bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of RefSeq protein-coding regions in human and vertebrate genomes
Authors: Fong Jessica H , Murphy Terence D , Pruitt Kim D 
Published: September 2013

Abstract

Background
Advances in high-throughput sequencing technology have yielded a large number of publicly available vertebrate genomes, many of which are selected for inclusion in NCBI’s RefSeq project and subsequently processed by NCBI’s eukaryotic annotation pipeline. Genome annotation results are affected by differences in available support evidence and may be impacted by annotation pipeline software changes over time. The RefSeq project has not previously assessed annotation trends across organisms or over time. To address this deficiency, we have developed a comparative protocol which integrates analysis of annotated protein-coding regions across a data set of vertebrate orthologs in genomic sequence coordinates, protein sequences, and protein features.

Results
We assessed an ortholog dataset that includes 34 annotated vertebrate RefSeq genomes including human. We confirm that RefSeq protein-coding gene annotations in mammals exhibit considerable similarity. Over 50% of the orthologous protein-coding genes in 20 organisms are supported at the level of splicing conservation with at least three selected reference genomes. Approximately 7,500 ortholog sets include at least half of the analyzed organisms, show highly similar sequence and conserved splicing, and may serve as a minimal set of mammalian “core proteins” for initial assessment of new mammalian genomes. Additionally, 80% of the proteins analyzed pass a suite of tests to detect proteins that lack splicing conservation and have unusual sequence or domain annotation. We use these tests to define an annotation quality metric that is based directly on the annotated proteins thus operates independently of other quality metrics such as availability of transcripts or assembly quality measures. Results are available on the RefSeq FTP site [http://ftp.ncbi.nlm.nih.gov/refseq/supplemental/ProtCore/SM1.txt].

Conclusions
Our multi-factored analysis demonstrates a high level of consistency in RefSeq protein representation among vertebrates. We find that the majority of the RefSeq vertebrate proteins for which we have calculated orthology are good as measured by these metrics. The process flow described provides specific information on the scope and degree of conservation for the analyzed protein sequences and annotations and will be used to enrich the quality of RefSeq records by identifying targets for further improvement in the computational annotation pipeline, and by flagging specific genes for manual curation.
Delivering enhanced cardiovascular (Hypertension) disease care through private health facilities in Pakistan
Authors: Khan Muhammad Amir , Javed Wajiha , Ahmed Maqsood , Walley John , Khan Haroon Jahangir 
Published: September 2013

Abstract

Background
Cardiovascular diseases (CVDs) are one of the leading causes of death and disability in the world. Over 80% of CVD deaths take place in low-and middle-income countries. One-third of the population aged above 40 years suffers from Hypertension (HTN) and this is largely unreported as there is no registry for CVDs. No guidelines are available for use in health care facilities, especially private health facilities where practice among GPs varies considerably. We aim to conduct a Cluster Randomized Controlled trial delivering a quality HTN-CVD care package at strengthened private health facilities as compared to current practice at private health facilities.

Methods/Design
A pragmatic cluster randomized trial, with qualitative and economic studies, will be conducted in Sargodha district of Punjab, Pakistan, from January 2012 to December 2016. At least 912 hypertensives will be registered in the two arms, six clusters per arm. The proposed cluster randomized controlled trial will evaluate the effects of delivering quality HTN-CVD care, through enabled private health care facilities, to achieve better case registration, adherence and hypertension control also blood glucose and serum cholesterol control. The trial will be conducted through the doctors and paramedics at private health facilities. Main outcomes are mean difference in Systolic blood pressure among the two arms. Secondary outcomes are mean change in total serum cholesterol levels and mean change in glycaemic control achieved in the adult hypertensive patients. Individual and Cluster level analysis will be done according to intention-to-treat.

Discussion
Due to the high burden of disease where 1 in 3 individuals aged above 45 suffers from hypertension, topped with the fact that there is a dearth of a set of available, standardised guidelines for management, the disease is constantly on a hike in Pakistan. The government has made no effort to issue a set of guidelines adapted specifically for our population and this becomes more of a problem when managing CVD in urban population through private practitioners whose practices vary widely.If our set of context sensitive guidelines show an effectiveness in the proposed intervention districts it will be replicated in other such settings.

Trial registration
Current Controlled Trials ISRCTN34381594
Cancer-testis gene expression is associated with the methylenetetrahydrofolate reductase 677 C>T polymorphism in non-small cell lung carcinoma
Authors: Senses Kerem M , Gonen Mithat , Barutcu Ahmet R , Kalaylioglu Zeynep , Isbilen Murat , Konu Ozlen , Chen Yao T , Altorki Nasser K , Gure Ali O 
Published: September 2013

Abstract

Background
Tumor-specific, coordinate expression of cancer-testis (CT) genes, mapping to the X chromosome, is observed in more than 60% of non-small cell lung cancer (NSCLC) patients. Although CT gene expression has been unequivocally related to DNA demethylation of promoter regions, the underlying mechanism leading to loss of promoter methylation remains elusive. Polymorphisms of enzymes within the 1-carbon pathway have been shown to affect S-adenosyl methionine (SAM) production, which is the sole methyl donor in the cell. Allelic variants of several enzymes within this pathway have been associated with altered SAM levels either directly, or indirectly as reflected by altered levels of SAH and Homocysteine levels, and altered levels of DNA methylation. We, therefore, asked whether the five most commonly occurring polymorphisms in four of the enzymes in the 1-carbon pathway associated with CT gene expression status in patients with NSCLC.

Methods
Fifty patients among a cohort of 763 with NSCLC were selected based on CT gene expression status and typed for five polymorphisms in four genes known to affect SAM generation by allele specific q-PCR and RFLP.

Results
We identified a significant association between CT gene expression and the MTHFR 677 CC genotype, as well as the C allele of the SNP, in this cohort of patients. Multivariate analysis revealed that the genotype and allele strongly associate with CT gene expression, independent of potential confounders.

Conclusions
Although CT gene expression is associated with DNA demethylation, in NSCLC, our data suggests this is unlikely to be the result of decreased MTHFR function.
Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections
Authors: Sherry Leighann , Millhouse Emma , Lappin David F , Murray Colin , Culshaw Shauna , Nile Christopher J , Ramage Gordon 
Published: September 2013

Abstract

Background
A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.

Methods
Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.

Results
CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.

Conclusions
Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.
In vitro antibacterial activity of Tabernaemontana alternifolia (Roxb) stem bark aqueous extracts against clinical isolates of methicillin resistant Staphylococcus aureus
Authors: Marathe Nachiket P , Rasane Mandar H , Kumar Himanshu , Patwardhan Ankur A , Shouche Yogesh S , Diwanay Sham S 
Published: September 2013

Abstract

Background
The rise of antibiotic resistance among methicillin resistant Staphylococcus aureus (MRSA), have caused concerns for the treatment of MRSA infections. Hence, search for an alternative therapy for these infections is inevitable. Folk Indian medicine refers to the use of leaf and stem bark powder of Tabernaemontana alternifolia (Roxb) in treatment of skin infections, but no scientific report establishes its antibacterial activity.

Methods
Direct aqueous extracts and sequential aqueous extracts of the stem bark of T. alternifolia (using petroleum ether and ethyl acetate as other solvents) were prepared by soxhlet extraction. The antibiotic sensitivity profiles of the clinical isolates were determined against 18 antibiotics using disc diffusion method. The isolates were identified by 16S rRNA gene sequencing. The methicillin resistance among S. aureus (MRSA) was confirmed by PCR amplification of mecA gene. The disc diffusion method was used to determine the antibacterial activity of the extracts. The micro-dilution method was used to determine the minimum inhibitory concentration (MIC) of the extract against the test organism. To further evaluate the therapeutic potential of the extract, cell cytotoxicity was checked on Vero cells by MTT assay. Chemical profiling of the extract was done by HPTLC method.

Results
The aqueous extracts of T. alternifolia stem bark exhibited antibacterial activity against Gram-positive microorganisms, particularly against clinical isolates of MRSA and vancomycin resistant S. aureus (VRSA). The minimum inhibitory concentration (MIC) of extract against the isolates ranged from 600–800 μg/ml. The extract did not exhibit cytotoxic activity against Vero cells even at the concentration of 4 mg/ml. The chemical profiling revealed presence of alkaloids, flavonoids, coumarins, saponins and steroids. Petroleum ether and ethyl acetate extracts did not exhibit antibacterial activity.

Conclusion
Our results offer a scientific basis for the traditional use of T. alternifolia in the treatment of skin infections, showing that the plant extract has an enormous potential as a prospective alternative therapy against MRSA skin infections. The present study lays the basis for future studies, to validate the possible use of T. alternifolia as a candidate in the treatment of MRSA infections.
GIS-aided planning of insecticide spraying to control dengue transmission
Authors: Chu Hone-Jay , Chan Ta-Chien , Jao Fang-Ju 
Published: September 2013

AbstractBackgroundThe purpose of this paper is to integrate a multi-objective integer programming formulation and geographic information system (GIS) into dynamically planning the insecticide spraying area for preventing the transmission of dengue fever.MethodsThe optimal spraying area to combat dengue infections is calculated by the multi-objective integer programming model using the dengue epidemic in 2007 in Tainan City of southern Taiwan and is compared with the areas actually sprayed by the local health department. The dynamic epidemic indicators (i.e. frequency, intensity and duration) that identify major temporal characteristics of the dynamic process of an epidemic are all incorporated into the model.ResultsThe results indicate that the model can design the spraying area effectively when the trade-off between the coverage of dengue epidemics risk and area compactness is considered.ConclusionsThe model provides an alternative way to obtain a cost-effective spraying area in controlling future dengue epidemics. The proposed model in this study will be beneficial for strategically allocating dengue control resources.
Genetic variance in Nitric Oxide Synthase and Endothelin Genes among children with and without Endothelial Dysfunction
Authors: Chatsuriyawong Siriporn , Gozal David , Kheirandish-Gozal Leila , Bhattacharjee Rakesh , Khalyfa Ahamed A , Wang Yang , Hakonarson Hakon , Keating Brendan , Sukhumsirichart Wasana , Khalyfa Abdelnaby 
Published: September 2013

Abstract

Background
The presence of endothelial dysfunction (ED) constitutes an early risk factor for cardiovascular disease (CVD) in children. Nitric oxide (NO) and endothelin (EDN) are generated in endothelial cells and are critical regulators of vascular function, with ED resulting from an imbalance between these two molecules. We hypothesized that genetic variants in NO synthase and EDN isoforms and its receptors (EDNRA and EDNRB) may account for a proportion of the risk for ED in developing children.

Methods
Consecutive children (ages 5–10 years) were prospectively recruited from the community. Time to peak post-occlusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax < 45 sec) or ED (Tmax ≥ 45 sec). Lipid profiles, high sensitivity C-reactive protein (hsCRP), fasting glucose and insulin were assayed using ELISA. Genomic DNA from peripheral blood was extracted and genotyped for NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), EDNRA (27 SNPs), and EDNRB (23 SNPs) using a custom SNPs array. Linkage disequilibrium was analyzed using Haploview version 4.2 software.

Results
The relative frequencies of SNPs were evaluated in 122 children, 84 with NEF and 38 with ED. The frequencies of NOS1 (11 SNPs), and EDN1 (2 SNPs) were differentially distributed between NEF vs. ED, and no significant differences emerged for all other genes. Significant SNPs for NOS1 and EDN1 SNPs were further validated with RT-PCR.

Conclusions
Genetic variants in the NOS1 and EDN1 genes appear to account for important components of the variance in endothelial function, particularly when concurrent risk factors such as obesity exist. Thus, analysis of genotype-phenotype interactions in children at risk for ED will be critical for more accurate formulation of categorical CVD risk estimates.
Evidence for the interaction of the human metapneumovirus G and F proteins during virus-like particle formation
Authors: Loo Liat Hui , Jumat Muhammad Raihan , Fu Yi , Ayi Teck Choon , Wong Pui San , Tee Nancy WS , Tan Boon Huan , Sugrue Richard J 
Published: September 2013

Abstract

Background
Human metapneumovirus (HMPV) is now a major cause of lower respiratory infection in children. Although primary isolation of HMPV has been achieved in several different cell lines, the low level of virus replication and the subsequent recovery of low levels of infectious HMPV have hampered biochemical studies on the virus. These experimental methodologies usually require higher levels of biological material that can be achieved following HMPV infection. In this study we demonstrate that expression of the HMPV F, G and M proteins in mammalian cells leads to HMPV virus-like particles (VLP) formation. This experimental strategy will serve as a model system to allow the process of HMPV virus assembly to be examined.

Methods
The HMPV F, G and M proteins were expressed in mammalian cell lines. Protein cross-linking studies, sucrose gradient centrifugation and in situ imaging was used to examine interactions between the virus proteins. VLP formation was examined using sucrose density gradient centrifugation and electron microscopy analysis.

Results
Analysis of cells co-expressing the F, G and M proteins demonstrated that these proteins interacted. Furthermore, in cells co-expression the three HMPV proteins the formation VLPs was observed. Image analysis revealed the VLPs had a similar morphology to the filamentous virus morphology that we observed on HMPV-infected cells. The capacity of each protein to initiate VLP formation was examined using a VLP formation assay. Individual expression of each virus protein showed that the G protein was able to form VLPs in the absence of the other virus proteins. Furthermore, co-expression of the G protein with either the M or F proteins facilitated their incorporation into the VLP fraction.

Conclusion
Co-expression of the F, G and M proteins leads to the formation of VLPs, and that incorporation of the F and M proteins into VLPs is facilitated by their interaction with the G protein. Our data suggests that the G protein plays a central role in VLP formation, and further suggests that the G protein may also play a role in the recruitment of the F and M proteins to sites of virus particle formation during HMPV infection.
Noise propagation through extracellular signaling leads to fluctuations in gene expression
Authors: Tabbaa Omar P , Nudelman German , Sealfon Stuart C , Hayot Fernand , Jayaprakash Ciriyam 
Published: September 2013

Abstract

Background
Cell-to-cell variability in mRNA and proteins has been observed in many biological systems, including the human innate immune response to viral infection. Most of these studies have focused on variability that arises from (a) intrinsic stochastic fluctuations in gene expression and (b) extrinsic sources (e.g. fluctuations in transcription factors). The main focus of our study is the effect of extracellular signaling on enhancing intrinsic stochastic fluctuations. As a new source of noise, the communication between cells with fluctuating numbers of components has received little attention. We use agent-based modeling to study this contribution to noise in a system of human dendritic cells responding to viral infection.

Results
Our results, validated by single-cell experiments, show that in the transient state cell-to-cell variability in an interferon-stimulated gene (DDX58) arises from the interplay between the spatial randomness of the cellular sources of the interferon and the temporal stochasticity of its own production. The numerical simulations give insight into the time scales on which autocrine and paracrine signaling act in a heterogeneous population of dendritic cells upon viral infection. We study the effect of different factors that influence the magnitude of the cell-to-cell-variability of the induced gene, including the cell density, multiplicity of infection, and the time scale over which the cellular sources begin producing the cytokine.

Conclusions
We propose a mechanism of noise propagation through extracellular communication and establish conditions under which the mechanism is operative. The cellular stochasticity of gene induction, which we investigate, is not limited to the specific interferon-induced gene we have studied; a broad distribution of copy numbers across cells is to be expected for other interferon-stimulated genes. This can lead to functional consequences for the system-level response to a viral challenge.
The nature of parts of speech
Authors: Lehmann Christian 
Published: September 2013

AbstractParts of speech have both semantic and structural aspects. The two sets of features are essentially incommensurate, since the semantic features derive from the functions of language in communication and cognition, while the structural features are essentially based in the combinatorial potential of signs in a text. Consequently, the two sets of features are largely independent of each other.Their combination in a language yields sets of parts of speech whose systematicity is largely language-internal. To the extent that there is a functional motivation for parts of speech, three restrictions must be made: 1) It is not, in the first place, a cognitive, but rather a communicative motivation. 2) The functional motivation of word classes is not direct, but mediated by semantic and syntactic categories of higher order. 3) Only the primary word classes (verb and noun) are motivated in this way. The secondary classes (adjectives, adverbs etc.) and the minor word classes (pronouns, subordinators etc.) increasingly have a systeminternal structural rather than a universal functional motivation. Given these heterogeneous functions and constraints, there is no uniform nature to all parts of speech.
Severe unilateral scissor bite and bimaxillary protrusion treated by horseshoe Le Fort I osteotomy combined with mid-alveolar osteotomy
Authors: Shimazaki Kazuo , Otsubo Kunihiko , Yonemitsu Ikuo , Kimizuka Sachiko , Omura Susumu , Ono Takashi 
Published: September 2013

ABSTRACT
This report describes an orthognathic surgical case employing horseshoe Le Fort I osteotomy (HLFO) combined with mid-alveolar osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) for a patient with severe unilateral scissor bite and bimaxillary protrusion. A female patient (aged 26 years, 2 months) presented with a chief complaint of dysmasesis caused by scissor bite on the right side. The clinical examination revealed difficulty in lip closure and a convex profile. Overerupted right maxillary premolars and molars and lingual tipping of the right mandibular premolars and molars were indicated before treatment. After 3 months of presurgical orthodontic treatment, two-jaw surgery involving a combination of HLFO with mid-alveolar osteotomy and BSSRO was performed. A good interdigitation in the right side was established by superior-posterior-medial movement of the dento-alveolar segment of the maxilla. Next, both the maxilla and mandible were moved superiorly and posteriorly to correct the improper lip protrusion, thereby improving the patient's profile. Our results suggest that this new orthognathic surgery technique—achieved by combining HLFO with mid-alveolar osteotomy and BSSRO—is effective for adult patients exhibiting severe unilateral scissor bite and bimaxillary protrusion.