bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results from Kenya’s 2014 Report Card on the Physical Activity and Body Weight of Children and Youth
Authors: Wachira Lucy-Joy M. , Muthuri Stella K. , Tremblay Mark S. , Onywera Vincent O. 
Published: May 2014

Background:The report card presents available evidence on the physical activity (PA) and body weight status of Kenyan children and youth. It highlights areas where Kenya is succeeding and those in which more action is needed.Methods:Comprehensive review and analysis of available data on core indicators for Kenyan children and youth 5−17 years were conducted. The grading system used was based on a set of specific criteria and existing grading schemes from similar report cards in other countries.Results:Of the 10 core indicators discussed, body composition was favorable (grade B) while overall PA levels, organized sport participation, and active play were assigned grades of C. Active transportation and sedentary behaviors were also favorable (grade B). Family/peers, school, governmental and nongovernmental strategies were graded C.Conclusions:The majority of Kenyan children and youth have healthy body composition levels and acceptable sedentary time, but are not doing as well in attaining the World Health Organization (WHO) recommendation on PA. Although Kenya seems to be doing well in most indicators compared with some developed countries, there is a need for action to address existing trends toward unhealthy lifestyles. More robust and representative data for all indicators are required.
Results from Canada’s 2014 Report Card on Physical Activity for Children and Youth
Authors: Gray Casey E. , Barnes Joel D. , Bonne Jennifer Cowie , Cameron Christine , Chaput Jean-Philippe , Faulkner Guy , Janssen Ian , Katzmarzyk Peter T. , Kolen Angela M. , Manske Stephen R. , Salmon Art , Spence John C. , Timmons Brian W. , Tremblay Mark S. 
Published: May 2014

Background:The Active Healthy Kids Canada (AHKC) Report Card consolidates and translates research and assesses how Canada is being responsible in providing physical activity opportunities for children (3- to 11-years-old) and youth (12- to 17-years-old). The primary aim of this article is to summarize the results of the 2014 AHKC 10th Anniversary Report Card.Methods:Ten physical activity indicators were graded using the AHKC Report Card development process, which includes a synthesis of the best available research, surveillance, policy and practice findings, and expert consensus.Results:Grades assigned were for: ‘Behaviors that Contribute to Overall Physical Activity Levels’ (Overall Physical Activity Levels, D-; Organized Sport Participation, C+; Active Play, INCOMPLETE; Active Transportation, D; Sedentary Behaviors, F), ‘Settings and Sources of Influence’ (Family and Peers, C; School, C+; and Community and the Built Environment, B+), and ‘Strategies and Investments’ (Government Strategies and Investments, C; and Non-Government Strategies and Investments, A-).Conclusions:Despite good availability of policies, programs, and infrastructure, the overall physical activity levels of Canadian children and youth remain low while sedentary behavior levels remain high. As with many nations, there is room for improvement in most physical activity behaviors and some sources of influence.
Results from Mozambique’s 2014 Report Card on Physical Activity for Children and Youth
Authors: Prista António , Picardo Salazar , Ribeiro Edmundo , Libombo Joel , Daca Timoteo 
Published: May 2014

Background:This paper describes the procedures and development of the first Mozambican Report Card on Physical Activity in Children and Adolescents.Methods:Comprehensive searches for data related to indicators of physical activity (PA) were completed by a committee of physical activity and sports specialists. Grades were assigned to each indicator consistent with the process and methodology outlined by the Active Healthy Kids Canada Report Card model.Results:Seven indicators of PA were graded. The following grades were assigned: Overall Physical Activity Levels, B; Organized Sport Participation, F; Active Play, C; Active Transportation, B; Schools, C; Community and the Built Environment, F; and Government, C. Sedentary Behaviors and Family and Peers were not graded due to the lack of available information.Conclusions:PA behaviors of children and young people of Mozambique are positively influenced by the rural environment and are largely related to subsistence activities and outdoor play, and absence of motorized transport. In turn, urban areas are declining in active habits and opportunities due largely to rapid urbanization and lack of planning that favors active transport and play.
d-Amino Acids Enhance the Activity of Antimicrobials against Biofilms of Clinical Wound Isolates of Staphylococcus aureus and Pseudomonas aeruginosa
Authors: Sanchez Carlos J. , Akers Kevin S. , Romano Desiree R. , Woodbury Ronald L. , Hardy Sharanda K. , Murray Clinton K. , Wenke Joseph C. 
Published: May 2014

ABSTRACTWithin wounds, microorganisms predominantly exist as biofilms. Biofilms are associated with chronic infections and represent a tremendous clinical challenge. As antibiotics are often ineffective against biofilms, use of dispersal agents as adjunctive, topical therapies for the treatment of wound infections involving biofilms has gained interest. We evaluatedin vitrothe dispersive activity ofd-amino acids (d-AAs) on biofilms from clinical wound isolates ofStaphylococcus aureusandPseudomonas aeruginosa; moreover, we determined whether combinations ofd-AAs and antibiotics (clindamycin, cefazolin, oxacillin, rifampin, and vancomycin forS. aureusand amikacin, colistin, ciprofloxacin, imipenem, and ceftazidime forP. aeruginosa) enhance activity against biofilms.d-Met,d-Phe, andd-Trp at concentrations of ≥5 mM effectively dispersed preformed biofilms ofS. aureusandP. aeruginosaclinical isolates, an effect that was enhanced when they were combined as an equimolar mixture (d-Met/d-Phe/d-Trp). When combined withd-AAs, the activity of rifampin was significantly enhanced against biofilms of clinical isolates ofS. aureus, as indicated by a reduction in the minimum biofilm inhibitory concentration (MBIC) (from 32 to 8 μg/ml) and a >2-log reduction of viable biofilm bacteria compared to treatment with antibiotic alone. The addition ofd-AAs was also observed to enhance the activity of colistin and ciprofloxacin against biofilms ofP. aeruginosa, reducing the observed MBIC and the number of viable bacteria by >2 logs and 1 log at 64 and 32 μg/ml in contrast to antibiotics alone. These findings indicate that the biofilm dispersal activity ofd-AAs may represent an effective strategy, in combination with antimicrobials, to release bacteria from biofilms, subsequently enhancing antimicrobial activity.
“Slow VISA,” a Novel Phenotype of Vancomycin Resistance, Found
In Vitro
in Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Strain Mu3
Authors: Saito Michie , Katayama Yuki , Hishinuma Tomomi , Iwamoto Akira , Aiba Yoshifumi , Kuwahara-Arai Kyoko , Cui Longzhu , Matsuo Miki , Aritaka Nanae , Hiramatsu Keiichi 
Published: May 2014

ABSTRACT

Heterogeneous vancomycin-intermediate
Staphylococcus aureus
(hVISA) clinical strain Mu3 spontaneously generates VISA strains at an extremely high frequency (≥1 × 10
−6
). The generated VISA strains usually grow more slowly than does the parent hVISA strain, but they form colonies on vancomycin-containing agar plates before 48 h of incubation. However, we noticed a curious group of VISA strains, designated “slow VISA” (sVISA), whose colonies appear only after 72 h of incubation. They have extremely prolonged doubling times but have vancomycin MICs of 8 to ∼24 mg/liter when determined after 72 to ∼144 h of incubation. We established strain Mu3-6R-P (6R-P), which has a vancomycin MIC of 16 mg/liter (at 72 h), as a representative sVISA strain. Its cell wall was thickened and autolytic activity was decreased compared to the respective qualities of the parent hVISA strain Mu3. Whole-genome sequencing of 6R-P revealed only one mutation, encoded by
rpoB
(R512P), which replaced the 512th arginine of the RNA polymerase β-subunit with proline. Its VISA phenotype was unstable, and the strain frequently reverted to hVISA with concomitant losses of pinpoint colony morphology and cell wall thickness and reduced autolytic activity. Sequencing of the
rpoB
genes of the phenotypic revertant strains revealed mutations affecting the 512th codon, where the proline of 6R-P was replaced with leucine, serine, or histidine. Slow VISA generated in the tissues of an infected patient serves as a temporary shelter for hVISA to survive vancomycin therapy. The sVISA strain spontaneously returns to hVISA when the threat of vancomycin is lifted. The
rpoB
(R512P) mutation may be regarded as a regulatory mutation that switches the reversible phenotype of sVISA on and off.
Radicicol Confers Mid-Schizont Arrest by Inhibiting Mitochondrial Replication in Plasmodium falciparum
Authors: Chalapareddy Sureshkumar , Bhattacharyya Mrinal Kanti , Mishra Seema , Bhattacharyya Sunanda 
Published: May 2014

ABSTRACT

Radicicol, an antifungal antibiotic, was previously identified as a compound having antimalarial activity. However, its mechanism of action in
Plasmodium falciparum
was not elucidated. While characterizing its antimalarial function, we observed that radicicol manifested two distinct developmental defects in cultured
P. falciparum
in a concentration-dependent manner. At a low concentration of radicicol, a significant percentage of drug-treated parasites were arrested at the schizont stage, while at a higher concentration, the parasites were unable to multiply from schizont to ring. Also, the newly formed rings and trophozoites were extremely delayed in development, eventually leading to cell death. We intended to characterize the potential molecular target of radicicol at its sublethal doses. Our results demonstrated that radicicol specifically impaired mitochondrial replication. This decrement was associated with a severalfold increment of the topoisomerase VIB transcript as well as protein in treated cells over that of untreated parasites. Topoisomerase VIB was found to be localized in the organelle fraction. Our docking study revealed that radicicol fits into the Bergerat fold of Pf topoisomerase VIB present in its ATPase domain. Altogether, these data allow us to conclude that
P. falciparum
topoisomerase VIB might be one of the targets of radicicol causing inhibition of mitochondrial replication. Hence, radicicol can be suitably employed to explore the mitochondrial physiology of malaria parasites.
In Vivo
Evolution to Colistin Resistance by PmrB Sensor Kinase Mutation in KPC-Producing Klebsiella pneumoniae Is Associated with Low-Dosage Colistin Treatment
Authors: Cannatelli Antonio , Di Pilato Vincenzo , Giani Tommaso , Arena Fabio , Ambretti Simone , Gaibani Paolo , D'Andrea Marco Maria , Rossolini Gian Maria 
Published: May 2014

ABSTRACT

Colistin is a key drug for the treatment of infections caused by extensively drug-resistant strains of
Enterobacteriaceae
producing carbapenemases. However, the emergence of colistin resistance is being increasingly reported, especially among
Klebsiella pneumoniae
strains producing KPC-type carbapenemases (KPC-KP). In this work, we investigated colistin-susceptible (KPB-1) and colistin-resistant (KPB-2) sequential isolates obtained from a patient with a KPC-KP infection before and after low-dosage colistin treatment, respectively. By using a next-generation sequencing approach and comparative genomic analysis of the two isolates, we detected in KPB-2 a nonsynonymous nucleotide substitution in the gene encoding the PmrB sensor kinase, resulting in a leucine-to-arginine substitution at amino acid position 82. Compared with KPB-1, KPB-2 exhibited upregulated transcription of
pmrA
and of
pmrK
, which is part of the
pmrHFIJKLM
operon responsible for modification of the colistin lipopolysaccharide target. Complementation with wild-type
pmrB
in KPB-2 restored colistin susceptibility and reduced the transcription of
pmrA
and
pmrK
to basal levels, while expression of PmrB
L82R
in KPB-1 did not alter colistin susceptibility or upregulate
pmrA
and
pmrK
expression, confirming the dominance of wild-type PmrB versus the PmrB
L82R
mutant. The present results indicated that PmrB mutations mediating colistin resistance may be selected during low-dosage colistin treatment. The colistin-resistant phenotype of KPB-2 was stable for up to 50 generations in the absence of selective pressure and was not associated with a significant fitness cost in a competition experiment.
A Novel Anti-PcrV Antibody Providing Enhanced Protection against Pseudomonas aeruginosa in Multiple Animal Infection Models
Authors: Warrener Paul , Varkey Reena , Bonnell Jessica C. , DiGiandomenico Antonio , Camara Maria , Cook Kimberly , Peng Li , Zha Jingying , Chowdury Partha , Sellman Bret , Stover C. Kendall 
Published: May 2014

ABSTRACTPseudomonas aeruginosais a major cause of hospital-acquired infections, particularly in mechanically ventilated patients, and it is the leading cause of death in cystic fibrosis patients. A key virulence factor associated with disease severity is theP. aeruginosatype III secretion system (T3SS), which injects bacterial toxins directly into the cytoplasm of host cells. The PcrV protein, located at the tip of the T3SS injectisome complex, is required for T3SS function and is a well-validated target in animal models of immunoprophylactic strategies targetingP. aeruginosa. In an effort to identify a highly potent and protective monoclonal antibody (MAb) that inhibits the T3SS, we generated and characterized a panel of novel anti-PcrV MAbs. Interestingly, some MAbs exhibiting potent inhibition of T3SSin vitrofailed to provide protection in a mouse model ofP. aeruginosainfection, suggesting that effectivein vivoinhibition of T3SS with anti-PcrV MAbs is epitope dependent. V2L2MD, while not the most potent MAb as assessed byin vitrocytotoxicity inhibition assays, provided strong prophylactic protection in several murine infection models and a postinfection therapeutic model. V2L2MD mediated significantly (P< 0.0001) betterin vivoprotection than that provided by a comparator antibody, MAb166, a well-characterized anti-PcrV MAb and the progenitor of a clinical candidate, KB001-A. The results described here support further development of a V2L2MD-containing immunotherapeutic and may suggest even greater potential than was previously recognized for the prevention and treatment ofP. aeruginosainfections in high-risk populations.
Interaction between Mutations and Regulation of Gene Expression during Development of
De Novo
Antibiotic Resistance
Authors: Händel Nadine , Schuurmans Jasper M. , Feng Yanfang , Brul Stanley , ter Kuile Benno H. 
Published: May 2014

ABSTRACT

Bacteria can become resistant not only by horizontal gene transfer or other forms of exchange of genetic information but also by
de novo
by adaptation at the gene expression level and through DNA mutations. The interrelationship between changes in gene expression and DNA mutations during acquisition of resistance is not well documented. In addition, it is not known whether the DNA mutations leading to resistance always occur in the same order and whether the final result is always identical. The expression of >4,000 genes in
Escherichia coli
was compared upon adaptation to amoxicillin, tetracycline, and enrofloxacin. During adaptation, known resistance genes were sequenced for mutations that cause resistance. The order of mutations varied within two sets of strains adapted in parallel to amoxicillin and enrofloxacin, respectively, whereas the buildup of resistance was very similar. No specific mutations were related to the rather modest increase in tetracycline resistance. Ribosome-sensed induction and efflux pump activation initially protected the cell through induction of expression and allowed it to survive low levels of antibiotics. Subsequently, mutations were promoted by the stress-induced SOS response that stimulated modulation of genetic instability, and these mutations resulted in resistance to even higher antibiotic concentrations. The initial adaptation at the expression level enabled a subsequent trial and error search for the optimal mutations. The quantitative adjustment of cellular processes at different levels accelerated the acquisition of antibiotic resistance.
Evaluation of SSYA10-001 as a Replication Inhibitor of Severe Acute Respiratory Syndrome, Mouse Hepatitis, and Middle East Respiratory Syndrome Coronaviruses
Authors: Adedeji Adeyemi O. , Singh Kamalendra , Kassim Ademola , Coleman Christopher M. , Elliott Ruth , Weiss Susan R. , Frieman Matthew B. , Sarafianos Stefan G. 
Published: May 2014

ABSTRACT
We have previously shown that SSYA10-001 blocks severe acute respiratory syndrome coronavirus (SARS-CoV) replication by inhibiting SARS-CoV helicase (nsp13). Here, we show that SSYA10-001 also inhibits replication of two other coronaviruses, mouse hepatitis virus (MHV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). A putative binding pocket for SSYA10-001 was identified and shown to be similar in SARS-CoV, MERS-CoV, and MHV helicases. These studies show that it is possible to target multiple coronaviruses through broad-spectrum inhibitors.
Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements
Authors: Koonin Eugene V. , Dolja Valerian V. 
Published: May 2014

SUMMARY

Viruses were defined as one of the two principal types of organisms in the biosphere, namely, as capsid-encoding organisms in contrast to ribosome-encoding organisms, i.e., all cellular life forms. Structurally similar, apparently homologous capsids are present in a huge variety of icosahedral viruses that infect bacteria, archaea, and eukaryotes. These findings prompted the concept of the capsid as the virus “self” that defines the identity of deep, ancient viral lineages. However, several other widespread viral “hallmark genes” encode key components of the viral replication apparatus (such as polymerases and helicases) and combine with different capsid proteins, given the inherently modular character of viral evolution. Furthermore, diverse, widespread, capsidless selfish genetic elements, such as plasmids and various types of transposons, share hallmark genes with viruses. Viruses appear to have evolved from capsidless selfish elements, and vice versa, on multiple occasions during evolution. At the earliest, precellular stage of life's evolution, capsidless genetic parasites most likely emerged first and subsequently gave rise to different classes of viruses. In this review, we develop the concept of a greater virus world which forms an evolutionary network that is held together by shared conserved genes and includes both
bona fide
capsid-encoding viruses and different classes of capsidless replicons. Theoretical studies indicate that selfish replicons (genetic parasites) inevitably emerge in any sufficiently complex evolving ensemble of replicators. Therefore, the key signature of the greater virus world is not the presence of a capsid but rather genetic, informational parasitism itself, i.e., various degrees of reliance on the information processing systems of the host.
N-Linked Glycosylation in Archaea: a Structural, Functional, and Genetic Analysis
Authors: Jarrell Ken F. , Ding Yan , Meyer Benjamin H. , Albers Sonja-Verena , Kaminski Lina , Eichler Jerry 
Published: May 2014

SUMMARYN-glycosylation of proteins is one of the most prevalent posttranslational modifications in nature. Accordingly, a pathway with shared commonalities is found in all three domains of life. While excellent model systems have been developed for studying N-glycosylation in bothEukaryaandBacteria, an understanding of this process inArchaeawas hampered until recently by a lack of effective molecular tools. However, within the last decade, impressive advances in the study of the archaeal version of this important pathway have been made for halophiles, methanogens, and thermoacidophiles, combining glycan structural information obtained by mass spectrometry with bioinformatic, genetic, biochemical, and enzymatic data. These studies reveal both features shared with the eukaryal and bacterial domains and novel archaeon-specific aspects. Unique features of N-glycosylation inArchaeainclude the presence of unusual dolichol lipid carriers, the use of a variety of linking sugars that connect the glycan to proteins, the presence of novel sugars as glycan constituents, the presence of two very different N-linked glycans attached to the same protein, and the ability to vary the N-glycan composition under different growth conditions. These advances are the focus of this review, with an emphasis on N-glycosylation pathways inHaloferax,Methanococcus, andSulfolobus.
The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus
Authors: Alonzo Francis , Torres Victor J. 
Published: May 2014

SUMMARY

The ability to produce water-soluble proteins with the capacity to oligomerize and form pores within cellular lipid bilayers is a trait conserved among nearly all forms of life, including humans, single-celled eukaryotes, and numerous bacterial species. In bacteria, some of the most notable pore-forming molecules are protein toxins that interact with mammalian cell membranes to promote lysis, deliver effectors, and modulate cellular homeostasis. Of the bacterial species capable of producing pore-forming toxic molecules, the Gram-positive pathogen
Staphylococcus aureus
is one of the most notorious.
S. aureus
can produce seven different pore-forming protein toxins, all of which are believed to play a unique role in promoting the ability of the organism to cause disease in humans and other mammals. The most diverse of these pore-forming toxins, in terms of both functional activity and global representation within
S. aureus
clinical isolates, are the bicomponent leucocidins. From the first description of their activity on host immune cells over 100 years ago to the detailed investigations of their biochemical function today, the leucocidins remain at the forefront of
S. aureus
pathogenesis research initiatives. Study of their mode of action is of immediate interest in the realm of therapeutic agent design as well as for studies of bacterial pathogenesis. This review provides an updated perspective on our understanding of the
S. aureus
leucocidins and their function, specificity, and potential as therapeutic targets.