bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability
Authors: Tan Suk Fei , Kirby Brian P , Stanslas Johnson , Basri Hamidon Bin 
Published: August 2017

Abstract

Objective
This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA).

Methods
Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood–brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain.

Key findings
Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80.

Conclusions
Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.
The contribution of behavioural science to nutrition: Appetite control
Authors: Blundell J. E. 
Published: August 2017

AbstractBehaviour and nutrition are inextricably linked. The behaviour of eating is the agency through which nutrients enter the body and exert their effects on physiology, metabolism and health. It is therefore inevitable that the study of eating behaviour (or appetite in general) is essential to an understanding of the discipline of nutrition and therefore to describing the ways in which nutrients can begin to exert their effects. The fact that humans are omnivores, with the potential to eat a huge diversity of foods, clearly denotes the importance of behaviour for nutrition. The roles of culture and biology in determining what foods people put into their mouths highlights the centrality of food choice for nutrition. In turn, behavioural science has made a huge contribution to defining the mechanisms responsible for food choice. This scientific approach has also specified the roles of homoeostatic and hedonic principles (and their interactions) in controlling the amount and type of food (nutrition) ingested. A substantial focus has been the investigation of the processes of satiation and satiety, with implications for understanding routes to over‐consumption and obesity. All of these investigations have been incorporated within a generally accepted and well‐described behavioural science methodology that involves the application of objective scientific principles to the study of eating behaviour. This methodology has been heavily implicated in the search for commercially viable functional foods for satiety. In recent years, behavioural science has engaged with the fields of energy balance and physical activity, recognising that nutrient intake is not independent of nutrient utilisation. This approach has been fostered by the pervasive problem of obesity and by its dependence on the interaction between over nutrition and under activity. The diversity of foods in the omnivore's repertoire is matched only by the diversity of humans themselves. This diversity is reality, and a future track for behavioural science seems destined to lead to understanding and managing individual differences.
Nutrition, epigenetics and health through life
Authors: Malcomson F. C. , Mathers J. C. 
Published: August 2017

AbstractEpigenetics describe heritable changes to the genome without changes to the DNA sequence itself. Epigenetic marks include DNA methylation and histone modifications, and epigenetic molecules include microRNAs. Epigenetic mechanisms modulate gene expression and so regulate many cellular processes such as cell proliferation and cell death. As a consequence, changes to the epigenome may have consequences for the function of cells, tissues and organs and may modify the risk of developing disease. Epigenetic marks and molecules change during development and also during ageing; as we age, global DNA methylation declines whilst some specific genes become hypermethylated. Unlike the genome (DNA sequence), the epigenome is not fixed and the constellation of epigenetic marks and molecules is influenced by environmental exposures, including diet. Therefore, epigenetics provides a mechanism though which nutrition modulates health and wellbeing throughout the life course and, importantly, a plausible mechanism for the long‐term effects of early life nutritional exposures. There is growing evidence of the specific nutrients and other food constituents that influence the epigenome but, to date, the molecular pathways through which nutritional exposures and status are transduced (received and recorded) remain to be elucidated. Epigenetic patterns are promising candidate diet‐related biomarkers of ageing and of disease risk and, therefore, may be useful as surrogate endpoints in nutritional epidemiology and in dietary intervention studies.
Dreamless: the silent epidemic of REM sleep loss
Authors: Naiman Rubin 
Published: August 2017

AbstractWe are at least as dream deprived as we are sleep deprived. Many of the health concerns attributed to sleep loss result from a silent epidemic of REM sleep deprivation. REM/dream loss is an unrecognized public health hazard that silently wreaks havoc with our lives, contributing to illness, depression, and an erosion of consciousness. This paper compiles data about the causes and extent of REM/dream loss associated with commonly used medications, endemic substance use disorders, rampant sleep disorders, and behavioral and lifestyle factors. It examines the consequences of REM/dream loss and concludes with recommendations for restoring healthy REM/dreaming.
Overexpression of DEMETER, a DNA demethylase, promotes early apical bud maturation in poplar
Authors: Conde Daniel , Moreno‐Cortés Alicia , Dervinis Christopher , Ramos‐Sánchez José M. , Kirst Matias , Perales Mariano , González‐Melendi Pablo , Allona Isabel 
Published: August 2017

AbstractThe transition from active growth to dormancy is critical for the survival of perennial plants. We identified a DEMETER‐like (CsDML) cDNA from a winter‐enriched cDNA subtractive library in chestnut (Castanea sativa Mill.), an economically and ecologically important species. Next, we characterized this DNA demethylase and its putative ortholog in the more experimentally tractable hybrid poplar (Populus tremula × alba), under the signals that trigger bud dormancy in trees. We performed phylogenetic and protein sequence analysis, gene expression profiling, and 5‐methyl‐cytosine methylation immunodetection studies to evaluate the role of CsDML and its homolog in poplar, PtaDML6. Transgenic hybrid poplars overexpressing CsDML were produced and analysed. Short days and cold temperatures induced CsDML and PtaDML6. Overexpression of CsDML accelerated short‐day‐induced bud formation, specifically from Stages 1 to 0. Buds acquired a red‐brown coloration earlier than wild‐type plants, alongside with the up‐regulation of flavonoid biosynthesis enzymes and accumulation of flavonoids in the shoot apical meristem and bud scales. Our data show that the CsDML gene induces bud formation needed for the survival of the apical meristem under the harsh conditions of winter.
A Risk Analysis Approach to Prioritizing Epidemics: Ebola Virus Disease in West Africa as a Case Study
Authors: Ajisegiri Whenayon Simeon , Chughtai Abrar Ahmad , MacIntyre C. Raina 
Published: August 2017

AbstractThe 2014 Ebola virus disease (EVD) outbreak affected several countries worldwide, including six West African countries. It was the largest Ebola epidemic in the history and the first to affect multiple countries simultaneously. Significant national and international delay in response to the epidemic resulted in 28,652 cases and 11,325 deaths. The aim of this study was to develop a risk analysis framework to prioritize rapid response for situations of high risk. Based on findings from the literature, sociodemographic features of the affected countries, and documented epidemic data, a risk scoring framework using 18 criteria was developed. The framework includes measures of socioeconomics, health systems, geographical factors, cultural beliefs, and traditional practices. The three worst affected West African countries (Guinea, Sierra Leone, and Liberia) had the highest risk scores. The scores were much lower in developed countries that experienced Ebola compared to West African countries. A more complex risk analysis framework using 18 measures was compared with a simpler one with 10 measures, and both predicted risk equally well. A simple risk scoring system can incorporate measures of hazard and impact that may otherwise be neglected in prioritizing outbreak response. This framework can be used by public health personnel as a tool to prioritize outbreak investigation and flag outbreaks with potentially catastrophic outcomes for urgent response. Such a tool could mitigate costly delays in epidemic response.
Validation of the Resilience Scale for Adolescents in Norwegian adolescents 13–18 years
Authors: Moksnes Unni K. , Haugan Gørill 
Published: August 2017

AimResilience is seen as a vital resource for coping and mental health in adolescents. However, there is no universally accepted theory or definition of resilience, leading to considerable challenges regarding how to operationalise and measure this construct. The study aimed at providing further knowledge of the psychometric properties (dimensionality, construct validity and internal consistency) of the 28‐item version of the Resilience Scale for Adolescents (READ) in N = 1183 Norwegian adolescents, 13–18 years old.MethodsDimensionality of READ was tested using confirmatory factor analysis (CFA). Convergent validity and reliability were tested using Pearson's correlation analysis, Cronbach's alpha and composite reliability.ResultsThe CFA supported a modified, 20‐item, five‐factor structure with high reliability, supporting the dimensionality and internal consistency of the instrument. Convergent validity was confirmed where all factors correlated in expected directions with measures of sense of coherence, self‐esteem, stress and depression.ConclusionThe psychometric properties of the READ need to be further evaluated in adolescents; however, the results indicate that a modified 20‐item version of READ is adequate for assessing resilience in the present sample of Norwegian adolescents.
Evolution of MNC and lymphocyte collection settings employing different Spectra Optia® Leukapheresis systems
Authors: Punzel M. , Kozlova A. , Quade A. , Schmidt A. H. , Smith R. 
Published: August 2017

Background and ObjectivesThe Spectra Optia® continuous mononuclear cell (CMNC apheresis) system has emerged as the preferred device in peripheral blood stem cell collections over the original two‐step Spectra Optia® mononuclear cell (MNC apheresis) system. Until now, no comparative data were available for non‐stimulated MNC collections that are required for immunotherapy.Materials and MethodsWe compared collection parameters and product composition for Spectra Optia MNC‐ as well as CMNC‐apheresis systems in non‐stimulated MNC collections from 35 registry donors intended for donor lymphocyte infusions. In a subsequent analysis, different centrifugation forces (determined as packing factor or PF) were investigated regarding target cell yield and contamination in 61 collections using the CMNC device only.ResultsComparable collection efficiencies as well as target cell yields could be achieved with the Spectra Optia MNC‐ versus CMNC program. Similar numbers of MNC, T, B and NK cells could be collected with both devices. This led to a more than twofold lymphocyte recruitment from lymphatic tissue into the blood during apheresis. However, significantly more blood had to be processed with longer procedure time using the MNC program resulting in larger product volumes compared to the CMNC setting. Red blood cell and platelet (PLT) contamination were similar. Lowering the centrifugation force from PF4·5 to PF4·0 significantly reduced PLT contamination without affecting target cell yield in the product.ConclusionThe Spectra Optia® CMNC device using lower centrifugal force (PF4·0) showed similar target cell yield and composition as well as collection efficiencies with superior performance parameters and lower PLT contamination compared to the MNC setting.
PBP4 Mediates β-Lactam Resistance by Altered Function
Authors: Chatterjee Som S. , Chen Liang , Gilbert Aubre , da Costa Thaina M. , Nair Vinod , Datta Sandip K. , Kreiswirth Barry N. , Chambers Henry F. 
Published: August 2017

ABSTRACT

Penicillin binding protein 4 (PBP4) can provide high-level β-lactam resistance in
Staphylococcus aureus
. A series of missense and promoter mutations associated with
pbp4
were detected in strains that displayed high-level resistance. We show here that the missense mutations facilitate the β-lactam resistance mediated by PBP4 and the promoter mutations lead to overexpression of
pbp4
. Our results also suggest a cooperative interplay among PBPs for β-lactam resistance.
Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection
Authors: Schooley Robert T. , Biswas Biswajit , Gill Jason J. , Hernandez-Morales Adriana , Lancaster Jacob , Lessor Lauren , Barr Jeremy J. , Reed Sharon L. , Rohwer Forest , Benler Sean , Segall Anca M. , Taplitz Randy , Smith Davey M. , Kerr Kim , Kumaraswamy Monika , Nizet Victor , Lin Leo , McCauley Melanie D. , Strathdee Steffanie A. , Benson Constance A. , Pope Robert K. , Leroux Brian M. , Picel Andrew C. , Mateczun Alfred J. , Cilwa Katherine E. , Regeimbal James M. , Estrella Luis A. , Wolfe David M. , Henry Matthew S. , Quinones Javier , Salka Scott , Bishop-Lilly Kimberly A. , Young Ry , Hamilton Theron 
Published: August 2017

ABSTRACTWidespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, includingAcinetobacter baumannii. We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDRA. baumanniiinfection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for anA. baumanniiisolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of theA. baumanniiinfection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.
Bedaquiline Inhibits the ATP Synthase in Mycobacterium abscessus and Is Effective in Infected Zebrafish
Authors: Dupont Christian , Viljoen Albertus , Thomas Sangeeta , Roquet-Banères Françoise , Herrmann Jean-Louis , Pethe Kevin , Kremer Laurent 
Published: August 2017

ABSTRACT

Pulmonary infections caused by
Mycobacterium abscessus
are emerging as a global threat, especially in cystic fibrosis patients. Further intensifying the concern of
M. abscessus
infection is the recent evidence of human-to-human transmission of the infection.
M. abscessus
is a naturally multidrug-resistant fast-growing pathogen for which pharmacological options are limited. Repurposing antitubercular drugs represents an attractive option for the development of chemotherapeutic alternatives against
M. abscessus
infections. Bedaquiline (BDQ), an ATP synthase inhibitor, has recently been approved for the treatment of multidrug-resistant tuberculosis. Herein, we show that BDQ has a very low MIC against a vast panel of clinical isolates. Despite being bacteriostatic
in vitro
, BDQ was highly efficacious in a zebrafish model of
M. abscessus
infection. Remarkably, a very short period of treatment was sufficient to protect the infected larvae from
M. abscessus
-induced killing. This was corroborated with reduced numbers of abscesses and cords, considered to be major pathophysiological signs in infected zebrafish. Mode-of-action studies revealed that BDQ triggered a rapid depletion of ATP in
M. abscessus
in vitro
, consistent with the drug targeting the F
o
F
1
ATP synthase. Importantly, despite a failure to select
in vitro
for spontaneous mutants that are highly resistant to BDQ, the transfer of single nucleotide polymorphisms leading to D29V or A64P substitutions in
atpE
conferred high resistance, thus resolving the target of BDQ in
M. abscessus
. Overall, this study indicates that BDQ is active against
M. abscessus
in vitro
and
in vivo
and should be considered for clinical use against the difficult-to-manage
M. abscessus
pulmonary infections.
Listeria monocytogenes and Shigella flexneri Activate the NLRP1B Inflammasome
Authors: Neiman-Zenevich Jana , Stuart Sarah , Abdel-Nour Mena , Girardin Stephen E. , Mogridge Jeremy 
Published: August 2017

ABSTRACT

Activation of the innate immune receptor NLRP1B leads to the formation of an inflammasome, which induces autoproteolytic processing of pro-caspase-1, and ultimately to the release of inflammatory cytokines and to the execution of pyroptosis. One of the signals to which NLRP1B responds is metabolic stress that occurs in cells deprived of glucose or treated with metabolic inhibitors. NLRP1B might therefore sense microbial infection, as intracellular pathogens such as
Listeria monocytogenes
and
Shigella flexneri
cause metabolic stress as a result of nutrient scavenging and host cell damage. Here we addressed whether these pathogens activate the NLRP1B inflammasome. We found that
Listeria
infection activated the NLRP1B inflammasome in a reconstituted fibroblast model. Activation of NLRP1B by
Listeria
was diminished in an NLRP1B mutant shown previously to be defective at detecting energy stress and was dependent on the expression of listeriolysin O (LLO), a protein required for vacuolar escape. Infections of either
Listeria
or
Shigella
activated NLRP1B in the RAW264.7 murine macrophage line, which expresses endogenous NLRP1B. We conclude that NLRP1B senses cellular infection by distinct invasive pathogens.
Incremental Contributions of FbaA and Other Impetigo-Associated Surface Proteins to Fitness and Virulence of a Classical Group A Streptococcal Skin Strain
Authors: Rouchon Candace N. , Ly Anhphan T. , Noto John P. , Luo Feng , Lizano Sergio , Bessen Debra E. 
Published: August 2017

ABSTRACT

Group A streptococci (GAS) are highly prevalent human pathogens whose primary ecological niche is the superficial epithelial layers of the throat and/or skin. Many GAS strains with a strong tendency to cause pharyngitis are distinct from strains that tend to cause impetigo; thus, genetic differences between them may confer host tissue-specific virulence. In this study, the FbaA surface protein gene was found to be present in most skin specialist strains but largely absent from a genetically related subset of pharyngitis isolates. In an Δ
fbaA
mutant constructed in the impetigo strain Alab49, loss of FbaA resulted in a slight but significant decrease in GAS fitness in a humanized mouse model of impetigo; the Δ
fbaA
mutant also exhibited decreased survival in whole human blood due to phagocytosis. In assays with highly sensitive outcome measures, Alab49ΔfbaA was compared to other isogenic mutants lacking virulence genes known to be disproportionately associated with classical skin strains. FbaA and PAM (i.e., the M53 protein) had additive effects in promoting GAS survival in whole blood. The pilus adhesin tip protein Cpa promoted Alab49 survival in whole blood and appears to fully account for the antiphagocytic effect attributable to pili. The finding that numerous skin strain-associated virulence factors make slight but significant contributions to virulence underscores the incremental contributions to fitness of individual surface protein genes and the multifactorial nature of GAS-host interactions.
Defining Electron Bifurcation in the Electron-Transferring Flavoprotein Family
Authors: Garcia Costas Amaya M. , Poudel Saroj , Miller Anne-Frances , Schut Gerrit J. , Ledbetter Rhesa N. , Fixen Kathryn R. , Seefeldt Lance C. , Adams Michael W. W. , Harwood Caroline S. , Boyd Eric S. , Peters John W. 
Published: August 2017

ABSTRACT
Electron bifurcation is the coupling of exergonic and endergonic redox reactions to simultaneously generate (or utilize) low- and high-potential electrons. It is the third recognized form of energy conservation in biology and was recently described for select electron-transferring flavoproteins (Etfs). Etfs are flavin-containing heterodimers best known for donating electrons derived from fatty acid and amino acid oxidation to an electron transfer respiratory chain via Etf-quinone oxidoreductase. Canonical examples contain a flavin adenine dinucleotide (FAD) that is involved in electron transfer, as well as a non-redox-active AMP. However, Etfs demonstrated to bifurcate electrons contain a second FAD in place of the AMP. To expand our understanding of the functional variety and metabolic significance of Etfs and to identify amino acid sequence motifs that potentially enable electron bifurcation, we compiled 1,314 Etf protein sequences from genome sequence databases and subjected them to informatic and structural analyses. Etfs were identified in diverse archaea and bacteria, and they clustered into five distinct well-supported groups, based on their amino acid sequences. Gene neighborhood analyses indicated that these Etf group designations largely correspond to putative differences in functionality. Etfs with the demonstrated ability to bifurcate were found to form one group, suggesting that distinct conserved amino acid sequence motifs enable this capability. Indeed, structural modeling and sequence alignments revealed that identifying residues occur in the NADH- and FAD-binding regions of bifurcating Etfs. Collectively, a new classification scheme for Etf proteins that delineates putative bifurcating versus nonbifurcating members is presented and suggests that Etf-mediated bifurcation is associated with surprisingly diverse enzymes.

IMPORTANCE
Electron bifurcation has recently been recognized as an electron transfer mechanism used by microorganisms to maximize energy conservation. Bifurcating enzymes couple thermodynamically unfavorable reactions with thermodynamically favorable reactions in an overall spontaneous process. Here we show that the electron-transferring flavoprotein (Etf) enzyme family exhibits far greater diversity than previously recognized, and we provide a phylogenetic analysis that clearly delineates bifurcating versus nonbifurcating members of this family. Structural modeling of proteins within these groups reveals key differences between the bifurcating and nonbifurcating Etfs.