bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the outer membrane proteome of Pasteurella multocida based on consensus prediction enhanced by results integration and manual confirmation
Authors: E-komon Teerasak , Burchmore Richard , Herzyk Pawel , Davies Robert 
Published: April 2012

Abstract

Background
Outer membrane proteins (OMPs) of Pasteurella multocida have various functions related to virulence and pathogenesis and represent important targets for vaccine development. Various bioinformatic algorithms can predict outer membrane localization and discriminate OMPs by structure or function. The designation of a confident prediction framework by integrating different predictors followed by consensus prediction, results integration and manual confirmation will improve the prediction of the outer membrane proteome.

Results
In the present study, we used 10 different predictors classified into three groups (subcellular localization, transmembrane β-barrel protein and lipoprotein predictors) to identify putative OMPs from two available P. multocida genomes: those of avian strain Pm70 and porcine non-toxigenic strain 3480. Predicted proteins in each group were filtered by optimized criteria for consensus prediction: at least two positive predictions for the subcellular localization predictors, three for the transmembrane β-barrel protein predictors and one for the lipoprotein predictors. The consensus predicted proteins were integrated from each group into a single list of proteins. We further incorporated a manual confirmation step including a public database search against PubMed and sequence analyses, e.g. sequence and structural homology, conserved motifs/domains, functional prediction, and protein-protein interactions to enhance the confidence of prediction. As a result, we were able to confidently predict 98 putative OMPs from the avian strain genome and 107 OMPs from the porcine strain genome with 83% overlap between the two genomes.

Conclusions
The bioinformatic framework developed in this study has increased the number of putative OMPs identified in P. multocida and allowed these OMPs to be identified with a higher degree of confidence. Our approach can be applied to investigate the outer membrane proteomes of other Gram-negative bacteria.
Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum
Authors: Terrapon Nicolas , Gascuel Olivier , Maréchal Éric , Bréhélin Laurent 
Published: May 2012

AbstractBackgroundHidden Markov Models (HMMs) are a powerful tool for protein domain identification. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in new sequenced organisms. In Pfam, each domain family is represented by a curated multiple sequence alignment from which a profile HMM is built. In spite of their high specificity, HMMs may lack sensitivity when searching for domains in divergent organisms. This is particularly the case for species with a biased amino-acid composition, such asP. falciparum, the main causal agent of human malaria. In this context, fitting HMMs to the specificities of the target proteome can help identify additional domains.ResultsUsingP. falciparumas an example, we compare approaches that have been proposed for this problem, and present two alternative methods. Because previous attempts strongly rely on known domain occurrences in the target species or its close relatives, they mainly improve the detection of domains which belong to already identified families. Our methods learn global correction rules that adjust amino-acid distributions associated with the match states of HMMs. These rules are applied to all match states of the whole HMM library, thus enabling the detection of domains from previously absent families. Additionally, we propose a procedure to estimate the proportion of false positives among the newly discovered domains. Starting with the Pfam standard library, we build several new libraries with the different HMM-fitting approaches. These libraries are first used to detect new domain occurrences with low E-values. Second, by applying the Co-Occurrence Domain Discovery (CODD) procedure we have recently proposed, the libraries are further used to identify likely occurrences among potential domains with higher E-values.ConclusionWe show that the new approaches allow identification of several domain families previously absent in theP. falciparumproteome and the Apicomplexa phylum, and identify many domains that are not detected by previous approaches. In terms of the number of new discovered domains, the new approaches outperform the previous ones when no close species are available or when they are used to identify likely occurrences among potential domains with high E-values. All predictions onP. falciparumhave been integrated into a dedicated website which pools all known/new annotations of protein domains and functions for this organism. A software implementing the two proposed approaches is available at the same address:http://www.lirmm.fr/~terrapon/HMMfit/
Accelerated maximum likelihood parameter estimation for stochastic biochemical systems
Authors: Daigle Bernie J , Roh Min K , Petzold Linda R , Niemi Jarad 
Published: May 2012

AbstractBackgroundA prerequisite for the mechanistic simulation of a biochemical system is detailed knowledge of its kinetic parameters. Despite recent experimental advances, the estimation of unknown parameter values from observed data is still a bottleneck for obtaining accurate simulation results. Many methods exist for parameter estimation in deterministic biochemical systems; methods for discrete stochastic systems are less well developed. Given the probabilistic nature of stochastic biochemical models, a natural approach is to choose parameter values that maximize the probability of the observed data with respect to the unknown parameters, a.k.a. the maximum likelihood parameter estimates (MLEs). MLE computation for all but the simplest models requires the simulation of many system trajectories that are consistent with experimental data. For models with unknown parameters, this presents a computational challenge, as the generation of consistent trajectories can be an extremely rare occurrence.ResultsWe have developed Monte Carlo Expectation-Maximization with Modified Cross-Entropy Method (MCEM2): an accelerated method for calculating MLEs that combines advances in rare event simulation with a computationally efficient version of the Monte Carlo expectation-maximization (MCEM) algorithm. Our method requires no prior knowledge regarding parameter values, and it automatically provides a multivariate parameter uncertainty estimate. We applied the method to five stochastic systems of increasing complexity, progressing from an analytically tractable pure-birth model to a computationally demanding model of yeast-polarization. Our results demonstrate that MCEM2substantially accelerates MLE computation on all tested models when compared to a stand-alone version of MCEM. Additionally, we show how our method identifies parameter values for certain classes of models more accurately than two recently proposed computationally efficient methods.ConclusionsThis work provides a novel, accelerated version of a likelihood-based parameter estimation method that can be readily applied to stochastic biochemical systems. In addition, our results suggest opportunities for added efficiency improvements that will further enhance our ability to mechanistically simulate biological processes.
Remobilization of Tol2 transposons in Xenopus tropicalis
Authors: Yergeau Donald A , Kelley Clair M , Kuliyev Emin , Zhu Haiqing , Sater Amy K , Wells Dan E , Mead Paul E 
Published: May 2012

Abstract

Background
The Class II DNA transposons are mobile genetic elements that move DNA sequence from one position in the genome to another. We have previously demonstrated that the naturally occurring Tol2 element from Oryzias latipes efficiently integrates its corresponding non-autonomous transposable element into the genome of the diploid frog, Xenopus tropicalis. Tol2 transposons are stable in the frog genome and are transmitted to the offspring at the expected Mendelian frequency.

Results
To test whether Tol2 transposons integrated in the Xenopus tropicalis genome are substrates for remobilization, we injected in vitro transcribed Tol2 mRNA into one-cell embryos harbouring a single copy of a Tol2 transposon. Integration site analysis of injected embryos from two founder lines showed at least one somatic remobilization event per embryo. We also demonstrate that the remobilized transposons are transmitted through the germline and re-integration can result in the generation of novel GFP expression patterns in the developing tadpole. Although the parental line contained a single Tol2 transposon, the resulting remobilized tadpoles frequently inherit multiple copies of the transposon. This is likely to be due to the Tol2 transposase acting in discrete blastomeres of the developing injected embryo during the cell cycle after DNA synthesis but prior to mitosis.

Conclusions
In this study, we demonstrate that single copy Tol2 transposons integrated into the Xenopus tropicalis genome are effective substrates for excision and random re-integration and that the remobilized transposons are transmitted through the germline. This is an important step in the development of 'transposon hopping' strategies for insertional mutagenesis, gene trap and enhancer trap screens in this highly tractable developmental model organism.
Knockout of the folate transporter folt-1 causes germline and somatic defects in C. elegans
Authors: Austin Misa U , Liau Wei-Siang , Balamurugan Krishnaswamy , Ashokkumar Balasubramaniem , Said Hamid M , LaMunyon Craig W 
Published: May 2012

Abstract

Background
The C. elegans gene folt-1 is an ortholog of the human reduced folate carrier gene. The FOLT-1 protein has been shown to transport folate and to be involved in uptake of exogenous folate by worms. A knockout mutation of the gene, folt-1(ok1460), was shown to cause sterility, and here we investigate the source of the sterility and the effect of the folt-1 knockout on somatic function.

Results
Our results show that folt-1(ok1460) knockout hermaphrodites have a substantially reduced germline, generate a small number of functional sperm, and only rarely produce a functional oocyte. We found no evidence of increased apoptosis in the germline of folt-1 knockout mutants, suggesting that germline proliferation is defective. While folt-1 knockout males are fertile, their rate of spermatogenesis was severely diminished, and the males were very poor maters. The mating defect is likely due to compromised metabolism and/or other somatic functions, as folt-1 knockout hermaphrodites displayed a shortened lifespan and elongated defecation intervals.

Conclusions
The FOLT-1 protein function affects both the soma and the germline. folt-1(ok1460) hermaphrodites suffer severely diminished lifespan and germline defects that result in sterility. Germline defects associated with folate deficiency appear widespread in animals, being found in humans, mice, fruit flies, and here, nematodes.
Comprehensive survey of human brain microRNA by deep sequencing
Authors: Shao Ning-Yi , Hu Hai Yang , Yan Zheng , Xu Ying , Hu Hao , Menzel Corinna , Li Na , Chen Wei , Khaitovich Philipp 
Published: May 2012

Abstract

Background
MicroRNA (miRNA) play an important role in gene expression regulation. At present, the number of annotated miRNA continues to grow rapidly, in part due to advances of high-throughput sequencing techniques. Here, we use deep sequencing to characterize a population of small RNA expressed in human and rhesus macaques brain cortex.

Results
Based on a total of more than 150 million sequence reads we identify 197 putative novel miRNA, in humans and rhesus macaques, that are highly conserved among mammals. These putative miRNA have significant excess of conserved target sites in genes' 3'UTRs, supporting their functional role in gene regulation. Additionally, in humans and rhesus macaques respectively, we identify 41 and 22 conserved putative miRNA originating from non-coding RNA (ncRNA) transcripts. While some of these molecules might function as conventional miRNA, others might be harmful and result in target avoidance.

Conclusions
Here, we further extend the repertoire of conserved human and rhesus macaque miRNA. Even though our study is based on a single tissue, the coverage depth of our study allows identification of functional miRNA present in brain tissue at background expression levels. Therefore, our study might cover large proportion of the yet unannotated conserved miRNA present in the human genome.
Clonal complexes and virulence factors of Staphylococcus aureus from several cities in India
Authors: Shambat Srikanth , Nadig Savitha , Prabhakara Sushma , Bes Michele , Etienne Jerome , Arakere Gayathri 
Published: May 2012

AbstractBackgroundDiseases fromStaphylococcus aureusare a major problem in Indian hospitals and recent studies point to infiltration of community associated methicillin resistantS. aureus(CA-MRSA) into hospitals. Although CA-MRSA are genetically different from nosocomial MRSA, the distinction between the two groups is blurring as CA-MRSA are showing multidrug resistance and are endemic in many hospitals. Our survey of samples collected from Indian hospitals between 2004 and 2006 had shown mainly hospital associated methicillin resistantStaphylococcus aureus(HA-MRSA) carrying staphylococcal cassette chromosomemec(SCCmec) type III and IIIA. ButS. aureusisolates collected from 2007 onwards from community and hospital settings in India have shown SCCmectype IV and V cassettes while several variations of type IV SCCmeccassettes from IVa to IVj have been found in other parts of the world. In the present study, we have collected nasal swabs from rural and urban healthy carriers and pus, blood etc from in patients from hospitals to study the distribution of SCCmecelements and sequence types (STs) in the community and hospital environment. We performed molecular characterization of all the isolates to determine their lineage and microarray of select isolates from each sequence type to analyze their toxins, virulence and immune-evasion factors.ResultsMolecular analyses of 68 S. aureusisolates from in and around Bengaluru and three other Indian cities have been carried out. The chosen isolates fall into fifteen STs with all major clonal complexes (CC) present along with some minor ones. The dominant MRSA clones are ST22 and ST772 among healthy carriers and patients. We are reporting three novel clones, two methicillin sensitiveS. aureus(MSSA) isolates belonging to ST291 (related to ST398 which is live stock associated), and two MRSA clones, ST1208 (CC8), and ST672 as emerging clones in this study for the first time. Sixty nine percent of isolates carry Panton- Valentine Leucocidin genes (PVL) along with many other toxins. There is more diversity of STs among methicillin sensitiveS. aureusthan resistant ones. Microarray analysis of isolates belonging to different STs gives an insight into major toxins, virulence factors, adhesion and immune evasion factors present among the isolates in various parts of India.ConclusionsS. aureusisolates reported in this study belong to a highly diverse group of STs and CC and we are reporting several new STs which have not been reported earlier along with factors influencing virulence and host pathogen interactions.
The mechanism of pollination drop withdrawal in Ginkgo biloba L.
Authors: Jin Biao , Zhang Lei , Lu Yan , Wang Di , Jiang Xiao X , Zhang Min , Wang Li 
Published: May 2012

Abstract

Background
The pollination drop (PD) is a characteristic feature of many wind-pollinated gymnosperms. Although accumulating evidence shows that the PD plays a critical role in the pollination process, the mechanism of PD withdrawal is still unclear. Here, we carefully observed the PD withdrawal process and investigated the underlying mechanism of PD withdrawal, which will aid the understanding of wind-pollination efficiency in gymnosperms.

Results
In Ginkgo biloba, PDs were secreted on the micropyle during the pollination period and persisted for about 240 h when not pollinated under laboratory conditions. The withdrawal of an isolated PD required only 1 h for evaporation, much less than a PD on the living ovule, which required 100 h. When pollinated with viable pollen, PDs withdrew rapidly within 4 h. In contrast, nonviable pollen and acetone-treated pollen did not cause PD withdrawal. Although 100% relative humidity significantly inhibited PD withdrawal, pollinated PDs still could withdraw completely within 48 h. Pollen grains of Cycas revoluta, which are similar to those of G. biloba, could induce PD withdrawal more rapidly than those of two distantly related gymnosperms (Pinus thunbergii and Abies firma) or two angiosperms (Paeonia suffruticosa and Orychophragmus violaceus). Furthermore, pollen of G. biloba and C. revoluta submerged immediately when encountering the PD, then sank to the bottom and entered the micropyle. The saccate pollen of P. thunbergii and A. firma submerged into the PD, but remained floating at the top and finally accumulated on the micropyle after PD withdrawal. In contrast, pollen of the angiosperms P. suffruticosa, Salix babylonica, and O. violaceus did not submerge, instead remaining clustered at the edge without entering the PD.

Conclusions
We conclude that PD withdrawal is primarily determined by the dynamic balance between evaporation and ovule secretion, of which pollen is a critical stimulator. When conspecific pollen grains were submerged in the PD, ovule secretion was subsequently terminated and active absorption occurred. These processes cooperated to influence PD withdrawal. In addition, pollen grain behavior within PDs varied dramatically among taxa, and PDs played a role in distinguishing and transporting pollen in G. biloba.
Microwave absorption properties of Ni/(C, silicides) nanocapsules
Authors: Jiang Jingjing , Wang Han , Guo Huaihong , Yang Teng , Tang Wen-Shu , Li Da , Ma Song , Geng Dianyu , Liu Wei , Zhang Zhidong 
Published: May 2012

Abstract
The microwave absorption properties of Ni/(C, silicides) nanocapsules prepared by an arc discharge method have been studied. The composition and the microstructure of the Ni/(C, silicides) nanocapsules were determined by means of X-ray diffraction, X-ray photoelectric spectroscopy, and transmission electron microscope observations. Silicides, in the forms of SiOx and SiC, mainly exist in the shells of the nanocapsules and result in a large amount of defects at the ‘core/shell’ interfaces as well as in the shells. The complex permittivity and microwave absorption properties of the Ni/(C, silicides) nanocapsules are improved by the doped silicides. Compared with those of Ni/C nanocapsules, the positions of maximum absorption peaks of the Ni/(C, silicides) nanocapsules exhibit large red shifts. An electric dipole model is proposed to explain this red shift phenomenon.
UK Dermatology Clinical Trials Network’s STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial
Authors: Craig Fiona F , Thomas Kim S , Mitchell Eleanor J , Williams Hywel C , Norrie John , Mason James M , Ormerod Anthony D 
Published: April 2012

Abstract

Background
Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network’s STOP GAP Trial has been designed to address this lack of trial evidence.

Methods
The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).
Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial.

Trial registration
Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.
The nature of personality disorder
Authors: Adshead Gwen , Sarkar Jaydip 
Published: May 2012

SummaryThe lack of a medically grounded approach to personality disorder and its management has led to its comparative neglect as a topic by many clinicians in the UK. In this article we present evidence that personality disorders are, like other mental disorders, the social manifestations of a pathological process. This process presents with characteristic clinical features that are developmental in nature. These cause disturbances in arousal, affect and reality testing that have an impact on interpersonal social functioning. Personality disorder may therefore be conceived of primarily as a socioemotional disability, not dissimilar to Axis I conditions.
Psychiatric and psychological aspects of fraud offending
Authors: Wallang Paul , Taylor Richard 
Published: May 2012

SummaryThere has been little research into the interaction between fraud offences and mental health. Fraud is perpetrated on a massive scale and a number of offenders will have psychiatric pathology either as a primary driver of the offence or as an associated phenomenon that will require psychiatric care and treatment. This article reviews the broad range of psychiatric conditions that have been associated with fraud offending, comments on management and discusses methods of psychiatric assessment in fraud offences.
From the gambler within: Dostoyevsky's The Gambler
Authors: George Sanju 
Published: May 2012

SummaryFyodor Dostoyevsky is widely regarded as the greatest 19th-century Russian writer and a giant in world literature. He is familiar to literary-inclined psychiatrists for his rich and accurate portrayal of mental illness in several of his works. But his own chronic addiction to gambling and its consequent perils are less well-known. This article discusses The Gambler, one of Dostoyevsky's early (1866) semi-autobiographical novellas, inspired by his own addiction to roulette, focusing on its depiction of gambling. To better understand Dostoyevsky the gambler, the article also presents brief excerpts from letters that he wrote to his wife in 1867, when his gambling addiction appears to have been at its worst. Finally, the relevance of the central theme of this work, gambling addiction, to the present-day psychiatrist is discussed.