bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteostasis and ageing: insights from long‐lived mutant mice
Authors: Sands William A. , Page Melissa M. , Selman Colin 
Published: July 2017

AbstractThe global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age‐related disease, and thus improving late‐life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis – where proteostasis is defined here as the maintenance of the proteome – appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)‐induced unfolded protein response (UPR), the ubiquitin–proteasome system (UPS) and autophagy, appear indispensable for longevity in many long‐lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long‐lived mouse mutants have been described, many of which carry single‐gene mutations within the growth‐hormone, insulin/IGF‐1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long‐lived mouse mutants.
A Human Biofilm-Disrupting Monoclonal Antibody Potentiates Antibiotic Efficacy in Rodent Models of both Staphylococcus aureus and Acinetobacter baumannii Infections
Authors: Xiong Yan Q. , Estellés Angeles , Li L. , Abdelhady W. , Gonzales R. , Bayer Arnold S. , Tenorio Edgar , Leighton Anton , Ryser Stefan , Kauvar Lawrence M. 
Published: July 2017

ABSTRACT

Many serious bacterial infections are antibiotic refractory due to biofilm formation. A key structural component of biofilm is extracellular DNA, which is stabilized by bacterial proteins, including those from the DNABII family. TRL1068 is a high-affinity human monoclonal antibody against a DNABII epitope conserved across both Gram-positive and Gram-negative bacterial species. In the present study, the efficacy of TRL1068 for the disruption of biofilm was demonstrated
in vitro
in the absence of antibiotics by scanning electron microscopy. The
in vivo
efficacy of this antibody was investigated in a well-characterized catheter-induced aortic valve infective endocarditis model in rats infected with a methicillin-resistant
Staphylococcus aureus
(MRSA) strain with the ability to form thick biofilms, obtained from the blood of a patient with persistent clinical infection. Animals were treated with vancomycin alone or in combination with TRL1068. MRSA burdens in cardiac vegetations and within intracardiac catheters, kidneys, spleen, and liver showed significant reductions in the combination arm versus vancomycin alone (
P
< 0.001). A trend toward mortality reduction was also observed (
P
= 0.09). In parallel, the
in vivo
efficacy of TRL1068 against a multidrug-resistant clinical
Acinetobacter baumannii
isolate was explored by using an established mouse model of skin and soft tissue catheter-related biofilm infection. Catheter segments infected with
A. baumannii
were implanted subcutaneously into mice; animals were treated with imipenem alone or in combination with TRL1068. The combination showed a significant reduction of catheter-adherent bacteria versus the antibiotic alone (
P
< 0.001). TRL1068 shows excellent promise as an adjunct to standard-of-care antibiotics for a broad range of difficult-to-treat bacterial infections.
Th17-Mediated Cross Protection against Pneumococcal Carriage by Vaccination with a Variable Antigen
Authors: Kuipers Kirsten , Jong Wouter S. P. , van der Gaast-de Jongh Christa E. , Houben Diane , van Opzeeland Fred , Simonetti Elles , van Selm Saskia , de Groot Ronald , Koenders Marije I. , Azarian Taj , Pupo Elder , van der Ley Peter , Langereis Jeroen D. , Zomer Aldert , Luirink Joen , de Jonge Marien I. 
Published: July 2017

ABSTRACT

Serotype-specific protection against
Streptococcus pneumoniae
is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from
Salmonella enterica
serovar Typhimurium displaying the variable N terminus of PspA (α1α2) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on
in silico
prediction combined with
ex vivo
screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.
Bacterial Tubulins A and B Exhibit Polarized Growth, Mixed-Polarity Bundling, and Destabilization by GTP Hydrolysis
Authors: Díaz-Celis César , Risca Viviana I. , Hurtado Felipe , Polka Jessica K. , Hansen Scott D. , Maturana Daniel , Lagos Rosalba , Mullins R. Dyche , Monasterio Octavio 
Published: July 2017

ABSTRACT

Bacteria of the genus
Prosthecobacter
express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB (BtubA/B), that have been observed to assemble into filaments in the presence of GTP. BtubA/B polymers are proposed to be composed
in vitro
by two to six protofilaments in contrast to that
in vivo
, where they have been reported to form 5-protofilament tubes named bacterial microtubules (bMTs). The
btubAB
genes likely entered the
Prosthecobacter
lineage via horizontal gene transfer and may be derived from an early ancestor of the modern eukaryotic microtubule (MT). Previous biochemical studies revealed that BtubA/B polymerization is reversible and that BtubA/B folding does not require chaperones. To better understand BtubA/B filament behavior and gain insight into the evolution of microtubule dynamics, we characterized
in vitro
BtubA/B assembly using a combination of polymerization kinetics assays and microscopy. Like eukaryotic microtubules, BtubA/B filaments exhibit polarized growth with different assembly rates at each end. GTP hydrolysis stimulated by BtubA/B polymerization drives a stochastic mechanism of filament disassembly that occurs via polymer breakage and/or fast continuous depolymerization. We also observed treadmilling (continuous addition and loss of subunits at opposite ends) of BtubA/B filament fragments. Unlike MTs, polymerization of BtubA/B requires KCl, which reduces the critical concentration for BtubA/B assembly and induces it to form stable mixed-orientation bundles in the absence of any additional BtubA/B-binding proteins. The complex dynamics that we observe in stabilized and unstabilized BtubA/B filaments may reflect common properties of an ancestral eukaryotic tubulin polymer.

IMPORTANCE
Microtubules are polymers within all eukaryotic cells that perform critical functions; they segregate chromosomes, organize intracellular transport, and support the flagella. These functions rely on the remarkable range of tunable dynamic behaviors of microtubules. Bacterial tubulin A and B (BtubA/B) are evolutionarily related proteins that form polymers. They are proposed to be evolved from the ancestral eukaryotic tubulin, a missing link in microtubule evolution. Using microscopy and biochemical approaches to characterize BtubA/B assembly
in vitro
, we observed that they exhibit complex and structurally polarized dynamic behavior like eukaryotic microtubules but differ in how they self-associate into bundles and how this bundling affects their stability. Our results demonstrate the diversity of mechanisms through which tubulin homologs promote filament dynamics and monomer turnover.
Human papillomavirus prevalence and genotype distribution among young women and men in Maputo city, Mozambique
Authors: Edna Omar Viegas , Orvalho Augusto , Nália Ismael , Kaliff Malin , Lillsunde-Larsson Gabriella , Ramqvist Torbjörn , Nilsson Charlotta , Falk Kerstin , Nafissa Osman , Ilesh Vindorai Jani , Andersson Sören 
Published: July 2017

ObjectivesHuman papillomavirus (HPV) is a well-known cause of cervical cancer, the second most frequent cancer in female African populations. This study aimed at determining the prevalence of HPV infections and the genotype distribution in young adults aged 18–24, in Maputo city, Mozambique, and to assess the suitability of commercially available HPV vaccines.MethodsThis cross-sectional study was conducted between 2009 and 2011 at a youth clinic in Maputo Central Hospital. Cervical and urethral samples were obtained from 236 women and 176 men, respectively. Demographic and behavioural data were collected using structured questionnaires. HPV genotyping was performed for 35 different high, probably or possibly high-risk and low-risk HPV types using the CLART Human Papillomavirus 2.ResultsHPV prevalence was 168/412 (40.8%; 95% CI 36.0 to 45.5) and was significantly higher in women than in men (63.6%vs10.2%). HPV52 was the most frequent type found in women, followed by HPV35, −16,–53, −58,–6 and −51. In men, HPV51 ranked the highest, followed by HPV6, −11,–52, −59 and −70. HIV infection and sexual debut before 18 years of age were associated with multiple HPV infections (OR 3.03; 95% CI 1.49 to 6.25 and OR 6.03; 95% CI 1.73 to 21.02, respectively). Women had a significantly higher HPV infection prevalence than men (p<0.001). The 9-valent HPV vaccine would cover 36.8% of the high-risk genotypes circulating in women in this study, compared with 26.3% and 15.8% coverage by the bivalent and quadrivalent vaccines, respectively.ConclusionThis study confirmed the high burden of HPV infections in young women in Maputo city, Mozambique. The HPV prevalence was associated with high-risk sexual behaviour. Sex education and sexually transmitted infection prevention interventions should be intensified in Mozambique. Only a proportion of the high-risk HPV genotypes (37%) were covered by currently available vaccines.
Factors associated with nicotine dependence during methadone maintenance treatment: findings from a multisite survey in Vietnam
Authors: Do Huyen Phuc , Nguyen Long Hoang , Thi Nguyen Nhung Phuong , Ngo Chau , Thi Nguyen Huong Lan , Le Giang Tong , Nguyen Linh Khanh , Nguyen Cuong Tat , Tran Bach Xuan , Le Huong Thi , Vu Thuc Minh Thi , Phan Huong Thu Thi , Tran Tho Dinh , Latkin Carl A , Dunne Michael P 
Published: July 2017

ObjectivesSmoking is associated with adverse health outcomes among drug users, including those in treatment. To date, however, there has been little evidence about smoking patterns among people receiving opioid-dependence treatment in developing countries. We examined self-reported nicotine dependence and associated factors in a large sample of opioid-dependent patients receiving methadone maintenance treatment (MMT) in northern Vietnam.SettingFive clinics in Hanoi (urban area) and Nam Dinh (rural area).ParticipantsPatients receiving MMT in the settings during the study period.Primary and secondary outcome measuresWe collected data about smoking patterns, levels of nicotine dependence and other covariates such as socioeconomic status, health status, alcohol use and drug use. The Fagerström test was used to measure nicotine dependence (FTND). Logistic regression and Tobit regression were employed to examine relationships between the smoking rate, nicotine dependence and potentially associated variables.ResultsAmong 1016 drug users undergoing MMT (98.7% male), 87.2% were current smokers. The mean FTND score was 4.5 (SD 2.4). Longer duration of MMT (OR 0.98, 95% CI 0.96 to 0.99) and being HIV-positive (OR 0.46, 95% CI 0.24 to 0.88) were associated with lower likelihood of smoking. Being employed, older age at first drug injection and having long duration of MMT were inversely related with FTND scores. Higher age and continuing drug and alcohol use were significantly associated with higher FTND scores.ConclusionSmoking prevalence is high among methadone maintenance drug users. Enhanced smoking cessation support should be integrated into MMT programmes in order to reduce risk factors for cigarette smoking and improve the health and well-being of people recovering from opiate dependence.
How do clinicians prepare family members for the role of surrogate decision-maker?
Authors: Cunningham Thomas V , Scheunemann Leslie P , Arnold Robert M , White Douglas 
Published: July 2017

PurposeAlthough surrogate decision-making (SDM) is prevalent in intensive care units (ICUs) and concerns with decision quality are well documented, little is known about how clinicians help family members understand the surrogate role. We investigated whether and how clinicians provide normative guidance to families regarding how to function as a surrogate.Subjects and methodsWe audiorecorded and transcribed 73 ICU family conferences in which clinicians anticipated discussing goals of care for incapacitated patients at high risk of death. We developed and applied a coding framework to identify normative statements by clinicians regarding what considerations should guide surrogates’ decisions, including whether clinicians explained one or more of Buchanan and Brock’s three standard principles of SDM to family members.ResultsClinicians made at least one statement about how to perform the surrogate role in 24 (34%) conferences (mean of 0.83 statements per conference (1.77; range 0–9)). We observed three general types of normative guidance provided to surrogates, with some conferences containing more than one type of guidance: counselling about one or more standard principles of SDM (24% of conferences); counselling surrogates to make decisions centred on the patient as a person, without specifying how to accomplish that (14% of conferences); and counselling surrogates to make decisions based on the family’s values (8% of conferences).ConclusionsClinicians did not provide normative guidance about the surrogate role in two-thirds of family conferences for incapacitated patients at high risk for death. When they did, clinicians’ guidance was often incomplete and sometimes conflicted with standard principles of SDM. Future work is needed to understand whether providing explicit guidance on how to perform the surrogate role improves decision-making or mitigates surrogates’ psychological distress.
Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis
Authors: Horner Patrick , Ingle Suzanne M , Garrett Frederick , Blee Karla , Kong Fabian , Muir Peter , Moi Harald 
Published: July 2017

BackgroundThere is increasing evidence that azithromycin 1 g is driving the emergence of macrolide resistance in Mycoplasma genitalium worldwide. We undertook a meta-analysis of M. genitalium treatment studies using azithromycin 1 g single dose and azithromycin 500 mg on day 1 then 250 mg daily for 4 days (5-day regimen) to determine rates of treatment failure and resistance in both regimens.MethodsThe online databases PubMed and Medline were searched using terms “Mycoplasma genitalium”, “macrolide” or “azithromycin” and “resistance” up to April 2016. Studies were eligible if they: used azithromycin 1 g or 5 days, assessed patients for macrolide resistant genetic mutations prior to treatment and patients who failed were again resistance genotyped. Random effects meta-analysis was used to estimate failure and resistance rates.ResultsEight studies were identified totalling 435 patients of whom 82 (18.9%) had received the 5-day regimen. The random effects pooled rate of treatment failure and development of macrolide antimicrobial resistance mutations with azithromycin 1 g was 13.9% (95% CI 7.7% to 20.1%) and 12.0% (7.1% to 16.9%), respectively. Of individuals treated with the 5-day regimen, with no prior doxycycline treatment, fewer (3.7%; 95% CI 0.8% to 10.3%, p=0.012) failed treatment, all of whom developed resistance (p=0.027).ConclusionAzithromycin 1 g is associated with high rates of treatment failure and development of macrolide resistance in M. genitalium infection with no pre-existing macrolide mutations. There is moderate but conflicting evidence that the 5-day regimen may be more effective and less likely to cause resistance.
Relative Contributions of Atmospheric Energy Transport and Sea Ice Loss to the Recent Warm Arctic Winter
Authors: Kim Hye-Mi , Kim Baek-Min 
Published: July 2017

Abstract
The relative contributions of atmospheric energy transport (via heat and moisture advection) and sea ice decline to recent Arctic warming were investigated using high-resolution reanalysis data up to 2017. During the Arctic winter, a variation of downward longwave radiation (DLR) is fundamental in modulating Arctic surface temperature. In the warm Arctic winter, DLR and precipitable water (PW) are increasing over the entire Arctic; however, the major drivers for such increases differ regionally. In areas such as the northern Greenland Sea, increasing DLR and PW are caused mainly by convergence of atmospheric energy transport from lower latitudes. In regions of maximum sea ice retreat (e.g., northern Barents–Kara Seas), continued sea ice melting from previous seasons drive the DLR and PW increases, consistent with the positive ice–insulation feedback. Distinct local feedbacks between open water and ice-retreat regions were further compared. In open water regions, a reduced ocean–atmosphere temperature gradient caused by atmospheric warming suppresses surface turbulent heat flux (THF) release from the ocean to the atmosphere; thus, surface warming cannot accelerate. Conversely, in ice-retreat regions, sea ice reduction allows the relatively warm ocean to interact with the colder atmosphere via surface THF release. This increases temperature and humidity in the lower troposphere consistent with the positive ice–insulation feedback. The implication of this study is that Arctic warming will slow as the open water fraction increases. Therefore, given sustained greenhouse warming, the roles of atmospheric heat and moisture transport from lower latitudes are likely to become increasingly critical in the future Arctic climate.
Assimilating Copernicus SST Data into a Pan-Arctic Ice–Ocean Coupled Model with a Local SEIK Filter
Authors: Liang Xi , Yang Qinghua , Nerger Lars , Losa Svetlana N. , Zhao Biao , Zheng Fei , Zhang Lin , Wu Lixin 
Published: July 2017

AbstractSea surface temperature (SST) data from the Copernicus Marine Environment Monitoring Service are assimilated into a pan-Arctic ice–ocean coupled model using the ensemble-based local singular evolutive interpolated Kalman (LSEIK) filter. This study found that the SST deviation between model hindcasts and independent SST observations is reduced by the assimilation. Compared with model results without data assimilation, the deviation between the model hindcasts and independent SST observations has decreased by up to 0.2°C at the end of summer. The strongest SST improvements are located in the Greenland Sea, the Beaufort Sea, and the Canadian Arctic Archipelago. The SST assimilation also changes the sea ice concentration (SIC). Improvements of the ice concentrations are found in the Canadian Arctic Archipelago, the Beaufort Sea, and the central Arctic basin, while negative effects occur in the west area of the eastern Siberian Sea and the Laptev Sea. Also, sea ice thickness (SIT) benefits from ensemble SST assimilation. A comparison with upward-looking sonar observations reveals that hindcasts of SIT are improved in the Beaufort Sea by assimilating reliable SST observations into light ice areas. This study illustrates the advantages of assimilating SST observations into an ice–ocean coupled model system and suggests that SST assimilation can improve SIT hindcasts regionally during the melting season.
Monastic Communities in Today's Europe and Their Future
Authors: Conacher Giles 
Published: July 2017

A meeting at Chantilly from 15–17 December 1990 on the theme ‘Monastic Community and European Community’ brought together just under a hundred monastic Cellarers of the Cistercian and Benedictine monasteries of France, together with some invited from Belgium and Luxembourg. Their principal concerns were economic, but as disciples of St. Benedict, they also considered the wider spectrum. Cardinal Jean Marie Lustiger opened the conference with a talk on the challenge that tomorrow's Europe throws down to monasticism. The text translated below appeared in the ‘Lettre de Maredsous’.
Early Tensile Bond Strengths of Several Enamel and Dentin Bonding Systems
Authors: Burrow M.F. , Tagami J. , Negishi T. , Nikaido T. , Hosoda H. 
Published: July 2017

Tensile bond strength tests are commonly used for the evaluation of adhesive dental materials. The majority of these tests are carried out after 24 h of storage in water. However, determination of the early tensile bond strength could be more important, especially in relation to gap formation between the cavity surface and the restorative material. This study investigated the tensile bond strengths of five enamel/ dentin bonding systems and two experimental dentin bonding systems. Tensile bond strengths were obtained at one min, ten min, and 24 h after the resin composite was cured. Bond strengths at the early stages were always somewhat less than the 24-hour test results. For the enamel/dentin bonding systems, a significant difference was found between the enamel and dentin bond strengths at all time periods, except with Superbond D-liner and Liner Bond. The experimental group with glyceryl methacrylate as the primer produced a good 24-hour result (14.3 MPa), but the early bond strengths were no different from those in the non-primer-treated groups. It was concluded that this material may actually retard the polymerization of the bonding resin. Previous workers have suggested that a tensile bond strength in the order of 20 MPa is necessary for gap-free restorations to be obtained. Should this be the case, then all of the materials tested, from the aspect of early bond strength, lack the strength for prevention of gap formation, although Superbond D-liner and Liner Bond approached this hypothetical figure. These systems, Superbond D-liner and Liner Bond, also exhibit small differences between the enamel and dentin tensile bond strengths.