bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide inference of regulatory networks in Streptomyces coelicolor
Authors: Castro-Melchor Marlene , Charaniya Salim , Karypis George , Takano Eriko , Hu Wei-Shou 
Published: October 2010

Abstract

Background
The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses.

Results
In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements.

Conclusions
Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.
Transcriptome analysis of parallel-evolved Escherichia coli strains under ethanol stress
Authors: Horinouchi Takaaki , Tamaoka Kuniyasu , Furusawa Chikara , Ono Naoaki , Suzuki Shingo , Hirasawa Takashi , Yomo Tetsuya , Shimizu Hiroshi 
Published: October 2010

Abstract

Background
Understanding ethanol tolerance in microorganisms is important for the improvement of bioethanol production. Hence, we performed parallel-evolution experiments using Escherichia coli cells under ethanol stress to determine the phenotypic changes necessary for ethanol tolerance.

Results
After cultivation of 1,000 generations under 5% ethanol stress, we obtained 6 ethanol-tolerant strains that showed an approximately 2-fold increase in their specific growth rate in comparison with their ancestor. Expression analysis using microarrays revealed that common expression changes occurred during the adaptive evolution to the ethanol stress environment. Biosynthetic pathways of amino acids, including tryptophan, histidine, and branched-chain amino acids, were commonly up-regulated in the tolerant strains, suggesting that activating these pathways is involved in the development of ethanol tolerance. In support of this hypothesis, supplementation of isoleucine, tryptophan, and histidine to the culture medium increased the specific growth rate under ethanol stress. Furthermore, genes related to iron ion metabolism were commonly up-regulated in the tolerant strains, which suggests the change in intracellular redox state during adaptive evolution.

Conclusions
The common phenotypic changes in the ethanol-tolerant strains we identified could provide a fundamental basis for designing ethanol-tolerant strains for industrial purposes.
Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages
Authors: Joshi Amrita D , Oak Sameer R , Hartigan Adam J , Finn William G , Kunkel Steven L , Duffy Karen E , Das Anuk , Hogaboam Cory M 
Published: October 2010

Abstract

Background
Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.e. classical activation) and M2 (i.e. alternative activation) chemokine marker expression in human bone marrow-derived macrophages were examined.

Results
Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors. M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells. When added to naïve macrophages alone, IL-33 directly enhanced the expression of CCL3. In combination with LPS, IL-33 blocked the expression of the M2 chemokine marker CCL18, but did not alter CCL3 expression in these naive cells. The addition of IL-33 to M1 macrophages markedly increased the expression of CCL18 above that detected in untreated M1 macrophages. Similarly, alternatively activated human macrophages treated with IL-33 exhibited enhanced expression of CCL18 and the M2 marker mannose receptor above that detected in M2 macrophages alone.

Conclusions
Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.
Fragile X astrocytes induce developmental delays in dendrite maturation and synaptic protein expression
Authors: Jacobs Shelley , Nathwani Meera , Doering Laurie C 
Published: October 2010

AbstractBackgroundFragile X syndrome is the most common inherited form of mental impairment characterized by cognitive impairment, attention deficit and autistic behaviours. The mouse model of Fragile X is used to study the underlying neurobiology associated with behavioral deficiencies. The effect of Fragile X glial cells on the development of neurons has not been studied. We used a co-culture technique in combination with morphometrics on immunostained neurons to investigate the role of astrocytes in the development delays associated with hippocampal neuron development.ResultsWe found that hippocampal neurons grown on Fragile X astrocytes exhibited a significant difference from the neurons grown with normal astrocytes after 7 days in vitro for many parameters including increases in dendritic branching and in area of the cell body. However, after 21 days in culture, the neurons grown on Fragile X astrocytes exhibited morphological characteristics that did not differ significantly from the neurons grown on normal astrocytes. With antibodies to the pre-synaptic protein, synapsin, and to the excitatory post-synaptic protein, PSD-95, we quantified the number of developing excitatory synapses on the dendrites. In addition to the delays in dendritic patterning, the development of excitatory synapses was also delayed in the hippocampal neurons.ConclusionsThese experiments are the first to establish a role for astrocytes in the delayed growth characteristics and abnormal morphological features in dendrites and synapses that characterize the Fragile X syndrome.
Exploratory factor analysis of self-reported symptoms in a large, population-based military cohort
Authors: Kelton Molly L , LeardMann Cynthia A , Smith Besa , Boyko Edward J , Hooper Tomoko I , Gackstetter Gary D , Bliese Paul D , Hoge Charles W , Smith Tyler C ,   the Millennium Cohort Study Team
Published: October 2010

Abstract

Background
US military engagements have consistently raised concern over the array of health outcomes experienced by service members postdeployment. Exploratory factor analysis has been used in studies of 1991 Gulf War-related illnesses, and may increase understanding of symptoms and health outcomes associated with current military conflicts in Iraq and Afghanistan. The objective of this study was to use exploratory factor analysis to describe the correlations among numerous physical and psychological symptoms in terms of a smaller number of unobserved variables or factors.

Methods
The Millennium Cohort Study collects extensive self-reported health data from a large, population-based military cohort, providing a unique opportunity to investigate the interrelationships of numerous physical and psychological symptoms among US military personnel. This study used data from the Millennium Cohort Study, a large, population-based military cohort. Exploratory factor analysis was used to examine the covariance structure of symptoms reported by approximately 50,000 cohort members during 2004-2006. Analyses incorporated 89 symptoms, including responses to several validated instruments embedded in the questionnaire. Techniques accommodated the categorical and sometimes incomplete nature of the survey data.

Results
A 14-factor model accounted for 60 percent of the total variance in symptoms data and included factors related to several physical, psychological, and behavioral constructs. A notable finding was that many factors appeared to load in accordance with symptom co-location within the survey instrument, highlighting the difficulty in disassociating the effects of question content, location, and response format on factor structure.

Conclusions
This study demonstrates the potential strengths and weaknesses of exploratory factor analysis to heighten understanding of the complex associations among symptoms. Further research is needed to investigate the relationship between factor analytic results and survey structure, as well as to assess the relationship between factor scores and key exposure variables.
Serial interferon-gamma release assays during treatment of active tuberculosis in young adults
Authors: Lee Sei Won , Lee Choon-Taek , Yim Jae-Joon 
Published: October 2010

Abstract

Background
The role of interferon-γ release assay (IGRA) in monitoring responses to anti-tuberculosis (TB) treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT) assay over time during the anti-TB treatment of adults with no underlying disease.

Methods
We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline) and at 1, 3, and 6 months after initiating anti-TB medication.

Results
Of 67 eligible patients, 59 (88.1%) completed the study protocol. All participants were males who were human immunodeficiency virus (HIV)-negative and had no chronic diseases. Their median age was 21 years (range, 20-48). Initially, 57 (96.6%) patients had positive QFT-GIT results, and 53 (89.8%), 42 (71.2%), and 39 (66.1%) had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C) at diagnosis were associated with negative reversion of the QFT-GIT assay.

Conclusion
Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.
Anemia and chronic kidney disease are potential risk factors for mortality in stroke patients: a historic cohort study
Authors: Del Fabbro Patrizia , Luthi Jean-Christophe , Carrera Emmanuel , Michel Patrik , Burnier Michel , Burnand Bernard 
Published: October 2010

Abstract

Background
Chronic kidney disease (CKD) is associated to a higher stroke risk. Anemia is a common consequence of CKD, and is also a possible risk factor for cerebrovascular diseases. The purpose of this study was to examine if anemia and CKD are independent risk factors for mortality after stroke.

Methods
This historic cohort study was based on a stroke registry and included patients treated for a first clinical stroke in the stroke unit of one academic hospital over a three-year period. Mortality predictors comprised demographic characteristics, CKD, glomerular filtration rate (GFR), anemia and other stroke risk factors. GFR was estimated by means of the simplified Modification of Diet in Renal Disease formula. Renal function was assessed according to the Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD classification in five groups. A value of hemoglobin < 120 g/L in women and < 130 g/L in men on admission defined anemia. Kaplan-Meier survival curves and Cox models were used to describe and analyze one-year survival.

Results
Among 890 adult stroke patients, the mean (Standard Deviation) calculated GFR was 64.3 (17.8) ml/min/1.73 m2 and 17% had anemia. Eighty-two (10%) patients died during the first year after discharge. Among those, 50 (61%) had K/DOQI CKD stages 3 to 5 and 32 (39%) stages 1 or 2 (p < 0.001). Anemia was associated with an increased risk of death one year after discharge (p < 0.001). After adjustment for other factors, a higher hemoglobin level was independently associated with decreased mortality one year after discharge [hazard ratio (95% CI) 0.98 (0.97-1.00)].

Conclusions
Both CKD and anemia are frequent among stroke patients and are potential risk factors for decreased one-year survival. The inclusion of patients with a first-ever clinical stroke only and the determination of anemia based on one single measure, on admission, constitute limitations to the external validity. We should investigate if an early detection and management of both CKD and anemia could improve survival in stroke patients.
Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis
Authors: Reeves Mark E , Baldwin Scott W , Baldwin Melissa L , Chen Shin-Tai , Moretz Jeremy M , Aragon Robert J , Li Xinmin , Strong Donna D , Mohan Subburaman , Amaar Yousef G 
Published: October 2010

AbstractBackgroundThe Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells.MethodsGene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed.ResultsIn this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migrationin vitro.ConclusionTogether, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.
Dose escalation study of an anti-thrombocytopenic agent in patients with chemotherapy induced thrombocytopenia
Authors: Levin Robert D , Daehler MaryAnn , Grutsch James F , Hall John L , Gupta Digant , Lis Christopher G 
Published: October 2010

Abstract

Background
Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs. There is anecdotal data supporting the same application in humans. The Phase I clinical trial described here was designed to investigate the relationship between the administration of small chain RNA fragments and the recovery in platelets following Chemotherapy-Induced Thrombocytopenia (CIT).

Methods
Cancer patients with solid tumors that experienced post chemotherapy thrombocytopenia with a nadir of < = 80,000 platelets/ml were eligible for this clinical trial. There were no exclusions based on ECOG status, tumor type, tumor burden or chemotherapeutic agents. Patients received a unique preparation of RNA derived from either E. coli or yeast. Ten patients per group received 20, 40, or 60 mg as a starting dose. Subjects self-administered RNA fragments sublingually on an every other day schedule while undergoing chemotherapy. The dose was escalated in 20 mg increments to a maximum dose of 80 mg if the nadir was < 80,000 platelets/ml at the start of the next cycle. Subjects were treated for three cycles of chemotherapy with the maximum effective dose of RNA fragments. Subjects continued on planned chemotherapy as indicated by tumor burden without RNA fragment support after the third cycle. Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects.

Results
Patients receiving E. coli RNA fragments demonstrated a more rapid recovery in platelet count and higher nadir platelet count. None of the patients receiving the E. coli RNA fragments required a chemotherapy dose reduction due to thrombocytopenia. The optimal dose for minimizing CIT was 80 mg. Conversely, subjects receiving yeast RNA fragments with dose escalation to 80 mg required a chemotherapy dose reduction per American Society of Clinical Oncology guidelines for grade 3 and 4 thrombocytopenia.

Conclusions
Patients receiving myelosuppressive chemotherapy experienced an improvement in the platelet nadir and shorter recovery time when receiving concurrent E coli RNA fragments, when compared to patients who received yeast RNA fragments. These data indicate that 60 and 80 mg doses of E. coli RNA accelerated platelet recovery. Further clinical investigations are planned to quantify the clinical benefits of the E. coli RNA at the 80 mg dose in patients with chemotherapy induced thrombocytopenia.

Trial Registration
Clinical Trials.gov Identifier: NCT01163110
Health literacy, health status, and healthcare utilization of Taiwanese adults: results from a national survey
Authors: Lee Shoou-Yih D , Tsai Tzu-I , Tsai Yi-Wen , Kuo Ken N 
Published: October 2010

Abstract

Background
Low health literacy is considered a worldwide health threat. The purpose of this study is to assess the prevalence and socio-demographic covariates of low health literacy in Taiwanese adults and to investigate the relationships between health literacy and health status and health care utilization.

Methods
A national survey of 1493 adults was conducted in 2008. Health literacy was measured using the Mandarin Health Literacy Scale. Health status was measured based on self-rated physical and mental health. Health care utilization was measured based on self-reported outpatient clinic visits, emergency room visits, and hospitalizations.

Results
Approximately thirty percent of adults were found to have low (inadequate or marginal) health literacy. They tended to be older, have fewer years of schooling, lower household income, and reside in less populated areas. Inadequate health literacy was associated with poorer mental health (OR, 0.57; 95% CI, 0.35-0.91). No association was found between health literacy and health care utilization even after adjusting for other covariates.

Conclusions
Low (inadequate and marginal) health literacy is prevalent in Taiwan. High prevalence of low health literacy is not necessarily indicative of the need for interventions. Systematic efforts to evaluate the impact of low health literacy on health outcomes in other countries would help to illuminate features of health care delivery and financing systems that may mitigate the adverse health effects of low health literacy.
Investigation and improvement of DNA cleavage models of polyamide + Cu(II) nuclease + OOH- ligands bound to DNA
Authors: Yue Hongwei , Zhu Yanyan , Wang Yan , Chen Guangju 
Published: October 2010

Abstract

Background
Copper nucleases as a famous class of artificial metallonucleases have attracted considerable interest in relation to their diverse potentials not only as therapeutic agents but also in genomic researches. Copper nucleases present high efficient oxidative cleavage of DNA, in which DNA strand scission occurs generally after hydrogen atom abstracted from a sugar moiety. In order to achieve the selective cleavage of DNA sequences by copper nucleases, the DNA specific recognition agents of the Dervan-type hairpin and cyclic polyamides can be considered as proper carriers of copper nucleases. Investigation of the DNA cleavage selectivity of copper nucleases assisted by the hairpin and cyclic polyamides at the molecular level has not yet been elucidated.

Results
We carried out a series of molecular dynamics simulations for the nuclease [Cu(BPA)]2+ or [Cu(IDB)]2+ bound to the hairpin/cyclic polyamide and associated with DNA to investigate the selective DNA cleavage properties of Cu(II)-based artificial nucleases. The simulated results demonstrate that the DNA cleavage selectivity of the two nucleases assisted by the hairpin polyamide is improved efficiently. The [Cu(BPA)]2+ or [Cu(IDB)]2+ nuclease with a substrate OOH- bound to the hairpin polyamide can be stably located at the minor groove of DNA, and possibly abstracts H atom from the sugar of DNA. However, the DNA cleavage properties of the two nucleases assisted by the cyclic polyamide are significantly poor due to the rigidity of linking region between the cyclic polyamide and nuclease. With introduction of the flexible linker -CH2CH2CH2NH2, the modified cyclic polyamide can assist the two copper nucleases to improve the selective DNA cleavage properties efficiently.

Conclusion
A flexible linker and a proper binding site of the polyamide-type recognition agents play an important role in improving the DNA cleavage selectivity of copper nucleases. Current investigations provide an insight into the DNA cleavage specificities of chemical nucleases assisted by an appropriate nucleic acid recognition agent.