bluuebunny/crossref_metadata_2025_split huggingface dataset:
The population genetics of cooperative gene regulation
Authors: Stewart Alexander J , Seymour Robert M , Pomiankowski Andrew , Plotkin Joshua B 
Published: September 2012

Abstract

Background
Changes in gene regulatory networks drive the evolution of phenotypic diversity both within and between species. Rewiring of transcriptional networks is achieved either by changes to transcription factor binding sites or by changes to the physical interactions among transcription factor proteins. It has been suggested that the evolution of cooperative binding among factors can facilitate the adaptive rewiring of a regulatory network.

Results
We use a population-genetic model to explore when cooperative binding of transcription factors is favored by evolution, and what effects cooperativity then has on the adaptive re-writing of regulatory networks. We consider a pair of transcription factors that regulate multiple targets and overlap in the sets of target genes they regulate. We show that, under stabilising selection, cooperative binding between the transcription factors is favoured provided the amount of overlap between their target genes exceeds a threshold. The value of this threshold depends on several population-genetic factors: strength of selection on binding sites, cost of pleiotropy associated with protein-protein interactions, rates of mutation and population size. Once it is established, we find that cooperative binding of transcription factors significantly accelerates the adaptive rewiring of transcriptional networks under positive selection. We compare our qualitative predictions to systematic data on Saccharomyces cerevisiae transcription factors, their binding sites, and their protein-protein interactions.

Conclusions
Our study reveals a rich set of evolutionary dynamics driven by a tradeoff between the beneficial effects of cooperative binding at targets shared by a pair of factors, and the detrimental effects of cooperative binding for non-shared targets. We find that cooperative regulation will evolve when transcription factors share a sufficient proportion of their target genes. These findings help to explain empirical pattens in datasets of transcription factors in Saccharomyces cerevisiae and, they suggest that changes to physical interactions between transcription factors can play a critical role in the evolution of gene regulatory networks.
Comparative genomics of the white-rot fungi, Phanerochaete carnosa and P. chrysosporium, to elucidate the genetic basis of the distinct wood types they colonize
Authors: Suzuki Hitoshi , MacDonald Jacqueline , Syed Khajamohiddin , Salamov Asaf , Hori Chiaki , Aerts Andrea , Henrissat Bernard , Wiebenga Ad , vanKuyk Patricia A , Barry Kerrie , Lindquist Erika , LaButti Kurt , Lapidus Alla , Lucas Susan , Coutinho Pedro , Gong Yunchen , Samejima Masahiro , Mahadevan Radhakrishnan , Abou-Zaid Mamdouh , de Vries Ronald P , Igarashi Kiyohiko , Yadav Jagjit S , Grigoriev Igor V , Master Emma R 
Published: September 2012

Abstract

Background
Softwood is the predominant form of land plant biomass in the Northern hemisphere, and is among the most recalcitrant biomass resources to bioprocess technologies. The white rot fungus, Phanerochaete carnosa, has been isolated almost exclusively from softwoods, while most other known white-rot species, including Phanerochaete chrysosporium, were mainly isolated from hardwoods. Accordingly, it is anticipated that P. carnosa encodes a distinct set of enzymes and proteins that promote softwood decomposition. To elucidate the genetic basis of softwood bioconversion by a white-rot fungus, the present study reports the P. carnosa genome sequence and its comparative analysis with the previously reported P. chrysosporium genome.

Results

P. carnosa encodes a complete set of lignocellulose-active enzymes. Comparative genomic analysis revealed that P. carnosa is enriched with genes encoding manganese peroxidase, and that the most divergent glycoside hydrolase families were predicted to encode hemicellulases and glycoprotein degrading enzymes. Most remarkably, P. carnosa possesses one of the largest P450 contingents (266 P450s) among the sequenced and annotated wood-rotting basidiomycetes, nearly double that of P. chrysosporium. Along with metabolic pathway modeling, comparative growth studies on model compounds and chemical analyses of decomposed wood components showed greater tolerance of P. carnosa to various substrates including coniferous heartwood.

Conclusions
The P. carnosa genome is enriched with genes that encode P450 monooxygenases that can participate in extractives degradation, and manganese peroxidases involved in lignin degradation. The significant expansion of P450s in P. carnosa, along with differences in carbohydrate- and lignin-degrading enzymes, could be correlated to the utilization of heartwood and sapwood preparations from both coniferous and hardwood species.
Phylogenetic analysis of a gene cluster encoding an additional, rhizobial-like type III secretion system that is narrowly distributed among Pseudomonas syringae strains
Authors: Gazi Anastasia D , Sarris Panagiotis F , Fadouloglou Vasiliki E , Charova Spyridoula N , Mathioudakis Nikolaos , Panopoulos Nicholas J , Kokkinidis Michael 
Published: September 2012

AbstractBackgroundThe central role of Type III secretion systems (T3SS) in bacteria-plant interactions is well established, yet unexpected findings are being uncovered through bacterial genome sequencing. SomePseudomonas syringaestrains possess an uncharacterized cluster of genes encoding putative components of a second T3SS (T3SS-2) in addition to the well characterizedHrc1T3SS which is associated with disease lesions in host plants and with the triggering of hypersensitive response in non-host plants. The aim of this study is to perform anin silicoanalysis of T3SS-2, and to compare it with other known T3SSs.ResultsBased on phylogenetic analysis and gene organization comparisons, the T3SS-2 cluster of theP. syringaepv. phaseolicola strain is grouped with a second T3SS found in the pNGR234b plasmid ofRhizobiumsp. These additional T3SS gene clusters define a subgroup within theRhizobiumT3SS family. Although, T3SS-2 is not distributed as widely as theHrc1T3SS inP. syringaestrains, it was found to be constitutively expressed inP. syringaepv phaseolicola through RT-PCR experiments.ConclusionsThe relatedness of theP. syringaeT3SS-2 to a second T3SS from the pNGR234b plasmid ofRhizobiumsp., member of subgroup II of the rhizobial T3SS family, indicates common ancestry and/or possible horizontal transfer events between these species. Functional analysis and genome sequencing of more rhizobia andP. syringaepathovars may shed light into why these bacteria maintain a second T3SS gene cluster in their genome.
Prevalence of Vitamin D insufficiency and low bone mineral density in elderly Thai nursing home residents
Authors: Kruavit Anuk , Chailurkit La-or , Thakkinstian Ammarin , Sriphrapradang Chutintorn , Rajatanavin Rajata 
Published: September 2012

Abstract

Background
Numerous emerging data from research on osteoporosis among Asians found differences from Caucasians. Therefore, the aim of this study was to determine the prevalence of vitamin D insufficiency and osteoporosis in elderly participants from two nursing homes in Thailand, a country located near the equator.

Methods
The subjects of this cross-sectional study comprised 93 elderly Thai women who were living in institutional long-term nursing homes for the aged. Demographic data, daily food and calcium intake, physical activity, and sunlight exposure were measured. Lumbar spine and femoral neck bone mineral density (BMD) and biochemical levels including serum 25 hydroxyvitamin D [25(OH)D] and bone turnover markers were assessed. Vitamin D insufficiency was defined as 25(OH)D level < 70 nmol/l.

Results
The mean age of subjects was 75.2 ± 6.0 (SD) years. Dietary calcium intake was low (322 ± 158 mg/day) The mean 25(OH)D level was 64.3 ± 14.9 nmol/L and the prevalence of vitamin D insufficiency was 38.7% (95% CI: 28.8%, 49.4%). There was no correlation between serum 25(OH)D concentrations and age (r = −.11, p = 0.3). The mean BMD of lumbar spine and femoral neck were 0.92 ± 0.19 and 0.65 ± 0.10 g/cm2, respectively. Nearly a half of the subjects had osteopenia (44.1%, 95% CI: 33.8%, 54.8%) and osteoporosis (47.3%, 95% CI: 36.9%, 57.9%). Circulating C-terminal telopeptide of type I collagen (CTx) level correlated significantly with both lumbar spine (r = −0.26, p = 0.01) and femoral neck BMD (r = −0.25, p = 0.02).

Conclusions
More than one-third of Thai elderly women residing in nursing homes had vitamin D insufficiency. Almost all nursing home residents had osteoporosis and/or osteopenia.
Appraising the performance of genotyping tools in the prediction of coreceptor tropism in HIV-1 subtype C viruses
Authors: Crous Saleema , Shrestha Ram Krishna , Travers Simon A 
Published: September 2012

AbstractBackgroundIn human immunodeficiency virus type 1 (HIV-1) infection, transmitted viruses generally use the CCR5 chemokine receptor as a coreceptor for host cell entry. In more than 50% of subtype B infections, a switch in coreceptor tropism from CCR5- to CXCR4-use occurs during disease progression. Phenotypic or genotypic approaches can be used to test for the presence of CXCR4-using viral variants in an individual’s viral population that would result in resistance to treatment with CCR5-antagonists. While genotyping approaches for coreceptor-tropism prediction in subtype B are well established and verified, they are less so for subtype C.MethodsHere, using a dataset comprising V3 loop sequences from 349 CCR5-using and 56 CXCR4-using HIV-1 subtype C viruses we perform a comparative analysis of the predictive ability of 11 genotypic algorithms in their prediction of coreceptor tropism in subtype C. We calculate the sensitivity and specificity of each of the approaches as well as determining their overall accuracy. By separating the CXCR4-using viruses into CXCR4-exclusive (25 sequences) and dual-tropic (31 sequences) we evaluate the effect of the possible conflicting signal from dual-tropic viruses on the ability of a of the approaches to correctly predict coreceptor phenotype.ResultsWe determined that geno2pheno with a false positive rate of 5% is the best approach for predicting CXCR4-usage in subtype C sequences with an accuracy of 94% (89% sensitivity and 99% specificity). Contrary to what has been reported for subtype B, the optimal approaches for prediction of CXCR4-usage in sequence from viruses that use CXCR4 exclusively, also perform best at predicting CXCR4-use in dual-tropic viral variants.ConclusionsThe accuracy of genotyping approaches at correctly predicting the coreceptor usage of V3 sequences from subtype C viruses is very high. We suggest that genotyping approaches can be used to test for coreceptor tropism in HIV-1 group M subtype C with a high degree of confidence that they will identify CXCR4-usage in both CXCR4-exclusive and dual tropic variants.
The injury mortality burden in Guinea
Authors: Mamady Keita , Yao Hongyan , Zhang Xujun , Xiang Huiyun , Tan Hongzhuan , Hu Guoqing 
Published: September 2012

Abstract

Background
The injury mortality burden of Guinea has been rarely addressed. The paper aimed to report patterns of injury mortality burden in Guinea.

Methods
We retrieved the mortality data from the Guinean Annual Health Statistics Report 2007. The information about underlying cause of deaths was collected based on Guinean hospital discharge data, Hospital Mortuary and City Council Mortuary data. The causes of death are coded in the 9th International Classification of Diseases (ICD-9). Multivariate Poisson regression was used to test the impacts of sex and age on mortality rates. The statistical analyses were performed using Statatm 10.0.

Results
In 2007, 7066 persons were reported dying of injuries in Guinea (mortality: 72.8 per 100,000 population). Transportation, fire/burn, falls, homicide and drowning were the five leading causes of fatal injuries for the whole population, accounting for 37%, 22%, 12%, 10% and 6% of total deaths, respectively. In general, age-specific injury causes displayed similar patterns of the whole population except that poisoning replaced falls as a leading cause among children under five years old. Males were at 30-50% more risk of dying from six commonest causes than females and old age groups had higher injury mortality rates than younger age groups.

Conclusion
Transportation, fire/burn, falls, homicide, and drowning accounted for the majority of total injury mortality burden in Guinea. Males and old adults were high-risk population of fatal injuries and should be targeted by injury prevention. Lots of work is needed to improve weak capacities for injury control in order to reduce the injury mortality burden.
Vectorial secretion of CTGF as a cell-type specific response to LPA and TGF-β in human tubular epithelial cells
Authors: Zuehlke Jonathan , Ebenau Astrid , Krueger Bettina , Goppelt-Struebe Margarete 
Published: September 2012

Abstract

Background
Increased expression of the pro-fibrotic protein connective tissue growth factor (CTGF) has been detected in injured kidneys and elevated urinary levels of CTGF are discussed as prognostic marker of chronic kidney disease. There is evidence that epithelial cells lining the renal tubular system contribute to uptake and secretion of CTGF. However, the role of different types of tubular epithelial cells in these processes so far has not been addressed in primary cultures of human cells.

Results
Tubular epithelial cells of proximal and distal origin were isolated from human kidneys and cultured as polarized cells in insert wells. The pro-fibrotic stimuli lysophosphatidic acid (LPA) and transforming growth factor β (TGF-β) were used to induce CTGF secretion.
LPA activated CTGF secretion in proximal tubular cells when applied from either the apical or the basolateral side as shown by immunocytochemistry. CTGF was secreted exclusively to the apical side. Signaling pathways activated by LPA included MAP kinase and Rho kinase signaling. TGF-β applied from either side also stimulated CTGF secretion primarily to the apical side with little basolateral release.
Interestingly, TGF-β activation induced different signaling pathways depending on the side of TGF-β application. Smad signaling was almost exclusively activated from the basolateral side most prominently in cells of distal origin. Only part of these cells also synthesized CTGF indicating that Smad activation alone was not sufficient for CTGF induction. MAP kinases were involved in apical TGF-β-mediated activation of CTGF synthesis in proximal cells and a subset of epithelial cells of distal origin. This subpopulation of distal tubular cells was also able to internalize recombinant apical CTGF, in addition to proximal cells which were the main cells to take up exogenous CTGF.

Conclusions
Analysis of polarized human primary renal epithelial cells in a transwell system shows that vectorial secretion of the pro-fibrotic protein CTGF depends on the cell type, the stimulus and the signaling pathway activated. In all conditions, CTGF was secreted mainly to the apical side upon TGF-β and LPA treatment and therefore, likely contributes to increased urinary CTGF levels in vivo. Moreover, CTGF secreted basolaterally may be active as paracrine pro-fibrotic mediator.
Characterization of hybrid cobalt-porous silicon systems: protective effect of the Matrix in the metal oxidation
Authors: Muñoz-Noval Álvaro , Gallach Darío , García Miguel Ángel , Ferro-Llanos Vicente , Herrero Pilar , Fukami Kazuhiro , Ogata Yukio H , Torres-Costa Vicente , Martín-Palma Raúl J , Ciment-Font Aurelio , Manso-Silván Miguel 
Published: September 2012

Abstract
In the present work, the characterization of cobalt-porous silicon (Co-PSi) hybrid systems is performed by a combination of magnetic, spectroscopic, and structural techniques. The Co-PSi structures are composed by a columnar matrix of PSi with Co nanoparticles embedded inside, as determined by Transmission Electron Microscopy (TEM). The oxidation state, crystalline structure, and magnetic behavior are determined by X-Ray Absorption Spectroscopy (XAS) and Alternating Gradient Field Magnetometry (AGFM). Additionally, the Co concentration profile inside the matrix has been studied by Rutherford Backscattering Spectroscopy (RBS). It is concluded that the PSi matrix can be tailored to provide the Co nanoparticles with extra protection against oxidation.
Structural variations of Si1−xC
x
and their light absorption controllability
Authors: Moon Jihyun , Baik Seung Jae , O Byungsung , Lee Jeong Chul 
Published: September 2012

Abstract
The emergence of third-generation photovoltaics based on Si relies on tunable bandgap materials with embedded nanocrystalline Si. One of the most promising approaches is based on the mixed-phase Si1 − x
C
x
. We have investigated the light absorption controllability of nanocrystalline Si-embedded Si1 − x
C
x
produced by thermal annealing of the Si-rich Si1 − x
C
x
and composition-modulated superlattice structure. In addition, stoichiometric SiC was also investigated to comparatively analyze the characteristic differences. As a result, it was found that stoichiometric changes of the matrix material and incorporation of oxygen play key roles in light absorption controllability. Based on the results of this work and literature, a design strategy of nanocrystalline Si-embedded absorber materials for third-generation photovoltaics is discussed.
Development and validation of a method for purification of mallein for the diagnosis of glanders in equines
Authors: de Carvalho Filho Maurício Baltazar , Ramos Rodrigo Mauro , Fonseca Antônio Augusto , de Lima Orzil Lívia , Sales Mariana Lázaro , de Assis Santana Vania Lucia , de Souza Marcilia Maria Alves , dos Reis Machado Evandro , Filho Paulo Rodrigues Lopes , Leite Rômulo Cerqueira , dos Reis Jenner Karlisson Pimenta 
Published: September 2012

Abstract

Background
The allergic test of mallein is one of the most frequently used tests, together with the Complement Fixation Test (CFT), for the diagnosis of glanders in endemic areas. Mallein, a purified protein derivative (PPD), is produced similarly to PPD tuberculin and the end product is a primarily proteic antigen, which is only poorly purified. The immuno-allergic activity of mallein is believed to be due to a high molecular weight group of proteins present in the antigen. To improve the quality of the antigen, in terms of sensitivity and specificity, a new method of mallein production was developed, in which purification was accomplished by ultrafiltration in a Tangential Flow Filtration system (TFF).

Results
The TFF methodology efficiently separated the high and low molecular weight protein groups of mallein. The five TFF-purified malleins, produced from Burkholderia mallei strains isolated from clinical cases of glanders in Brazil, proved to be more potent than standard mallein in the induction of an allergic reaction in sensitized animals. Regarding specificity, two of the purified malleins were equivalent to the standard and three were less specific.

Conclusion
Some of the TFF-purified malleins showed considerable potential to be used as an auxiliary test in the diagnosis of glanders.
Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3
Authors: Eisenberger Tobias , Slim Rima , Mansour Ahmad , Nauck Markus , Nürnberg Gudrun , Nürnberg Peter , Decker Christian , Dafinger Claudia , Ebermann Inga , Bergmann Carsten , Bolz Hanno Jörn 
Published: September 2012

Abstract

Background
Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family.

Methods
Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing.

Results
Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype.

Conclusion
Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (p olyneuropathy, h earing loss, a taxia, r etinitis pigmentosa, and early-onset c ataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis.
An integer optimization algorithm for robust identification of non-linear gene regulatory networks
Authors: Chemmangattuvalappil Nishanth , Task Keith , Banerjee Ipsita 
Published: September 2012

Abstract

Background
Reverse engineering gene networks and identifying regulatory interactions are integral to understanding cellular decision making processes. Advancement in high throughput experimental techniques has initiated innovative data driven analysis of gene regulatory networks. However, inherent noise associated with biological systems requires numerous experimental replicates for reliable conclusions. Furthermore, evidence of robust algorithms directly exploiting basic biological traits are few. Such algorithms are expected to be efficient in their performance and robust in their prediction.

Results
We have developed a network identification algorithm to accurately infer both the topology and strength of regulatory interactions from time series gene expression data in the presence of significant experimental noise and non-linear behavior. In this novel formulism, we have addressed data variability in biological systems by integrating network identification with the bootstrap resampling technique, hence predicting robust interactions from limited experimental replicates subjected to noise. Furthermore, we have incorporated non-linearity in gene dynamics using the S-system formulation. The basic network identification formulation exploits the trait of sparsity of biological interactions. Towards that, the identification algorithm is formulated as an integer-programming problem by introducing binary variables for each network component. The objective function is targeted to minimize the network connections subjected to the constraint of maximal agreement between the experimental and predicted gene dynamics. The developed algorithm is validated using both in silico and experimental data-sets. These studies show that the algorithm can accurately predict the topology and connection strength of the in silico networks, as quantified by high precision and recall, and small discrepancy between the actual and predicted kinetic parameters. Furthermore, in both the in silico and experimental case studies, the predicted gene expression profiles are in very close agreement with the dynamics of the input data.

Conclusions
Our integer programming algorithm effectively utilizes bootstrapping to identify robust gene regulatory networks from noisy, non-linear time-series gene expression data. With significant noise and non-linearities being inherent to biological systems, the present formulism, with the incorporation of network sparsity, is extremely relevant to gene regulatory networks, and while the formulation has been validated against in silico and E. Coli data, it can be applied to any biological system.