bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genome analysis of central nitrogen metabolism and its control by GlnR in the class Bacilli
Authors: Kormelink Tom Groot , Koenders Eric , Hagemeijer Yanick , Overmars Lex , Siezen Roland J , de Vos Willem M , Francke Christof 
Published: May 2012

Abstract

Background
The assimilation of nitrogen in bacteria is achieved through only a few metabolic conversions between alpha-ketoglutarate, glutamate and glutamine. The enzymes that catalyze these conversions are glutamine synthetase, glutaminase, glutamate dehydrogenase and glutamine alpha-ketoglutarate aminotransferase. In low-GC Gram-positive bacteria the transcriptional control over the levels of the related enzymes is mediated by four regulators: GlnR, TnrA, GltC and CodY. We have analyzed the genomes of all species belonging to the taxonomic families Bacillaceae, Listeriaceae, Staphylococcaceae, Lactobacillaceae, Leuconostocaceae and Streptococcaceae to determine the diversity in central nitrogen metabolism and reconstructed the regulation by GlnR.

Results
Although we observed a substantial difference in the extent of central nitrogen metabolism in the various species, the basic GlnR regulon was remarkably constant and appeared not affected by the presence or absence of the other three main regulators. We found a conserved regulatory association of GlnR with glutamine synthetase (glnRA operon), and the transport of ammonium (amtB-glnK) and glutamine/glutamate (i.e. via glnQHMP, glnPHQ, gltT, alsT). In addition less-conserved associations were found with, for instance, glutamate dehydrogenase in Streptococcaceae, purine catabolism and the reduction of nitrite in Bacillaceae, and aspartate/asparagine deamination in Lactobacillaceae.

Conclusions
Our analyses imply GlnR-mediated regulation in constraining the import of ammonia/amino-containing compounds and the production of intracellular ammonia under conditions of high nitrogen availability. Such a role fits with the intrinsic need for tight control of ammonia levels to limit futile cycling.
Comparative transcriptomic analysis of streptococcus pseudopneumoniae with viridans group streptococci
Authors: Park Hee Kuk , Myung Soon Chul , Kim Wonyong 
Published: May 2012

Abstract

Background

Streptococcus pseudopneumoniae, is a novel member of the genus Streptococcus, falling close to related members like S. pneumoniae, S. mitis, and S. oralis. Its recent appearance has shed light on streptococcal infections, which has been unclear till recently. In this study, the transcriptome of S. pseudopneumoniae CCUG 49455T was analyzed using the S. pneumoniae R6 microarray platform and compared with those of S. pneumoniae KCTC 5080T, S. mitis KCTC 3556T, and S. oralis KCTC 13048T strains.

Results
Comparative transcriptome analysis revealed the extent of genetic relatedness among the species, and implies that S. pseudopneumoniae is the most closely related to S. pneumoniae. A total of 489, 444 and 470 genes were upregulated while 347, 484 and 443 were downregulated relative to S. pneumoniae in S. pseudopneumoniae, S. oralis and S. mitis respectively. Important findings were the up-regulation of TCS (two component systems) and transposase which were found to be specific to S. pseudopneumoniae.

Conclusions
This study provides insight to the current understanding of the genomic content of S. pseudopneumoniae. The comparative transcriptome analysis showed hierarchical clustering of expression data of S. pseudopneumoniae with S. pneumoniae and S. mitis with S. oralis. This proves that transcriptional profiling can facilitate in elucidating the genetic distance between closely related strains.
Genetic basis of unstable expression of high gamma-tocopherol content in sunflower seeds
Authors: García-Moreno María J , Fernández-Martínez José M , Velasco Leonardo , Pérez-Vich Begoña 
Published: May 2012

Abstract

Background
Tocopherols are natural antioxidants with both in vivo (vitamin E) and in vitro activity. Sunflower seeds contain predominantly alpha-tocopherol (>90% of total tocopherols), with maximum vitamin E effect but lower in vitro antioxidant action than other tocopherol forms such as gamma-tocopherol. Sunflower germplasm with stable high levels of gamma-tocopherol (>85%) has been developed. The trait is controlled by recessive alleles at a single locus Tph2 underlying a gamma-tocopherol methyltransferase (gamma-TMT). Additionally, unstable expression of increased gamma-tocopherol content in the range from 5 to 85% has been reported. The objective of this research was to determine the genetic basis of unstable expression of high gamma-tocopherol content in sunflower seeds.

Results
Male sterile plants of nuclear male sterile line nmsT2100, with stable high gamma-tocopherol content, were crossed with plants of line IAST-1, with stable high gamma-tocopherol content but derived from a population that exhibited unstable expression of the trait. F2 seeds showed continuous segregation for gamma-tocopherol content from 1.0 to 99.7%. Gamma-tocopherol content in F2 plants (average of 24 individual F3 seeds) segregated from 59.4 to 99.4%. A genetic linkage map comprising 17 linkage groups (LGs) was constructed from this population using 109 SSR and 20 INDEL marker loci, including INDEL markers for tocopherol biosynthesis genes. QTL analysis revealed a major QTL on LG 8 that corresponded to the gamma-TMT Tph2 locus, which suggested that high gamma-tocopherol lines nmsT2100 and IAST-1 possess different alleles at this locus. Modifying genes were identified at LGs 1, 9, 14 and 16, corresponding in most cases with gamma-TMT duplicated loci.

Conclusions
Unstable expression of high gamma-tocopherol content is produced by the effect of modifying genes on tph2

a
allele at the gamma-TMT Tph2 gene. This allele is present in line IAST-1 and is different to allele tph2 present in line nmsT2100, which is not affected by modifying genes. No sequence differences at the gamma-TMT gene were found associated to allelic unstability. Our results suggested that modifying genes are mostly epistatically interacting gamma-TMT duplicated loci.
A national study of socioeconomic status and tuberculosis rates by country of birth, United States, 1996–2005
Authors: Olson Nicole A , Davidow Amy L , Winston Carla A , Chen Michael P , Gazmararian Julie A , Katz Dolores J 
Published: May 2012

Abstract

Background
Tuberculosis (TB) in developed countries has historically been associated with poverty and low socioeconomic status (SES). In the past quarter century, TB in the United States has changed from primarily a disease of native-born to primarily a disease of foreign-born persons, who accounted for more than 60% of newly-diagnosed TB cases in 2010. The purpose of this study was to assess the association of SES with rates of TB in U.S.-born and foreign-born persons in the United States, overall and for the five most common foreign countries of origin.

Methods
National TB surveillance data for 1996–2005 was linked with ZIP Code-level measures of SES (crowding, unemployment, education, and income) from U.S. Census 2000. ZIP Codes were grouped into quartiles from low SES to high SES and TB rates were calculated for foreign-born and U.S.-born populations in each quartile.

Results
TB rates were highest in the quartiles with low SES for both U.S.-born and foreign-born populations. However, while TB rates increased five-fold or more from the two highest to the two lowest SES quartiles among the U.S.-born, they increased only by a factor of 1.3 among the foreign-born.

Conclusions
Low SES is only weakly associated with TB among foreign-born persons in the United States. The traditional associations of TB with poverty are not sufficient to explain the epidemiology of TB among foreign-born persons in this country and perhaps in other developed countries. TB outreach and research efforts that focus only on low SES will miss an important segment of the foreign-born population.
Estimation of plasma apolipoprotein B concentration using routinely measured lipid biochemical tests in apparently healthy Asian adults
Authors: Cho Dong-Sik , Woo Sookyoung , Kim Seonwoo , Byrne Christopher D , Kong Joon-Hyuk , Sung Ki-Chul 
Published: May 2012

Abstract

Background
Increased low-density lipoprotein cholesterol (LDL) concentration is associated with increased risk of coronary heart disease (CHD) but a substantial risk of cardiovascular disease often remains after LDL concentrations have been treated to target. Apolipoprotein B (apo B) is the major apolipoprotein contained within atherogenic lipoproteins such as LDL, and apo B is a more reliable indicator of cardiovascular risk than LDL concentration.

Aim and methods
Our aim was to develop a formula for calculating apo B using lipid biochemistry measurements that are commonly available in clinical practice. We examined the clinical and laboratory data from 73,047 Koreans who underwent a medical health check that included apolipoprotein B concentration. The study sample was randomly divided into a training set for prediction model building and a validation set of equal size. Multivariable linear regression analysis was used to develop a prediction model equation for estimating apo B and to validate the developed model.

Results
The best results for estimating apo B were derived from an equation utilising LDL and triglyceride (TG) concentrations [ApoB = −33.12 + 0.675*LDL + 11.95*ln(tg)]. This equation predicted the apo B result with a concordance correlation coefficient (CCC and 95%CIs) = 0.936 (0.935,0.937)).

Conclusion
Our equation for predicting apo B concentrations from routine analytical lipid biochemistry provides a simple method for obtaining precise information about an important cardiovascular risk marker.
Enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from S-sulfocysteine increases L-cysteine production in Escherichia coli
Authors: Nakatani Takeshi , Ohtsu Iwao , Nonaka Gen , Wiriyathanawudhiwong Natthawut , Morigasaki Susumu , Takagi Hiroshi 
Published: May 2012

Abstract

Background

Escherichia coli has two L-cysteine biosynthetic pathways; one is synthesized from O-acetyl L-serine (OAS) and sulfate by L-cysteine synthase (CysK), and another is produced via S-sulfocysteine (SSC) from OAS and thiosulfate by SSC synthase (CysM). SSC is converted into L-cysteine and sulfite by an uncharacterized reaction. As thioredoxins (Trx1 and Trx2) and glutaredoxins (Grx1, Grx2, Grx3, Grx4, and NrdH) are known as reductases of peptidyl disulfides, overexpression of such reductases might be a good way for improving L-cysteine production to accelerate the reduction of SSC in E. coli.

Results
Because the redox enzymes can reduce the disulfide that forms on proteins, we first tested whether these enzymes catalyze the reduction of SSC to L-cysteine. All His-tagged recombinant enzymes, except for Grx4, efficiently convert SSC into L-cysteine in vitro. Overexpression of Grx1 and NrdH enhanced a 15-40% increase in the E. coli L-cysteine production. On the other hand, disruption of the cysM gene cancelled the effect caused by the overexpression of Grx1 and NrdH, suggesting that its improvement was due to the efficient reduction of SSC under the fermentative conditions. Moreover, L-cysteine production in knockout mutants of the sulfite reductase genes (ΔcysI and ΔcysJ) and the L-cysteine synthase gene (ΔcysK) each decreased to about 50% of that in the wild-type strain. Interestingly, there was no significant difference in L-cysteine production between wild-type strain and gene deletion mutant of the upstream pathway of sulfite (ΔcysC or ΔcysH). These results indicate that sulfite generated from the SSC reduction is available as the sulfur source to produce additional L-cysteine molecule. It was finally found that in the E. coli L-cysteine producer that co-overexpress glutaredoxin (NrdH), sulfite reductase (CysI), and L-cysteine synthase (CysK), there was the highest amount of L-cysteine produced per cell.

Conclusions
In this work, we showed that Grx1 and NrdH reduce SSC to L-cysteine, and the generated sulfite is then utilized as the sulfur source to produce additional L-cysteine molecule through the sulfate pathway in E. coli. We also found that co-overexpression of NrdH, CysI, and CysK increases L-cysteine production. Our results propose that the enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from SSC is a novel method for improvement of L-cysteine production.
Vigilin interacts with signal peptide peptidase
Authors: Lu Stephen Hsueh-Jeng , Jeon Amy Hye Won , Schmitt-Ulms Gerold , Qamar Seema , Dodd Roger , McDonald Beth , Li Yi , Meadows William , Cox Katie , Bohm Christopher , Chen Fusheng , Fraser Paul , George-Hyslop Peter St 
Published: May 2012

Abstract

Background
Signal peptide peptidase (SPP), a member of the presenilin-like intra-membrane cleaving aspartyl protease family, migrates on Blue Native (BN) gels as 100 kDa, 200 kDa and 450 kDa species. SPP has recently been implicated in other non-proteolytic functions such as retro-translocation of MHC Class I molecules and binding of misfolded proteins in the endoplasmic reticulum (ER). These high molecular weight SPP complexes might contain additional proteins that regulate the proteolytic activity of SPP or support its non-catalytic functions.

Results
In this study, an unbiased iTRAQ-labeling mass spectrometry approach was used to identify SPP-interacting proteins. We found that vigilin, a ubiquitous multi-KH domain containing cytoplasmic protein involved in RNA binding and protein translation control, selectively enriched with SPP. Vigilin interacted with SPP and both proteins co-localized in restricted intracellular domains near the ER, biochemically co-fractionated and were part of the same 450 kDa complex on BN gels. However, vigilin does not alter the protease activity of SPP, suggesting that the SPP-vigilin interaction might be involved in the non-proteolytic functions of SPP.

Conclusions
We have identified and validated vigilin as a novel interacting partner of SPP that could play an important role in the non-proteolytic functions of SPP. This data adds further weight to the idea that intramembrane-cleaving aspartyl proteases, such as presenilin and SPPs, could have other functions besides the proteolysis of short membrane stubs.
Inflammation-Induced Changes in BKCa Currents in Cutaneous Dorsal Root Ganglion Neurons from the Adult Rat
Authors: Zhang Xiu-Lin , Mok Lee-Peng , Lee Kwan Yeop , Charbonnet Marcel , Gold Michael S 
Published: May 2012

Background: Inflammation-induced sensitization of primary afferents is associated with a decrease in K+ current. However, the type of K+ current and basis for the decrease varies as a function of target of innervation. Because glabrous skin of the rat hindpaw is used often to assess changes in nociception in models of persistent pain, the purpose of the present study was to determine the type and extent to which K+ currents contribute to the inflammation-induced sensitization of cutaneous afferents. Acutely dissociated retrogradely labeled cutaneous dorsal root ganglion neurons from naïve and inflamed (3 days post complete Freund's adjuvant injection) rats were studied with whole cell and perforated patch techniques. Results: Inflammation-induced sensitization of small diameter cutaneous neurons was associated with an increase in action potential duration and rate of decay of the afterhyperpolarization. However, no changes in voltage-gated K+ currents were detected. In contrast, Ca2+ modulated iberiotoxin sensitive and paxilline sensitive K+ (BKCa) currents were significantly smaller in small diameter IB4+ neurons. This decrease in current was not associated with a detectable change in total protein levels of the BKCa channel α or β subunits. Single cell PCR analysis revealed a significant change in the pattern of expression of α subunit splice variants and β subunits that were consistent, at least in part, with inflammation-induced changes in the biophysical properties of BKCa currents in cutaneous neurons. Conclusions: Results of this study provide additional support for the conclusion that it may be possible, if not necessary to selectively treat pain arising from specific body regions. Because a decrease in BKCa current appears to contribute to the inflammation-induced sensitization of cutaneous afferents, BKCa channel openers may be effective for the treatment of inflammatory pain.
Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients
Authors: Odili Augustine N , Ezeala-Adikaibe Birinus , Ndiaye Mouhamadou B , Anisiuba Benedict C , Kamdem Marius M , Ijoma Chinwuba K , Kaptue Joseph , Boombhi Hilaire J , Kolo Philip M , Shu Elvis N , Thijs Lutgarde , Staessen Jan A , Omotoso Babatunde A , Kingue Samuel , Ba Serigne A , Lemogoum Daniel , M’Buyamba-Kabangu Jean-René , Ulasi Ifeoma I 
Published: May 2012

Abstract

Background
The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic.

Methods
Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa.

Results
At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m2), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study.

Conclusions
NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible.
Chronic modulation of AMP-Kinase, Akt and mTOR pathways by ionizing radiation in human lung cancer xenografts
Authors: Storozhuk Yaryna , Sanli Toran , Hopmans Sarah N , Schultz Carrie , Farrell Tom , Cutz Jean-Claude , Steinberg Gregory R , Wright James , Singh Gurmit , Tsakiridis Theodoros 
Published: May 2012

Abstract

Introduction
Earlier, we showed that in cancer cells, AMP-activated kinase (AMPK) participates in a signal transduction pathway involving ATM-AMPK-p53/p21cip1 which is activated by ionizing radiation (IR) to mediate G2-M arrest and enhanced cytotoxicity. We also observed that AMPK modulates ATM expression and activity and the IR response of the Akt-mTOR pathway. Since the ATM, AMPK and Akt pathways are key targets of novel radio-sensitizing therapeutics, we examined the chronic modultion of expression and activity of those pathways by IR alone in xenograft models of lung cancer.

Methods
Immuno-compromised mice were grafted with human lung A549 and H1299 cells, were treated with a single fraction of 0 or 10 Gy, and left to grow for 8 weeks. Extracted tumors were subjected to lysis and immunoblotting or fixation and immunohistochemical analysis.

Results
IR inhibited significantly xenograft growth and was associated with increased expression of Ataxia Telengiectasia Mutated (ATM) and enhanced phosphorylation of two ATM targets, H2Ax and checkpoint kinase Chk2. Irradiated tumours showed increased total AMPK levels and phosphorylation of AMPK and its substrate Acetyl-CoA Carboxylase (ACC). IR led to enhanced expression and phosphorylation of p53 and cyclin dependent kinase inhibitors p21cip1 and p27kip1. However, irradiated tumours had reduced phosphorylation of Akt, mTOR and it‘s target translation initiation inhibitor 4EBP1. Irradiated xenografts showed reduced microvessel density, reduced expression of CD31 but increased expression of hypoxia-induced factor 1A (HIF1a) compared to controls.

Conclusion
IR inhibits epithelial cancer tumour growth and results in sustained expression and activation of ATM-Chk2, and AMPK-p53/p21cip1/p27kip1 but partial inhibition of the Akt-mTOR signaling pathways. Future studies should examine causality between those events and explore whether further modulation of the AMPK and Akt-mTOR pathways by novel therapeutics can sensitize lung tumours to radiation.
In Italy, healthy life expectancy drop dramatically: from 2004 to 2008 there was a 10 years drop among newborn girls
Authors: Gennaro Valerio , Ghirga Giovanni , Corradi Laura 
Published: May 2012

Abstract

Introduction
In this short essay, we would like to address a severe divergence observed in Italy between Life Expectancy (LE) and Healthy Life Expectancy (Healthy LE) and a unique trend of worsening in Healthy LE, compared to the other European countries. Both issues emerge in recent data by EUROSTAT Report.

Methods
The analysis used by the authors of the EUROSTAT report is based on Sullivan method which combines 2 type of variables: mortality and morbidity data.

Results
While several European countries started to deal with comparable data about LE since 1960, in Italy, analogous data were available for the first time in EUROSTAT Report only in 1985. In Italy, in the period 1985-2008, there was a good progressive increase in L.E., following the best European values. Nevertheless, while until 2004 Italy was among the European best countries in terms of both LE and Healthy LE at birth, four years later in 2008 there was a shocking loss of 10 years of Healthy LE at birth in newborn girls. In the process, they lost their 2-years previous advantage with respect to males (the latter lost only 6 years of Healthy LE, in the same time span). Looking at healthy LE at age 65 in respect to 2004, Italian women in 2008 could expect to live healthy only about 7 years (as much as men) versus the almost 15 years of the European best values (14 years for men).

Conclusions
It is legitimate to wonder why no one official comment has been produced as a reaction after the first year of spectacular decline in Healthy Life Years in Italy: in counter-tendency with European values, from 2004 to 2008 there is a clear evidence of a 10 years drop in Healthy LE among newborn girls. The problem has not been taken into consideration even when the situation clearly appeared to worsen in the following years, dropping 4-6 more years for males and females in 2006 (for newborn babies); two more years of healthy life expectancy have been lost between 2006 and 2007 for each gender. One more year of Healthy Life Expectancy is lost in 2008. And data have not been made available any more, since then, from Italy.