bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure-based and ligand-based virtual screening of novel methyltransferase inhibitors of the dengue virus
Authors: Lim See Ven , Rahman Mohd Basyaruddin A , Tejo Bimo A 
Published: December 2011

AbstractBackgroundThe dengue virus is the most significant arthropod-borne human pathogen, and an increasing number of cases have been reported over the last few decades. Currently neither vaccines nor drugs against the dengue virus are available. NS5 methyltransferase (MTase), which is located on the surface of the dengue virus and assists in viral attachment to the host cell, is a promising antiviral target. In order to search for novel inhibitors of NS5 MTase, we performed a computer-aided virtual screening of more than 5 million commercially available chemical compounds using two approaches: i) structure-based screening using the crystal structure of NS5 MTase and ii) ligand-based screening using active ligands of NS5 MTase. Structure-based screening was performed using the LIDAEUS (LIgand Discovery At Edinburgh UniverSity) program. The ligand-based screening was carried out using the EDULISS (EDinburgh University LIgand Selection System) program.ResultsThe selection of potential inhibitors of dengue NS5 MTase was based on two criteria: the compounds must bind to NS5 MTase with a higher affinity than that of active NS5 MTase ligands, such as ribavirin triphosphate (RTP) andS-adenosyl-L-homocysteine (SAH); and the compounds must interact with residues that are catalytically important for the function of NS5 MTase. We found several compounds that bind strongly to the RNA cap site and theS-adenosyl-L-methionine (SAM) binding site of NS5 MTase with better binding affinities than that of RTP and SAH. We analyzed the mode of binding for each compound to its binding site, and our results suggest that all compounds bind to their respective binding sites by interacting with, and thus blocking, residues that are vital for maintaining the catalytic activity of NS5 MTase.ConclusionsWe discovered several potential compounds that are active against dengue virus NS5 MTase through virtual screening using structure-based and ligand-based methods. These compounds were predicted to bind into the SAM binding site and the RNA cap site with higher affinities than SAH and RTP. These compounds are commercially available and can be purchased for further biological activity tests.
HabiSign: a novel approach for comparison of metagenomes and rapid identification of habitat-specific sequences
Authors: Ghosh Tarini Shankar , Mohammed Monzoorul Haque , Rajasingh Hannah , Chadaram Sudha , Mande Sharmila S 
Published: December 2011

Abstract

Background
One of the primary goals of comparative metagenomic projects is to study the differences in the microbial communities residing in diverse environments. Besides providing valuable insights into the inherent structure of the microbial populations, these studies have potential applications in several important areas of medical research like disease diagnostics, detection of pathogenic contamination and identification of hitherto unknown pathogens. Here we present a novel and rapid, alignment-free method called HabiSign, which utilizes patterns of tetra-nucleotide usage in microbial genomes to bring out the differences in the composition of both diverse and related microbial communities.

Results
Validation results show that the metagenomic signatures obtained using the HabiSign method are able to accurately cluster metagenomes at biome, phenotypic and species levels, as compared to an average tetranucleotide frequency based approach and the recently published dinucleotide relative abundance based approach. More importantly, the method is able to identify subsets of sequences that are specific to a particular habitat. Apart from this, being alignment-free, the method can rapidly compare and group multiple metagenomic data sets in a short span of time.

Conclusions
The proposed method is expected to have immense applicability in diverse areas of metagenomic research ranging from disease diagnostics and pathogen detection to bio-prospecting. A web-server for the HabiSign algorithm is available at http://metagenomics.atc.tcs.com/HabiSign/.
Interrogation of alternative splicing events in duplicated genes during evolution
Authors: Chen Ting-Wen , Wu Timothy H , Ng Wailap V , Lin Wen-Chang 
Published: December 2011

Abstract

Background
Gene duplication provides resources for developing novel genes and new functions while retaining the original functions. In addition, alternative splicing could increase the complexity of expression at the transcriptome and proteome level without increasing the number of gene copy in the genome. Duplication and alternative splicing are thought to work together to provide the diverse functions or expression patterns for eukaryotes. Previously, it was believed that duplication and alternative splicing were negatively correlated and probably interchangeable.

Results
We look into the relationship between occurrence of alternative splicing and duplication at different time after duplication events. We found duplication and alternative splicing were indeed inversely correlated if only recently duplicated genes were considered, but they became positively correlated when we took those ancient duplications into account. Specifically, for slightly or moderately duplicated genes with gene families containing 2 - 7 paralogs, genes were more likely to evolve alternative splicing and had on average a greater number of alternative splicing isoforms after long-term evolution compared to singleton genes. On the other hand, those large gene families (contain at least 8 paralogs) had a lower proportion of alternative splicing, and fewer alternative splicing isoforms on average even when ancient duplicated genes were taken into consideration. We also found these duplicated genes having alternative splicing were under tighter evolutionary constraints compared to those having no alternative splicing, and had an enrichment of genes that participate in molecular transducer activities.

Conclusions
We studied the association between occurrences of alternative splicing and gene duplication. Our results implicate that there are key differences in functions and evolutionary constraints among singleton genes or duplicated genes with or without alternative splicing incidences. It implies that the gene duplication and alternative splicing may have different functional significance in the evolution of speciation diversity.
DetoxiProt: an integrated database for detoxification proteins
Authors: Yang Zhen , Yu Ying , Yao Lei , Li Guangui , Wang Lin , Hu Yiyao , Wei Haibin , Wang Li , Hammami Riadh , Razavi Roxanne , Zhong Yang , Liang Xufang 
Published: December 2011

Abstract

Background
Detoxification proteins are a class of proteins for degradation and/or elimination of endogenous and exogenous toxins or medicines, as well as reactive oxygen species (ROS) produced by these materials. Most of these proteins are generated as a response to the stimulation of toxins or medicines. They are essential for the clearance of harmful substances and for maintenance of physiological balance in organisms. Thus, it is important to collect and integrate information on detoxification proteins.

Results
To store, retrieve and analyze the information related to their features and functions, we developed the DetoxiProt, a comprehensive database for annotation of these proteins. This database provides detailed introductions about different classes of the detoxification proteins. Extensive annotations of these proteins, including sequences, structures, features, inducers, inhibitors, substrates, chromosomal location, functional domains as well as physiological-biochemical properties were generated. Furthermore, pre-computed BLAST results, multiple sequence alignments and evolutionary trees for detoxification proteins are also provided for evolutionary study of conserved function and pathways. The current version of DetoxiProt contains 5956 protein entries distributed in 628 organisms. An easy to use web interface was designed, so that annotations about each detoxification protein can be retrieved by browsing with a specific method or by searching with different criteria.

Conclusions
DetoxiProt provides an effective and efficient way of accessing the detoxification protein sequences and other high-quality information. This database would be a valuable source for toxicologists, pharmacologists and medicinal chemists. DetoxiProt database is freely available at http://lifecenter.sgst.cn/detoxiprot/.
Comparative genomics study of polyhydroxyalkanoates (PHA) and ectoine relevant genes from Halomonas sp. TD01 revealed extensive horizontal gene transfer events and co-evolutionary relationships
Authors: Cai Lei , Tan Dan , Aibaidula Gulsimay , Dong Xin-Ran , Chen Jin-Chun , Tian Wei-Dong , Chen Guo-Qiang 
Published: December 2011

Abstract

Background
Halophilic bacteria have shown their significance in industrial production of polyhydroxyalkanoates (PHA) and are gaining more attention for genetic engineering modification. Yet, little information on the genomics and PHA related genes from halophilic bacteria have been disclosed so far.

Results
The draft genome of moderately halophilic bacterium, Halomonas sp. TD01, a strain of great potential for industrial production of short-chain-length polyhydroxyalkanoates (PHA), was analyzed through computational methods to reveal the osmoregulation mechanism and the evolutionary relationship of the enzymes relevant to PHA and ectoine syntheses. Genes involved in the metabolism of PHA and osmolytes were annotated and studied in silico. Although PHA synthase, depolymerase, regulator/repressor and phasin were all involved in PHA metabolic pathways, they demonstrated different horizontal gene transfer (HGT) events between the genomes of different strains. In contrast, co-occurrence of ectoine genes in the same genome was more frequently observed, and ectoine genes were more likely under coincidental horizontal gene transfer than PHA related genes. In addition, the adjacent organization of the homologues of PHA synthase phaC1 and PHA granule binding protein phaP was conserved in the strain TD01, which was also observed in some halophiles and non-halophiles exclusively from γ-proteobacteria. In contrast to haloarchaea, the proteome of Halomonas sp. TD01 did not show obvious inclination towards acidity relative to non-halophilic Escherichia coli MG1655, which signified that Halomonas sp. TD01 preferred the accumulation of organic osmolytes to ions in order to balance the intracellular osmotic pressure with the environment.

Conclusions
The accessibility of genome information would facilitate research on the genetic engineering of halophilic bacteria including Halomonas sp. TD01.
The apolipoprotein A-I mimetic peptide, ETC-642, reduces chronic vascular inflammation in the rabbit
Authors: Di Bartolo Belinda A , Vanags Laura Z , Tan Joanne TM , Bao Shisan , Rye Kerry-Anne , Barter Philip J , Bursill Christina A 
Published: December 2011

Abstract

Background
High-density lipoproteins (HDL) and their main apolipoprotein, apoA-I, exhibit anti-inflammatory properties. The development of peptides that mimic HDL apolipoproteins offers a promising strategy to reduce inflammatory disease. This study aimed to compare the anti-inflammatory effects of ETC-642, an apoA-I mimetic peptide, with that of discoidal reconstituted HDL (rHDL), consisting of full-length apoA-I complexed with phosphatidylcholine, in rabbits with chronic vascular inflammation.

Results
New Zealand White rabbits (n = 10/group) were placed on chow supplemented with 0.2% (w/w) cholesterol for 6-weeks. The animals received two infusions of saline, rHDL (8 mg/kg apoA-I) or ETC-642 (30 mg/kg peptide) on the third and fifth days of the final week. The infusions of rHDL and ETC-642 were able to significantly reduce cholesterol-induced expression of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the thoracic aorta (p < 0.05). When isolated rabbit HDL was pre-incubated with human coronary artery endothelial cells (HCAECs), prior to stimulation with TNF-α, it was found that HDL from ETC-642 treated rabbits were more effective at inhibiting the TNF-α-induced increase in ICAM-1, VCAM-1 and p65 than HDL isolated from saline treated rabbits (p < 0.05). There were, however, no changes in HDL lipid composition between treatment groups.

Conclusions
Infusion of ETC-642 causes anti-inflammatory effects that are comparable to rHDL in an animal model of chronic vascular inflammation and highlights that apoA-I mimetic peptides present a viable strategy for the treatment of inflammatory disease.
Notch1 binds and induces degradation of Snail in hepatocellular carcinoma
Authors: Lim Seung-Oe , Kim Hyeon Seop , Quan Xiaoyuan , Ahn Sun-Min , Kim Hongtae , Hsieh David , Seong Je Kyung , Jung Guhung 
Published: December 2011

Abstract

Background
Hepatocellular carcinoma (HCC) is a common, highly invasive malignant tumor associated with a high mortality rate. We previously reported that the aberrant expression of Snail via activation of reactive oxygen species contributes to the invasive property of HCC, in part by downregulation of E-cadherin through both transcriptional repression and epigenetic modification of the E-cadherin promoter. Having demonstrated the ability of Snail to bind and recruit histone deacetylase 1 and DNA methyltransferase 1 in this context, we set out to look for other interactions that could affect its ability to promote oncogenic transformation and cancer cell invasion.

Results
Using cells that stably expressed Snail, we characterized Snail protein interactors by tandem affinity purification and mass spectrometry. Immunoprecipitation and subcellular colocalization studies were performed to confirm our identification of the Notch1 intracellular domain (NICD) as a novel Snail-binding partner. NICD interaction with Snail was found to induce ubiquitination and MDM2-dependent degradation of Snail. Interestingly, NICD inhibited Snail-dependent invasive properties in both HCC cells and mouse embryonic fibroblasts.

Conclusions
Our study demonstrates that NICD can oppose Snail-dependent HCC cell invasion by binding and inducing proteolytic degradation of Snail. Although Notch signaling and Snail are both widely considered tumor-promoting factors, our findings indicate that the individual oncogenic contribution of Notch1 and Snail in malignant systems should be interpreted carefully, particularly when they are conjointly expressed.
Residual HIV-1 DNA Flap-independent nuclear import of cPPT/CTS double mutant viruses does not support spreading infection
Authors: Iglesias Candela , Ringeard Mathieu , Di Nunzio Francesca , Fernandez Juliette , Gaudin Raphael , Souque Philippe , Charneau Pierre , Arhel Nathalie 
Published: December 2011

Abstract

Background
The human immunodeficiency virus type 1 (HIV-1) central DNA Flap is generated during reverse transcription as a result of (+) strand initiation at the central polypurine tract (cPPT) and termination after a ca. 100 bp strand displacement at the central termination sequence (CTS). The central DNA Flap is a determinant of HIV-1 nuclear import, however, neither cPPT nor CTS mutations entirely abolish nuclear import and infection. Therefore, to determine whether or not the DNA Flap is essential for HIV-1 nuclear import, we generated double mutant (DM) viruses, combining cPPT and CTS mutations to abolish DNA Flap formation.

Results
The combination of cPPT and CTS mutations reduced the proportion of viruses forming the central DNA Flap at the end of reverse transcription and further decreased virus infectivity in one-cycle titration assays. The most affected DM viruses were unable to establish a spreading infection in the highly permissive MT4 cell line, nor in human primary peripheral blood mononuclear cells (PBMCs), indicating that the DNA Flap is required for virus replication. Surprisingly, we found that DM viruses still maintained residual nuclear import levels, amounting to 5-15% of wild-type virus, as assessed by viral DNA circle quantification. Alu-PCR quantification of integrated viral genome also indicated 5-10% residual integration levels compared to wild-type virus.

Conclusion
This work establishes that the central DNA Flap is required for HIV-1 spreading infection but points to a residual DNA Flap independent nuclear import, whose functional significance remains unclear since it is not sufficient to support viral replication.
Schizophrenia medication adherence in a resource-poor setting: randomised controlled trial of supervised treatment in out-patients for schizophrenia (STOPS)
Authors: Farooq Saeed , Nazar Zahid , Irfan Muhammad , Akhter Javed , Gul Ejaz , Irfan Uma , Naeem Farooq 
Published: December 2011

BackgroundMost people with schizophrenia in low- and middle-income (LAMI) countries receive minimal formal care, and there are high rates of non-adherence to medication.AimsTo evaluate the effectiveness of an intervention that involves a family member in supervising medication administration – supervised treatment in out-patients for schizophrenia (STOPS) – in improving treatment adherence and clinical outcomes.MethodIndividuals (n = 110) with schizophrenia or schizoaffective disorders were allocated to STOPS or to treatment as usual (TAU) and followed up for 1 year. The primary outcome was adherence to the treatment regimen. Positive and Negative Syndrome Scale for Schizophrenia and Global Assessment of Functioning scores were also assessed.ResultsParticipants in the STOPS group had better adherence (complete adherence: 37 (67.3%) in STOPS v. 25 (45.5%) in TAU; P<0.02) and significant improvement in symptoms and functioning.ConclusionsSTOPS may be useful in enhancing adherence to treatment for schizophrenia in LAMI countries.
Developing large-group teaching in child and adolescent psychiatry to undergraduate medical students
Authors: Vallance Aaron K. , Hill Victoria , Ani Cornelius , Doig Alex , Garralda Elena 
Published: December 2011

Aims and methodWe developed material for a lecture hall teaching programme in child and adolescent psychiatry for medical students. Although lecture hall settings are not traditionally seen as conducive to exploring concepts, debating positions and encouraging higher-order thinking, we aimed to integrate these processes into the programme alongside educational theory and teaching strategies. We evaluated student and teacher perception of the new material through questionnaires before and after the introduction of the teaching package.ResultsSix 1.5-hour teaching sessions were prepared. The evaluation study received 133 student and 4 teacher questionnaires on the previous teaching package, and 99 student and 7 teacher questionnaires on the new material. The questionnaires showed that the redesign resulted in significant improvements in various predefined measures, such as clarity and interactivity of the material.Clinical implicationsA vivid and memorable teaching programme is essential in shaping students' understanding of the concepts in child and adolescent psychiatry as well as potentially making the specialty more attractive to medical undergraduates.
Patients' knowledge about treatment for opiate dependence
Authors: Alves Paula , Winstock Adam 
Published: December 2011

Aims and methodA cross-sectional survey was conducted to assess patient knowledge and information provision about opioid substitution treatment among individuals with opiate dependence receiving treatment at four treatment centres in South London.ResultsIn total 118 people were recruited to the study. Participants answered a mean of 14 out of 34 questions assessing a range of factors such as medication, blood-borne viruses and overdose correctly. Participants overestimated their performance on average by almost 40%. Individuals with a history of previous treatments scored significantly higher than those in their first treatment episode. The majority reported having been given written information on most of the topics assessed.Clinical implicationsThe results of this study highlight the need to improve education about opioid dependence and its treatment. Poorly informed patients are unlikely to make optimal treatment choices. Improving patients' knowledge and understanding about treatment may lead to better engagement, retention, treatment adherence and, ultimately, better health outcomes.
Evaluation of Proposed Lateral Load Pattern for Estimating Seismic Demands on RC-Tall Buildings with Shear Walls in Pushover Analysis
Authors: Faramarz Khoshnoudian , Mehdi Kafaeikivi 
Published: December 2011

The nonlinear static procedure (NSP) is becoming preferred as it favourite by virtue of its simplicity rather than nonlinear time history analysis for building evaluation and design verification. However, NSP is restricted to only a single mode response, thus this is appropriate for low-rise buildings in which the behaviour is dominated by the first vibration mode. The use of FEMA force distributions has certain flaws when high-rise buildings are evaluated; since the seismic demands are greatly underestimated especially at top stories of tall buildings. Hence, in this paper a new pushover procedure is proposed with takes into account higher mode effects. The procedure utilizes consecutive modal pushover (CMP) analyses using mode shapes obtained from a linear elastic analysis of the structure. The methodology is applied to three Reinforced Concrete frames with shear walls. It is demonstrated that the CMP procedure is able to estimate the seismic demands accurately enough and to overcome the shortcomings of FEMA load distributions when the higher mode effects are significant. Plastic hinge rotations are noticeably improved by this procedure when compared with those obtained by the MPA procedure and FEMA load distributions.
An Integrated Biochemistry and Genetics Outreach Program Designed for Elementary School Students
Authors: Ross Eric D , Lee Sarah K , Radebaugh Catherine A , Stargell Laurie A 
Published: December 2011

Abstract
Exposure to genetic and biochemical experiments typically occurs late in one’s academic career. By the time students have the opportunity to select specialized courses in these areas, many have already developed negative attitudes toward the sciences. Given little or no direct experience with the fields of genetics and biochemistry, it is likely that many young people rule these out as potential areas of study or career path. To address this problem, we developed a 7-week (∼1 hr/week) hands-on course to introduce fifth grade students to basic concepts in genetics and biochemistry. These young students performed a series of investigations (ranging from examining phenotypic variation, in vitro enzymatic assays, and yeast genetic experiments) to explore scientific reasoning through direct experimentation. Despite the challenging material, the vast majority of students successfully completed each experiment, and most students reported that the experience increased their interest in science. Additionally, the experiments within the 7-week program are easily performed by instructors with basic skills in biological sciences. As such, this program can be implemented by others motivated to achieve a broader impact by increasing the accessibility of their university and communicating to a young audience a positive impression of the sciences and the potential for science as a career.