bluuebunny/crossref_metadata_2025 huggingface dataset:
Ca2+ leakage out of the sarcoplasmic reticulum is increased in type I skeletal muscle fibres in aged humans
Authors: Lamboley C. R. , Wyckelsma V. L. , McKenna M. J. , Murphy R. M. , Lamb G. D.
Published: November 2015

Key points

The amount of Ca2+ stored in the sarcoplasmic reticulum (SR) of muscle fibres is decreased in aged individuals, and an important question is whether this results from increased Ca2+ leakage out through the Ca2+ release channels (ryanodine receptors; RyRs).

The present study examined the effects of blocking the RyRs with Mg2+, or applying a strong reducing treatment, on net Ca2+ accumulation by the SR in skinned muscle fibres from Old (∼70 years) and Young (∼24 years) adults.

Raising cytoplasmic [Mg2+] and reducing treatment increased net SR Ca2+ accumulation in type I fibres of Old subjects relative to that in Young.

The densities of RyRs and dihydropyridine receptors were not significantly changed in the muscle of Old subjects.

These findings indicate that oxidative modification of the RyRs causes increased Ca2+ leakage from the SR in muscle fibres in Old subjects, which probably deleteriously affects normal muscle function both directly and indirectly.

The present study examined whether the lower Ca2+ storage levels in the sarcoplasmic reticulum (SR) in vastus lateralis muscle fibres in Old (70 ± 4 years) relative to Young (24 ± 4 years) human subjects is the result of increased leakage of Ca2+ out of the SR through the Ca2+ release channels/ryanodine receptors (RyRs) and due to oxidative modification of the RyRs. SR Ca2+ accumulation in mechanically skinned muscle fibres was examined in the presence of 1, 3 or 10 mm cytoplasmic Mg2+ because raising [Mg2+] strongly inhibits Ca2+ efflux through the RyRs. In type I fibres of Old subjects, SR Ca2+ accumulation in the presence of 1 mm Mg2+ approached saturation at shorter loading times than in Young subjects, consistent with Ca2+ leakage limiting net uptake, and raising [Mg2+] to 10 mm in such fibres increased maximal SR Ca2+ accumulation. No significant differences were seen in type II fibres. Treatment with dithiothreitol (10 mm for 5 min), a strong reducing agent, also increased maximal SR Ca2+ accumulation at 1 mm Mg2+ in type I fibres of Old subjects but not in other fibres. The densities of dihydropyridine receptors and RyRs were not significantly different in muscles of Old relative to Young subjects. These findings indicate that Ca2+ leakage from the SR is increased in type I fibres in Old subjects by reversible oxidative modification of the RyRs; this increased SR Ca2+ leak is expected to have both direct and indirect deleterious effects on Ca2+ movements and muscle function.
Compromised blood–brain barrier permeability: novel mechanism by which circulating angiotensin II signals to sympathoexcitatory centres during hypertension
Authors: Biancardi V. C. , Stern J. E.
Published: November 2015

Angiotensin II (AngII) is a pivotal peptide implicated in the regulation of blood pressure. In addition to its systemic vascular and renal effects, AngII acts centrally to modulate the activities of neuroendocrine and sympathetic neuronal networks, influencing in turn sympatho‐humoral outflows to the circulation. Moreover, a large body of evidence supports AngII signalling dysregulation as a key mechanism contributing to exacerbated sympathoexcitation during hypertension. Due to its hydrophilic actions, circulating AngII does not cross the blood–brain barrier (BBB), signalling to the brain via the circumventricular organs which lack a tight BBB. In this review, we present and discuss recent studies from our laboratory showing that elevated circulating levels of AngII during hypertension result in disruption of the BBB integrity, allowing access of circulating AngII to critical sympathoexcitatory brain centres such as the paraventricular nucleus of the hypothalamus and the rostral ventrolateral medulla. We propose the novel hypothesis that AngII‐driven BBB breakdown constitutes a complementary mechanism by which circulating AngII, working in tandem with the central renin–angiotensin system, further exacerbates sympatho‐humoral activation during hypertension. These results are discussed within the context of a growing body of evidence in the literature supporting AngII as a pro‐inflammatory signal, and brain microglia as key cell targets mediating central AngII actions during hypertension.

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Here’s the Pitch: The Dilemma of Selecting a New Outdoor Playing Field for Sunshine State University
Authors: Simmons Jason , Popp Nels , Greenhalgh Greg
Published: November 2015

The outdoor athletic fields of Sunshine State University are in poor condition. Overuse, insufficient drainage, and a lack of human and financial resources have contributed to the fields’ deterioration. Sunshine State University’s director of athletics, Emily Rodriguez, has decided to replace the existing fields, but that decision is just the tip of the iceberg. Rodriguez now must decide on a natural or synthetic surface for the new fields. This decision is complex because cost, maintenance, durability, player safety, and player preference must all be considered. Both surfaces have their advantages and disadvantages. In the end, Rodriguez must decide which surface is right for Sunshine State University.
Influence of Position and Power Output on Upper Limb Kinetics in Cycling
Authors: Costes Antony , Turpin Nicolas A. , Villeger David , Moretto Pierre , Watier Bruno
Published: November 2015

Several suggestions on the upper limb involvement in cycling exist but, to date, no study has quantified upper limb kinetics in this task. The aim of this study was to determine how crank power and pedaling position (seated or standing) affect upper limb kinetics. Handlebar loadings and upper limb kinematics were collected from 17 participants performing seated or standing pedaling trials in a random order at 6 crank powers ranging from 20% (112 ± 19 W) to 120% (675 ± 113 W) of their spontaneous sit-to-stand transition power. An inverse dynamics approach was used to compute 3D moments, powers, and works at the wrist, elbow, and shoulder joints. Over 29 parameters investigated, increases in crank power were associated with increases in the magnitudes of 23 and 20 of the kinetic variables assessed in seated and standing positions, respectively. The standing position was associated with higher magnitudes of upper limb kinetics. These results suggest that both upper and lower limbs should be considered in future models to better understand whole body coordination in cycling.
Writing Quality Peer Reviews of Research Manuscripts
Authors: Ward Phillip , Graber Kim C. , Mars Hans van der
Published: November 2015

Peer review is an important mechanism for advancing knowledge in a manner deemed as acceptable by the research community. It can also serve the function of providing guidance to an author(s) to improve the likelihood that manuscripts will be accepted in peer reviewed journals. There is, however, little assistance for new or existing reviewers of journals beyond the guidelines for reviewers that some journals provide. Moreover, reviewers seldom, if ever, receive feedback on their reviews that might help them to provide higher quality reviews in the future. In this paper, we provide specific recommendations for drafting quality and constructive peer reviews of manuscripts. While we point to the Journal of Teaching in Physical Education as an example, our focus is on encouraging quality reviews across all journals in our field. We base our recommendations on empirical reports, recommendations of editors that have been published in the research literature, and our own experiences as reviewers. Examples of recommended and not recommended review elements are also provided.
Systemic trade risk of critical resources
Authors: Klimek Peter , Obersteiner Michael , Thurner Stefan
Published: November 2015

Price volatility of critical resources can largely be understood through the topology of their trade networks.
Molecular Characterization of a Voriconazole-Resistant, Posaconazole-Susceptible Aspergillus fumigatus Isolate in a Lung Transplant Recipient in the United States
Authors: Vazquez Jose A. , Manavathu Elias K.
Published: November 2015

Molecular characterization of
cyp51A
from the azole-resistant
Aspergillus fumigatus
isolate 50593 from a lung transplant patient showed Y121F/T289A changes coupled with a 46-bp tandem repeat (TR46) on the promoter, whereas
cyp51A
from the pretherapy isolate,
A. fumigatus
47381, showed no changes. This is the first reported case of
A. fumigatus
azole resistance due to Y121F/T289A/TR46 in the United States, suggesting that multiple mutational alterations of
cyp51A
resulting in high-level azole resistance could occur during prolonged antifungal therapy.
Selective Inactivity of Pyrazinamide against Tuberculosis in C3HeB/FeJ Mice Is Best Explained by Neutral pH of Caseum
Authors: Lanoix Jean-Philippe , Ioerger Thomas , Ormond Aimee , Kaya Firat , Sacchettini James , Dartois Véronique , Nuermberger Eric
Published: November 2015

Pyrazinamide (PZA) is one of only two sterilizing drugs in the first-line antituberculosis regimen. Its activity is strongly pH dependent; the MIC changes by several orders of magnitude over a range of pH values that may be encountered in variousin vivocompartments. We recently reported selective inactivity of PZA in a subset of C3HeB/FeJ mice with large caseous lung lesions. In the present study, we evaluated whether such inactivity was explained by poor penetration of PZA into such lesions or selection of drug-resistant mutants. Despite demonstrating similar dose-proportional PZA exposures in plasma, epithelial lining fluid, and lung lesions, no dose response was observed in a subset of C3HeB/FeJ mice with the highest CFU burden. Although PZA-resistant mutants eventually replaced the susceptible bacilli in BALB/c mice and in C3HeB/FeJ mice with low total CFU burdens, they never exceeded 1% of the total population in nonresponding C3HeB/FeJ mice. The selective inactivity of PZA in large caseous lesions of C3HeB/FeJ mice is best explained by the neutral pH of liquefying caseum.
Characterization of the Antimicrobial Peptide Penisin, a Class Ia Novel Lantibiotic from Paenibacillus sp. Strain A3
Authors: Baindara Piyush , Chaudhry Vasvi , Mittal Garima , Liao Luciano M. , Matos Carolina O. , Khatri Neeraj , Franco Octavio L. , Patil Prabhu B. , Korpole Suresh
Published: November 2015

Attempts to isolate novel antimicrobial peptides from microbial sources have been on the rise recently, despite their low efficacy in therapeutic applications. Here, we report identification and characterization of a new efficient antimicrobial peptide from a bacterial strain designated A3 that exhibited highest identity with
Paenibacillus ehimensis
. Upon purification and subsequent molecular characterization of the antimicrobial peptide, referred to as penisin, we found the peptide to be a bacteriocin-like peptide. Consistent with these results, RAST analysis of the entire genome sequence revealed the presence of a lantibiotic gene cluster containing genes necessary for synthesis and maturation of a lantibiotic. While circular dichroism and one-dimension nuclear magnetic resonance experiments confirmed a random coil structure of the peptide, similar to other known lantibiotics, additional biochemical evidence suggests posttranslational modifications of the core peptide yield six thioether cross-links. The deduced amino acid sequence of the putative biosynthetic gene
penA
showed approximately 74% similarity with elgicin A and 50% similarity with the lantibiotic paenicidin A. Penisin effectively killed methicillin-resistant
Staphylococcus aureus
(MRSA) and did not exhibit hemolysis activity. Unlike other lantibiotics, it effectively inhibited the growth of Gram-negative bacteria. Furthermore, 80 mg/kg of body weight of penisin significantly reduced bacterial burden in a mouse thigh infection model and protected BALB/c mice in a bacteremia model entailing infection with
Staphylococcus aureus
MTCC 96, suggesting that it could be a promising new antimicrobial peptide.
Genome Analysis of Kingella kingae Strain KWG1 Reveals How a β-Lactamase Gene Inserted in the Chromosome of This Species
Authors: Bidet Philippe , Basmaci Romain , Guglielmini Julien , Doit Catherine , Jost Christelle , Birgy André , Bonacorsi Stéphane
Published: November 2015

We describe the genome of a penicillinase-producing
Kingella kingae
strain (KWG1), the first to be isolated in continental Europe, whose
bla
TEM-1
gene was, for the first time in this species, found to be chromosomally inserted. The
bla
TEM
gene is located in an integrative and conjugative element (ICE) inserted in Met-tRNA and comprising genes that encode resistance to sulfonamides, streptomycin, and tetracycline. This ICE is homologous to resistance-conferring plasmids of
K. kingae
and other Gram-negative bacteria.
Identification of a Pyridoxine-Derived Small-Molecule Inhibitor Targeting Dengue Virus RNA-Dependent RNA Polymerase
Authors: Xu Hong-Tao , Colby-Germinario Susan P. , Hassounah Said , Quashie Peter K. , Han Yingshan , Oliveira Maureen , Stranix Brent R. , Wainberg Mark A.
Published: November 2015

The viral RNA-dependent RNA polymerase (RdRp) activity of the dengue virus (DENV) NS5 protein is an attractive target for drug design. Here, we report the identification of a novel class of inhibitor (i.e., an active-site metal ion chelator) that acts against DENV RdRp activity. DENV RdRp utilizes a two-metal-ion mechanism of catalysis; therefore, we constructed a small library of compounds, through mechanism-based drug design, aimed at chelating divalent metal ions in the catalytic site of DENV RdRp. We now describe a pyridoxine-derived small-molecule inhibitor that targets DENV RdRp and show that 5-benzenesulfonylmethyl-3-hydroxy-4-hydroxymethyl-pyridine-2-carboxylic acid hydroxyamide (termed DMB220) inhibited the RdRp activity of DENV serotypes 1 to 4 at low micromolar 50% inhibitory concentrations (IC
50s
of 5 to 6.7 μM) in an enzymatic assay. The antiviral activity of DMB220 against DENV infection was also verified in a cell-based assay and showed a 50% effective concentration (EC
50
) of <3 μM. Enzyme assays proved that DMB220 was competitive with nucleotide incorporation. DMB220 did not inhibit the enzymatic activity of recombinant HIV-1 reverse transcriptase and showed only weak inhibition of HIV-1 integrase strand transfer activity, indicating high specificity for DENV RdRp. S600T substitution in the DENV RdRp, which was previously shown to confer resistance to nucleoside analogue inhibitors (NI), conferred 3-fold hypersusceptibility to DMB220, and enzymatic analyses showed that this hypersusceptibility may arise from the decreased binding/incorporation efficiency of the natural NTP substrate without significantly impacting inhibitor binding. Thus, metal ion chelation at the active site of DENV RdRp represents a viable anti-DENV strategy, and DMB220 is the first of a new class of DENV inhibitor.
Inhibition of Pseudomonas aeruginosa ExsA DNA-Binding Activity by
N
-Hydroxybenzimidazoles
Authors: Marsden Anne E. , King Jessica M. , Spies M. Ashley , Kim Oak K. , Yahr Timothy L.
Published: November 2015

The
Pseudomonas aeruginosa
type III secretion system (T3SS) is a primary virulence determinant and a potential target for antivirulence drugs. One candidate target is ExsA, a member of the AraC family of DNA-binding proteins required for expression of the T3SS. A previous study identified small molecules based on an
N
-hydroxybenzimidazole scaffold that inhibit the DNA-binding activity of several AraC proteins, including ExsA. In this study, we further characterized a panel of
N
-hydroxybenzimidazoles. The half-maximal inhibitory concentrations (IC
50
s) for the tested
N
-hydroxybenzimidazoles ranged from 8 to 45 μM in DNA-binding assays. Each of the
N
-hydroxybenzimidazoles protected mammalian cells from T3SS-dependent cytotoxicity, and protection correlated with reduced T3SS gene expression in a coculture infection model. Binding studies with the purified ExsA DNA-binding domain (i.e., lacking the amino-terminal self-association domain) confirmed that the activity of
N
-hydroxybenzimidazoles results from interactions with the DNA-binding domain. The interaction is specific, as an unrelated DNA-binding protein (Vfr) was unaffected by
N
-hydroxybenzimidazoles. ExsA homologs that control T3SS gene expression in
Yersinia pestis
,
Aeromonas hydrophila
, and
Vibrio parahaemolyticus
were also sensitive to
N
-hydroxybenzimidazoles. Although ExsA and
Y. pestis
LcrF share 79% sequence identity in the DNA-binding domain, differential sensitivities to several of the
N
-hydroxybenzimidazoles were observed. Site-directed mutagenesis based on
in silico
docking of inhibitors to the DNA-binding domain, and on amino acid differences between ExsA and LcrF, resulted in the identification of several substitutions that altered the sensitivity of ExsA to
N
-hydroxybenzimidazoles. Development of second-generation compounds targeted to the same binding pocket could lead to drugs with improved pharmacological properties.
Whole-Genome Sequencing in Microbial Forensic Analysis of Gamma-Irradiated Microbial Materials
Authors: Broomall Stacey M. , Ait Ichou Mohamed , Krepps Michael D. , Johnsky Lauren A. , Karavis Mark A. , Hubbard Kyle S. , Insalaco Joseph M. , Betters Janet L. , Redmond Brady W. , Rivers Bryan A. , Liem Alvin T. , Hill Jessica M. , Fochler Edward T. , Roth Pierce A. , Rosenzweig C. Nicole , Skowronski Evan W. , Gibbons Henry S.
Published: November 2015

Effective microbial forensic analysis of materials used in a potential biological attack requires robust methods of morphological and genetic characterization of the attack materials in order to enable the attribution of the materials to potential sources and to exclude other potential sources. The genetic homogeneity and potential intersample variability of many of the category A to C bioterrorism agents offer a particular challenge to the generation of attributive signatures, potentially requiring whole-genome or proteomic approaches to be utilized. Currently, irradiation of mail is standard practice at several government facilities judged to be at particularly high risk. Thus, initial forensic signatures would need to be recovered from inactivated (nonviable) material. In the study described in this report, we determined the effects of high-dose gamma irradiation on forensic markers of bacterial biothreat agent surrogate organisms with a particular emphasis on the suitability of genomic DNA (gDNA) recovered from such sources as a template for whole-genome analysis. While irradiation of spores and vegetative cells affected the retention of Gram and spore stains and sheared gDNA into small fragments, we found that irradiated material could be utilized to generate accurate whole-genome sequence data on the Illumina and Roche 454 sequencing platforms.
Characterization of the Vibrio fischeri Fatty Acid Chemoreceptors, VfcB and VfcB2
Authors: Nikolakakis K. , Monfils K. , Moriano-Gutierrez S. , Brennan C. A. , Ruby E. G.
Published: November 2015

Bacteria use a wide variety of methyl-accepting chemotaxis proteins (MCPs) to mediate their attraction to or repulsion from different chemical signals in their environment. The bioluminescent marine bacterium
Vibrio fischeri
is the monospecific symbiont of the Hawaiian bobtail squid,
Euprymna scolopes
, and encodes a large repertoire of MCPs that are hypothesized to be used during different parts of its complex, multistage lifestyle. Here, we report the initial characterization of two such MCPs from
V. fischeri
that are responsible for mediating migration toward short- and medium-chain aliphatic (or fatty) acids. These receptors appear to be distributed among only members of the family
Vibrionaceae
and are likely descended from a receptor that has been lost by the majority of the members of this family. While chemotaxis greatly enhances the efficiency of host colonization by
V. fischeri
, fatty acids do not appear to be used as a chemical cue during this stage of the symbiosis. This study presents an example of straight-chain fatty acid chemoattraction and contributes to the growing body of characterized MCP-ligand interactions.
Bromochloromethane, a Methane Analogue, Affects the Microbiota and Metabolic Profiles of the Rat Gastrointestinal Tract
Authors: Yang Yu-Xiang , Mu Chun-Long , Luo Zhen , Zhu Wei-Yun
Published: November 2015

Bromochloromethane (BCM), an inhibitor of methanogenesis, has been used in animal production. However, little is known about its impact on the intestinal microbiota and metabolic patterns. The present study aimed to investigate the effect of BCM on the colonic bacterial community and metabolism by establishing a Wistar rat model. Twenty male Wistar rats were randomly divided into two groups (control and treated with BCM) and raised for 6 weeks. Bacterial fermentation products in the cecum were determined, and colonic methanogens and sulfate-reducing bacteria (SRB) were quantified. The colonic microbiota was analyzed by pyrosequencing of the 16S rRNA genes, and metabolites were profiled by gas chromatography and mass spectrometry. The results showed that BCM did not affect body weight and feed intake, but it did significantly change the intestinal metabolic profiles. Cecal protein fermentation was enhanced by BCM, as methylamine, putrescine, phenylethylamine, tyramine, and skatole were significantly increased. Colonic fatty acid and carbohydrate concentrations were significantly decreased, indicating the perturbation of lipid and carbohydrate metabolism by BCM. BCM treatment decreased the abundance of methanogen populations, while SRB were increased in the colon. BCM did not affect the total colonic bacterial counts but significantly altered the bacterial community composition by decreasing the abundance of actinobacteria, acidobacteria, and proteobacteria. The results demonstrated that BCM treatment significantly altered the microbiotic and metabolite profiles in the intestines, which may provide further information on the use of BCM in animal production.
Targeted Amplicon Sequencing for Single-Nucleotide-Polymorphism Genotyping of Attaching and Effacing Escherichia coli O26:H11 Cattle Strains via a High-Throughput Library Preparation Technique
Authors: Ison Sarah A. , Delannoy Sabine , Bugarel Marie , Nagaraja Tiruvoor G. , Renter David G. , den Bakker Henk C. , Nightingale Kendra K. , Fach Patrick , Loneragan Guy H.
Published: November 2015

Enterohemorrhagic
Escherichia coli
(EHEC) O26:H11, a serotype within Shiga toxin-producing
E. coli
(STEC) that causes severe human disease, has been considered to have evolved from attaching and effacing
E. coli
(AEEC) O26:H11 through the acquisition of a Shiga toxin-encoding gene. Targeted amplicon sequencing using next-generation sequencing technology of 48 phylogenetically informative single-nucleotide polymorphisms (SNPs) and three SNPs differentiating Shiga toxin-positive (
stx
-positive) strains from Shiga toxin-negative (
stx
-negative) strains were used to infer the phylogenetic relationships of 178
E. coli
O26:H11 strains (6
stx
-positive strains and 172
stx
-negative AEEC strains) from cattle feces to 7 publically available genomes of human clinical strains. The AEEC cattle strains displayed synonymous SNP genotypes with
stx
2
-positive sequence type 29 (ST29) human O26:H11 strains, while
stx
1
ST21 human and cattle strains clustered separately, demonstrating the close phylogenetic relatedness of these Shiga toxin-negative AEEC cattle strains and human clinical strains. With the exception of seven
stx
-negative strains, five of which contained
espK
, three
stx
-related SNPs differentiated the STEC strains from non-STEC strains, supporting the hypothesis that these AEEC cattle strains could serve as a potential reservoir for new or existing pathogenic human strains. Our results support the idea that targeted amplicon sequencing for SNP genotyping expedites strain identification and genetic characterization of
E. coli
O26:H11, which is important for food safety and public health.
Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice
Authors: Nishiya Casey T. , Boxx Gayle M. , Robison Kerry , Itatani Carol , Kozel Thomas R. , Zhang Mason X.
Published: November 2015

Candida albicansis a yeast-like pathogen and can cause life-threatening systemic candidiasis. Its cell surface is enriched with mannan that is resistant to complement activation. Previously, we developed the recombinant human IgG1 antimannan antibody M1g1. M1g1 was found to promote complement activation and phagocytosis and protect mice from systemic candidiasis. Here, we evaluate the influence of IgG subclass on antimannan antibody-mediated protection. Three IgG subclass variants of M1g1 were constructed: M1g2, M1g3, and M1g4. The IgG subclass identity for each variant was confirmed with DNA sequence and subclass-specific antibodies. These variants contain identical M1 Fabs and exhibited similar binding affinities forC. albicansyeast and purified mannan. Yeast cells and hyphae recovered from the kidney of antibody-treated mice with systemic candidiasis showed uniform binding of each variant, indicating constitutive expression of the M1 epitope and antibody opsonization in the kidney. All variants promoted deposition of both murine and human C3 onto the yeast cell surface, with M1g4 showing delayed activation, as determined by flow cytometry and immunofluorescence microscopy. M1g4-mediated complement activation was found to be associated with its M1 Fab that activates the alternative pathway in an Fc-independent manner. Treatment with each subclass variant extended the survival of mice with systemic candidiasis (P< 0.001). However, treatment with M1g1, M1g3, or M1g4, but not with M1g2, also reduced the kidney fungal burden (P< 0.001). Thus, the role of human antimannan antibody in host resistance to systemic candidiasis is influenced by its IgG subclass.
Host Genetic Variations and Sex Differences Potentiate Predisposition, Severity, and Outcomes of Group A Streptococcus-Mediated Necrotizing Soft Tissue Infections
Authors: Chella Krishnan Karthickeyan , Mukundan Santhosh , Alagarsamy Jeyashree , Laturnus Donna , Kotb Malak
Published: November 2015

Host genetic variations play an important role in several pathogenic diseases, and we previously provided strong evidence that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive group A
Streptococcus
(GAS) patients, including sepsis and necrotizing soft tissue infections (NSTIs). The goal of the present study was to investigate how genetic variations and sex differences among four commonly used mouse strains contribute to variation in severity, manifestations, and outcomes of NSTIs. DBA/2J mice were more susceptible to NSTIs than C57BL/6J, BALB/c, and CD-1 mice, as exhibited by significantly greater bacteremia, excessive dissemination to the spleen, and significantly higher mortality. Differences in the sex of the mice also contributed to differences in disease severity and outcomes: DBA/2J female mice were relatively resistant compared to their male counterparts. However, DBA/2J mice exhibited minimal weight loss and developed smaller lesions than did the aforementioned strains. Moreover, at 48 h after infection, compared with C57BL/6J mice, DBA/2J mice had increased bacteremia, excessive dissemination to the spleen, and excessive concentrations of inflammatory cytokines and chemokines. These results indicate that variations in the host genetic context as well as sex play a dominant role in determining the severity of and susceptibility to GAS NSTIs.
2-Aminoacrylate Stress Induces a Context-Dependent Glycine Requirement in
ridA
Strains of Salmonella enterica
Authors: Ernst Dustin C. , Downs Diana M.
Published: November 2015

The reactive enamine 2-aminoacrylate (2AA) is a metabolic stressor capable of damaging cellular components. Members of the broadly conserved Rid (RidA/YER057c/UK114) protein family mitigate 2AA stress
in vivo
by facilitating enamine and/or imine hydrolysis. Previous work showed that 2AA accumulation in
ridA
strains of
Salmonella enterica
led to the inactivation of multiple target enzymes, including serine hydroxymethyltransferase (GlyA). However, the specific cause of a
ridA
strain's inability to grow during periods of 2AA stress had yet to be determined. Work presented here shows that glycine supplementation suppressed all 2AA-dependent
ridA
strain growth defects described to date. Depending on the metabolic context, glycine appeared to suppress
ridA
strain growth defects by eliciting a GcvB small RNA-dependent regulatory response or by serving as a precursor to one-carbon units produced by the glycine cleavage complex (GCV). In either case, the data suggest that GlyA is the most physiologically sensitive target of 2AA inactivation in
S. enterica
. The universally conserved nature of GlyA among free-living organisms highlights the importance of RidA in mitigating 2AA stress.

IMPORTANCE
The RidA stress response prevents 2-aminoacrylate (2AA) damage from occurring in prokaryotes and eukaryotes alike. 2AA inactivation of serine hydroxymethyltransferase (GlyA) from
Salmonella enterica
restricts glycine and one-carbon production, ultimately reducing fitness of the organism. The cooccurrence of genes encoding 2AA production enzymes and serine hydroxy-methyltransferase (SHMT) in many genomes may in part underlie the evolutionary selection for Rid proteins to maintain appropriate glycine and one-carbon metabolism throughout life.
Biochemical Characterization of the Flagellar Rod Components of Rhodobacter sphaeroides: Properties and Interactions
Authors: Osorio-Valeriano Manuel , de la Mora Javier , Camarena Laura , Dreyfus Georges
Published: November 2015

The flagellar basal body is a rotary motor that spans the cytoplasmic and outer membranes. The rod is a drive shaft that transmits torque generated by the motor through the hook to the filament that propels the bacterial cell. The assembly and structure of the rod are poorly understood. In a first attempt to characterize this structure in the alphaproteobacterium
Rhodobacter sphaeroides
, we overexpressed and purified FliE and the four related rod proteins (FlgB, FlgC, FlgF, and FlgG), and we analyzed their ability to form homo-oligomers. We found that highly purified preparations of these proteins formed high-molecular-mass oligomers that tended to dissociate in the presence of NaCl. As predicted by
in silico
modeling, the four rod proteins share architectural features. Using affinity blotting, we detected the heteromeric interactions between these proteins. In addition, we observed that deletion of the N- and C-terminal regions of FlgF and FlgG severely affected heteromeric but not homomeric interactions. On the basis of our findings, we propose a model of rod assembly in this bacterium.

IMPORTANCE
Despite the considerable amount of research on the structure and assembly of other flagellar axial structures that has been conducted, the rod has been barely studied. An analysis of the biochemical characteristics of the flagellar rod components of the Fla1 system of
R. sphaeroides
is presented in this work. We also analyze the interactions of these proteins with each other and with their neighbors, and we propose a model for the order in which they are assembled.
Rethinking the Hierarchy of Sugar Utilization in Bacteria
Authors: Beisel Chase L. , Afroz Taliman
Published: November 2015

Bacteria are known to consume some sugars over others, although recent work reported by Koirala and colleagues in this issue of theJournal of Bacteriology(S. Koirala, X. Wang, and C. V. Rao, J Bacteriol 198:386–393, 2016,http://dx.doi.org/10.1128/JB.00709-15) revealed that individual cells do not necessarily follow this hierarchy. By studying the preferential consumption ofl-arabinose overd-xylose inEscherichia coli, those authors found that subpopulations consume one, the other, or both sugars through cross-repression between utilization pathways. Their findings challenge classic assertions about established hierarchies and can guide efforts to engineer the simultaneous utilization of multiple sugars.
Successful laparoscopic transabdominal cerclage in uterus didelphys
Authors: Ades Alex , Hong Phoebe
Published: November 2015

The incidence of uterus didelphys is around 3/10 000 women. It is a class III Müllerian duct anomaly resulting from a complete non-fusion of the paired Müllerian ducts between the 12th and 16th weeks of gestation. Although the prevalence of cervical insufficiency in women with uterus didelphys is unknown, the incidence of cervical insufficiency in women with Müllerian anomalies has been reported as high as 30%. We present a case of successful pregnancy outcome following a laparoscopic transabdominal cerclage in a woman with uterus didelphys and cervical insufficiency. The case demonstrates that laparoscopic transabdominal cerclage can be performed successfully in women with uterus didelphys and a satisfactory obstetric outcome can be achieved.
The efficacy of extraembryonic stem cells in improving blood flow within animal models of lower limb ischaemia
Authors: Mohamed Omer Safraz , Krishna Smriti Murali , Li Jiaze , Moxon Joseph Vaughan , Nsengiyumva Vianne , Golledge Jonathan
Published: November 2015

Background

Stem cell (SC) administration is a potential therapeutic strategy to improve blood supply in patients with peripheral artery disease (PAD). The aim of this systematic review and meta-analysis was to investigate the efficacy of extraembryonic tissue-derived SC (ETSC) in improving blood flow within animal models of hindlimb ischaemia (HLI).

Methods

PubMed, ScienceDirect and Web of Science were searched to identify studies which investigated ETSCs within animal HLI models. A meta-analysis was performed focusing on the effect of ETSCs on limb blood flow assessed by laser Doppler imaging using a random effects model. Methodological quality was assessed using a newly devised quality assessment tool.

Results

Five studies investigating umbilical cord-derived SCs (three studies), placental SCs (one study), amnion and chorionic SCs (one study) were included. A meta-analysis suggested that administration of ETSCs improved the restoration of blood flow within the HLI models used. The methodological quality of the included studies was assessed as poor. Problems identified included lack of randomised design and blinding of outcome assessors; that the animal models did not incorporate recognised risk factors for human PAD or atherosclerosis; the models used did not have established chronic ischaemia as is the cases in most patients presenting with PAD; and the studies lacked a clear rationale for the dosage and frequency of SCs administered.

Conclusions

The identified studies suggest that ETSCs improve recovery of limb blood supply within current animal HLI models. Improved study quality is, however, needed to provide support for the likelihood of translating these findings to patients with PAD.
‘First, do no harm’: are disability assessments associated with adverse trends in mental health? A longitudinal ecological study
Authors: Barr B , Taylor-Robinson D , Stuckler D , Loopstra R , Reeves A , Whitehead M
Published: November 2015

Background

In England between 2010 and 2013, just over one million recipients of the main out-of-work disability benefit had their eligibility reassessed using a new functional checklist—the Work Capability Assessment. Doctors and disability rights organisations have raised concerns that this has had an adverse effect on the mental health of claimants, but there are no population level studies exploring the health effects of this or similar policies.

Method

We used multivariable regression to investigate whether variation in the trend in reassessments in each of 149 local authorities in England was associated with differences in local trends in suicides, self-reported mental health problems and antidepressant prescribing rates, while adjusting for baseline conditions and trends in other factors known to influence mental ill-health.

Results

Each additional 10 000 people reassessed in each area was associated with an additional 6 suicides (95% CI 2 to 9), 2700 cases of reported mental health problems (95% CI 548 to 4840), and the prescribing of an additional 7020 antidepressant items (95% CI 3930 to 10100). The reassessment process was associated with the greatest increases in these adverse mental health outcomes in the most deprived areas of the country, widening health inequalities.

Conclusions

The programme of reassessing people on disability benefits using the Work Capability Assessment was independently associated with an increase in suicides, self-reported mental health problems and antidepressant prescribing. This policy may have had serious adverse consequences for mental health in England, which could outweigh any benefits that arise from moving people off disability benefits.
Two-color 3D–3D fusion of selective rotational cerebral angiograms: a novel approach to imaging in cerebrovascular neurosurgery
Authors: Jalali Ali , Srinivasan Visish M , Chinnadurai Ponraj , Kan Peter , Arthur Adam , Duckworth Edward A M
Published: November 2015

Background

Since its introduction, digital subtraction angiography has been considered the gold standard in diagnostic imaging for neurovascular disease. Modern post-processing techniques have made angiography even more informative to the cerebrovascular neurosurgeon or neurointerventionalist. Open neurosurgical procedures such as aneurysm clipping, extirpation of arteriovenous malformations, and extracranial–intracranial bypass remain important techniques in the armamentarium of a comprehensive cerebrovascular neurosurgeon. In-depth study of the anatomy of vascular pathology prior to and after surgery, often via selective cerebral angiography, is a critical component of surgical planning. However, when a vascular lesion or relevant anatomical region is perfused by two or more vascular territories, each selective angiographic imaging volume may provide an incomplete anatomical picture.

Methods

An institutional database was searched for cases in which thesyngoInspace 3D–3D fusion software was used and assisted in diagnosis and surgical management.

Results

In the six cases reviewed, the 3D–3D fusion imaging was crucial in understanding the anatomy of the vascular lesion and aided in surgical decision-making. The cases included two unique anterior communicating artery aneurysms, an arteriovenous malformation, an extracranial–intracranial bypass, and an angiographically negative subarachnoid hemorrhage.

Conclusions

This is a novel strategy of combining two independently acquired selective cerebral angiography volumes to create a more accurate representation of the vascular anatomy. Given the increasing availability of the relevant image acquisition and processing technologies, we propose this strategy as a valuable adjunct in cerebrovascular procedures.
Combined whole-body vibration training and l-citrulline supplementation improves pressure wave reflection in obese postmenopausal women
Authors: Wong Alexei , Alvarez-Alvarado Stacey , Jaime Salvador J. , Kinsey Amber W. , Spicer Maria T. , Madzima Takudzwa A. , Figueroa Arturo
Published: November 2015

Postmenopausal women have increased wave reflection (augmentation pressure (AP) and index (AIx)) and reduced muscle function that predispose them to cardiac diseases and disability. Our aim was to examine the combined and independent effects of whole-body vibration training (WBVT) and l-citrulline supplementation on aortic hemodynamics and plasma nitric oxide metabolites (NOx) in postmenopausal women. Forty-one obese postmenopausal women were randomized to 3 groups: l-citrulline, WBVT+l-citrulline and WBVT+Placebo for 8 weeks. Brachial and aortic systolic blood pressure, diastolic blood pressure, AP, AIx, AIx adjusted to 75 beats/min (AIx@75), and NOx were measured before and after 8 weeks. All groups similarly decreased (P < 0.05) brachial and aortic pressures as well as AP, and similarly increased (P < 0.05) NOx levels. AIx and AIx@75 decreased (P < 0.01) in the WBVT+l-citrulline and WBVT+Placebo groups, but not in the l-citrulline group. The improvement in AIx@75 (−10.5% ± 8.8%, P < 0.05) in the WBVT+l-citrulline group was significant compared with the l-citrulline group. l-Citrulline supplementation and WBVT alone and combined decreased blood pressures. The combined intervention reduced AIx@75. This study supports the effectiveness of WBVT+l-citrulline as a potential intervention for prevention of hypertension-related cardiac diseases in obese postmenopausal women.
Responses of the mosses Sphagnum capillifolium and Polytrichum strictum to nitrogen deposition in a bog: growth, ground cover, and CO2 exchange
Authors: Juutinen Sari , Moore Tim R. , Laine Anna M. , Bubier Jill L. , Tuittila Eeva-Stiina , De Young Allison , Chong Mandy
Published: November 2015

Previous studies have shown that atmospheric nitrogen (N) deposition is detrimental to sphagna, which are a group of mosses that are important for carbon cycling in northern peatlands. Little is known about species interactions, such as relative responses of tall moss Polytrichum strictum Menzies ex Brid. and sphagna. We studied the effects of N deposition on growth, abundance, and CO2 exchange of the moss species Sphagnum capillifolium (Ehrh.) Hedw. and Polytrichum strictum in an experiment at a temperate bog. Sphagnum growth and cover decreased significantly with high-dose N treatment (6.4 g N·m−2·year−1) in years 4 and 5 of treatment, whereas the same parameters increased for Polytrichum compared with the control. Net CO2 exchange, gross photosynthesis (Pg), and dark respiration (R) in the intact moss cores, which were measured in year 5 of treatment, were elevated in the cores that had been treated with the high-dose of N, compared with the control, and this was associated with increased abundance of Polytrichum. The moss cores where Polytrichum was removed, however, had increased mass-based R with the high-dose N treatment. Our results showed that S. capillifolium at Mer Bleue may be close to N saturation, as 5 years of high-dose N loading (6.4 g N·m−2·year−1 + background) was harmful to this species, possibly as a result of increased respiratory cost. Polytrichum strictum had a competitive advantage, at least in the short-term, through allocating excess N to growth. This change in moss layer composition deserves further attention, as a shift to more easily decomposable litter, without corresponding increases in plant production, could reduce the carbon sequestration of the bog.
On topological properties of dominating David derived networks
Authors: Imran Muhammad , Baig Abdul Qudair , Ali Haidar
Published: November 2015

Topological indices are numerical parameters of a graph that characterize its molecular topology and are usually graph invariant. In a QSAR/QSPR study, the physico-chemical properties and topological indices such as the Randić, atom–bond connectivity (ABC), and geometric–arithmetic (GA) indices are used to predict the bioactivity of chemical compounds. Graph theory has found a considerable use in this important area of research. All of the studied interconnection networks in this paper are constructed by the Star of David network. In this paper, we study the general Randić, first Zagreb, ABC, GA, ABC4 and GA5, indices for the first, second, and third types of dominating David derived networks and give closed formulas of these indices for these networks. These results are useful in network science to understand the underlying topologies of these networks.
Establishing ecologically relevant management boundaries: linking movement ecology with the conservation ofScaphirhynchussturgeon
Authors: Porreca Anthony P. , Hintz William D. , Whitledge Gregory W. , Rude Neil P. , Heist Edward J. , Garvey James E.
Published: November 2015

We investigated the environmental life history of widely distributed threatened and endangered sturgeons in large rivers of the central United States that experience different regulatory regimes and management priorities. Using microchemistry techniques, our goal was to assess how to improve species conservation by dampening the incongruity that often occurs between management and species’ ecological requirements, particularly at large spatial scales. Pallid sturgeon (Scaphirhynchus albus), shovelnose sturgeon (Scaphirhynchus platorynchus), and their hybrids were analyzed for88Sr and44Ca and related to a geographically relevant range of Sr:Ca values for the Missouri and Mississippi rivers to quantify large-scale environmental history. We found natal origin of 81% of all wild sturgeon collected was the lower Missouri River. Pallid and hybrid sturgeon used the middle and upper Mississippi rivers more frequently as they aged, whereas shovelnose sturgeon occupied the lower Missouri River more often throughout life. Our results highlight a mismatch between conservation boundaries and sturgeon river use. Managers should consider expanding current protections for pallid sturgeon to include the unprotected sections of the Mississippi River and that research and conservation actions consider the importance of Mississippi River habitats to Scaphirhynchus sturgeon throughout their life history. Our findings have implications for conserving wide-ranging riverine species at large spatial scales using the framework described here.
Anisotropic universe and generalized ghost dark energy in Brans–Dicke theory
Authors: Fayaz V. , Hossienkhani H. , Pasqua A. , Zarei Z. , Ganji M.
Published: November 2015

In this paper, we consider the generalized ghost dark energy in a Bianchi type-I metric (which is a spatially homogeneous and anisotropic) in the framework of Brans–Dicke theory. For this purpose, we use the squared sound speed [Formula: see text] the sign of which determines the stability of the model. At first, we obtain the equation of state parameter, ωΛ = pΛ/ρΛ, the deceleration parameter q and the evolution equation of the generalized ghost dark energy. We find that, in this case, ωΛ cannot cross the phantom line (ωΛ > –1) and eventually the universe approaches a de-Sitter phase of expansion (ωΛ → –1). Then, we extend our study to the case of generalized ghost dark energy in a non-isotropic and Brans–Dicke framework and find out that the transition of ωΛ to the phantom regime can be more easily accounted for than when it is restored into the Einstein field equations. In conclusion, we find evidence that the generalized ghost dark energy in BD theory can lead to a stable universe favored by observations at the present time.
Recent Developments of Entrepreneurship in Poland: The Country Entrepreneurial Profile
Authors: Ruminski Robert
Published: November 2015

This paper is concerned with entrepreneurship and its development in Poland - one of the fastest growing EU economies and the key market player in Central and Eastern Europe. The issues of growth and development perspectives of enterprises as well as their role in growth creation are investigated. Special emphasis is put on measures of entrepreneurship, determinants of its development, the country’s competitive position and the conditions for the development of entrepreneurship. Moreover, the perception of business by society is discussed. The support of the Special Economic Zones, the cluster initiatives and the state policy are important for entrepreneurs and they contribute to further business development.

Poland is seeing positive rates of development despite the recent economic downturn. Its high level of competitiveness, strong economic fundamentals and high flexibility will allow to benefit from the global recovery over the next few years. In order to evaluate the development potential of enterprises and the business environment, a SWOT analysis of the Polish SMEs was conducted.