifreeze trait, perpetuating the unawareness that the AFGP gene family is missing.

Conclusions
We recovered some of the missing AFGP coding sequences and reconstructed a partial AFGP locus in the Atlantic cod genome, bringing to light that not all repetitive sequences lack protein coding information. Also, reliance on genomes of model organisms as reference for annotating protein-coding gene content of a newly sequenced non-model species could lead to omission of novel genetic traits.
Evolutionary analysis of the ENTH/ANTH/VHS protein superfamily reveals a coevolution between membrane trafficking and metabolism
Authors: De Craene Johan-Owen , Ripp Raymond , Lecompte Odile , Thompson Julie D , Poch Olivier , Friant Sylvie 
Published: July 2012

Abstract

Background
Membrane trafficking involves the complex regulation of proteins and lipids intracellular localization and is required for metabolic uptake, cell growth and development. Different trafficking pathways passing through the endosomes are coordinated by the ENTH/ANTH/VHS adaptor protein superfamily. The endosomes are crucial for eukaryotes since the acquisition of the endomembrane system was a central process in eukaryogenesis.

Results
Our in silico analysis of this ENTH/ANTH/VHS superfamily, consisting of proteins gathered from 84 complete genomes representative of the different eukaryotic taxa, revealed that genomic distribution of this superfamily allows to discriminate Fungi and Metazoa from Plantae and Protists. Next, in a four way genome wide comparison, we showed that this discriminative feature is observed not only for other membrane trafficking effectors, but also for proteins involved in metabolism and in cytokinesis, suggesting that metabolism, cytokinesis and intracellular trafficking pathways co-evolved. Moreover, some of the proteins identified were implicated in multiple functions, in either trafficking and metabolism or trafficking and cytokinesis, suggesting that membrane trafficking is central to this co-evolution process.

Conclusions
Our study suggests that membrane trafficking and compartmentalization were not only key features for the emergence of eukaryotic cells but also drove the separation of the eukaryotes in the different taxa.
An alternative method for quantifying coronary artery calcification: the multi-ethnic study of atherosclerosis (MESA)
Authors: Liang C Jason , Budoff Matthew J , Kaufman Joel D , Kronmal Richard A , Brown Elizabeth R 
Published: July 2012

Abstract

Background
Extent of atherosclerosis measured by amount of coronary artery calcium (CAC) in computed tomography (CT) has been traditionally assessed using thresholded scoring methods, such as the Agatston score (AS). These thresholded scores have value in clinical prediction, but important information might exist below the threshold, which would have important advantages for understanding genetic, environmental, and other risk factors in atherosclerosis. We developed a semi-automated threshold-free scoring method, the spatially weighted calcium score (SWCS) for CAC in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods
Chest CT scans were obtained from 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). The SWCS and the AS were calculated for each of the scans. Cox proportional hazards models and linear regression models were used to evaluate the associations of the scores with CHD events and CHD risk factors. CHD risk factors were summarized using a linear predictor.

Results
Among all participants and participants with AS > 0, the SWCS and AS both showed similar strongly significant associations with CHD events (hazard ratios, 1.23 and 1.19 per doubling of SWCS and AS; 95% CI, 1.16 to 1.30 and 1.14 to 1.26) and CHD risk factors (slopes, 0.178 and 0.164; 95% CI, 0.162 to 0.195 and 0.149 to 0.179). Even among participants with AS = 0, an increase in the SWCS was still significantly associated with established CHD risk factors (slope, 0.181; 95% CI, 0.138 to 0.224). The SWCS appeared to be predictive of CHD events even in participants with AS = 0, though those events were rare as expected.

Conclusions
The SWCS provides a valid, continuous measure of CAC suitable for quantifying the extent of atherosclerosis without a threshold, which will be useful for examining novel genetic and environmental risk factors for atherosclerosis.
Epidemiologic trends in chronic renal replacement therapy over forty years: A Swiss dialysis experience
Authors: Lehmann Petra Rhyn , Ambühl Manon , Corleto Domenica , Klaghofer Richard , Ambühl Patrice M 
Published: July 2012

AbstractBackgroundLong term longitudinal data are scarce on epidemiological characteristics and patient outcomes in patients on maintenance dialysis, especially in Switzerland. We examined changes in epidemiology of patients undergoing renal replacement therapy by either hemodialysis or peritoneal dialysis over four decades.MethodsSingle center retrospective study including all patients which initiated dialysis treatment for ESRD between 1970 and 2008. Analyses were performed for subgroups according to dialysis vintage, based on stratification into quartiles of date of first treatment. A multivariate model predicting death and survival time, using time-dependent Cox regression, was developed.Results964 patients were investigated. Incident mean age progressively increased from 48 ± 14 to 64 ± 15 years from 1stto 4thquartile (p < 0.001), with a concomitant decrease in 3- and 5-year survival from 72.2 to 67.7%, and 64.1 to 54.8%, respectively. Nevertheless, live span continuously increased from 57 ± 13 to 74 ± 11 years (p < 0.001). Patients transplanted at least once were significantly younger at dialysis initiation, with significantly better survival, however, shortened live span vs. individuals remaining on dialysis. Among age at time of initiating dialysis therapy, sex, dialysis modality and transplant status, only transplant status is a significant independent covariate predicting death (HR: 0.10 for transplanted vs. non-transplanted patients, p = 0.001). Dialysis vintage was associated with better survival during the second vs. the first quartile (p = 0.026).DiscussionWe document an increase of a predominantly elderly incident and prevalent dialysis population, with progressively shortened survival after initiation of renal replacement over four decades, and, nevertheless, a prolonged lifespan. Analysis of the data is limited by lack of information on comorbidity in the study population.ConclusionsSurvival in patients on renal replacement therapy seems to be affected not only by medical and technical advances in dialysis therapy, but may mostly reflect progressively lower mortality of individuals with cardiovascular and metabolic complications, as well as a policy of accepting older and polymorbid patients for dialysis in more recent times. This is relevant to make demographic predictions in face of the ESRD epidemic nephrologists and policy makers are facing in industrialized countries.
Perinatal stress, brain inflammation and risk of autism-Review and proposal
Authors: Angelidou Asimenia , Asadi Shahrzad , Alysandratos Konstantinos-Dionysios , Karagkouni Anna , Kourembanas Stella , Theoharides Theoharis C 
Published: July 2012

AbstractBackgroundAutism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by varying deficits in social interactions, communication, and learning, as well as stereotypic behaviors. Despite the significant increase in ASD, there are few if any clues for its pathogenesis, hampering early detection or treatment. Premature babies are also more vulnerable to infections and inflammation leading to neurodevelopmental problems and higher risk of developing ASD. Many autism “susceptibility” genes have been identified, but “environmental” factors appear to play a significant role. Increasing evidence suggests that there are different ASD endophenotypes.DiscussionWe review relevant literature suggestingin uteroinflammation can lead to preterm labor, while insufficient development of the gut-blood–brain barriers could permit exposure to potential neurotoxins. This risk apparently may increase in parents with “allergic” or autoimmune problems during gestation, or if they had been exposed to stressors. The presence of circulating auto-antibodies against fetal brain proteins in mothers is associated with higher risk of autism and suggests disruption of the blood–brain-barrier (BBB). A number of papers have reported increased brain expression or cerebrospinal fluid (CSF) levels of pro-inflammatory cytokines, especially TNF, which is preformed in mast cells. Recent evidence also indicates increased serum levels of the pro-inflammatory mast cell trigger neurotensin (NT), and of extracellular mitochondrial DNA (mtDNA), which is immunogenic. Gene mutations of phosphatase and tensin homolog (PTEN), the negative regulator of the mammalian target of rapamycin (mTOR), have been linked to higher risk of autism, but also to increased proliferation and function of mast cells.SummaryPremature birth and susceptibility genes may make infants more vulnerable to allergic, environmental, infectious, or stress-related triggers that could stimulate mast cell release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in an endophenotype of ASD patients.
Thrombolytic effects of Douchi Fibrinolytic enzyme from Bacillus subtilis LD-8547 in vitro and in vivo
Authors: Yuan Jun , Yang Jing , Zhuang Zhenhong , Yang Yanling , Lin Ling , Wang Shihua 
Published: July 2012

Abstract

Background
Today, thrombosis is one of the most widely occurring diseases in modern life. Drugs with thrombolytic functions are the most effective methods in the treatment of thrombosis. Among them, Douchi fibrinolytic enzyme (DFE) is a promising agent. DFE was isolated from Douchi, a typical and popular soybean-fermented food in China, and it can dissolve fibrin directly and efficiently. A strain, Bacillus subtilis LD-8547 produced DFE with high fibrinolytic activity has been isolated in our lab previously.

Results
In the study, thrombolytic effect of DFE from Bacillus subtilis LD-8547 was studied in vitro and in vivo systematically. The results showed that DFE played a significant role in thrombolysis and anticoagulation in vitro. And the thrombolytic effects correlated with DFE in a dose-dependent manner. In vivo, the acute toxicity assay showed that DFE had no obvious acute toxicity to mice. Test of carrageenan-induced thrombosis in mice indicated that the DFE significantly prevented tail thrombosis, and arterial thrombosis model test indicated that Douchi fibrinolytic enzyme DFE had thrombolytic effect on carotid thrombosis of rabbits in vivo. Other results in vivo indicated that DFE could increase bleeding and clotting time obviously.

Conclusions
The DFE isolated from Bacillus subtilis LD-8547 has obvious thrombolytic effects in vitro and in vivo. This function demonstrates that this enzyme can be a useful tool for preventing and treating clinical thrombus.
Structural characterization of S100A15 reveals a novel zinc coordination site among S100 proteins and altered surface chemistry with functional implications for receptor binding
Authors: Murray Jill I , Tonkin Michelle L , Whiting Amanda L , Peng Fangni , Farnell Benjamin , Cullen Jay T , Hof Fraser , Boulanger Martin J 
Published: July 2012

Abstract

Background
S100 proteins are a family of small, EF-hand containing calcium-binding signaling proteins that are implicated in many cancers. While the majority of human S100 proteins share 25-65% sequence similarity, S100A7 and its recently identified paralog, S100A15, display 93% sequence identity. Intriguingly, however, S100A7 and S100A15 serve distinct roles in inflammatory skin disease; S100A7 signals through the receptor for advanced glycation products (RAGE) in a zinc-dependent manner, while S100A15 signals through a yet unidentified G-protein coupled receptor in a zinc-independent manner. Of the seven divergent residues that differentiate S100A7 and S100A15, four cluster in a zinc-binding region and the remaining three localize to a predicted receptor-binding surface.

Results
To investigate the structural and functional consequences of these divergent clusters, we report the X-ray crystal structures of S100A15 and S100A7D24G, a hybrid variant where the zinc ligand Asp24 of S100A7 has been substituted with the glycine of S100A15, to 1.7 Å and 1.6 Å resolution, respectively. Remarkably, despite replacement of the Asp ligand, zinc binding is retained at the S100A15 dimer interface with distorted tetrahedral geometry and a chloride ion serving as an exogenous fourth ligand. Zinc binding was confirmed using anomalous difference maps and solution binding studies that revealed similar affinities of zinc for S100A15 and S100A7. Additionally, the predicted receptor-binding surface on S100A7 is substantially more basic in S100A15 without incurring structural rearrangement.

Conclusions
Here we demonstrate that S100A15 retains the ability to coordinate zinc through incorporation of an exogenous ligand resulting in a unique zinc-binding site among S100 proteins. The altered surface chemistry between S100A7 and S100A15 that localizes to the predicted receptor binding site is likely responsible for the differential recognition of distinct protein targets. Collectively, these data provide novel insight into the structural and functional consequences of the divergent surfaces between S100A7 and S100A15 that may be exploited for targeted therapies.
Translation and validation of the vertigo symptom scale into German: A cultural adaption to a wider German-speaking population
Authors: Gloor-Juzi Thomas , Kurre Annette , Straumann Dominik , de Bruin Eling D 
Published: July 2012

AbstractBackgroundDizziness and comorbid anxiety may cause severe disability of patients with vestibulopathy, but can be addressed effectively with rehabilitation. For an individually adapted treatment, a structured assessment is needed. The Vertigo Symptom Scale (VSS) with two subscales assessing vertigo symptoms (VSS-VER) and associated symptoms (VSS-AA) might be used for this purpose. As there was no validated VSS available in German, the aim of the study was the translation and cross-cultural adaptation in German (VSS-G) and the investigation of its reliability, internal and external validity.MethodsThe VSS was translated into German according to recognized guidelines. Psychometric properties were tested on 52 healthy controls and 202 participants with vestibulopathy. Internal validity and reliability were investigated with factor analysis, Cronbach’s α and ICC estimations. Discriminant validity was analysed with the Mann–Whitney-U-Test between patients and controls and the ROC-Curve. Convergent validity was estimated with the correlation with the Hospital Anxiety Subscale (HADS-A), Dizziness Handicap Inventory (DHI) and frequency of dizziness.ResultsInternal validity: factor analysis confirmed the structure of two subscales. Reliability: VSS-G: α = 0.904 and ICC (CI) =0.926 (0.826, 0.965). Discriminant validity: VSS-VER differentiate patients and controls ROC (CI) =0.99 (0.98, 1.00). Convergent validity: VSS-G correlates with DHI (r = 0.554) and frequency (T = 0.317). HADS-A correlates with VSS-AA (r = 0.452) but not with VSS-VER (r = 0.186).ConclusionsThe VSS-G showed satisfactory psychometric properties to assess the severity of vertigo or vertigo-related symptoms. The VSS-VER can differentiate between healthy subjects and patients with vestibular disorders. The VSS-AA showed some screening properties with high sensitivity for patients with abnormal anxiety.
A national study of chaplaincy services and end-of-life outcomes
Authors: Flannelly Kevin J , Emanuel Linda L , Handzo George F , Galek Kathleen , Silton Nava R , Carlson Melissa 
Published: July 2012

AbstractBackgroundMedicine has long acknowledged the role of chaplains in healthcare, but there is little research on the relationship between chaplaincy care and health outcomes. The present study examines the association between chaplaincy services and end-of-life care service choices.MethodsHealthCare Chaplaincy purchased the AHA survey database from the American Hospital Association. The Dartmouth Atlas of Health Care database was provided to HealthCare Chaplaincy by The Dartmouth Institute for Health Policy & Clinical Practice, with the permission of Dartmouth Atlas Co-Principal Investigator Elliot S. Fisher, M.D., M.P.H. The Dartmouth Atlas of Health Care is available interactively on-line athttp://www.dartmouthatlas.org/. Patient data are aggregated at the hospital level in the Dartmouth Atlas of Health Care. IRB approval was not sought for the project because the data are available to the public through one means or another, and neither database contains data about individual patients, i.e. all the variables are measures of hospital characteristics. We combined and analyzed data from the American Hospital Association’s Annual Survey and outcome data from The Dartmouth Atlas of Health Care in a cross-sectional study of 3,585 hospitals. Two outcomes were examined: the percent of patients who (1) died in the hospital, and (2) were enrolled in hospice. Ordinary least squares regression was used to measure the association between the provision of chaplaincy services and each of the outcomes, controlling for six factors associated with hospital death rates.Results and discussionThe analyses found significantly lower rates of hospital deaths (β = .04,p < .05) and higher rates of hospice enrollment (β = .06,p < .001) for patients cared for in hospitals that provided chaplaincy services compared to hospitals that did not.ConclusionsThe findings suggest that chaplaincy services may play a role in increasing hospice enrollment. This may be attributable to chaplains’ assistance to patients and families in making decisions about care at the end-of-life, perhaps by aligning their values and wishes with actual treatment plans. Additional research is warranted.