bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast and transferability of parameters of lumped water balance models in the Segura River Basin (Spain)
Authors: Pellicer‐Martinez Francisco , Martínez‐Paz José M.
Published: May 2014

Knowing the water resources in a river basin is a key aspect to appropriate water planning, and they can be estimated by lumped water balance models. The possibility to transfer the calibrated parameters of a contrasted model to non‐gauged ones improves this knowledge with no need for direct measurements. This work studies the transferability of the parameters of the lumped models in five catchments in the southeast of Spain, testing the influence of the snow and the effect of serial autocorrelation in the goodness of fit. The results are also compared with those of the distributed model of reference in Spain (SIMPA). As principal results, the abcd model is the selected one, the snow effect is negligible, the transferability of parameters for this case is not totally possible, and serial autocorrelation must be included for this kind of modelling.
Causes and consequences of epigenetic regulation in wound healing
Authors: Ti Dongdong , Li Meirong , Fu Xiaobing , Han Weidong
Published: May 2014

Wound healing is a complex and systematic tissue level response to mechanical and chemical injuries that may cause the release of growth factors, cytokines, and chemokines by damaged tissues. For the complex features of these restorative processes, it is a crucial challenge to identify the relevant cell types and biochemical pathways that are involved in wound healing. Epigenetic mechanisms, such as DNA methylation, histone modification, and noncoding regulatory RNA editing, play important roles in many biological processes, including cell proliferation, migration and differentiation, signal pathway activation or inhibition, and cell senescence. Epigenetic regulations can coordinately control a considerable subset of known repair genes and thus serve as master regulators of wound healing. An abundance of evidence has also shown that epigenetic modifications participate in the short‐ and long‐term control of crucial gene expression and cell signal transduction that are involved in the healing process. These data provide a foundation for probable epigenetic‐based therapeutic strategies that are aimed at stimulating tissue regeneration. This review describes the epigenetic alterations in different cellular types at injury sites, induced signals, and resulting tissue repair. With the increased interest in the epigenetics of wound and repair processes, this field will soon begin to flourish.
Identification of a transcriptional signature for the wound healing continuum
Authors: Peake Matthew A. , Caley Mathew , Giles Peter J. , Wall Ivan , Enoch Stuart , Davies Lindsay C. , Kipling David , Thomas David W. , Stephens Phil
Published: May 2014

There is a spectrum/continuum of adult human wound healing outcomes ranging from the enhanced (nearly scarless) healing observed in oral mucosa to scarring within skin and the nonhealing of chronic skin wounds. Central to these outcomes is the role of the fibroblast. Global gene expression profiling utilizing microarrays is starting to give insight into the role of such cells during the healing process, but no studies to date have produced a gene signature for this wound healing continuum. Microarray analysis of adult oral mucosal fibroblast (OMF), normal skin fibroblast (NF), and chronic wound fibroblast (CWF) at 0 and 6 hours post‐serum stimulation was performed. Genes whose expression increases following serum exposure in the order OMF < NF < CWF are candidates for a negative/impaired healing phenotype (the dysfunctional healing group), whereas genes with the converse pattern are potentially associated with a positive/preferential healing phenotype (the enhanced healing group). Sixty‐six genes in the enhanced healing group and 38 genes in the dysfunctional healing group were identified. Overrepresentation analysis revealed pathways directly and indirectly associated with wound healing and aging and additional categories associated with differentiation, development, and morphogenesis. Knowledge of this wound healing continuum gene signature may in turn assist in the therapeutic assessment/treatment of a patient's wounds.
Comparison studies of the in vivo treatment of full‐thickness excisional wounds and burns by an artificial bilayer dermal equivalent and J‐1 acellular dermal matrix
Authors: Guo Rui , Teng Jianying , Xu Shaojun , Ma Lie , Huang Aibin , Gao Changyou
Published: May 2014

The effects upon skin repair were compared between a homemade bilayer dermal equivalent (BDE), composed of a collagen/chitosan porous scaffold and a silicone membrane, and J‐1 acellular dermal matrix (ADM), a commercial ADM that is used widely in China to treat various skin defects. Full‐thickness excisional and burn wounds were prepared on the backs of pigs and then treated with the BDE and J‐1 ADM. Biopsy specimens were harvested on days 7, 14, and 21 after surgery for gross, biochemical, and molecular examinations. In comparison with the burn wounds, the excisional wounds showed accelerated granular tissue formation and superior integration with the equivalents, regardless of their type. Immunohistochemical, immunofluorescence, real time quantitative polymerase chain reaction and Western blotting analyses showed that the vascularization rates in the excisional wounds group were also significantly faster than those of the burn group for both dermal equivalents. There was no significant difference between J‐1 ADM and BDE treatment on the formation of newly formed blood vessels for the excisional wounds at days 7, 14, and 21. However, there was a significant difference in the number of nascent blood vessels formed in the burn wounds after treatment with J‐1 ADM compared with BDE. The highest numbers of newly formed and mature blood vessels were present in the J‐1 ADM‐treated excisional wounds after 21 days. Ultrathin skin grafts were further transplanted on to the regenerated dermis for 28 days, resulting in the repair of the full‐thickness wounds and production of a structure similar to normal skin.
Full‐thickness splinted skin wound healing models in db/db and heterozygous mice: Implications for wound healing impairment
Authors: Park Shin Ae , Teixeira Leandro B. C. , Raghunathan Vijay Krishna , Covert Jill , Dubielzig Richard R. , Isseroff Roslyn Rivkah , Schurr Michael , Abbott Nicholas L. , McAnulty Jonathan , Murphy Christopher J.
Published: May 2014

Abstracts

The excisional dorsal full‐thickness skin wound model with or without splinting is widely utilized in wound healing studies using diabetic or normal mice. However, the effects of splinting on dermal wound healing have not been fully characterized, and there are limited data on the direct comparison of wound parameters in the splinted model between diabetic and normal mice. We compared full‐thickness excisional dermal wound healing in db/db and heterozygous mice by investigating the effects of splinting, semi‐occlusive dressing, and poly(ethylene glycol) treatment. Two 8‐mm full‐thickness wounds were made with or without splinting in db/db and heterozygous mice. Body weights, splint maintenance, wound contraction, wound closure, and histopathological parameters including reepithelialization, wound bed collagen deposition, and inflammation were compared between groups. Our results show that silicone splint application effectively reduced wound contraction in heterozygous and db/db mice. Splinted wounds, as opposed to nonsplinted wounds, exhibited no significant differences in wound closure between heterozygous and db/db mice. Finally, polyethylene glycol and the noncontact dressing had no significant effect on wound healing in heterozygous or db/db mice. We believe these findings will help investigators in selection of the appropriate wound model and data interpretation with fully defined parameters.
Wound research funding from alternative sources of federal funds in 2012
Authors: Baquerizo Nole Katherine L. , Yim Elizabeth , Van Driessche Freya , Davidson Jeffrey M. , Martins‐Green Manuela , Sen Chandan K. , Tomic‐Canic Marjana , Kirsner Robert S.
Published: May 2014

Chronic wounds represent a major healthcare burden, costing $25 billion annually, and are associated with high mortality. We previously reported that cutaneous wound healing represented only 0.1% ($29.8 million) of the National Institutes of Health budget. This current study focuses on quantifying the contribution by federal agencies other than the National Institutes of Health for fiscal year 2012. Federal databases including USA Spending, Veterans Affairs, Tracking Accountability in Government Grants Systems, Health Services Research Projects in Progress, and Patient‐Centered Outcomes Research Institute, were searched for individual projects addressing wound healing. Twenty‐seven projects were identified, totaling funding of $16,588,623 (median: $349,856). Four sponsor institutions accounted for 74% of awarded funds: Department of the Army, National Science Foundation, Department of Veterans Affairs, and Agency for Healthcare Research & Quality. Research projects and cooperative agreements comprised 44% and 37% of awarded grants. New applications and continuing projects represented 52% and 37%. Wound healing represented 0.15% of total medical research funded by the non‐National Institutes of Health federal sector. Compared with potential impact on US public health, federal investment in wound research is exiguous. This analysis will draw attention to a disproportionately low investment in wound research and its perils to American public health.
Recurring pressure ulcers: Identifying the definitions. A National Pressure Ulcer Advisory Panel white paper
Authors: Tew Cindy , Hettrick Heather , Holden‐Mount Sarah , Grigsby Rebekah , Rhodovi Julie , Moore Lyn , Ghaznavi Amir M. , Siddiqui Aamir
Published: May 2014

Currently, there is a lack of consensus regarding the accepted terminology pertaining to the pressure ulcer healing progression and recidivism. This lack of uniformity can negatively impact initiation of treatment pathways, completion of appropriate interventions, clinical documentation, medical coding, patient education, discharge planning and healthcare revenue through out the healthcare system. The purpose of this paper is to introduce a standard nomenclature as it pertains to pressure ulcer healing progression and any recidivism that may occur. The National Pressure Ulcer Advisory Panel has formulated a framework of terms regarding pressure ulcer progression. We also developed a clearer nomenclature for lack of progress and recidivism of pressure ulcers. This document should serve as a starting point for the discussion of the pressure ulcer care, research, and terminology.
Nonlinear Vibration Analysis of an Elastic Rotor Supported on Angular Contact Ball Bearings Considering Six Degrees of Freedom and Waviness on Balls and Races
Authors: Babu C. K. , Tandon N. , Pandey R. K.
Published: May 2014

Nonlinear vibration analysis of an elastically deformable shaft supported on two lubricated angular contact ball bearings is reported herein considering six-degrees of freedom (6-DOF) and waviness on races and balls. This is an extension work of the investigation published by the authors Babu, C. K., Tandon, N., and Pandey, R. K., 2012, “Vibration Modeling of a Rigid Rotor Supported on the Lubricated Angular Contact Ball Bearings Considering Six Degree of Freedom and Waviness on Balls and Races,” ASME J. Vib. Acoust., 134, p. 011006. Elastic deformation of shaft, frictional moment, and waviness on races and balls have been incorporated in the model for the vibration investigations of rotor's CG. Two noded 3D Timoshenko beam element having 6-DOF has been employed in the computation of the shaft's deformation. Governing equations with appropriate boundary conditions have been solved using 4th order Runge–Kutta method. It is observed that vibration amplitude enhances considerably after incorporating the elastic deformation in comparison to the amplitude achieved using rigid rotor model approach. Moreover, the influence of outer race's radial waviness is large on the amplitudes of vibrations in comparison to radial waviness of inner race. However, it is worth noting here that in case of rigid rotor model the presence of radial waviness on inner race yields high amplitudes of vibrations.
Results from Ireland’s 2014 Report Card on Physical Activity in Children and Youth
Authors: Harrington Deirdre M. , Belton Sarahjane , Coppinger Tara , Cullen Muireann , Donnelly Alan , Dowd Kieran , Keating Teresa , Layte Richard , Murphy Marie , Murphy Niamh , Murtagh Elaine , Woods Catherine
Published: May 2014

Background:

Physical activity (PA) levels are a key performance indicator for policy documents in Ireland. The first Ireland Report Card on Physical Activity in Children and Youth aims to set a robust baseline for future surveillance of indicators related to PA in children and youth.

Methods:

Data collected between 2003−2010 on more than 35,000 7- to 18-year-old children and youth were used and graded using a standardized grading system for 10 indicators.

Results:

Grades assigned for the indicators were as follows: overall physical activity levels, D-; sedentary behavior (TV viewing), C-; organized sport participation, C-: physical education, D-; active play, inconclusive (INC); active transportation, D; school, C-, community and the built environment, B; family, INC; and government, INC.

Conclusions:

PA recommendations exist in Ireland but this Report Card has shown that participation is still low. A number of promising policies, programs and services are in place but these require thorough evaluation and adequate resourcing. Agreement and implementation of a common framework for the systematic surveillance of indictors related to PA of children and youth is necessary to monitor change over time and ensure the impact of promising work is captured.
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.
Physical Activity of Children: A Global Matrix of Grades Comparing 15 Countries
Authors: Tremblay Mark S. , Gray Casey E. , Akinroye Kingsley , Harrington Dierdre M. , Katzmarzyk Peter T. , Lambert Estelle V. , Liukkonen Jarmo , Maddison Ralph , Ocansey Reginald T. , Onywera Vincent O. , Prista Antonio , Reilly John J. , Martínez María del Pilar Rodríguez , Duenas Olga L. Sarmiento , Standage Martyn , Tomkinson Grant
Published: May 2014

The Active Healthy Kids Canada (AHKC) Report Card on Physical Activity for Children and Youth has been effective in powering the movement to get kids moving by influencing priorities, policies, and practice in Canada. The AHKC Report Card process was replicated in 14 additional countries from 5 continents using 9 common indicators (Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behavior, Family and Peers, School, Community and Built Environment, and Government Strategies and Investments), a harmonized process and a standardized grading framework. The 15 Report Cards were presented at the Global Summit on the Physical Activity of Children in Toronto on May 20, 2014. The consolidated findings are summarized here in the form of a global matrix of grades. There is a large spread in grades across countries for most indicators. Countries that lead in certain indicators lag in others. Overall, the grades for indicators of physical activity (PA) around the world are low/poor. Many countries have insufficient information to assign a grade, particularly for the Active Play and Family and Peers indicators. Grades for Sedentary Behaviors are, in general, better in low income countries. The Community and Built Environment indicator received high grades in high income countries and notably lower grades in low income countries. There was a pattern of higher PA and lower sedentary behavior in countries reporting poorer infrastructure, and lower PA and higher sedentary behavior in countries reporting better infrastructure, which presents an interesting paradox. Many surveillance and research gaps and weaknesses were apparent. International cooperation and cross-fertilization is encouraged to tackle existing challenges, understand underlying mechanisms, derive innovative solutions, and overcome the expanding childhood inactivity crisis.
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.
Science Signaling
Podcast: 20 May 2014
Authors: Pilz Renate B. , VanHook Annalisa M.
Published: May 2014

An alternative form of a thyroid hormone receptor mediates nongenomic signaling at the plasma membrane.
The Hormone’s Message
Authors: Ray L. Bryan
Published: May 2014

A molecular mechanism for transmembrane signaling by the growth hormone receptor is elucidated.
Degrees of Separation
Authors: Hines Pamela J.
Published: May 2014

A membrane and signaling protein interaction network for gene discovery and hypothesis generation is identified in
Arabidopsis
.
Signaling Dynamics
Authors: Ray L. Bryan
Published: May 2014

The molecular basis of an all-or-none response in B cells is revealed.
Nerves Have the Nerve to Ask for It
Authors: Berndt Jason D.
Published: May 2014

Peripheral nerves release factors that trigger invasion by cancer cells.
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

Within 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

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

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

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

Pseudomonas 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

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

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

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

N-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

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.
Patient satisfaction with in-centre haemodialysis care: an international survey
Authors: Palmer Suetonia C , de Berardis Giorgia , Craig Jonathan C , Tong Allison , Tonelli Marcello , Pellegrini Fabio , Ruospo Marinella , Hegbrant Jörgen , Wollheim Charlotta , Celia Eduardo , Gelfman Ruben , Ferrari Juan Nin , Törok Marietta , Murgo Marco , Leal Miguel , Bednarek-Skublewska Anna , Dulawa Jan , Strippoli Giovanni F M
Published: May 2014

Objectives

To evaluate patient experiences of specific aspects of haemodialysis care across several countries.

Design

Cross-sectional survey using the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) questionnaire.

Setting

Haemodialysis clinics within a single provider in Europe and South America.

Participants

2748 adults treated in haemodialysis.

Primary and secondary outcomes

The primary outcome was patient satisfaction with overall care. Secondary outcomes included patient experiences of individual aspects of dialysis care.

Results

2145 (78.1%) adults responded to the questionnaire. Fewer than half (46.5% (95% CI 44.5% to 48.6%)) rated their overall care as excellent. Global perceptions of care were uninfluenced by most respondent characteristics except age and depressive symptoms; older respondents were less critical of their care (adjusted OR for excellent rating 1.44 (1.01 to 2.04)) and those with depressive symptoms were less satisfied (0.56 (0.44 to 0.71)). Aspects of care that respondents most frequently ranked as excellent were staff attention to dialysis vascular access (54% (52% to 56%)); caring of nurses (53% (51% to 55%)); staff responsiveness to pain or discomfort (51% (49% to 53%)); caring, helpfulness and sensitivity of dialysis staff (50% (48% to 52%)); and ease of reaching dialysis staff by telephone (48% (46% to 50%)). The aspects of care least frequently ranked as excellent were information provided when choosing a dialysis modality (23% (21% to 25%)), ease of seeing a social worker (28% (24% to 32%)), information provided about dialysis (34% (32% to 36%)), accuracy of information from nephrologist (eg, about prognosis or likelihood of a kidney transplant; 37% (35% to 39%)) and accuracy of nephrologists’ instructions (39% (36% to 41%)).

Conclusions

Haemodialysis patients are least satisfied with the complex aspects of care. Patients’ expectations for accurate information, prognosis, the likelihood of kidney transplantation and their options when choosing dialysis treatment need to be considered when planning healthcare research and practices.
Keeping children safe at home: protocol for a case–control study of modifiable risk factors for scalds
Authors: Wynn P , Stewart J , Kumar A , Clacy R , Coffey F , Cooper N , Coupland C , Deave T , Hayes M , McColl E , Reading R , Sutton A , Watson M , Kendrick D
Published: May 2014

Background

Scalds are one of the most common forms of thermal injury in young children worldwide. Childhood scald injuries, which mostly occur in the home, result in substantial health service use and considerable morbidity and mortality. There is little research on effective interventions to prevent scald injuries in young children.

Objectives

To determine the relationship between a range of modifiable risk factors for medically attended scalds in children under the age of 5 years.

Design

A multicentre case-control study in UK hospitals and minor injury units with parallel home observation to validate parental reported exposures. Cases will be 0–4 years old with a medically attended scald injury which occurred in their home or garden, matched on gender and age with community controls. An additional control group will comprise unmatched hospital controls drawn from children aged 0–4 years attending the same hospitals and minor injury units for other types of injury. Conditional logistic regression will be used for the analysis of cases and matched controls, and unconditional logistic regression for the analysis of cases and unmatched controls to estimate ORs and 95% CI, adjusted and unadjusted for confounding variables.

Main exposure measures

Use of safety equipment and safety practices for scald prevention and scald hazards.

Discussion

This large case-control study will investigate modifiable risk factors for scalds injuries, adjust for potential confounders and validate measures of exposure. Its findings will enhance the evidence base for prevention of scalds injuries in young children.
Import of ribosomal proteins into yeast mitochondria
Authors: Woellhaf Michael W. , Hansen Katja G. , Garth Christoph , Herrmann Johannes M.
Published: May 2014

Mitochondrial ribosomes of baker’s yeast contain at least 78 protein subunits. All but one of these proteins are nuclear-encoded, synthesized on cytosolic ribosomes, and imported into the matrix for biogenesis. The import of matrix proteins typically relies on N-terminal mitochondrial targeting sequences that form positively charged amphipathic helices. Interestingly, the N-terminal regions of many ribosomal proteins do not closely match the characteristics of matrix targeting sequences, suggesting that the import processes of these proteins might deviate to some extent from the general import route. So far, the biogenesis of only two ribosomal proteins, Mrpl32 and Mrp10, was studied experimentally and indeed showed surprising differences to the import of other preproteins. In this review article we summarize the current knowledge on the transport of proteins into the mitochondrial matrix, and thereby specifically focus on proteins of the mitochondrial ribosome.
Digital subtraction cineangiography using proton-induced quasi-monochromatic pulsed X-rays
Authors: Oguri Y. , Hu Y. , Kondo K. , Fukuda H. , Hasegawa J.
Published: May 2014

Two different kinds of metallic plates on a rotating disk target were irradiated with a MeV proton beam, and quasi-monochromatic pulsed X-rays with different energies around the absorption edge of the contrast medium were alternately produced. By using these dual-energy X-rays and a high-sensitivity X-ray movie camera, we took a motion picture of the transmission image of a periodically moving phantom, which simulated a rat heart as a test animal. We found that the enhanced movie imaging of the contrast agent is available by subtraction between adjacent picture frames.
High-resolution ion luminescence analysis with external proton microbeam probe
Authors: Kada Wataru , Yokoyama Akihito , Koka Masashi , Sato Takahiro , Kamiya Tomihiro
Published: May 2014

Multiwavelength optics was improved to create a high-resolution ion luminescence (IL) spectroscopy system. An electrically cooled back-thinned CCD array with an effective wavelength range from 200 nm to 980 nm was used for the IL detector. The spectra of IL were acquired during microbeam irradiation of targets with 3 MeV H+ ions. The IL spectroscopy system provides IL spectra with a wavelength resolution of approximately 2 nm. IL spectroscopy was combined with in-air micro-particle-induced X-ray emission (micro-PIXE) at a beam current of approximately 100 pA, and a specific analysis allows us to determine the chemical composition of the target. Compared with the conventional wavelength-dispersive IL systems, the proposed IL spectroscopy system is more sensitive to IL, making it possible to observe the changes in spectra that correspond to changes in the chemical state of the elements inside the target.
Technologies for delivery of proton and ion beams for radiotherapy
Authors: Owen Hywel , Holder David , Alonso Jose , Mackay Ranald
Published: May 2014

Recent developments for the delivery of proton and ion beam therapy have been significant, and a number of technological solutions now exist for the creation and utilisation of these particles for the treatment of cancer. In this paper we review the historical development of particle accelerators used for external beam radiotherapy and discuss the more recent progress towards more capable and cost-effective sources of particles.
q-Deformed Tamm–Dancoff oscillators: Coherent state and thermostatistics
Authors: Chung Won Sang , Algin Abdullah
Published: May 2014

The q-deformed bosonic Tamm–Dancoff oscillator algebra is considered. The coherent state of the q-deformed bosonic Tamm–Dancoff oscillator algebra is first constructed in detail. Second, the high-temperature thermostatistical properties of a gas of the Tamm–Dancoff oscillators are investigated. For high temperatures, the specific heat, the entropy and the equation of state for the system are derived in terms of the real deformation parameter q. The results obtained by the effects of Tamm–Dancoff type q-deformation show that they could be useful for further researches on understanding of mutual interactions between bosons and fermions in many-body quantum systems.