bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary history of tall fescue morphotypes inferred from molecular phylogenetics of the Lolium-Festucaspecies complex
Authors: Hand Melanie L , Cogan Noel OI , Stewart Alan V , Forster John W 
Published: October 2010

AbstractBackgroundThe agriculturally important pasture grass tall fescue (Festuca arundinaceaSchreb. syn.Lolium arundinaceum(Schreb.) Darbysh.) is an outbreeding allohexaploid, that may be more accurately described as a species complex consisting of three major (Continental, Mediterranean and rhizomatous) morphotypes. Observation of hybrid infertility in some crossing combinations between morphotypes suggests the possibility of independent origins from different diploid progenitors. This study aims to clarify the evolutionary relationships between each tall fescue morphotype through phylogenetic analysis using two low-copy nuclear genes (encoding plastid acetyl-CoA carboxylase [Acc1] andcentroradialis[CEN]), the nuclear ribosomal DNA internal transcribed spacer (rDNA ITS) and the chloroplast DNA (cpDNA) genome-locatedmatKgene. Other taxa within the closely relatedLolium-Festucaspecies complex were also included in the study, to increase understanding of evolutionary processes in a taxonomic group characterised by multiple inter-specific hybridisation events.ResultsPutative homoeologous sequences from both nuclear genes were obtained from each polyploid species and compared to counterparts from 15 diploid taxa. Phylogenetic reconstruction confirmedF. pratensisandF. arundinaceavar.glaucescensas probable progenitors to Continental tall fescue, and these species are also likely to be ancestral to the rhizomatous morphotype. However, these two morphotypes are sufficiently distinct to be located in separate clades based on the ITS-derived data set. All four of the generated data sets suggest independent evolution of the Mediterranean and Continental morphotypes, with minimal affinity between cognate sequence haplotypes. No obvious candidate progenitor species for Mediterranean tall fescues were identified, and only two putative sub-genome-specific haplotypes were identified for this morphotype.ConclusionsThis study describes the first phylogenetic analysis of theFestucagenus to include representatives of each tall fescue morphotype, and to use low copy nuclear gene-derived sequences to identify putative progenitors of the polyploid species. The demonstration of distinct tall fescue lineages has implications for both taxonomy and molecular breeding strategies, and may facilitate the generation of morphotype and/or sub-genome-specific molecular markers.
A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins
Authors: Pawłowski Krzysztof , Muszewska Anna , Lenart Anna , Szczepińska Teresa , Godzik Adam , Grynberg Marcin 
Published: October 2010

Abstract
Background
Peroxide turnover and signalling are involved in many biological phenomena relevant to human diseases. Yet, all the players and mechanisms involved in peroxide perception are not known. Elucidating very remote evolutionary relationships between proteins is an approach that allows the discovery of novel protein functions. Here, we start with three human proteins, SRPX, SRPX2 and CCDC80, involved in tumor suppression and progression, which possess a conserved region of similarity. Structure and function prediction allowed the definition of P-DUDES, a phylogenetically widespread, possibly ancient protein structural domain, common to vertebrates and many bacterial species.

Results
We show, using bioinformatics approaches, that the P-DUDES domain, surprisingly, adopts the thioredoxin-like (Thx-like) fold. A tentative, more detailed prediction of function is made, namely, that of a 2-Cys peroxiredoxin. Incidentally, consistent overexpression of all three human P-DUDES genes in two public glioblastoma microarray gene expression datasets was discovered. This finding is discussed in the context of the tumor suppressor role that has been ascribed to P-DUDES proteins in several studies. Majority of non-redundant P-DUDES proteins are found in marine metagenome, and among the bacterial species possessing this domain a trend for a higher proportion of aquatic species is observed.

Conclusions
The new protein structural domain, now with a broad enzymatic function predicted, may become a drug target once its detailed molecular mechanism of action is understood in detail.
Incidence, risk factors and clinical epidemiology of melioidosis: a complex socio-ecological emerging infectious disease in the Alor Setar region of Kedah, Malaysia
Authors: Hassan Muhammad RA , Pani Subhada P , Peng Ng P , Voralu Kirtanaa , Vijayalakshmi Natesan , Mehanderkar Ranjith , Aziz Norasmidar A , Michael Edwin 
Published: October 2010

Abstract

Background
Melioidosis, a severe and fatal infectious disease caused by Burkholderia pseudomallei, is believed to an emerging global threat. However, data on the natural history, risk factors, and geographic epidemiology of the disease are still limited.

Methods
We undertook a retrospective analysis of 145 confirmed cases extracted from a hospital-based Melioidosis Registry set up from 2005 in Hospital Sultanah Bahiyah, Alor Setar, Kedah state, Malaysia, in order to provide a first description of the contemporary incidence, risk factors, and clinical epidemiology of the disease in this putatively high risk region of the country.

Results
The incidence of melioidosis in Alor Setar is remarkably high at 16.35 per 100,000 population per year. The mean age of patients was 50.40 years, with infection varying nonlinearly with age. Males (75.2%; P < 0.0001) predominated and the majority of cases were Malays (88.9%). The overall, crude mortality rate among the study patients was 33.8%. The proportions of cases and deaths were significantly greater among patients involved in farming, forestry and fishing and the unemployed (χ2 = 30.57, P < 0.0001). A majority of cases (62.75%) were culture positive, with mortality in these patients being 45.05%. A large proportion (83.0%) of culture positives was also bacteremic. Pneumonia accounted for 42.06% of primary diagnoses followed in importance by soft tissue abscess. In patients with pneumonia and who were culture positive, the mortality rate was as high as 65.00%. Diabetes mellitus constituted the major underlying risk factor for developing and dying from melioidosis, occurring in 57% of all diagnosed cases. The age distribution of diabetes paralleled that of melioidosis cases. There were linear associations between cases and deaths with monthly rainfall.

Conclusions
Melioidosis represents a complex socio-ecological public health problem in Kedah, being strongly related with age, occupation, rainfall and predisposing chronic diseases, such as diabetes mellitus. Among cases, bacteremic patients were associated with significantly high mortality despite provision of the recommended antibacterial therapy. The burden of this disease is likely to grow in this region unless better informed interventions targeted at high-risk groups and associated diseases are urgently implemented.
Genome profiling of ERBB2-amplified breast cancers
Authors: Sircoulomb Fabrice , Bekhouche Ismahane , Finetti Pascal , Adélaïde José , Hamida Azza Ben , Bonansea Julien , Raynaud Stéphane , Innocenti Charlène , Charafe-Jauffret Emmanuelle , Tarpin Carole , Ayed Farhat Ben , Viens Patrice , Jacquemier Jocelyne , Bertucci François , Birnbaum Daniel , Chaffanet Max 
Published: October 2010

Abstract

Background
Around 20% of breast cancers (BC) show ERBB2 gene amplification and overexpression of the ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs, genomically and biologically heterogeneous, may help understand their behavior and design new therapeutic strategies.

Methods
We defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. Expression of ERBB2, phosphorylated ERBB2, EGFR, IGF1R and FOXA1 proteins was assessed by immunohistochemistry to evaluate the functional ERBB2 status and identify co-expressions.

Results
First, we identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common 17q12-q21 amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, GISTIC analysis identified 17 other genome regions affected by copy number aberration (CNA) (amplifications, gains, losses). The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+) and negative (ER-) ERBB2-amplified BCs were different. The WNT/β-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2 amplicon was different in inflammatory (IBC) and non-inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. IHC results showed (i) a linear relationship between ERBB2 gene amplification and its gene and protein expressions with a good correlation between ERBB2 expression and phosphorylation status; (ii) a potential signaling cross-talk between EGFR or IGF1R and ERBB2, which could influence response of ERBB2-positive BCs to inhibitors. FOXA1 was frequently coexpressed with ERBB2 but its expression did not impact on the outcome of patients with ERBB2-amplified tumors.

Conclusion
We have shown that ER+ and ER- ERBB2-amplified BCs are different, distinguished ERBB2 amplicons in IBC and non-IBC, and identified genomic features that may be useful in the design of alternative therapeutical strategies.
Standards of lithium monitoring in mental health trusts in the UK
Authors: Collins Noel , Barnes Thomas RE , Shingleton-Smith Amber , Gerrett David , Paton Carol 
Published: October 2010

AbstractBackgroundLithium is a commonly prescribed drug with a narrow therapeutic index, and recognised adverse effects on the kidneys and thyroid. Clinical guidelines for the management of bipolar affective disorder published by The National Institute for Health and Clinical Excellence (NICE) recommend checks of renal and thyroid function before lithium is prescribed. They further recommend that all patients who are prescribed lithium should have their renal and thyroid function checked every six months, and their serum lithium checked every three months. Adherence to these recommendations has not been subject to national UK audit.MethodsThe Prescribing Observatory for Mental Health (POMH-UK) invited all National Health Service Mental Health Trusts in the UK to participate in a benchmarking audit of lithium monitoring against recommended standards. Data were collected retrospectively from clinical records and submitted electronically.Results436 clinical teams from 38 Trusts submitted data for 3,373 patients. In patients recently starting lithium, there was a documented baseline measure of renal or thyroid function in 84% and 82% respectively. For patients prescribed lithium for a year or more, the NICE standards for monitoring lithium serum levels, and renal and thyroid function were met in 30%, 55% and 50% of cases respectively.ConclusionsThe quality of lithium monitoring in patients who are in contact with mental health services falls short of recognised standards and targets. Findings from this audit, along with reports of harm received by the National Patient Safety Agency, prompted a Patient Safety Alert mandating primary care, mental health and acute Trusts, and laboratory staff to work together to ensure systems are in place to support recommended lithium monitoring by December 2010.
Risk-reducing strategies for women carrying brca1/2 mutations with a focus on prophylactic surgery
Authors: Salhab Mohamed , Bismohun Selina , Mokbel Kefah 
Published: October 2010

Abstract

Background
Women who have inherited mutations in the BRCA1 or BRCA2 genes have substantially elevated risks of breast and ovarian cancer. Mutation carriers have various options, including extensive and regular surveillance, chemoprevention and risk-reducing surgery. The aim of this review is to provide an up-to-date analysis and to subsequently summarise the available literature in relation to risk-reducing strategies, with a keen focus on prophylactic surgery.

Methods
The literature review is facilitated by Medline and PubMed databases. The cross-referencing of the obtained articles was used to identify other relevant studies.

Results
Prophylactic surgery (bilateral mastectomy, bilateral salpingo-oophorectomy or a combination of both procedures) has proved to be the most effective risk-reducing strategy. There are no randomised controlled trials able to demonstrate the potential benefits or harms of prophylactic surgery; therefore, the evidence has been derived from retrospective and short follow-up prospective studies, in addition to hypothetical mathematical models.
Based on the current knowledge, it is reasonable to recommend prophylactic oophorectomy for BRCA1 or BRCA2 mutation carriers when childbearing is completed in order to reduce the risk of developing breast and ovarian cancer. In addition, women should be offered the options of rigorous breast surveillance, chemoprevention with anti-oestrogens--especially for carriers of BRCA2--or bilateral prophylactic mastectomy.

Conclusion
The selection of the most appropriate risk-reducing strategy is not a straightforward task. The impact of risk-reducing strategies on cancer risk, survival, and overall quality of life are the key criteria considered for decision-making. Notably, various other factors should be taken into consideration when evaluating individual mutation carriers' individual circumstances, namely woman's age, morbidity, type of mutation, and individual preferences and expectations.
Although prospective randomised controlled trials concerned with examining the various interventions in relation to the woman's age and type of mutation are needed, randomisation is extremely difficult and rather deemed unethical given the current available evidence from retrospective studies.
Caloric beverage consumption patterns in Mexican children
Authors: Barquera Simon , Campirano Fabricio , Bonvecchio Anabelle , Hernández-Barrera Lucia , Rivera Juan A , Popkin Barry M 
Published: October 2010

Abstract

Background
Mexico has seen a very steep increase in child obesity level. Little is known about caloric beverage intake in this country as well as all other countries outside a few high income countries. This study examines overall patterns and trends in all caloric beverages from two nationally representative surveys from Mexico.

Methods
The two nationally representative dietary intake surveys (1999 and 2006) from Mexico are used to study caloric beverage intake in 17, 215 children. The volume (ml) and caloric energy (kcal) contributed by all beverages consumed by the sample subjects were measured. Results are weighted to be nationally representative.

Results
The trends from the dietary intake surveys showed very large increases in caloric beverages among pre-school and school children. The contribution of whole milk and sugar-sweetened juices was an important finding. Mexican pre-school children consumed 27.8% of their energy from caloric beverages in 2006 and school children consumed 20.7% of their energy from caloric beverages during the same time. The three major categories of beverage intake are whole milk, fruit juice with various sugar and water combinations and carbonated and noncarbonated sugared-beverages.

Conclusion
The Mexican government, greatly concerned about obesity, has identified the large increase in caloric beverages from whole milk, juices and soft drinks as a key target and is initiating major changes to address this problem. They have already used the data to shift 20 million persons in their welfare and feeding programs from whole to 1.5% fat milk and in a year will shift to nonfat milk. They are using these data to revise school beverage policies and national regulations and taxation policies related to an array of less healthful caloric beverages.
TRIzol treatment of secretory phase endometrium allows combined proteomic and mRNA microarray analysis of the same sample in women with and without endometriosis
Authors: Fassbender Amelie , Simsa Peter , Kyama Cleophas M , Waelkens Etienne , Mihalyi Attila , Meuleman Christel , Gevaert Olivier , Van de Plas Raf , de Moor Bart , D'Hooghe Thomas M 
Published: October 2010

Abstract

Background
According to mRNA microarray, proteomics and other studies, biological abnormalities of eutopic endometrium (EM) are involved in the pathogenesis of endometriosis, but the relationship between mRNA and protein expression in EM is not clear. We tested for the first time the hypothesis that EM TRIzol extraction allows proteomic Surface Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (SELDI-TOF MS) analysis and that these proteomic data can be related to mRNA (microarray) data obtained from the same EM sample from women with and without endometriosis.

Methods
Proteomic analysis was performed using SELDI-TOF-MS of TRIzol-extracted EM obtained during secretory phase from patients without endometriosis (n = 6), patients with minimal-mild (n = 5) and with moderate-severe endometriosis (n = 5), classified according to the system of the American Society of Reproductive Medicine. Proteomic data were compared to mRNA microarray data obtained from the same EM samples.

Results
In our SELDI-TOF MS study 32 peaks were differentially expressed in endometrium of all women with endometriosis (stages I-IV) compared with all controls during the secretory phase. Comparison of proteomic results with those from microarray revealed no corresponding genes/proteins.

Conclusion
TRIzol treatment of secretory phase EM allows combined proteomic and mRNA microarray analysis of the same sample, but comparison between proteomic and microarray data was not evident, probably due to post-translational modifications.
The VHL-dependent regulation of microRNAs in renal cancer
Authors: Neal Calida S , Michael Michael Z , Rawlings Lesley H , Van der Hoek Mark B , Gleadle Jonathan M 
Published: October 2010

AbstractBackgroundThe commonest histological type of renal cancer, clear cell renal cell carcinoma (cc RCC), is associated with genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumour suppressor. VHL inactivation leads to induction of hypoxia-inducible factors (HIFs) and a hypoxic pattern of gene expression. Differential levels of specific microRNAs (miRNAs) are observed in several tumours when compared to normal tissue. Given the central role of VHL in renal cancer formation, we examined the VHL-dependent regulation of miRNAs in renal cancer.MethodsVHL-dependent miRNA expression in cc RCC was determined by microarray analysis of renal cell line RCC4 with mutated VHL (RCC4-VHL) and reintroduced wild-type VHL (RCC4 + VHL). Five miRNAs highly upregulated in RCC4 + VHL and five miRNAs highly downregulated in RCC4 + VHL were studied further, in addition to miR-210, which is regulated by the HIF-VHL system. miRNA expression was also measured in 31 cc RCC tumours compared to adjacent normal tissue.ResultsA significant increase in miR-210, miR-155 and miR-21 expression was observed in the tumour tissue. miR-210 levels also showed a correlation with a HIF-regulated mRNA, carbonic anhydrase IX (CAIX), and with VHL mutation or promoter methylation. An inverse correlation was observed between miR-210 expression and patient survival, and a putative target of miR-210, iron-sulfur cluster assembly protein (ISCU1/2), shows reciprocal levels of mRNA expression in the tumours.ConclusionsWe have identified VHL-regulated miRNAs and found that for some the regulation is HIF-dependent and for others it is HIF-independent. This pattern of regulation was also seen in renal cancer tissue for several of these miRNAs (miR-210, miR-155, let-7i and members of the miR-17-92 cluster) when compared with normal tissue. miR-210 showed marked increases in expression in renal cancer and levels correlated with patient survival. The inverse correlation between miR-210 levels and ISCU1/2 provides support for the hypothesis that ISCU1/2 is a target of miR-210 and that it may contribute to the anaerobic respiration seen in renal (and other) tumours.See Commentary:http://www.biomedcentral.com/1741-7015/8/65
Genetic background modifies neurodegeneration and neuroinflammation driven by misfolded human tau protein in rat model of tauopathy: implication for immunomodulatory approach to Alzheimer's disease
Authors: Stozicka Zuzana , Zilka Norbert , Novak Petr , Kovacech Branislav , Bugos Ondrej , Novak Michal 
Published: October 2010

AbstractBackgroundNumerous epidemiological studies demonstrate that genetic background modifies the onset and the progression of Alzheimer's disease and related neurodegenerative disorders. The efficacious influence of genetic background on the disease pathway of amyloid beta has been meticulously described in rodent models. Since the impact of genetic modifiers on the neurodegenerative and neuroinflammatory cascade induced by misfolded tau protein is yet to be elucidated, we have addressed the issue by using transgenic lines expressing the same human truncated tau protein in either spontaneously hypertensive rat (SHR) or Wistar-Kyoto (WKY) genetic background.MethodsBrains of WKY and SHR transgenic rats in the terminal stage of phenotype and their age-matched non-transgenic littermates were examined by means of immunohistochemistry and unbiased stereology. Basic measures of tau-induced neurodegeneration (load of neurofibrillary tangles) and neuroinflammation (number of Iba1-positive microglia, their activated morphology, and numbers of microglia immunoreactive for MHCII and astrocytes immunoreactive for GFAP) were quantified with an optical fractionator in brain areas affected by neurofibrillary pathology (pons, medulla oblongata). The stereological data were evaluated using two-way ANOVA and Student's t-test.ResultsTau neurodegeneration (neurofibrillary tangles (NFTs), axonopathy) and neuroinflammation (microgliosis, astrocytosis) appeared in both WKY and SHR transgenic rats. Although identical levels of transgene expression in both lines were present, terminally-staged WKY transgenic rats displayed significantly lower final NFT loads than their SHR transgenic counterparts. Interestingly, microglial responses showed a striking difference between transgenic lines. Only 1.6% of microglia in SHR transgenic rats expressed MHCII in spite of having a robust phagocytic phenotype, whereas in WKY transgenic rats, 23.2% of microglia expressed MHCII despite displaying a considerably lower extent of transformation into phagocytic phenotype.ConclusionsThese results show that the immune response represents a pivotal and genetically variable modifying factor that is able to influence vulnerability to neurodegeneration. Therefore, targeted immunomodulation could represent a prospective therapeutic approach to Alzheimer's disease.