bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower-Body Muscle Structure and Jump Performance of Stronger and Weaker Surfing Athletes
Authors: Secomb Josh L. , Nimphius Sophia , Farley Oliver R.L. , Lundgren Lina , Tran Tai T. , Sheppard Jeremy M. 
Published: November 2015

Purpose:To identify whether there are any significant differences in the lower-body muscle structure and countermovement-jump (CMJ) and squat-jump (SJ) performance between stronger and weaker surfing athletes.Methods:Twenty elite male surfers had their lower-body muscle structure assessed with ultrasonography and completed a series of lower-body strength and jump tests including isometric midthigh pull (IMTP), CMJ, and SJ. Athletes were separated into stronger (n = 10) and weaker (n = 10) groups based on IMTP performance.Results:Large significant differences were identified between the groups for vastus lateralis (VL) thickness (P = .02, ES = 1.22) and lateral gastrocnemius (LG) pennation angle (P = .01, ES = 1.20), and a large nonsignificant difference was identified in LG thickness (P = .08, ES = 0.89). Furthermore, significant differences were present between the groups for peak force, relative peak force, and jump height in the CMJ and SJ (P < .01−.05, ES = 0.90−1.47) and eccentric peak velocity, as well as vertical displacement of the center of mass during the CMJ (P < .01, ES = 1.40−1.41).Conclusion:Stronger surfing athletes in this study had greater VL and LG thickness and LG pennation angle. These muscle structures may explain their better performance in the CMJ and SJ. A unique finding in this study was that the stronger group appeared to better use their strength and muscle structure for braking as they had significantly higher eccentric peak velocity and vertical displacement during the CMJ. This enhanced eccentric phase may have resulted in a greater production and subsequent utilization of stored elastic strain energy that led to the significantly better CMJ performance in the stronger group.
Carriage of Enterobacteria Producing Extended-Spectrum β-Lactamases and Composition of the Gut Microbiota in an Amerindian Community
Authors: Gosalbes María José , Vázquez-Castellanos Jorge F. , Angebault Cécile , Woerther Paul-Louis , Ruppé Etienne , Ferrús María Loreto , Latorre Amparo , Andremont Antoine , Moya Andrés 
Published: November 2015

ABSTRACT

Epidemiological and individual risk factors for colonization by enterobacteria producing extended-spectrum beta-lactamases (E-ESBL) have been studied extensively, but whether such colonization is associated with significant changes in the composition of the rest of the microbiota is still unknown. To address this issue, we assessed in an isolated Amerindian Guianese community whether intestinal carriage of E-ESBL was associated with specificities in gut microbiota using metagenomic and metatranscriptomic approaches. While the richness of taxa of the active microbiota of carriers was similar to that of noncarriers, the taxa were less homogeneous. In addition, species of four genera,
Desulfovibrio
,
Oscillospira
,
Parabacteroides
, and
Coprococcus
, were significantly more abundant in the active microbiota of noncarriers than in the active microbiota of carriers, whereas such was the case only for species of
Desulfovibrio
and
Oscillospira
in the total microbiota. Differential genera in noncarrier microbiota could either be associated with resistance to colonization or be the consequence of the colonization by E-ESBL.
Ertapenem-Containing Double-Carbapenem Therapy for Treatment of Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae
Authors: Cprek Jessica B. , Gallagher Jason C. 
Published: November 2015

ABSTRACT

We describe outcomes of patients with infections with carbapenem-resistant
Klebsiella pneumoniae
(CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, 0/2 (0%); urinary tract infections, 2/3 (67%); and a skin and skin structure infection, 1/1 (100%). Microbiologic success was observed in 11/14 (79%) evaluable patients; 5/18 (28%) patients died. ECDCT may be effective for CRKP infections with limited treatment options.
Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1)
In Vitro
by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture
Authors: Kuhlenschmidt Theresa B. , Rutaganira Florentine U. , Long Shaojun , Tang Keliang , Shokat Kevan M. , Kuhlenschmidt Mark S. , Sibley L. David 
Published: November 2015

ABSTRACT

Cryptosporidiosis is a serious diarrheal disease in immunocompromised patients and malnourished children, and treatment is complicated by a lack of adequate drugs. Recent studies suggest that the natural occurrence of a small gatekeeper residue in serine threonine calcium-dependent protein kinase 1 (CDPK1) of
Cryptosporidium parvum
might be exploited to target this enzyme and block parasite growth. Here were explored the potency with which a series of pyrazolopyrimidine analogs, which are selective for small gatekeeper kinases, inhibit
C. parvum
CDPK1 and block
C. parvum
growth in tissue culture
in vitro
. Although these compounds potently inhibited kinase activity
in vitro
, most had no effect on parasite growth. Moreover, among those that were active against parasite growth, there was a very poor correlation with their 50% inhibitory concentrations against the enzyme. Active compounds also had no effect on cell invasion, unlike the situation in
Toxoplasma gondii
, where these compounds block CDPK1, prevent microneme secretion, and disrupt cell invasion. These findings suggest that CPDK1 is not essential for
C. parvum
host cell invasion or growth and therefore that it is not the optimal target for therapeutic intervention. Nonetheless, several inhibitors with low micromolar 50% effective concentrations were identified, and these may affect other essential targets in
C. parvum
that are worthy of further exploration.
Interactions of OP0595, a Novel Triple-Action Diazabicyclooctane, with β-Lactams against OP0595-Resistant Enterobacteriaceae Mutants
Authors: Livermore David M. , Warner Marina , Mushtaq Shazad , Woodford Neil 
Published: November 2015

ABSTRACT

OP0595 is a novel diazabicyclooctane which, like avibactam, inhibits class A and C β-lactamases. In addition, unlike avibactam, it has antibacterial activity, with MICs of 0.5 to 4 μg/ml for most members of the family
Enterobacteriaceae
, owing to inhibition of PBP2; moreover, it acts synergistically with PBP3-active β-lactams independently of β-lactamase inhibition, via an “enhancer effect.”
Enterobacteriaceae
mutants stably resistant to 16 μg/ml OP0595 were selected on agar at frequencies of approximately 10
−7
. Unsurprisingly, OP0595 continued to potentiate substrate β-lactams against mutants derived from
Enterobacteriaceae
with OP0595-inhibited class A and C β-lactamases. Weaker potentiation of partners, especially aztreonam, cefepime, and piperacillin—less so meropenem—remained frequent for OP0595-resistant
Enterobacteriaceae
mutants lacking β-lactamases or with OP0595-resistant metallo-β-lactamases (MBLs), indicating that the enhancer effect is substantially retained even when antibiotic activity is lost.
Insights into the Molecular Mechanism of Polymerization and Nucleoside Reverse Transcriptase Inhibitor Incorporation by Human PrimPol
Authors: Mislak Andrea C. , Anderson Karen S. 
Published: November 2015

ABSTRACT
Human PrimPol is a newly identified DNA and RNA primase-polymerase of the archaeo-eukaryotic primase (AEP) superfamily and only the second known polymerase in the mitochondria. Mechanistic studies have shown that interactions of the primary mitochondrial DNA polymerase γ (mtDNA Pol γ) with nucleoside reverse transcriptase inhibitors (NRTIs), key components in treating HIV infection, are a major source of NRTI-associated toxicity. Understanding the interactions of host polymerases with antiviral and anticancer nucleoside analog therapies is critical for preventing life-threatening adverse events, particularly in AIDS patients who undergo lifelong treatment. Since PrimPol has only recently been discovered, the molecular mechanism of polymerization and incorporation of natural nucleotide and NRTI substrates, crucial for assessing the potential for PrimPol-mediated NRTI-associated toxicity, has not been explored. We report for the first time a transient-kinetic analysis of polymerization for each nucleotide and NRTI substrate as catalyzed by PrimPol. These studies reveal that nucleotide selectivity limits chemical catalysis while the release of the elongated DNA product is the overall rate-limiting step. Remarkably, PrimPol incorporates four of the eight FDA-approved antiviral NRTIs with a kinetic profile distinct from that of mtDNA Pol γ that may manifest in toxicity.
Heterologous Expression and Functional Characterization of the Exogenously Acquired Aminoglycoside Resistance Methyltransferases RmtD, RmtD2, and RmtG
Authors: Corrêa Laís L. , Witek Marta A. , Zelinskaya Natalia , Picão Renata C. , Conn Graeme L. 
Published: November 2015

ABSTRACT

The exogenously acquired 16S rRNA methyltransferases RmtD, RmtD2, and RmtG were cloned and heterologously expressed in
Escherichia coli
, and the recombinant proteins were purified to near homogeneity. Each methyltransferase conferred an aminoglycoside resistance profile consistent with m
7
G1405 modification, and this activity was confirmed by
in
vitro
30S methylation assays. Analyses of protein structure and interaction with
S
-adenosyl-
l
-methionine suggest that the molecular mechanisms of substrate recognition and catalysis are conserved across the 16S rRNA (m
7
G1405) methyltransferase family.
Suppression of CD4+Effector Responses by Naturally Occurring CD4+CD25+Foxp3+Regulatory T Cells Contributes to Experimental Cerebral Malaria
Authors: Blanc Anne-Laurence , Keswani Tarun , Gorgette Olivier , Bandeira Antonio , Malissen Bernard , Cazenave Pierre-André , Pied Sylviane 
Published: November 2015

ABSTRACTThe role of naturally occurring CD4+CD25+Foxp3+regulatory T cells (nTreg) in the pathogenesis of cerebral malaria (CM), which involves both pathogenic T cell responses and parasite sequestration in the brain, is still unclear. To assess the contribution and dynamics of nTreg during the neuropathogenesis, we unbalanced the ratio between nTreg and naive CD4+T cells in an attenuated model ofPlasmodium bergheiANKA-induced experimental CM (ECM) by using a selective cell enrichment strategy. We found that nTreg adoptive transfer accelerated the onset and increased the severity of CM in syngeneic C57BL/6 (B6)P. bergheiANKA-infected mice without affecting the level of parasitemia. In contrast, naive CD4+T cell enrichment prevented CM and promoted parasite clearance. Furthermore, early during the infection nTreg expanded in the spleen but did not efficiently migrate to the site of neuroinflammation, suggesting that nTreg exert their pathogenic action early in the spleen by suppressing the protective naive CD4+T cell response toP. bergheiANKA infectionin vivoin both CM-susceptible (B6) and CM-resistant (B6-CD4−/−) mice. However, their sole transfer was not sufficient to restore CM susceptibility in two CM-resistant congenic strains tested. Altogether, these results demonstrate that nTreg are activated and functional duringP. bergheiANKA infection and that they contribute to the pathogenesis of CM. They further suggest that nTreg may represent an early target for the modulation of the immune response to malaria.
Global Changes in Mycoplasma gallisepticum Phase-Variable Lipoprotein Gene
vlhA
Expression during
In Vivo
Infection of the Natural Chicken Host
Authors: Pflaum K. , Tulman E. R. , Beaudet J. , Liao X. , Geary S. J. 
Published: November 2015

ABSTRACT

Mycoplasma gallisepticum
is the primary etiologic agent of chronic respiratory disease in poultry, a disease largely affecting the respiratory tract and causing significant economic losses worldwide. Immunodominant proteins encoded by members of the variable lipoprotein and hemagglutinin (
vlhA
) gene family are thought to be important for mechanisms of
M. gallisepticum
-host interaction, pathogenesis, and immune evasion, but their exact role and the overall nature of their phase variation are unknown. To better understand these mechanisms, we assessed global transcriptomic
vlhA
gene expression directly from
M. gallisepticum
populations present on tracheal mucosae during a 7-day experimental infection in the natural chicken host. Here we report differences in both dominant and minor
vlhA
gene expression levels throughout the first week of infection and starting as early as day 1 postinfection, consistent with a functional role not dependent on adaptive immunity for driving phase variation. Notably, data indicated that, at given time points, specific
vlhA
genes were similarly dominant in multiple independent hosts, suggesting a nonstochastic temporal progression of dominant
vlhA
gene expression in the colonizing bacterial population. The dominant expression of a given
vlhA
gene was not dependent on the presence of 12-copy GAA trinucleotide repeats in the promoter region and did not revert to the predominate
vlhA
gene when no longer faced with host pressures. Overall, these data indicate that
vlhA
phase variation is dynamic throughout the earliest stages of infection and that the pattern of dominant
vlhA
expression may be nonrandom and regulated by previously unrecognized mechanisms.
Accumulation of Regulatory T Cells and Chronic Inflammation in the Middle Ear in a Mouse Model of Chronic Otitis Media with Effusion Induced by Combined Eustachian Tube Blockage and Nontypeable Haemophilus influenzae Infection
Authors: Hirano Takashi , Kodama Satoru , Kawano Toshiaki , Suzuki Masashi 
Published: November 2015

ABSTRACTNontypeableHaemophilus influenzae(NTHi) is associated with chronic otitis media (COM). In this study, we generated a murine model of COM by using eustachian tube (ET) obstruction and NTHi (107CFU) inoculation into the tympanic bulla, and we investigated the relationship between regulatory T cells (Treg) and chronic inflammation in the middle ear. Middle ear effusions (MEEs) and middle ear mucosae (MEM) were collected at days 3 and 14 and at 1 and 2 months after inoculation. Untreated mice served as controls. MEEs were used for bacterial counts and to measure the concentrations of cytokines. MEM were collected for histological evaluation and flow cytometric analysis. Inflammation of the MEM was prolonged throughout this study, and the incidence of NTHi culture-positive MEE was 38% at 2 months after inoculation. The levels of interleukin-1β (IL-β), tumor necrosis factor alpha, IL-10, and transforming growth factor β were increased in the middle ear for up to 2 months after inoculation. CD4+CD25+FoxP3+Treg accumulated in the middle ear, and the percentage of Treg in the MEM increased for up to 2 months after inoculation. Treg depletion induced a 99.9% reduction of bacterial counts in MEEs and also significantly reduced the ratio of NTHi culture-positive MEE. The levels of these cytokines were also reduced in MEEs. In summary, we developed a murine model of COM, and our findings indicate that Treg confer infectious tolerance to NTHi in the middle ear.
The Stringent Response Regulator DksA Is Required for Salmonella enterica Serovar Typhimurium Growth in Minimal Medium, Motility, Biofilm Formation, and Intestinal Colonization
Authors: Azriel Shalhevet , Goren Alina , Rahav Galia , Gal-Mor Ohad 
Published: November 2015

ABSTRACT

Salmonella enterica
serovar Typhimurium is a facultative intracellular human and animal bacterial pathogen posing a major threat to public health worldwide.
Salmonella
pathogenicity requires complex coordination of multiple physiological and virulence pathways. DksA is a conserved Gram-negative regulator that belongs to a distinct group of transcription factors that bind directly to the RNA polymerase secondary channel, potentiating the effect of the signaling molecule ppGpp during a stringent response. Here, we established that in
S.
Typhimurium,
dksA
is induced during the logarithmic phase and DksA is essential for growth in minimal defined medium and plays an important role in motility and biofilm formation. Furthermore, we determined that DksA positively regulates the
Salmonella
pathogenicity island 1 and motility-chemotaxis genes and is necessary for
S.
Typhimurium invasion of human epithelial cells and uptake by macrophages. In contrast, DksA was found to be dispensable for
S.
Typhimurium host cell adhesion. Finally, using the colitis mouse model, we found that
dksA
is spatially induced at the midcecum during the early stage of the infection and required for gastrointestinal colonization and systemic infection
in vivo
. Taken together, these data indicate that the ancestral stringent response regulator DksA coordinates various physiological and virulence
S.
Typhimurium programs and therefore is a key virulence regulator of
Salmonella
.
Expression and Genetic Activation of Cyclic Di-GMP-Specific Phosphodiesterases in Escherichia coli
Authors: Reinders Alberto , Hee Chee-Seng , Ozaki Shogo , Mazur Adam , Boehm Alex , Schirmer Tilman , Jenal Urs 
Published: November 2015

ABSTRACT

Intracellular levels of the bacterial second messenger cyclic di-GMP (c-di-GMP) are controlled by antagonistic activities of diguanylate cyclases and phosphodiesterases. The phosphodiesterase PdeH was identified as a key regulator of motility in
Escherichia coli
, while deletions of any of the other 12 genes encoding potential phosphodiesterases did not interfere with motility. To analyze the roles of
E. coli
phosphodiesterases, we demonstrated that most of these proteins are expressed under laboratory conditions. We next isolated suppressor mutations in six phosphodiesterase genes, which reinstate motility in the absence of PdeH by reducing cellular levels of c-di-GMP. Expression of all mutant alleles also led to a reduction of biofilm formation. Thus, all of these proteins are
bona fide
phosphodiesterases that are capable of interfering with different c-di-GMP-responsive output systems by affecting the global c-di-GMP pool. This argues that
E. coli
possesses several phosphodiesterases that are inactive under laboratory conditions because they lack appropriate input signals. Finally, one of these phosphodiesterases, PdeL, was studied in more detail. We demonstrated that this protein acts as a transcription factor to control its own expression. Motile suppressor alleles led to a strong increase of PdeL activity and elevated
pdeL
transcription, suggesting that enzymatic activity and transcriptional control are coupled. In agreement with this, we showed that overall cellular levels of c-di-GMP control
pdeL
transcription and that this control depends on PdeL itself. We thus propose that PdeL acts both as an enzyme and as a c-di-GMP sensor to couple transcriptional activity to the c-di-GMP status of the cell.

IMPORTANCE
Most bacteria possess multiple diguanylate cyclases and phosphodiesterases. Genetic studies have proposed that these enzymes show signaling specificity by contributing to distinct cellular processes without much cross talk. Thus, spatial separation of individual c-di-GMP signaling units was postulated. However, since most cyclases and phosphodiesterases harbor N-terminal signal input domains, it is equally possible that most of these enzymes lack their activating signals under laboratory conditions, thereby simulating signaling specificity on a genetic level. We demonstrate that a subset of
E. coli
phosphodiesterases can be activated genetically to affect the global c-di-GMP pool and thus influence different c-di-GMP-dependent processes. Although this does not exclude spatial confinement of individual phosphodiesterases, this study emphasizes the importance of environmental signals for activation of phosphodiesterases.
SepM, a Streptococcal Protease Involved in Quorum Sensing, Displays Strict Substrate Specificity
Authors: Biswas Saswati , Cao Luyang , Kim Albert , Biswas Indranil 
Published: November 2015

ABSTRACT

Streptococcus mutans
, a causative agent of dental caries, relies on multiple quorum-sensing (QS) pathways that coordinate the expression of factors needed for colonization in the oral cavity.
S. mutans
uses small peptides as QS signaling molecules that typically are secreted into the outside milieu. Competence-stimulating peptide (CSP) is one such QS signaling molecule that functions through the ComDE two-component signal transduction pathway. CSP is secreted through NlmTE, a dedicated ABC transporter that cleaves off the N-terminal leader peptide to generate a mature peptide that is 21 residues long (CSP-21). We recently identified a surface-localized protease, SepM, which further cleaves the CSP-21 peptide at the C-terminal end and removes the last 3 residues to generate CSP-18. CSP-18 is the active QS molecule that interacts with the ComD sensor kinase to activate the QS pathway. In this study, we show that SepM specifically cleaves CSP-21 between the Ala18 and Leu19 residues. We also show that SepM recognizes only Ala at position 18 and Leu at position 19, although some CSP-18 variants with a substitution at position 18 can function equally as well as the QS peptide. Furthermore, we demonstrate that SepM homologs from other streptococci are capable of processing CSP-21 to generate functional CSP-18.

IMPORTANCE
SepM is a membrane-associated streptococcal protease that processes competence-stimulating peptide (CSP) to generate an active quorum-sensing molecule in
S. mutans
. SepM belongs to the S16 family of serine proteases, and in this study, we found that SepM behaves as an endopeptidase. SepM displays strict substrate specificity and cleaves the peptide bond between the Ala and Leu residues. This is the first report of an endopeptidase that specifically cleaves these two residues.
The effects of malnutrition on cardiac function in African children
Authors: Silverman Jonathan A , Chimalizeni Yamikani , Hawes Stephen E , Wolf Elizabeth R , Batra Maneesh , Khofi Harriet , Molyneux Elizabeth M 
Published: November 2015

ObjectiveCardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children.DesignProspective cross-sectional study.SettingPublic referral hospital in Blantyre, Malawi.PatientsWe enrolled 272 stable, hospitalised children ages 6–59 months, with and without WHO-defined severe acute malnutrition.Main outcome measuresCardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia.ResultsOur primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m2 (95% CI −0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=−8.6 mm Hg (95% CI −12.7 to −4.6) and difference=−200 dyne s/cm5/m2 (95% CI −320 to −80), respectively.ConclusionsIn this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children.