bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single nucleotide polymorphism in the genes of mce1 and mce4 operons of Mycobacterium tuberculosis: analysis of clinical isolates and standard reference strains
Authors: Pasricha Rashmi , Chandolia Amita , Ponnan Prija , Saini Neeraj Kumar , Sharma Sangeeta , Chopra Madhu , Basil Mandira Varma , Brahmachari Vani , Bose Mridula 
Published: February 2011

Abstract

Background
The presence of four mammalian cell entry (mce) operons in Mycobacterium tuberculosis suggests the essentiality of the functions of the genes in these operons. The differential expression of the four mce operons in different phases of in vitro growth and in infected animals reported earlier from our laboratory further justifies the apparent redundancy for these genes in the genome.
Here we investigate the extent of polymorphism in eight genes in the mce1 and mce4 operons of M. tuberculosis from four standard reference strains (H37Rv, H37Ra, LVS (Low Virulent Strain) and BCG) and 112 clinical isolates varying in their drug susceptibility profile, analysed by direct sequencing and Sequenom MassARRAY platform.

Results
We discovered 20 single nucleotide polymorphisms (SNPs) in the two operons. The comparative analysis of the genes of mce1 and mce4 operons revealed that yrbE1A [Rv0167] was most polymorphic in mce1 operon while yrbE4A [Rv3501c] and lprN [Rv3495c] had the highest number of SNPs in the mce4 operon. Of 20 SNPs, 12 were found to be nonsynonymous and were further analysed for their pathological relevance to M. tuberculosis using web servers PolyPhen and PMut, which predicted five deleterious nonsynonymous SNPs. A mutation from proline to serine at position 359 of the native Mce1A protein was most deleterious as predicted by both PolyPhen and PMut servers. Energy minimization of the structure of native Mce1A protein and mutated protein was performed using InsightII. The mutated Mce1A protein showed structural changes that could account for the effects of this mutation.

Conclusions
Our results show that SNPs in the coding sequences of mce1 and mce4 operons in clinical isolates can be significantly high. Moreover, mce4 operon is significantly more polymorphic than mce1 operon (p < 0.001). However, the frequency of nonsynonymous substitutions is higher in mce1 operon and synonymous substitutions are more in mce4 operon. In silico modeling predict that nonsynonymous SNP at mce1A [Rv0169], a virulence gene could play a pivotal role in causing functional changes in M. tuberculosis that may reflect upon the biology of the bacteria.
The development and geometry of shape change in Arabidopsis thalianacotyledon pavement cells
Authors: Zhang Chunhua , Halsey Leah E , Szymanski Daniel B 
Published: February 2011

Abstract

Background
The leaf epidermis is an important architectural control element that influences the growth properties of underlying tissues and the overall form of the organ. In dicots, interdigitated pavement cells are the building blocks of the tissue, and their morphogenesis includes the assembly of specialized cell walls that surround the apical, basal, and lateral (anticlinal) cell surfaces. The microtubule and actin cytoskeletons are highly polarized along the cortex of the anticlinal wall; however, the relationships between these arrays and cell morphogenesis are unclear.

Results
We developed new quantitative tools to compare population-level growth statistics with time-lapse imaging of cotyledon pavement cells in an intact tissue. The analysis revealed alternating waves of lobe initiation and a phase of lateral isotropic expansion that persisted for days. During lateral isotropic diffuse growth, microtubule organization varied greatly between cell surfaces. Parallel microtubule bundles were distributed unevenly along the anticlinal surface, with subsets marking stable cortical domains at cell indentations and others clearly populating the cortex within convex cell protrusions.

Conclusions
Pavement cell morphogenesis is discontinuous, and includes punctuated phases of lobe initiation and lateral isotropic expansion. In the epidermis, lateral isotropic growth is independent of pavement cell size and shape. Cortical microtubules along the upper cell surface and stable cortical patches of anticlinal microtubules may coordinate the growth behaviors of orthogonal cell walls. This work illustrates the importance of directly linking protein localization data to the growth behavior of leaf epidermal cells.
BYPASS1: synthesis of the mobile root-derived signal requires active root growth and arrests early leaf development
Authors: Van Norman Jaimie M , Murphy Caroline , Sieburth Leslie E 
Published: February 2011

Abstract

Background
The Arabidopsis bypass1 (bps1) mutant root produces a biologically active mobile compound that induces shoot growth arrest. However it is unknown whether the root retains the capacity to synthesize the mobile compound, or if only shoots of young seedlings are sensitive. It is also unknown how this compound induces arrest of shoot growth. This study investigated both of these questions using genetic, inhibitor, reporter gene, and morphological approaches.

Results
Production of the bps1 root-synthesized mobile compound was found to require active root growth. Inhibition of postembryonic root growth, by depleting glutathione either genetically or chemically, allowed seedlings to escape shoot arrest. However, the treatments were not completely effective, as the first leaf pair remained radialized, but elongated. This result indicated that the embryonic root transiently synthesized a small amount of the mobile substance. In addition, providing glutathione later in vegetative development caused shoot growth arrest to be reinstated, revealing that these late-arising roots were still capable of producing the mobile substance, and that the older vegetative leaves were still responsive.
To gain insight into how leaf development responds to the mobile signal, leaf development was followed morphologically and using the CYCB1,1::GUS marker for G2/M phase cells. We found that arrest of leaf growth is a fully penetrant phenotype, and a dramatic decrease in G2/M phase cells was coincident with arrest. Analyses of stress phenotypes found that late in development, bps1 cotyledons produced necrotic lesions, however neither hydrogen peroxide nor superoxide were abundant as leaves underwent arrest.

Conclusions

bps1 roots appear to require active growth in order to produce the mobile bps1 signal, but the potential for this compound's synthesis is present both early and late during vegetative development. This prolonged capacity to synthesize and respond to the mobile compound is consistent with a possible role for the mobile compound in linking shoot growth to subterranean conditions. The specific growth-related responses in the shoot indicated that the mobile substance prevents full activation of cell division in leaves, although whether cell division is a direct response remains to be determined.
Structure, expression differentiation and evolution of duplicated fiber developmental genes in Gossypium barbadense and G. hirsutum
Authors: Zhu Huayu , Han Xiaoyong , Lv Junhong , Zhao Liang , Xu Xiaoyang , Zhang Tianzhen , Guo Wangzhen 
Published: February 2011

Abstract

Background
Both Gossypium hirsutum and G. barbadense probably originated from a common ancestor, but they have very different agronomic and fiber quality characters. Here we selected 17 fiber development-related genes to study their structures, tree topologies, chromosomal location and expression patterns to better understand the interspecific divergence of fiber development genes in the two cultivated tetraploid species.

Results
The sequence and structure of 70.59% genes were conserved with the same exon length and numbers in different species, while 29.41% genes showed diversity. There were 15 genes showing independent evolution between the A- and D-subgenomes after polyploid formation, while two evolved via different degrees of colonization. Chromosomal location showed that 22 duplicate genes were located in which at least one fiber quality QTL was detected. The molecular evolutionary rates suggested that the D-subgenome of the allotetraploid underwent rapid evolutionary differentiation, and selection had acted at the tetraploid level. Expression profiles at fiber initiation and early elongation showed that the transcripts levels of most genes were higher in Hai7124 than in TM-1. During the primary-secondary transition period, expression of most genes peaked earlier in TM-1 than in Hai7124. Homeolog expression profile showed that A-subgenome, or the combination of A- and D-subgenomes, played critical roles in fiber quality divergence of G. hirsutum and G. barbadense. However, the expression of D-subgenome alone also played an important role.

Conclusion
Integrating analysis of the structure and expression to fiber development genes, suggests selective breeding for certain desirable fiber qualities played an important role in divergence of G. hirsutum and G. barbadense.
Salmonella entericaserotype Virchow associated with human infections in Switzerland: 2004-2009
Authors: Bonalli Mario , Stephan Roger , Käppeli Ursula , Cernela Nicole , Adank Luzius , Hächler Herbert 
Published: February 2011

Abstract

Background
Salmonellosis is one of the most important foodborne diseases and a major threat to public health. Salmonella serotype Virchow ranks among the top five serovars in Europe.

Method
A total of 153 strains isolated from different patients from 2004 through 2009 in Switzerland were further characterized by (i) assessing phenotypic antibiotic resistance profiles using the disk diffusion method and (ii) by genotyping using pulsed-field gel electrophoresis (PFGE) after macrorestriction with XbaI in order to evaluate strain relationship.

Results
The relative frequency of S. Virchow among other Salmonella serovars varied between 4th to 8th rank. The annual incidence ranged from 0.45/100'000 in 2004 to 0.40/100'000 in 2009. A total of 48 strains (32%) were resistant to one to 3 antimicrobials, 54 strains (36%) displayed resistance patterns to more than three antibiotics. No trend was identifiable over the years 2004 to 2009. We found a high prevalence (62%) of nalidixic acid resistant strains, suggesting an equally high rate of decreased fluoroqionolone susceptibility, whereas intermediate resistance to ciprofloxacin was negligible. Two strains were extended spectrum β-lactamase (ESBL) producers. Analysis of PFGE patterns uncovered a predominant cluster (similarity coefficient above 80%) consisting of 104 of the 153 strains.

Conclusion
The worldwide increase of antibiotic resistances in Salmonella is an emerging public health problem. For Switzerland, no clear trend is identifiable over the years 2004 to 2009 for S. Virchow. Antimicrobial susceptibility and resistance profiles varied considerably within this period. Nevertheless, the situation in Switzerland coincided with findings in other European countries. Genotyping results of this strain collection revealed no evidence for an undetected outbreak within this time period.
Evidence for population variation in TSC1 and TSC2 gene expression
Authors: Jentarra Garilyn M , Rice Stephen G , Olfers Shannon , Saffen David , Narayanan Vinodh 
Published: February 2011

AbstractBackgroundTuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder caused by mutations in one of two genes,TSC1orTSC2, which encode the proteins hamartin and tuberin, respectively [1–3]. Common features of TSC include intractable epilepsy, mental retardation, and autistic features. TSC is associated with specific brain lesions, including cortical tubers, subependymal nodules and subependymal giant cell astrocytomas. In addition, this disease frequently produces characteristic tumors, termed hamartomas, in the kidneys, heart, skin, retina, and lungs. Disease severity in TSC can be quite variable and is not determined by the primary mutation alone. In fact, there is often considerable variability in phenotype within single families, where all affected individuals carry the same mutation. Factors suspected to influence phenotype in TSC include the specific primary mutation, random occurrence of second-hit somatic mutations, mosaicism, "modifying genes", and environmental factors. In addition to these factors, we hypothesize that differences in mRNA expression from the non-mutated TSC allele, or possibly from the mutated allele, play a part in modifying disease severity. Common genetic variants that regulate mRNA expression have previously been shown to play important roles in human phenotypic variability, including disease susceptibility. A prediction based on this idea is that common regulatory variants that influence disease severity in TSC should be detectable in non-affected individuals.MethodsA PCR/primer extension assay was used to measure allele specific expression ofTSC1andTSC2mRNAs in leukocytes isolated from normal volunteers. This assay can be used to measure "allelic expression imbalance" (AEI) in individuals by making use of heterozygous "marker" single nucleotide polymorphisms (SNPs) located within their mRNA.ResultsIn this study we show for the first time thatTSC1andTSC2genes exhibit allele-specific differences in mRNA expression in blood leukocytes isolated from normal individuals.ConclusionsThese results support the possibility that allele-specific variation inTSCmRNA expression contributes to the variable severity of symptoms in TSC patients.
Management of breakthrough disease in patients with multiple sclerosis: when an increasing of Interferon beta dose should be effective?
Authors: Prosperini Luca , Borriello Giovanna , De Giglio Laura , Leonardi Laura , Barletta Valeria , Pozzilli Carlo 
Published: February 2011

Abstract

Background
In daily clinical setting, some patients affected by relapsing-remitting Multiple Sclerosis (RRMS) are switched from the low-dose to the high-dose Interferon beta (IFNB) in order to achieve a better control of the disease.

Purpose
In this observational, post-marketing study we reported the 2-year clinical outcomes of patients switched to the high-dose IFNB; we also evaluated whether different criteria adopted to switch patients had an influence on the clinical outcomes.

Methods
Patients affected by RRMS and switched from the low-dose to the high-dose IFNB due to the occurrence of relapses, or contrast-enhancing lesions (CELs) as detected by yearly scheduled MRI scans, were followed for two years. Expanded Disability Status Scale (EDSS) scores, as well as clinical relapses, were evaluated during the follow-up period.

Results
We identified 121 patients switched to the high-dose IFNB. One hundred patients increased the IFNB dose because of the occurrence of one or more relapses, and 21 because of the presence of one or more CELs, even in absence of clinical relapses. At the end of the 2-year follow-up, 72 (59.5%) patients had a relapse, and 51 (42.1%) reached a sustained progression on EDSS score. Overall, 85 (70.3%) patients showed some clinical disease activity (i.e. relapses or disability progression) after the switch.
Relapse risk after increasing the IFNB dose was greater in patients who switched because of relapses than those switched only for MRI activity (HR: 5.55, p = 0.001). A high EDSS score (HR: 1.77, p < 0.001) and the combination of clinical and MRI activity at switch raised the risk of sustained disability progression after increasing the IFNB dose (HR: 2.14, p = 0.01).

Conclusion
In the majority of MS patients, switching from the low-dose to the high-dose IFNB did not reduce the risk of further relapses or increased disability in the 2-year follow period.
Although we observed that patients who switched only on the basis on MRI activity (even in absence of clinical attacks) had a lower risk of further relapses, larger studies are warranted before to recommend a switch algorithm based on MRI findings.
Women-focused development intervention reduces delays in accessing emergency obstetric care in urban slums in Bangladesh: a cross-sectional study
Authors: Nahar Shamsun , Banu Morsheda , Nasreen Hashima E 
Published: February 2011

Abstract

Background
Recognizing the burden of maternal mortality in urban slums, in 2007 BRAC (formally known as Bangladesh Rural Advancement Committee) has established a woman-focused development intervention, Manoshi (the Bangla abbreviation of mother, neonate and child), in urban slums of Bangladesh. The intervention emphasizes strengthening the continuum of maternal, newborn and child care through community, delivery centre (DC) and timely referral of the obstetric complications to the emergency obstetric care (EmOC) facilities. This study aimed to assess whether Manoshi DCs reduces delays in accessing EmOC.

Methods
This cross-sectional study was conducted during October 2008 to January 2009 in the slums of Dhaka city among 450 obstetric complicated cases referred either from DCs of Manoshi or from their home to the EmOC facilities. Trained female interviewers interviewed at their homestead with structured questionnaire. Pearson's chi-square test, t-test and Mann-Whitney test were performed.

Results
The median time for making the decision to seek care was significantly longer among women who were referred from home than referred from DCs (9.7 hours vs. 5.0 hours, p < 0.001). The median time to reach a facility and to receive treatment was found to be similar in both groups. Time taken to decide to seek care was significantly shorter in the case of life-threatening complications among those who were referred from DC than home (0.9 hours vs.2.3 hours, p = 0.002). Financial assistance from Manoshi significantly reduced the first delay in accessing EmOC services for life-threatening complications referred from DC (p = 0.006). Reasons for first delay include fear of medical intervention, inability to judge maternal condition, traditional beliefs and financial constraints. Role of gender was found to be an important issue in decision making. First delay was significantly higher among elderly women, multiparity, non life-threatening complications and who were not involved in income-generating activities.

Conclusions
Manoshi program reduces the first delay for life-threatening conditions but not non-life-threatening complications even though providing financial assistance. Programme should give more emphasis on raising awareness through couple/family-based education about maternal complications and dispel fear of clinical care to accelerate seeking EmOC.
Perioperative cancer cell dissemination detected with a real-time RT-PCR assay for EpCAM is not associated with worse prognosis in pancreatic ductal adenocarcinoma
Authors: Sergeant Gregory , Roskams Tania , van Pelt Jos , Houtmeyers François , Aerts Raymond , Topal Baki 
Published: February 2011

Abstract

Background
Epithelial cell adhesion molecule (EpCAM) has been used as surrogate marker for the quantification of circulating tumour cells (CTC). Our aim was to prospectively study the value of a real-time RT-PCR assay for EpCAM detection in the peripheral blood and peritoneal cavity of patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).

Methods
From 48 patients with PDAC (40 resectable, 8 unresectable) and 10 patients with chronic pancreatitis undergoing pancreatectomy 10 ml of venous blood was drawn preoperatively (PB) and postoperatively (POB, day 1 (D1B), day 7 (D7B) and after 6 weeks (6WB). Of all patients undergoing pancreatectomy, 40 ml peritoneal lavage fluid was taken preoperatively and postoperatively. A real-time RT-PCR assay (TaqMan, ABI Prism 7700) was developed for the detection of EpCAM mRNA. To discriminate between EpCAM-positive and negative samples a cut-off was applied. Median postoperative follow-up was 24.0 months (range: 0.7 - 41.3).

Results
PB was EpCAM-positive (+) in 25% of patients versus 65% of patients in POB (p < 0.0001). EpCAM(+) was noted at D1B, D7B and 6WB was found in 28.6%, 23.1% and 23.5% of patients respectively. Preoperative peritoneal lavage fluid was EpCAM(+) in 10.3% versus 53.8% of patients postoperatively (p < 0.0001).
At none of the time-points, an association was found between EpCAM positivity in blood and/or peritoneal cavity and cancer-specific or disease-free survival. Also, no significant associations were found between clinicopathological variables and perioperative EpCAM positivity.

Conclusions
Despite a significant increase in EpCAM counts in postoperative blood and peritoneal lavage fluid this was not associated with worse prognosis after pancreatectomy for PDAC.

Trial registration
Clinicaltrials.gov NCT00495924
"Booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods: internal pilot and feasibility study
Authors: Scott Emma J , Dimairo Munyaradzi , Hind Daniel , Goyder Elizabeth , Copeland Robert J , Breckon Jeff D , Crank Helen , Walters Stephen J , Loban Amanda , Cooper Cindy L 
Published: February 2011

Abstract

Background
Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. A randomised controlled trial is needed to assess whether providing motivational interviewing, three months after giving initial advice, sustains physical activity levels in those who recently became physically active. This paper reports the results of an internal pilot study designed to test the feasibility of the study in terms of recruitment, per protocol delivery of the intervention and retention at three months.

Methods
Participants were: aged 40-64 years; resident in deprived areas of Sheffield, UK; and, had recently become physically active as a result of using a brief intervention following an invitation from a mass mailout. Interventions: Motivational Interviewing 'boosters' aimed at sustaining change in physical activity status delivered face-to-face or over the telephone compared with no further intervention. Outcomes of the feasibility study: recruitment of 60 participants from mailout of 3,300; retention of 45 participants with 3-month follow-up accelerometry measurements; 70% of those randomised to boosters receiving intervention per protocol. Sample size and power were recalculated using the accelerometry data collected.

Results
Forty-seven participants were randomised (78% of the feasibility target); 37 participants were retained at three months, 29 with at least four days of accelerometry data (64% of the feasibility target); 79% of those allocated boosters received them per protocol (surpassing the feasibility target). The proposed sample size of 600 was confirmed as appropriate and power is expected to be sufficient to detect a difference between groups.

Conclusions
The main study will continue with the original recruitment target of 600 participants but to ensure feasibility, it is necessary to increase recruitment and improve the numbers of those followed-up who have evaluable data. Strategies will include increasing the number of initial invitations sent out and improving the training of research assistants and participants in the positioning of the accelerometer.

Trial Registration
ISRCTN: ISRCTN56495859, ClinicalTrials (NCT): NCT00836459