bluuebunny/crossref_metadata_2025_split huggingface dataset:
NETGEM: Network Embedded Temporal GEnerative Model for gene expression data
Authors: Jethava Vinay , Bhattacharyya Chiranjib , Dubhashi Devdatt , Vemuri Goutham N 
Published: August 2011

Abstract

Background
Temporal analysis of gene expression data has been limited to identifying genes whose expression varies with time and/or correlation between genes that have similar temporal profiles. Often, the methods do not consider the underlying network constraints that connect the genes. It is becoming increasingly evident that interactions change substantially with time. Thus far, there is no systematic method to relate the temporal changes in gene expression to the dynamics of interactions between them. Information on interaction dynamics would open up possibilities for discovering new mechanisms of regulation by providing valuable insight into identifying time-sensitive interactions as well as permit studies on the effect of a genetic perturbation.

Results
We present NETGEM, a tractable model rooted in Markov dynamics, for analyzing the dynamics of the interactions between proteins based on the dynamics of the expression changes of the genes that encode them. The model treats the interaction strengths as random variables which are modulated by suitable priors. This approach is necessitated by the extremely small sample size of the datasets, relative to the number of interactions. The model is amenable to a linear time algorithm for efficient inference. Using temporal gene expression data, NETGEM was successful in identifying (i) temporal interactions and determining their strength, (ii) functional categories of the actively interacting partners and (iii) dynamics of interactions in perturbed networks.

Conclusions
NETGEM represents an optimal trade-off between model complexity and data requirement. It was able to deduce actively interacting genes and functional categories from temporal gene expression data. It permits inference by incorporating the information available in perturbed networks. Given that the inputs to NETGEM are only the network and the temporal variation of the nodes, this algorithm promises to have widespread applications, beyond biological systems.
The source code for NETGEM is available from https://github.com/vjethava/NETGEM
A formalized description of the standard human variant nomenclature in Extended Backus-Naur Form
Authors: Laros Jeroen FJ , Blavier André , den Dunnen Johan T , Taschner Peter EM 
Published: August 2011

Abstract

Background
The use of a standard human sequence variant nomenclature is advocated by the Human Genome Variation Society in order to unambiguously describe genetic variants in databases and literature. There is a clear need for tools that allow the mining of data about human sequence variants and their functional consequences from databases and literature. Existing text mining focuses on the recognition of protein variants and their effects. The recognition of variants at the DNA and RNA levels is essential for dissemination of variant data for diagnostic purposes. Development of new tools is hampered by the complexity of the current nomenclature, which requires processing at the character level to recognize the specific syntactic constructs used in variant descriptions.

Results
We approached the gene variant nomenclature as a scientific sublanguage and created two formal descriptions of the syntax in Extended Backus-Naur Form: one at the DNA-RNA level and one at the protein level. To ensure compatibility to older versions of the human sequence variant nomenclature, previously recommended variant description formats have been included. The first grammar versions were designed to help build variant description handling in the Alamut mutation interpretation software. The DNA and RNA level descriptions were then updated and used to construct the context-free parser of the Mutalyzer 2 sequence variant nomenclature checker, which has already been used to check more than one million variant descriptions.

Conclusions
The Extended Backus-Naur Form provided an overview of the full complexity of the syntax of the sequence variant nomenclature, which remained hidden in the textual format and the division of the recommendations across the DNA, RNA and protein sections of the Human Genome Variation Society nomenclature website (http://www.hgvs.org/mutnomen/). This insight into the syntax of the nomenclature could be used to design detailed and clear rules for software development. The Mutalyzer 2 parser demonstrated that it facilitated decomposition of complex variant descriptions into their individual parts. The Extended Backus-Naur Form or parts of it can be used or modified by adding rules, allowing the development of specific sequence variant text mining tools and other programs, which can generate or handle sequence variant descriptions.
The BioAssay network and its implications to future therapeutic discovery
Authors: Zhang Jintao , Lushington Gerald H , Huan Jun 
Published: August 2011

Abstract

Background
Despite intense investment growth and technology development, there is an observed bottleneck in drug discovery and development over the past decade. NIH started the Molecular Libraries Initiative (MLI) in 2003 to enlarge the pool for potential drug targets, especially from the “undruggable” part of human genome, and potential drug candidates from much broader types of drug-like small molecules. All results are being made publicly available in a web portal called PubChem.

Results
In this paper we construct a network from bioassay data in PubChem, apply network biology concepts to characterize this bioassay network, integrate information from multiple biological databases (e.g. DrugBank, OMIM, and UniHI), and systematically analyze the potential of bioassay targets being new drug targets in the context of complex biological networks. We propose a model to quantitatively prioritize this druggability of bioassay targets, and literature evidence was found to confirm our prioritization of bioassay targets at a roughly 70% accuracy.

Conclusions
Our analysis provide some measures of the value of the MLI data as a resource for both basic chemical biology research and future therapeutic discovery.
Hypoxia-mimetic agents inhibit proliferation and alter the morphology of human umbilical cord-derived mesenchymal stem cells
Authors: Zeng Hui-Lan , Zhong Qi , Qin Yong-Liang , Bu Qian-Qian , Han Xin-Ai , Jia Hai-Tao , Liu Hong-Wei 
Published: August 2011

Abstract

Background
The therapeutic efficacy of human mesenchymal stem cells (hMSCs) for the treatment of hypoxic-ischemic diseases is closely related to level of hypoxia in the damaged tissues. To elucidate the potential therapeutic applications and limitations of hMSCs derived from human umbilical cords, the effects of hypoxia on the morphology and proliferation of hMSCs were analyzed.

Results
After treatment with DFO and CoCl2, hMSCs were elongated, and adjacent cells were no longer in close contact. In addition, vacuole-like structures were observed within the cytoplasm; the rough endoplasmic reticulum expanded, and expanded ridges were observed in mitochondria. In addition, DFO and CoCl2 treatments for 48 h significantly inhibited hMSCs proliferation in a concentration-dependent manner (P < 0.05). This treatment also increased the number of cells in G0/G1 phase and decreased those in G2/S/M phase.

Conclusions
The hypoxia-mimetic agents, DFO and CoCl2, alter umbilical cord-derived hMSCs morphology and inhibit their proliferation through influencing the cell cycle.
A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests
Authors: Johansson Henrik , Lindstedt Malin , Albrekt Ann-Sofie , Borrebaeck Carl AK 
Published: August 2011

Abstract

Background
Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power.

Results
We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization.

Conclusions
A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.
On the quest for selective constraints shaping the expressivity of the genes casting retropseudogenes in human
Authors: Sen Kamalika , Podder Soumita , Ghosh Tapash C 
Published: August 2011

AbstractBackgroundPseudogenes, the nonfunctional homologues of functional genes are now coming to light as important resources regarding the study of human protein evolution. Processed pseudogenes arising by reverse transcription and reinsertion can provide molecular record on the dynamics and evolution of genomes. Researches on the progenitors of human processed pseudogenes delved out their highly expressed and evolutionarily conserved characters. They are reported to be short and GC-poor indicating their high efficiency for retrotransposition. In this article we focused on their high expressivity and explored the factors contributing for that and their relevance in the milieu of protein sequence evolution.ResultsWe here, analyzed the high expressivity of these genes configuring processed or retropseudogenes by their immense connectivity in protein-protein interaction network, an inclination towards alternative splicing mechanism, a lower rate of mRNA disintegration and a slower evolutionary rate. While the unusual trend of the upraised disorder in contrast with the high expressivity of the proteins encoded by processed pseudogene ancestors is accredited by a predominance of hub-protein encoding genes, a high propensity of repeat sequence containing genes, elevated protein stability and the functional constraint to perform the transcription regulatory jobs. Linear regression analysis demonstrates mRNA decay rate and protein intrinsic disorder as the influential factors controlling the expressivity of these retropseudogene ancestors while the latter one is found to have the most significant regulatory power.ConclusionsOur findings imply that, the affluence of disordered regions elevating the network attachment to be involved in important cellular assignments and the stability in transcriptional level are acting as the prevailing forces behind the high expressivity of the human genes configuring processed pseudogenes.
Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A
Authors: Livas Daniela , Almering Marinka JH , Daran Jean-Marc , Pronk Jack T , Gancedo Juana M 
Published: August 2011

AbstractBackgroundThe pattern of gene transcripts in the yeastSaccharomyces cerevisiaeis strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. InS. cerevisiaethree genes,TPK1, TPK2, andTPK3, encode catalytic subunits of PKA. The lack of viability oftpk1 tpk2 tpk3triple mutants may be suppressed by mutations such asyak1ormsn2/msn4. To investigate the requirement for PKA in glucose control of gene expression, we have compared the effects of glucose on global transcription in a wild-type strain and in two strains devoid of PKA activity,tpk1 tpk2 tpk3 yak1andtpk1 tpk2 tpk3 msn2 msn4.ResultsWe have identified different classes of genes that can be induced -or repressed- by glucose in the absence of PKA. Representative examples are genes required for glucose utilization and genes involved in the metabolism of other carbon sources, respectively. Among the genes responding to glucose in strains devoid of PKA some are also controlled by a redundant signalling pathway involving PKA activation, while others are not affected when PKA is activated through an increase in cAMP concentration. On the other hand, among genes that do not respond to glucose in the absence of PKA, some give a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways. We show also that, for a number of genes controlled by glucose through a PKA-dependent pathway, the changes in mRNA levels are transient. We found that, in cells grown in gluconeogenic conditions, expression of a small number of genes, mainly connected with the response to stress, is reduced in the strains lacking PKA.ConclusionsInS. cerevisiae, the transcriptional responses to glucose are triggered by a variety of pathways, alone or in combination, in which PKA is often involved. Redundant signalling pathways confer a greater robustness to the response to glucose, while cooperative pathways provide a greater flexibility.
Genome-wide functional annotation and structural verification of metabolic ORFeome of Chlamydomonas reinhardtii
Authors: Ghamsari Lila , Balaji Santhanam , Shen Yun , Yang Xinping , Balcha Dawit , Fan Changyu , Hao Tong , Yu Haiyuan , Papin Jason A , Salehi-Ashtiani Kourosh 
Published: August 2011

Abstract

Background
Recent advances in the field of metabolic engineering have been expedited by the availability of genome sequences and metabolic modelling approaches. The complete sequencing of the C. reinhardtii genome has made this unicellular alga a good candidate for metabolic engineering studies; however, the annotation of the relevant genes has not been validated and the much-needed metabolic ORFeome is currently unavailable. We describe our efforts on the functional annotation of the ORF models released by the Joint Genome Institute (JGI), prediction of their subcellular localizations, and experimental verification of their structural annotation at the genome scale.

Results
We assigned enzymatic functions to the translated JGI ORF models of C. reinhardtii by reciprocal BLAST searches of the putative proteome against the UniProt and AraCyc enzyme databases. The best match for each translated ORF was identified and the EC numbers were transferred onto the ORF models. Enzymatic functional assignment was extended to the paralogs of the ORFs by clustering ORFs using BLASTCLUST.
In total, we assigned 911 enzymatic functions, including 886 EC numbers, to 1,427 transcripts. We further annotated the enzymatic ORFs by prediction of their subcellular localization. The majority of the ORFs are predicted to be compartmentalized in the cytosol and chloroplast. We verified the structure of the metabolism-related ORF models by reverse transcription-PCR of the functionally annotated ORFs. Following amplification and cloning, we carried out 454FLX and Sanger sequencing of the ORFs. Based on alignment of the 454FLX reads to the ORF predicted sequences, we obtained more than 90% coverage for more than 80% of the ORFs. In total, 1,087 ORF models were verified by 454 and Sanger sequencing methods. We obtained expression evidence for 98% of the metabolic ORFs in the algal cells grown under constant light in the presence of acetate.

Conclusions
We functionally annotated approximately 1,400 JGI predicted metabolic ORFs that can facilitate the reconstruction and refinement of a genome-scale metabolic network. The unveiling of the metabolic potential of this organism, along with structural verification of the relevant ORFs, facilitates the selection of metabolic engineering targets with applications in bioenergy and biopharmaceuticals. The ORF clones are a resource for downstream studies.
Isolates from hospital environments are the most virulent of the Candida parapsilosiscomplex
Authors: Sabino Raquel , Sampaio Paula , Carneiro Catarina , Rosado Laura , Pais Célia 
Published: August 2011

AbstractBackgroundCandida parapsilosisis frequently isolated from hospital environments, like air and surfaces, and causes serious nosocomial infections. Molecular studies provided evidence of great genetic diversity within theC. parapsilosisspecies complex but, despite their growing importance as pathogens, little is known about their potential to cause disease, particularly their interactions with phagocytes. In this study, clinical and environmentalC. parapsilosisisolates, and strains of the related speciesC. orthopsilosisandC. metapsilosiswere assayed for their ability to induce macrophage cytotocixity and secretion of the pro-inflammatory cytokine TNF-α, to produce pseudo-hyphae and to secrete hydrolytic enzymes.ResultsEnvironmentalC. parapsilosisisolates caused a statistically significant (p= 0.0002) higher cell damage compared with the clinical strains, whileC. orthopsilosisandC. metapsilosiswere less cytotoxic. On the other hand, clinical isolates induced a higher TNF-α production compared with environmental strains (p< 0.0001). Whereas the amount of TNF-α produced in response toC. orthopsilosisstrains was similar to the obtained withC. parapsilosisenvironmental isolates, it was lower forC. metapsilosisstrains. No correlation between pseudo-hyphae formation or proteolytic enzymes secretion and macrophage death was detected (p> 0.05). However, a positive correlation between pseudo-hyphae formation and TNF-α secretion was observed (p= 0.0119).ConclusionsWe show that environmentalC. parapsilosisstrains are more resistant to phagocytic host defences than bloodstream isolates, being potentially more deleterious in the course of infection than strains from a clinical source. Thus, active environmental surveillance and application of strict cleaning procedures should be implemented in order to prevent cross-infection and hospital outbreaks.
Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1
Authors: Gregor Anne , Albrecht Beate , Bader Ingrid , Bijlsma Emilia K , Ekici Arif B , Engels Hartmut , Hackmann Karl , Horn Denise , Hoyer Juliane , Klapecki Jakub , Kohlhase Jürgen , Maystadt Isabelle , Nagl Sandra , Prott Eva , Tinschert Sigrid , Ullmann Reinhard , Wohlleber Eva , Woods Geoffrey , Reis André , Rauch Anita , Zweier Christiane 
Published: August 2011

AbstractBackgroundHeterozygous copy-number and missense variants inCNTNAP2andNRXN1have repeatedly been associated with a wide spectrum of neuropsychiatric disorders such as developmental language and autism spectrum disorders, epilepsy and schizophrenia. Recently, homozygous or compound heterozygous defects in either gene were reported as causative for severe intellectual disability.Methods99 patients with severe intellectual disability and resemblance to Pitt-Hopkins syndrome and/or suspected recessive inheritance were screened for mutations inCNTNAP2andNRXN1. Molecular karyotyping was performed in 45 patients. In 8 further patients with variable intellectual disability and heterozygous deletions in eitherCNTNAP2orNRXN1, the remaining allele was sequenced.ResultsBy molecular karyotyping and mutational screening ofCNTNAP2andNRXN1in a group of severely intellectually disabled patients we identified a heterozygous deletion inNRXN1in one patient and heterozygous splice-site, frameshift and stop mutations inCNTNAP2in four patients, respectively. Neither in these patients nor in eight further patients with heterozygous deletions withinNRXN1orCNTNAP2we could identify a defect on the second allele. One deletion inNRXN1and one deletion inCNTNAP2occurredde novo, in another family the deletion was also identified in the mother who had learning difficulties, and in all other tested families one parent was shown to be healthy carrier of the respective deletion or mutation.ConclusionsWe report on patients with heterozygous defects inCNTNAP2orNRXN1associated with severe intellectual disability, which has only been reported for recessive defects before. These results expand the spectrum of phenotypic severity in patients with heterozygous defects in either gene. The large variability between severely affected patients and mildly affected or asymptomatic carrier parents might suggest the presence of a second hit, not necessarily located in the same gene.
The Chinese version of the Obsessive-Compulsive Inventory-Revised scale: Replication and extension to non-clinical and clinical individuals with OCD symptoms
Authors: Peng Zi-wen , Yang Wen-han , Miao Guo-dong , Jing Jin , Chan Raymond CK 
Published: August 2011

Abstract

Background
The Obsessive-Compulsive Inventory-Revised (OCI-R) was designed to evaluate the severity of obsessive-compulsive symptoms in both clinical and non-clinical samples. The aim of the study was to evaluate the psychometric properties of a Chinese version of this scale.

Methods
The Chinese version of the OCI-R was administered to both a non-clinical sample (209 undergraduate students) and a clinical sample (56 obsessive-compulsive disorder (OCD) patients). Confirmatory factor analysis was conducted to examine the construct validity of the OCI-R in the non-clinical sample. The internal consistency at baseline and test-retest reliabilities at 4-week interval was examined in both the non-clinical and clinical samples.

Results
The confirmatory factor analysis of the non-clinical sample confirmed a 6-factor model suggested by the original authors of the instrument (df = 120, RMSEA = 0.068, CFI = 0.88, NNFI = 0.85, GFI = 0.89). The internal consistency and test-retest reliability were at an acceptable range for both the non-clinical and clinical samples. The OCI-R also showed good clinical discrimination for patients with OCD from healthy controls.

Conclusions
The Chinese version of the OCI-R is a valid and reliable instrument for measuring OCD symptoms in the Chinese context.