bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution and factors associated with salivary secretory leukocyte protease inhibitor concentrations
Authors: Rahman S , Pierce Campbell CM , Torres BN , O'Keefe MT , Ingles DJ , Villa LL , Carvalho da Silva RJ , Cintra RC , Lazcano‐Ponce E , Salmeron J , Quiterio M , Giuliano AR 
Published: August 2016

ObjectivesThis cross‐sectional study examined the distribution and correlates of salivary secretory leukocyte protease inhibitor (SLPI) concentrations within a multinational cohort of men.MethodsExtracellular SLPI was measured in oral gargle cell supernatants of 378 men from three countries using an ELISA‐based assay. Risk factor data were collected by a questionnaire. Factors associated with SLPI were assessed using linear and logistic regression for continuous and categorical SLPI, respectively.ResultsAmong men aged 18–73 years, the median SLPI concentration was 492.0 ng ml−1 (range: 2.3–1919.9). In multivariable modeling, men in Brazil and younger men (18–30 years) were more likely to have higher levels of SLPI [adjusted odds ratio (aOR) 3.84; 95% confidence interval (CI): 1.94–7.59, and aOR 3.84; 95% CI: 1.98–7.43, respectively]. Men with a self‐reported sexually transmitted diseases diagnosis in the past 6 months were more likely to have higher SLPI levels (aOR 2.98; 95% CI: 1.1–7.83) and men reporting bleeding/swollen gums were less likely to have higher SLPI (aOR 0.34; 95% CI: 0.15–0.79). Similar results were observed for linear regression models.ConclusionsSecretory leukocyte protease inhibitor concentrations varied significantly by country and decreased with increasing age. The interaction between SLPI, modifiable factors, and oral infections that influence cancer risk warrants further investigation.
A Survey of Ismaili Studies Part 1: Early Ismailism and Fatimid Ismailism
Authors: Andani Khalil 
Published: August 2016

AbstractThis article discusses the major scholarly developments in the study of Ismaili Muslim history and thought. Scholarship on the Ismailis, the second largest branch of Shi‘i Islam, once relied on hostile depictions produced by their adversaries. With the recovery of more primary sources over the last several decades, Ismaili studies is now progressing at a rapid pace. The Ismaili movement originated from a schism in the Imami Shi‘i community over the succession to Ja‘far al‐Sadiq, the fifth Shi‘i Imam. The Ismailis upheld the succession rights of al‐Sadiq's son and designated heir, Isma‘il, and his lineal descendants. The earliest Ismailis directed a revolutionaryda‘wahin the ninth century and established the Fatimid Caliphate (909‐1171). Ismaili doctrine during these periods evolved from a gnostic cosmology into a Neoplatonic metaphysics. It also featured cyclical conceptions of Prophethood and Imamat and stressed the distinction between the exoteric (zahir) and esoteric (batin) dimensions of Islam. Major scholarly debates and thematic areas in the study of the pre‐Fatimid and Fatimid periods of Ismaili history pertain to the doctrinal character of early Imami Shi‘ism,Ismaili historiography, the origins of the earliest Ismailis, the emergence of the Ismailida‘wah, the earliest Ismaili conceptions of Imamat, the different facets of Fatimid rule, the genealogy of the Fatimid Imam‐Caliphs, and the philosophical dimensions of Fatimid Ismaili thought.
ERIL1, the plant homologue of ERI‐1, is involved in the processing of chloroplastic rRNAs
Authors: Mermigka Glykeria , Helm Jutta Maria , Vlatakis Ioannis , Schumacher Heiko Tobias , Vamvaka Evgenia , Kalantidis Kriton 
Published: August 2016

SummaryProteins belonging to the enhancer of RNA interference‐1 subfamily of 3′–5′ exoribonucleases participate in divergent RNA pathways. They degrade small interfering RNAs (siRNAs), thus suppressing RNA interference, and are involved in the maturation of ribosomal RNAs and the degradation of histone messenger RNAs (mRNAs). Here, we report evidence for the role of the plant homologue of these proteins, which we termed ENHANCED RNA INTERFERENCE‐1‐LIKE‐1 (ERIL1), in chloroplast function. In vitro assays with AtERIL1 proved that the conserved 3′–5′ exonuclease activity is shared among all homologues studied. Confocal microscopy revealed that ERL1, a nucleus‐encoded protein, is targeted to the chloroplast. To gain insight into its role in plants, we used Nicotiana benthamiana and Arabidopsis thaliana plants that constitutively overexpress or suppress ERIL1. In the mutant lines of both species we observed malfunctions in photosynthetic ability. Molecular analysis showed that ERIL1 participates in the processing of chloroplastic ribosomal RNAs (rRNAs). Lastly, our results suggest that the missexpression of ERIL1 may have an indirect effect on the microRNA (miRNA) pathway. Altogether our data point to an additional piece of the puzzle in the complex RNA metabolism of chloroplasts.
A simulation study on the constancy of cardiac energy metabolites during workload transition
Authors: Saito Ryuta , Takeuchi Ayako , Himeno Yukiko , Inagaki Nobuya , Matsuoka Satoshi 
Published: August 2016

Key points
The cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant during physiological cardiac workload transition.
How this is accomplished is not yet clarified, though Ca2+ has been suggested to be one of the possible mechanisms.
We constructed a detailed mathematical model of cardiac mitochondria based on experimental data and studied whether known Ca2+‐dependent regulation mechanisms play roles in the metabolite constancy.
Model simulations revealed that the Ca2+‐dependent regulation mechanisms have important roles under the in vitro condition of isolated mitochondria where malate and glutamate were mitochondrial substrates, while they have only a minor role and the composition of substrates has marked influence on the metabolite constancy during workload transition under the simulated in vivo condition where many substrates exist.
These results help us understand the regulation mechanisms of cardiac energy metabolism during physiological cardiac workload transition.
AbstractThe cardiac energy metabolites such as ATP, phosphocreatine, ADP and NADH are kept relatively constant over a wide range of cardiac workload, though the mechanisms are not yet clarified. One possible regulator of mitochondrial metabolism is Ca2+, because it activates several mitochondrial enzymes and transporters. Here we constructed a mathematical model of cardiac mitochondria, including oxidative phosphorylation, substrate metabolism and ion/substrate transporters, based on experimental data, and studied whether the Ca2+‐dependent activation mechanisms play roles in metabolite constancy. Under the in vitro condition of isolated mitochondria, where malate and glutamate were used as mitochondrial substrates, the model well reproduced the Ca2+ and inorganic phosphate (Pi) dependences of oxygen consumption, NADH level and mitochondrial membrane potential. The Ca2+‐dependent activations of the aspartate/glutamate carrier and the F1Fo‐ATPase, and the Pi‐dependent activation of Complex III were key factors in reproducing the experimental data. When the mitochondrial model was implemented in a simple cardiac cell model, simulation of workload transition revealed that cytoplasmic Ca2+ concentration ([Ca2+]cyt) within the physiological range markedly increased NADH level. However, the addition of pyruvate or citrate attenuated the Ca2+ dependence of NADH during the workload transition. Under the simulated in vivo condition where malate, glutamate, pyruvate, citrate and 2‐oxoglutarate were used as mitochondrial substrates, the energy metabolites were more stable during the workload transition and NADH level was almost insensitive to [Ca2+]cyt. It was revealed that mitochondrial substrates have a significant influence on metabolite constancy during cardiac workload transition, and Ca2+ has only a minor role under physiological conditions.
Mechanical activation of angiotensin II type 1 receptors causes actin remodelling and myogenic responsiveness in skeletal muscle arterioles
Authors: Hong Kwangseok , Zhao Guiling , Hong Zhongkui , Sun Zhe , Yang Yan , Clifford Philip S. , Davis Michael J. , Meininger Gerald A. , Hill Michael A. 
Published: August 2016

Key points
Candesartan, an inverse agonist of the type 1 angiotensin II receptor (AT1R), causes a concentration‐dependent inhibition of pressure‐dependent myogenic tone consistent with previous reports of mechanosensitivity of this G protein‐coupled receptor.
Mechanoactivation of the AT1R occurs independently of local angiotensin II production and the type 2 angiotensin receptor.
Mechanoactivation of the AT1R stimulates actin polymerization by a protein kinase C‐dependent mechanism, but independently of a change in intracellular Ca2+.
Using atomic force microscopy, changes in single vascular smooth muscle cell cortical actin are observed to remodel following mechanoactivation of the AT1R.
AbstractThe Gq/11 protein‐coupled angiotensin II type 1 receptor (AT1R) has been shown to be activated by mechanical stimuli. In the vascular system, evidence supports the AT1R being a mechanosensor that contributes to arteriolar myogenic constriction. The aim of this study was to determine if AT1R mechanoactivation affects myogenic constriction in skeletal muscle arterioles and to determine underlying cellular mechanisms. Using pressure myography to study rat isolated first‐order cremaster muscle arterioles the AT1R inhibitor candesartan (10−7–10−5 m) showed partial but concentration‐dependent inhibition of myogenic reactivity. Inhibition was demonstrated by a rightward shift in the pressure–diameter relationship over the intraluminal pressure range, 30–110 mmHg. Pressure‐induced changes in global vascular smooth muscle intracellular Ca2+ (using Fura‐2) were similar in the absence or presence of candesartan, indicating that AT1R‐mediated myogenic constriction relies on Ca2+‐independent downstream signalling. The diacylglycerol analogue 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG) reversed the inhibitory effect of candesartan, while this rescue effect was prevented by the protein kinase C (PKC) inhibitor GF 109203X. Both candesartan and PKC inhibition caused increased G‐actin levels, as determined by Western blotting of vessel lysates, supporting involvement of cytoskeletal remodelling. At the single vascular smooth muscle cell level, atomic force microscopy showed that cell swelling (stretch) with hypotonic buffer also caused thickening of cortical actin fibres and this was blocked by candesartan. Collectively, the present studies support growing evidence for novel modes of activation of the AT1R in arterioles and suggest that mechanically activated AT1R generates diacylglycerol, which in turn activates PKC which induces the actin cytoskeleton reorganization that is required for pressure‐induced vasoconstriction.
Multidrug Intrinsic Resistance Factors in Staphylococcus aureus Identified by Profiling Fitness within High-Diversity Transposon Libraries
Authors: Rajagopal Mithila , Martin Melissa J. , Santiago Marina , Lee Wonsik , Kos Veronica N. , Meredith Tim , Gilmore Michael S. , Walker Suzanne 
Published: August 2016

ABSTRACT

Staphylococcus aureus
is a leading cause of life-threatening infections worldwide. The MIC of an antibiotic against
S. aureus
, as well as other microbes, is determined by the affinity of the antibiotic for its target in addition to a complex interplay of many other cellular factors. Identifying nontarget factors impacting resistance to multiple antibiotics could inform the design of new compounds and lead to more-effective antimicrobial strategies. We examined large collections of transposon insertion mutants in
S. aureus
using
t
ransposo
n seq
uencing (Tn-Seq) to detect transposon mutants with reduced fitness in the presence of six clinically important antibiotics—ciprofloxacin, daptomycin, gentamicin, linezolid, oxacillin, and vancomycin. This approach allowed us to assess the relative fitness of many mutants simultaneously within these libraries. We identified pathways/genes previously known to be involved in resistance to individual antibiotics, including
graRS
and
vraFG
(
graRS/vraFG
),
mprF
, and
fmtA
, validating the approach, and found several to be important across multiple classes of antibiotics. We also identified two new, previously uncharacterized genes,
SAOUHSC_01025
and
SAOUHSC_01050
, encoding polytopic membrane proteins, as important in limiting the effectiveness of multiple antibiotics. Machine learning identified similarities in the fitness profiles of
graXRS/vraFG
,
SAOUHSC_01025
, and
SAOUHSC_01050
mutants upon antibiotic treatment, connecting these genes of unknown function to modulation of crucial cell envelope properties. Therapeutic strategies that combine a known antibiotic with a compound that targets these or other intrinsic resistance factors may be of value for enhancing the activity of existing antibiotics for treating otherwise-resistant
S. aureus
strains
.

IMPORTANCE
Bacterial resistance to every major class of antibiotics has emerged, and we are entering a “post-antibiotic era” where relatively minor infections can lead to serious complications or even death. The utility of an antibiotic for a specific pathogen is limited by both intrinsic and acquired factors. Identifying the repertoire of intrinsic resistance factors of an antibiotic for
Staphylococcus aureus
, a leading cause of community- and hospital-acquired infections, would inform the design of new drugs as well as the identification of compounds that enhance the activity of existing drugs. To identify factors that limit the activity of antibiotics against
S. aureus
, we used Tn-Seq to simultaneously assess fitness of transposon mutants in every nonessential gene in the presence of six clinically important antibiotics. This work provides an efficient approach for identifying promising targets for drugs that can enhance susceptibility or restore sensitivity to existing antibiotics.
Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus, a New Twist on ATP Formation
Authors: James Kimberly L. , Ríos-Hernández Luis A. , Wofford Neil Q. , Mouttaki Housna , Sieber Jessica R. , Sheik Cody S. , Nguyen Hong H. , Yang Yanan , Xie Yongming , Erde Jonathan , Rohlin Lars , Karr Elizabeth A. , Loo Joseph A. , Ogorzalek Loo Rachel R. , Hurst Gregory B. , Gunsalus Robert P. , Szweda Luke I. , McInerney Michael J. 
Published: August 2016

ABSTRACT

Syntrophus aciditrophicus
is a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation by
S. aciditrophicus
. However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome of
S. aciditrophicus
leaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show that
S. aciditrophicus
uses AMP-forming, acetyl-CoA synthetase (Acs1) for ATP synthesis from acetyl-CoA.
acs1
mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, of
S. aciditrophicus
grown in pure culture and coculture. Cell extracts of
S. aciditrophicus
had low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified from
S. aciditrophicus
and recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) in
S. aciditrophicus
cells support the operation of Acs1 in the acetate-forming direction. Thus,
S. aciditrophicus
has a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase.

IMPORTANCE
Bacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA.
Syntrophus aciditrophicus
apparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as its genome does not have homologs to the genes for phosphate acetyltransferase and acetate kinase. Here, we show that
S. aciditrophicus
uses an alternative approach, an AMP-forming, acetyl-CoA synthetase, to make ATP from acetyl-CoA. AMP-forming, acetyl-CoA synthetases were previously thought to function only in the activation of acetate to acetyl-CoA.
Oxygen as a Virulence Determinant in Polymicrobial Infections
Authors: Selleck Elizabeth M. , Gilmore Michael S. 
Published: August 2016

ABSTRACT

Infections caused by multiple organisms, or polymicrobial infections, are likely more common than is broadly appreciated. Interaction among microbial communities (and with their host) can change the infection landscape by subverting immunity, providing nutrients and inhibiting competing microbes. Stacy et al. (A. Stacy, D. Fleming, R. J. Lamont, K. P. Rumbaugh, and M. Whiteley, mBio 7:e00782-16, 2016,
http://dx.doi.org/10.1128/mBio.00782-16
) described a novel mechanism that results in synergistic growth of oral microbes
Aggregatibacter actinomycetemcomitans
and
Streptococcus gordonii
. The authors used whole-genome fitness profiling by transposon sequencing (Tn-seq) to identify genes differentially required for growth
in vitro
versus in a mono- or coinfection in a thigh abscess model. They found that coinfection with
S. gordonii
allowed
A. actinomycetemcomitans
to shift from an anaerobic to an aerobic mode of growth. This shift involved the production of a terminal electron acceptor H
2
O
2
by
S. gordonii
and increased
A. actinomycetemcomitans
persistence—an interaction termed “cross-respiration.”
Helmet use and risk of head injuries in alpine skiers and snowboarders: changes after an interval of one decade
Authors: Sulheim Steinar , Ekeland Arne , Holme Ingar , Bahr Roald 
Published: August 2016

BackgroundIn a previous study, we concluded that a safety helmet can reduce the risk for head injury by 60%. Other studies reported similar effects, resulting in a general recommendation to wear a helmet while skiing or snowboarding.AimTo determine the effect of the expected increased helmet wear on the risk of head injury one decade after the recommendation.MethodsSki patrols reported injury cases in major Norwegian alpine ski resorts. Injury type, helmet use and other risk factors were recorded. A multiple logistic regression analysis was used to assess the relation between individual risk factors and the risk of head injuries by comparing head injured skiers (cases) with skiers and snowboarders who reported other injuries (controls).ResultsHelmet use was associated with improved odds for head injuries (OR: 0.45, 95% CI 0.34 to 0.60; p<0.001) in 2002; this effect was attenuated in 2010 (OR: 0.79, 95% CI 0.63 to 0.98; p=0.02), and not significant in 2011 (OR: 0.80, 95% CI 0.60 to 1.06; p=0.12). For potentially severe head injuries, the protective effect of using a helmet was better sustained over the observation period, from an OR of 0.44 (95% CI 0.28 to 0.68, p<0.001) in 2002 to an OR of 0.74 (95% CI 0.57 to 0.97, p=0.02) in 2010 and 0.67 (95% CI 0.47 to 0.96; p=0.03) in 2011.ConclusionsWe observed an unexpected reduction in the protective effect of a skiing helmet. This may be due to new skiing trends in the alpine resorts.
Wealth, education and urban–rural inequality and maternal healthcare service usage in Malawi
Authors: Yaya Sanni , Bishwajit Ghose , Shah Vaibhav 
Published: August 2016

BackgroundMalawi is among the 5 sub-Saharan African countries presenting with very high maternal mortality rates, which remain a challenge. This study aims to examine the impact of wealth inequality and area of residence (urban vs rural) and education on selected indicators of maternal healthcare services (MHS) usage in Malawi.MethodsThis study was based on data from the 5th round of Multiple Indicator Cluster Surveys (MICS) conducted in 2013–2014 in Malawi. Study participants were 7572 mothers aged between 15 and 49 years. The outcome variable was usage status of maternal health services of the following types: antenatal care, skilled delivery assistance and postpartum care. Univariate, bivariate and multivariate methods were used to describe the pattern of MHS usage in the sample population. Association between household wealth status, education as well as the type of residence, whether urban or rural, as independent variables and usage of MHS as dependent variables were analysed using the generalised estimating equations (GEE) method.ResultsMean age of the sample population was 26.88 (SD 6.68). Regarding the usage of MHS, 44.7% of women had at least 4 ANC visits, 87.8% used skilled delivery attendants and 82.2% of women had used postnatal care. Regarding the wealth index, about a quarter of the women were in the poorest wealth quintile (23.6%) while about 1/6 were in the highest wealth quintile (15%). Rate of usage for all 3 types of services was lowest among women belonging to the lowest wealth quintile. In terms of education, only 1/5 completed their secondary or a higher degree (20.1%) and nearly 1/10 of the population lives in urban areas (11.4%) whereas the remaining majority live in rural areas (88.6%). The rates of usage of MHS, although reasonable on an overall basis, were consistently lower in women with lower education and those residing in rural areas.ConclusionsMaternal health service usage in Malawi appears to be reasonable, yet the high maternal mortality rate is disturbing and calls for analysing factors hindering the achievement of maternal health-related Sustainable Development Goals (SDGs). The findings of this study underscore the need to minimise the wealth inequality, urban–rural divide and the low level of education among mothers to improve the usage of MHS. An equity-based policy approach considering the sociodemographic inequity in terms of wealth index, education and urban–rural divide might prove beneficial in further improving the MHS usage, as well as addressing the possible issues of quality gaps in MHS, which might be beneficial towards reducing maternal mortality. It should be noted that the study of quality gaps in MHS is beyond the scope of this paper and calls for further research in this arena.