bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Stress in Understanding Differences in Sedentary Behavior in Hispanic/Latino Adults: Results From the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study
Authors: Vásquez Elizabeth , Strizich Garrett , Gallo Linda , Marshall Simon J. , Merchant Gina C. , Murillo Rosenda , Penedo Frank J. , Salazar Christian , Sotres-Alvarez Daniela , Shaw Benjamin A. , Isasi Carmen R. 
Published: July 2015

Background:Chronic stress and/or lifetime traumatic stress can create a self-reinforcing cycle of unhealthy behaviors, such as overeating and sedentary behavior, that can lead to further increases in stress. This study examined the relationship between stress and sedentary behavior in a sample of Hispanic/Latino adults (N = 4244) from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.Methods:Stress was measured as the number of ongoing difficulties lasting 6 months or more and as lifetime exposure to traumatic events. Sedentary behavior was measured by self-report and with accelerometer. Multivariable regression models examined associations of stress measures with time spent in sedentary behaviors adjusting by potential confounders.Results:Those who reported more than one chronic stressor spent, on average, 8 to 10 additional minutes per day in objectively measured sedentary activities (P < .05), whereas those with more than one lifetime traumatic stressor spent (after we adjusted for confounders) 10 to 14 additional minutes in sedentary activities (P < .01) compared with those who did not report any stressors. Statistical interactions between the 2 stress measures and age or sex were not significant.Conclusion:Interventions aimed at reducing sedentary behaviors might consider incorporating stress reduction into their approaches.
Phylogeny and Comparative Genomics Unveil Independent Diversification Trajectories of
qnrB
and Genetic Platforms within Particular Citrobacter Species
Authors: Ribeiro Teresa G. , Novais Ângela , Branquinho Raquel , Machado Elisabete , Peixe Luísa 
Published: July 2015

ABSTRACT

To gain insights into the diversification trajectories of
qnrB
genes, a phylogenetic and comparative genomics analysis of these genes and their surrounding genetic sequences was performed. For this purpose,
Citrobacter
sp. isolates (
n
= 21) and genome or plasmid sequences (
n
= 56) available in public databases harboring complete or truncated
qnrB
genes were analyzed.
Citrobacter
species identification was performed by phylogenetic analysis of different genotypic markers. The clonal relatedness among isolates, the location of
qnrB
genes, and the genetic surroundings of
qnrB
genes were investigated by pulsed-field gel electrophoresis (PFGE), S1-/I-CeuI-PFGE and hybridization, and PCR mapping and sequencing, respectively. Identification of
Citrobacter
isolates was achieved using
leuS
and
recN
gene sequences, and isolates characterized in this study were diverse and harbored chromosomal
qnrB
genes. Phylogenetic analysis of all known
qnrB
genes revealed seven main clusters and two branches, with most of them included in two clusters. Specific platforms (comprising
pspF
and
sapA
and varying in synteny and/or identity of other genes and intergenic regions) were associated with each one of these
qnrB
clusters, and the reliable identification of all
Citrobacter
isolates revealed that each platform evolved in different recognizable (
Citrobacter freundii
,
C. braakii
,
C. werkmanii
, and
C. pasteurii
) and putatively new species. A high identity was observed between some of the platforms identified in the chromosome of
Citrobacter
spp. and in different plasmids of
Enterobacteriaceae
. Our data corroborate
Citrobacter
as the origin of
qnrB
and further suggest divergent evolution of closely related
qnrB
genes/platforms in particular
Citrobacter
spp., which were delineated using particular genotypic markers.
Mucin Binding Reduces Colistin Antimicrobial Activity
Authors: Huang Johnny X. , Blaskovich Mark A. T. , Pelingon Ruby , Ramu Soumya , Kavanagh Angela , Elliott Alysha G. , Butler Mark S. , Montgomery A. Bruce , Cooper Matthew A. 
Published: July 2015

ABSTRACT
Colistin has found increasing use in treating drug-resistant bacterial lung infections, but potential interactions with pulmonary biomolecules have not been investigated. We postulated that colistin, like aminoglycoside antibiotics, may bind to secretory mucin in sputum or epithelial mucin that lines airways, reducing free drug levels. To test this hypothesis, we measured binding of colistin and other antibiotics to porcine mucin, a family of densely glycosylated proteins used as a surrogate for human sputum and airway mucin. Antibiotics were incubated in dialysis tubing with or without mucin, and concentrations of unbound antibiotics able to penetrate the dialysis tubing were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The percentage of antibiotic measured in the dialysate after 4 h in the presence of mucin, relative to the amount without mucin, was 15% for colistin, 16% for polymyxin B, 19% for tobramycin, 52% for ciprofloxacin, and 78% for daptomycin. Antibiotics with the strongest mucin binding had an overall polybasic positive charge, whereas those with comparatively little binding were less basic. When comparing MICs measured with or without added mucin, colistin and polymyxin B showed >100-fold increases in MICs for multiple Gram-negative bacteria. Preclinical evaluation of mucin binding should become a standard procedure when considering the potential pulmonary use of new or existing antibiotics, particularly those with a polybasic overall charge. In the airways, mucin binding may reduce the antibacterial efficacy of inhaled or intravenously administered colistin, and the presence of sub-MIC effective antibiotic concentrations could result in the development of antibiotic resistance.
Sulfamethoxazole Susceptibility of Mycobacterium tuberculosis Isolates from HIV-Infected Ugandan Adults with Tuberculosis Taking Trimethoprim-Sulfamethoxazole Prophylaxis
Authors: Ogwang Sam , Good Caryn E. , Okware Brenda , Nsereko Mary , Jacobs Michael R. , Boom W. Henry , Bark Charles M. 
Published: July 2015

ABSTRACT

Additional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to have
in vitro
activity against
Mycobacterium tuberculosis
; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40
Mycobacterium tuberculosis
isolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.
Residues Distal to the Active Site Contribute to Enhanced Catalytic Activity of Variant and Hybrid β-Lactamases Derived from CTX-M-14 and CTX-M-15
Authors: He Dandan , Chiou Jiachi , Zeng Zhenling , Liu Lanping , Chen Xiaojie , Zeng Li , Chan Edward Wai Chi , Liu Jian-Hua , Chen Sheng 
Published: July 2015

ABSTRACT

A variety of CTX-M-type extended-spectrum β-lactamases (ESBLs), including hybrid ones, have been reported in China that are uncommon elsewhere. To better characterize the substrate profiles and enzymatic mechanisms of these enzymes, we performed comparative kinetic analyses of both parental and hybrid CTX-M enzymes, including CTX-M-15, -132, -123, -64, -14 and -55, that are known to confer variable levels of β-lactam resistance in the host strains. All tested enzymes were susceptible to serine β-lactamase inhibitors, with sulbactam exhibiting the weakest inhibitory effects. CTX-M-55, which differs from CTX-M-15 by one substitution, A
77
V, displayed enhanced catalytic activity (

k
cat

/

K
m

) against expanded-spectrum cephalosporins (ESCs). CTX-M-55 exhibits higher structure stability, most likely by forming hydrophobic interactions between A
77
V and various key residues in different helices, thereby stabilizing the core architecture of the helix cluster, and indirectly contributes to a more stable active site conformation, which in turn shows higher catalytic efficiency and is more tolerant to temperature change. Analyses of the hybrids and their parental prototypes showed that evolution from CTX-M-15 to CTX-M-132, CTX-M-123, and CTX-M-64, characterized by gradual enhancement of catalytic activity to ESCs, was attributed to introduction of different substitutions to amino acids distal to the active site of CTX-M-15. Similarly, the increased hydrolytic activities against cephalosporins and sensitivity to β-lactamase inhibitors, clavulanic acid and sulbactam, of CTX-M-64 were partly due to the amino acids that were different from CTX-M-14 and located at both the C and N termini of CTX-M-64. These data indicate that residues distal to the active site of CTX-Ms contributed to their enhanced catalytic activities to ESCs.
Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India
Authors: Dalko Esther , Das Bidyut , Herbert Fabien , Fesel Constantin , Pathak Sulabha , Tripathy Rina , Cazenave Pierre-André , Ravindran Balachandran , Sharma Shobhona , Pied Sylviane 
Published: July 2015

ABSTRACTSeveral immunomodulatory factors are involved in malaria pathogenesis. Among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. Circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237Plasmodium falciparum-infected patients living in the state of Odisha, India, where malaria is endemic. All patients were categorized into well-defined groups of mild malaria, cerebral malaria (CM), or severe noncerebral malaria, which included acute renal failure (ARF) and hepatopathy. Our results show a significant increase in total plasma heme levels with malaria severity, especially for CM and malarial ARF. Spearman rank correlation and canonical correlation analyses have shown a correlation between total heme, hemopexin, interleukin-10, tumor necrosis factor alpha, gamma interferon-induced protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels. In addition, canonical correlations revealed that heme, along with IP-10, was associated with the CM pathophysiology, whereas both IP-10 and MCP-1 together with heme discriminated ARF. Altogether, our data indicate that heme, in association with cytokines and chemokines, is involved in the pathophysiology of both CM and ARF but through different mechanisms.
A Periplasmic Complex of the Nitrite Reductase NirS, the Chaperone DnaK, and the Flagellum Protein FliC Is Essential for Flagellum Assembly and Motility in Pseudomonas aeruginosa
Authors: Borrero-de Acuña José Manuel , Molinari Gabriella , Rohde Manfred , Dammeyer Thorben , Wissing Josef , Jänsch Lothar , Arias Sagrario , Jahn Martina , Schobert Max , Timmis Kenneth N. , Jahn Dieter 
Published: July 2015

ABSTRACT

Pseudomonas aeruginosa
is a ubiquitously occurring environmental bacterium and opportunistic pathogen responsible for various acute and chronic infections. Obviously, anaerobic energy generation via denitrification contributes to its ecological success. To investigate the structural basis for the interconnection of the denitrification machinery to other essential cellular processes, we have sought to identify the protein interaction partners of the denitrification enzyme nitrite reductase NirS in the periplasm. We employed NirS as an affinity-purifiable bait to identify interacting proteins
in
vivo
. Results obtained revealed that both the flagellar structural protein FliC and the protein chaperone DnaK form a complex with NirS in the periplasm. The interacting domains of NirS and FliC were tentatively identified. The NirS-interacting stretch of amino acids lies within its cytochrome
c
domain. Motility assays and ultrastructure analyses revealed that a
nirS
mutant was defective in the formation of flagella and correspondingly in swimming motility. In contrast, the
fliC
mutant revealed an intact denitrification pathway. However, deletion of the
nirF
gene, coding for a heme
d
1
biosynthetic enzyme, which leads to catalytically inactive NirS, did not abolish swimming ability. This pointed to a structural function for the NirS protein. FliC and NirS were found colocalized with DnaK at the cell surface of
P. aeruginosa
. A function of the detected periplasmic NirS-DnaK-FliC complex in flagellum formation and motility was concluded and discussed.

IMPORTANCE
Physiological functions in Gram-negative bacteria are connected with the cellular compartment of the periplasm and its membranes. Central enzymatic steps of anaerobic energy generation and the motility mediated by flagellar activity use these cellular structures in addition to multiple other processes. Almost nothing is known about the protein network functionally connecting these processes in the periplasm. Here, we demonstrate the existence of a ternary complex consisting of the denitrifying enzyme NirS, the chaperone DnaK, and the flagellar protein FliC in the periplasm of the pathogenic bacterium
P. aeruginosa
. The dependence of flagellum formation and motility on the presence of an intact NirS was shown, structurally connecting both cellular processes, which are important for biofilm formation and pathogenicity of the bacterium.
Mycobacterium smegmatis HelY Is an RNA-Activated ATPase/dATPase and 3′-to-5′ Helicase That Unwinds 3′-Tailed RNA Duplexes and RNA:DNA Hybrids
Authors: Uson Maria Loressa , Ordonez Heather , Shuman Stewart 
Published: July 2015

ABSTRACT

Mycobacteria have a large and distinctive ensemble of DNA helicases that function in DNA replication, repair, and recombination. Little is known about the roster of RNA helicases in mycobacteria or their roles in RNA transactions. The 912-amino-acid
Mycobacterium smegmatis
HelY (MSMEG_3885) protein is a bacterial homolog of the Mtr4 and Ski2 helicases that regulate RNA 3′ processing and turnover by the eukaryal exosome. Here we characterize HelY as an RNA-stimulated ATPase/dATPase and an ATP/dATP-dependent 3′-to-5′ helicase. HelY requires a 3′ single-strand RNA tail (a loading RNA strand) to displace the complementary strand of a tailed RNA:RNA or RNA:DNA duplex. The findings that HelY ATPase is unresponsive to a DNA polynucleotide cofactor and that HelY is unable to unwind a 3′-tailed duplex in which the loading strand is DNA distinguish HelY from other mycobacterial nucleoside triphosphatases/helicases characterized previously. The biochemical properties of HelY, which resemble those of Mtr4/Ski2, hint at a role for HelY in mycobacterial RNA catabolism.

IMPORTANCE
RNA helicases play crucial roles in transcription, RNA processing, and translation by virtue of their ability to alter RNA secondary structure or remodel RNA-protein interactions. In eukarya, the RNA helicases Mtr4 and Ski2 regulate RNA 3′ resection by the exosome.
Mycobacterium smegmatis
HelY, a bacterial homolog of Mtr4/Ski2, is characterized here as a unidirectional helicase, powered by RNA-dependent ATP/dATP hydrolysis, that tracks 3′ to 5′ along a loading RNA strand to displace the complementary strand of a tailed RNA:RNA or RNA:DNA duplex. The biochemical properties of HelY suggest a role in bacterial RNA transactions. HelY homologs are present in pathogenic mycobacteria (e.g.,
M. tuberculosis
and
M. leprae
) and are widely prevalent in
Actinobacteria
and
Cyanobacteria
but occur sporadically elsewhere in the bacterial domain.
Structural Features Reminiscent of ATP-Driven Protein Translocases Are Essential for the Function of a Type III Secretion-Associated ATPase
Authors: Kato Junya , Lefebre Matthew , Galán Jorge E. 
Published: July 2015

ABSTRACT

Many bacterial pathogens and symbionts utilize type III secretion systems to interact with their hosts. These machines have evolved to deliver bacterial effector proteins into eukaryotic target cells to modulate a variety of cellular functions. One of the most conserved components of these systems is an ATPase, which plays an essential role in the recognition and unfolding of proteins destined for secretion by the type III pathway. Here we show that structural features reminiscent of other ATP-driven protein translocases are essential for the function of InvC, the ATPase associated with a
Salmonella enterica
serovar Typhimurium type III secretion system. Mutational and functional analyses showed that a two-helix-finger motif and a conserved loop located at the entrance of and within the predicted pore formed by the hexameric ATPase are essential for InvC function. These findings provide mechanistic insight into the function of this highly conserved component of type III secretion machines.

IMPORTANCE
Type III secretion machines are essential for the virulence or symbiotic relationships of many bacteria. These machines have evolved to deliver bacterial effector proteins into host cells to modulate cellular functions, thus facilitating bacterial colonization and replication. An essential component of these machines is a highly conserved ATPase, which is necessary for the recognition and secretion of proteins destined to be delivered by the type III secretion pathway. Using modeling and structure and function analyses, we have identified structural features of one of these ATPases from
Salmonella enterica
serovar Typhimurium that help to explain important aspects of its function.
Mutations That Stimulate
flhDC
Expression in Escherichia coli K-12
Authors: Fahrner Karen A. , Berg Howard C. 
Published: July 2015

ABSTRACT

Motility is a beneficial attribute that enables cells to access and explore new environments and to escape detrimental ones. The organelle of motility in
Escherichia coli
is the flagellum, and its production is initiated by the activating transcription factors FlhD and FlhC. The expression of these factors by the
flhDC
operon is highly regulated and influenced by environmental conditions. The
flhDC
promoter is recognized by σ
70
and is dependent on the transcriptional activator cyclic AMP (cAMP)-cAMP receptor protein complex (cAMP-CRP). A number of K-12 strains exhibit limited motility due to low expression levels of
flhDC
. We report here a large number of mutations that stimulate
flhDC
expression in such strains. They include single nucleotide changes in the −10 element of the promoter, in the promoter spacer, and in the cAMP-CRP binding region. In addition, we show that insertion sequence (IS) elements or a kanamycin gene located hundreds of base pairs upstream of the promoter can effectively enhance transcription, suggesting that the topology of a large upstream region plays a significant role in the regulation of
flhDC
expression. None of the mutations eliminated the requirement for cAMP-CRP for activation. However, several mutations allowed expression in the absence of the nucleoid organizing protein, H-NS, which is normally required for
flhDC
expression.

IMPORTANCE
The
flhDC
operon of
Escherichia coli
encodes transcription factors that initiate flagellar synthesis, an energetically costly process that is highly regulated. Few deregulating mutations have been reported thus far. This paper describes new single nucleotide mutations that stimulate
flhDC
expression, including a number that map to the promoter spacer region. In addition, this work shows that insertion sequence elements or a kanamycin gene located far upstream from the promoter or repressor binding sites also stimulate transcription, indicating a role of regional topology in the regulation of
flhDC
expression.
Statin use in adults at high risk of cardiovascular disease mortality: cross-sectional analysis of baseline data from The Irish Longitudinal Study on Ageing (TILDA)
Authors: Murphy Catriona , Bennett Kathleen , Fahey Tom , Shelley Emer , Graham Ian , Kenny Rose Anne 
Published: July 2015

ObjectivesThis study aims to examine the extent to which statins are used by adults at high risk of cardiovascular disease (CVD) compared to European clinical guidelines. The high-risk groups examined are those with (1) known CVD, (2) known diabetes and (3) a high or very high risk (≥5%) of CVD mortality based on Systematic COronary Risk Evaluation (SCORE).DesignThis study is cross-sectional in design using data from the first wave (2009–2011) of The Irish Longitudinal Study on Ageing (TILDA).Setting and participantsThe sample (n=3372) is representative of community living adults aged 50–64 years in Ireland.ResultsStatins were used by 68.6% (95% CI 61.5% to 75.8%) of those with known CVD, 57.4% (95% CI 49.1% to 65.7%) of those with known diabetes and by 19.7% (95% CI 13.0% to 26.3%) of adults with a SCORE risk ≥5%. Over a third (38.5%, 95% CI 31.0% to 46.0%) of those with known CVD, 46.8% (95% CI 38.4% to 55.1%) of those with known diabetes and 85.2% (95% CI 79.3% to 91.1%) of those with a SCORE risk ≥5% were at or above the low-density lipoprotein cholesterol (LDL-C) target of 2.5 mmol/L specified in the 2007 European guidelines.ConclusionsDespite strong evidence and clinical guidelines recommending the use of statins for secondary prevention, a gap exists between guidelines and practice in this cohort. It is also of concern that a low proportion of adults with a SCORE risk ≥5% were taking statins. A policy response that strengthens secondary prevention, and improves risk assessment and shared decision-making in the primary prevention of CVD is required.