bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial effects on mineral–radionuclide interactions and radionuclide solid-phase capture processes
Authors: Brookshaw D. R. , Pattrick R. A. D. , Lloyd J. R. , Vaughan D. J. 
Published: July 2012

AbstractUnderstanding the environmental and biogeochemical behaviour of radionuclides is essential for managing our nuclear legacy safely. Remediation efforts and the concept of geological disposal of nuclear waste focus on immobilizing radionuclides within the subsurface. Here we review recent developments in the understanding of solid-phase capture processes of Cs, Sr, Tc, U, Pu and Np. Abiotic interactions between minerals and these radionuclides (including sorption, reductive precipitation and co-precipitation) have been studied in various conditions. Microbially driven processes are much less well characterized, for example the effects of microbial reduction on the structure and reactivity of existing minerals, or their role in the formation of new minerals. Metabolites released by bacteria can play a role in both mineral dissolution and formation, and better understanding their release and role in mineralization has great potential in the development of solid-phase capture processes for radionuclides.With the aid of a map of the research landscape covered by this review (created using a cluster-analysis tool, a self-organizing map), we highlight the most promising sequestration processes for specific radionuclides. However, radionuclides exhibit highly species-specific behaviour in their interactions with minerals and microorganisms. More research is required to characterize the role mineral surfaces play in bioreductive immobilization of Pu and Np, the reduction products formed, and their relative stability. Further studies should concentrate on more environmentally relevant experiments that include bacteria, minerals and radionuclides.
Minimalist ensemble algorithms for genome-wide protein localization prediction
Authors: Lin Jhih-Rong , Mondal Ananda Mohan , Liu Rong , Hu Jianjun 
Published: July 2012

Abstract

Background
Computational prediction of protein subcellular localization can greatly help to elucidate its functions. Despite the existence of dozens of protein localization prediction algorithms, the prediction accuracy and coverage are still low. Several ensemble algorithms have been proposed to improve the prediction performance, which usually include as many as 10 or more individual localization algorithms. However, their performance is still limited by the running complexity and redundancy among individual prediction algorithms.

Results
This paper proposed a novel method for rational design of minimalist ensemble algorithms for practical genome-wide protein subcellular localization prediction. The algorithm is based on combining a feature selection based filter and a logistic regression classifier. Using a novel concept of contribution scores, we analyzed issues of algorithm redundancy, consensus mistakes, and algorithm complementarity in designing ensemble algorithms. We applied the proposed minimalist logistic regression (LR) ensemble algorithm to two genome-wide datasets of Yeast and Human and compared its performance with current ensemble algorithms. Experimental results showed that the minimalist ensemble algorithm can achieve high prediction accuracy with only 1/3 to 1/2 of individual predictors of current ensemble algorithms, which greatly reduces computational complexity and running time. It was found that the high performance ensemble algorithms are usually composed of the predictors that together cover most of available features. Compared to the best individual predictor, our ensemble algorithm improved the prediction accuracy from AUC score of 0.558 to 0.707 for the Yeast dataset and from 0.628 to 0.646 for the Human dataset. Compared with popular weighted voting based ensemble algorithms, our classifier-based ensemble algorithms achieved much better performance without suffering from inclusion of too many individual predictors.

Conclusions
We proposed a method for rational design of minimalist ensemble algorithms using feature selection and classifiers. The proposed minimalist ensemble algorithm based on logistic regression can achieve equal or better prediction performance while using only half or one-third of individual predictors compared to other ensemble algorithms. The results also suggested that meta-predictors that take advantage of a variety of features by combining individual predictors tend to achieve the best performance. The LR ensemble server and related benchmark datasets are available at http://mleg.cse.sc.edu/LRensemble/cgi-bin/predict.cgi.
Exogenous erythropoietin administration attenuates intermittent hypoxia-induced cognitive deficits in a murine model of sleep apnea
Authors: Dayyat Ehab A , Zhang Shelley X , Wang Yang , Cheng Zixi Jack , Gozal David 
Published: July 2012

Abstract

Background
In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Such findings are markedly attenuated in rodents exposed to sustained hypoxia 9SH) of similar magnitude. The hypoxia-sensitive gene erythropoietin (EPO) has emerged as a major endogenous neuroprotectant, and could be involved in IH-induced neuronal dysfunction.

Methods and Results
IH induced only transiently increased expression of EPO mRNA in hippocampus, which was continued in (SH)-exposed mice. IH, but not SH, adversely affected two forms of spatial learning in the water maze, and increased markers of oxidative stress. However, on a standard place training task, mice treated with exogenously administered EPO displayed normal learning, and were protected from the spatial learning deficits observed in vehicle-treated (C) littermates exposed to IH. Moreover, anxiety levels were increased in IH as compared to normoxia, while no changes in anxiety emerged in EPO-treated mice. Additionally, C mice, but not EPO-treated IH-exposed mice had significantly elevated levels of NADPH oxidase expression, as well as increased MDA and 8-OHDG levels in cortical and hippocampal lysates.

Conclusions
The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by imbalances between EPO expression and increased NADPH oxidase activity, and thus pharmacological agents targeting EPO expression in CNS may provide a therapeutic strategy in sleep-disordered breathing.
Phosphorylation of transglutaminase 2 (TG2) at serine-216 has a role in TG2 mediated activation of nuclear factor-kappa B and in the downregulation of PTEN
Authors: Wang Yi , Ande Sudharsana R , Mishra Suresh 
Published: July 2012

Abstract

Background
Transglutaminase 2 (TG2) and its phosphorylation have been consistently found to be upregulated in a number of cancer cell types. At the molecular level, TG2 has been associated with the activation of nuclear factor-kappa B (NF-κB), protein kinase B (PKB/Akt) and in the downregulation of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). However, the underlying mechanism involved is not known. We have reported that protein kinase A (PKA) induced phosphorylation of TG2 at serine-216 (Ser216) regulates TG2 function and facilitates protein-protein interaction. However, the role of TG2 phosphorylation in the modulation of NF-κB, Akt and PTEN is not explored.

Methods
In this study we have investigated the effect of TG2 phosphorylation on NF-κB, Akt and PTEN using embryonic fibroblasts derived from TG2 null mice (MEF
tg2-/-
) overexpressing native TG2 or mutant-TG2 (m-TG2) lacking Ser216 phosphorylation site with and without dibutyryl cyclic-AMP (db-cAMP) stimulation. Functional consequences on cell cycle and cell motility were determined by fluorescence activated cell sorting (FACS) analysis and cell migration assay respectively.

Results
PKA activation in TG2 overexpressing MEF
tg2-/-
cells resulted in an increased activation of NF-κB and Akt phosphorylation in comparison to empty vector transfected control cells as determined by the reporter-gene assay and immunoblot analysis respectively. These effects were not observed in MEF
tg2-/-
cells overexpressing m-TG2. Similarly, a significant downregulation of PTEN at both, the mRNA and protein levels were found in cells overexpressing TG2 in comparison to empty vector control and m-TG2 transfected cells. Furthermore, Akt activation correlated with the simultaneous activation of NF-κB and a decrease in PTEN suggesting that the facilitatory effect of TG2 on Akt activation occurs in a PTEN-dependent manner. Similar results were found with MCF-7 and T-47D breast cancer cells overexpressing TG2 and m-TG2 further supporting the role of TG2 phosphorylation in NF-κB activation and in the downregulation of PTEN.

Conclusions
Collectively, these data suggest that phosphorylation of TG2 at Ser216 plays a role in TG2 mediated activation of NF-κB, Akt and in the downregulation of PTEN. Blocking TG2 phosphorylation may provide a novel strategy to attenuate NF-κB activation and downregulation of PTEN in TG2 overexpressing cancers.
Effect of physical activity and sun exposure on vitamin D status of Saudi children and adolescents
Authors: Al-Othman Abdulaziz , Al-Musharaf Sara , Al-Daghri Nasser M , Krishnaswamy Soundararajan , Yusuf Deqa S , Alkharfy Khalid M , Al-Saleh Yousef , Al-Attas Omar S , Alokail Majed S , Moharram Osama , Sabico Shaun , Chrousos George P 
Published: July 2012

Abstract

Background
Accumulating evidence suggests an increased prevalence of vitamin D deficiency in the Middle East. In this context, we aimed to determine whether the prevalence of vitamin D deficiency is related to degree of physical activity and sun exposure among apparently healthy Saudi children and adolescents, a little studied population.

Methods
A total of 331 Saudi children aged 6–17 years (153 boys and 178 girls) were included in this cross sectional study. Levels of physical activity and sun exposure were determined using a standard questionnaire. Anthropometry, serum calcium and 25-(OH) vitamin D were analyzed.

Results
All subjects were vitamin D deficient, the majority being moderately deficient (71.6%). Age was the single most significant predictor affecting 25 (OH) Vitamin D levels, explaining 21% of the variance perceived (p = 1.68 x 10-14). Age-matched comparisons revealed that for groups having the same amount of sun exposure, those with moderate or are physically active will have higher levels of vitamin D status, though levels in across groups remained deficient.

Conclusion
Vitamin D deficiency is common among Saudi children and adolescents, and is influenced by both sun exposure and physical activity. Promotion of an active outdoor lifestyle among Saudi children in both homes and schools may counteract the vitamin D deficiency epidemic in this vulnerable population. Vitamin D supplementation is suggested in all groups, including those with the highest sun exposure and physical activity.
Glycoside Hydrolases from a targeted Compost Metagenome, activity-screening and functional characterization
Authors: Dougherty Michael J , D’haeseleer Patrik , Hazen Terry C , Simmons Blake A , Adams Paul D , Hadi Masood Z 
Published: July 2012

Abstract

Background
Metagenomics approaches provide access to environmental genetic diversity for biotechnology applications, enabling the discovery of new enzymes and pathways for numerous catalytic processes. Discovery of new glycoside hydrolases with improved biocatalytic properties for the efficient conversion of lignocellulosic material to biofuels is a critical challenge in the development of economically viable routes from biomass to fuels and chemicals.

Results
Twenty-two putative ORFs (open reading frames) were identified from a switchgrass-adapted compost community based on sequence homology to related gene families. These ORFs were expressed in E. coli and assayed for predicted activities. Seven of the ORFs were demonstrated to encode active enzymes, encompassing five classes of hemicellulases. Four enzymes were over expressed in vivo, purified to homogeneity and subjected to detailed biochemical characterization. Their pH optima ranged between 5.5 - 7.5 and they exhibit moderate thermostability up to ~60-70°C.

Conclusions
Seven active enzymes were identified from this set of ORFs comprising five different hemicellulose activities. These enzymes have been shown to have useful properties, such as moderate thermal stability and broad pH optima, and may serve as the starting points for future protein engineering towards the goal of developing efficient enzyme cocktails for biomass degradation under diverse process conditions.
An inverse metabolic engineering approach for the design of an improved host platform for over-expression of recombinant proteins in Escherichia coli
Authors: Ghosh Chaitali , Gupta Rashmi , Mukherjee Krishna Jyoti 
Published: July 2012

Abstract

Background
A useful goal for metabolic engineering would be to generate non-growing but metabolically active quiescent cells which would divert the metabolic fluxes towards product formation rather than growth. However, for products like recombinant proteins, which are intricately coupled to the growth process it is difficult to identify the genes that need to be knocked-out/knocked-in to get this desired phenotype. To circumvent this we adopted an inverse metabolic engineering strategy which would screen for the desired phenotype and thus help in the identification of genetic targets which need to be modified to get overproducers of recombinant protein. Such quiescent cells would obviate the need for high cell density cultures and increase the operational life span of bioprocesses.

Results
A novel strategy for generating a library, consisting of randomly down regulated metabolic pathways in E. coli was designed by cloning small genomic DNA fragments in expression vectors. Some of these DNA fragments got inserted in the reverse orientation thereby generating anti-sense RNA upon induction. These anti-sense fragments would hybridize to the sense mRNA of specific genes leading to gene ‘silencing’. This library was first screened for slow growth phenotype and subsequently for enhanced over-expression ability. Using Green Fluorescent Protein (GFP) as a reporter protein on second plasmid, we were able to identify metabolic blocks which led to significant increase in expression levels. Thus down-regulating the ribB gene (3, 4 dihydroxy-2-butanone-4-phosphate synthase) led to a 7 fold increase in specific product yields while down regulating the gene kdpD (histidine kinase) led to 3.2 fold increase in specific yields.

Conclusion
We have designed a high throughput screening approach which is a useful tool in the repertoire of reverse metabolic engineering strategies for the generation of improved hosts for recombinant protein expression.
Diesel exhaust increases EGFR and phosphorylated C-terminal Tyr 1173 in the bronchial epithelium
Authors: Pourazar Jamshid , Blomberg Anders , Kelly Frank J , Davies Donna E , Wilson Susan J , Holgate Stephen T , Sandström Thomas 
Published: July 2012

AbstractBackgroundEpidemiological studies have demonstrated adverse health effects of environmental pollution. Diesel exhaust (DE) is a major contributor to particulate matter pollution. DE exposure has been shown to induce a pronounced inflammatory response in the airways, together with an enhanced epithelial expression of cytokines such as IL-8, Gro-α, IL-13 and activation of redox sensitive transcription factors (NFκB, AP-1), and MAP kinases (p38, JNK). The aim of the present investigation was to elucidate the involvement of the epidermal growth factor receptor (EGFR) signalling pathway in the epithelial response to DEin-vivo.ResultsImmunohistochemical staining was used to quantify the expression of the EGFR, phosphorylated Tyrosine residues, MEK and ERK in the bronchial epithelium of archived biopsies from 15 healthy subjects following exposure to DE (PM10, 300 μg/m3) and air. DE induced a significant increases in the expression of EGFR (p = 0.004) and phosphorylated C-terminal Tyr 1173 (p = 0.02). Other investigated EGFR tyrosine residues, Src related tyrosine (Tyr 416), MEK and ERK pathway were not changed significantly by DE.ConclusionExposure to DE (PM10, 300 μg/m3) caused enhanced EGFR expression and phosphorylation of the tyrosine residue (Tyr 1173) which is in accordance with the previously demonstrated activation of the JNK, AP-1, p38 MAPK and NFkB pathways and associated downstream signalling and cytokine production. No effects were seen on the MEK and ERK pathway suggesting that at the investigated time point (6 hours post exposure) there was no proliferative/differentiation signalling in the bronchial epithelium. The present findings suggest a key role for EGFR in the bronchial response to diesel exhaust.
Cutaneous Tactile Allodynia Associated with Microvascular Dysfunction in Muscle
Authors: Laferrière Andre , Millecamps Magali , Xanthos Dimitris N , Xiao Wen Hua , Siau Chiang , de Mos Marissa , Sachot Christelle , Ragavendran J Vaigunda , Huygen Frank JPM , Bennett Gary J , Coderre Terence J 
Published: July 2012

Background: Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia. Results: Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist. Conclusion: Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia.
Pathway-based classification of cancer subtypes
Authors: Kim Shinuk , Kon Mark , DeLisi Charles 
Published: July 2012

AbstractBackgroundMolecular markers based on gene expression profiles have been used in experimental and clinical settings to distinguish cancerous tumors in stage, grade, survival time, metastasis, and drug sensitivity. However, most significant gene markers are unstable (not reproducible) among data sets. We introduce a standardized method for representing cancer markers as 2-level hierarchical feature vectors, with a basic gene level as well as a second level of (more stable) pathway markers, for the purpose of discriminating cancer subtypes. This extends standard gene expression arrays with new pathway-level activation features obtained directly from off-the-shelf gene set enrichment algorithms such as GSEA. Such so-called pathway-based expression arrays are significantly more reproducible across datasets. Such reproducibility will be important for clinical usefulness of genomic markers, and augment currently accepted cancer classification protocols.ResultsThe present method produced more stable (reproducible) pathway-based markers for discriminating breast cancer metastasis and ovarian cancer survival time. Between two datasets for breast cancer metastasis, the intersection of standard significant gene biomarkers totaled 7.47% of selected genes, compared to 17.65% using pathway-based markers; the corresponding percentages for ovarian cancer datasets were 20.65% and 33.33% respectively. Three pathways, consisting of Type_1_diabetes mellitus, Cytokine-cytokine_receptor_interaction and Hedgehog_signaling (all previously implicated in cancer), are enriched in both the ovarian long survival and breast non-metastasis groups. In addition, integrating pathway and gene information, we identified five (ID4, ANXA4, CXCL9, MYLK, FBXL7) and six (SQLE, E2F1, PTTG1, TSTA3, BUB1B, MAD2L1) known cancer genes significant for ovarian and breast cancer respectively.ConclusionsStandardizing the analysis of genomic data in the process of cancer staging, classification and analysis is important as it has implications for both pre-clinical as well as clinical studies. The paradigm of diagnosis and prediction using pathway-based biomarkers as features can be an important part of the process of biomarker-based cancer analysis, and the resulting canonical (clinically reproducible) biomarkers can be important in standardizing genomic data. We expect that identification of such canonical biomarkers will improve clinical utility of high-throughput datasets for diagnostic and prognostic applications.ReviewersThis article was reviewed by John McDonald (nominated by I. King Jordon), Eugene Koonin, Nathan Bowen (nominated by I. King Jordon), and Ekaterina Kotelnikova (nominated by Mikhail Gelfand).