bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organic Cation Transporter 2 Overexpression May Confer an Increased Risk of Gentamicin-Induced Nephrotoxicity
Authors: Gai Zhibo , Visentin Michele , Hiller Christian , Krajnc Evelin , Li Tongzhou , Zhen Junhui , Kullak-Ublick Gerd A. 
Published: July 2016

ABSTRACT

Nephrotoxicity is a relevant limitation of gentamicin, and obese patients have an increased risk for gentamicin-induced kidney injury. This damage is thought to depend on the accumulation of the drug in the renal cortex. Obese rats showed substantially higher levels of gentamicin in the kidney than did lean animals. This study characterized the role of organic cation transporters (OCTs) in gentamicin transport and elucidated their possible contribution in the increased renal accumulation of gentamicin in obesity. The mRNA and protein expression levels of the organic cation transporters Oct2 (Slc22a2) and Oct3 (Slc22a3) were increased in kidney samples from obese mice fed a high-fat diet. Similarly, OCT2 (∼2-fold) and OCT3 (∼3-fold) showed increased protein expression in the kidneys of obese patients compared with those of nonobese individuals. Using HEK293 cells overexpressing the different OCTs, human OCT2 was found to transport [
3
H]gentamicin with unique sigmoidal kinetics typical of homotropic positive cooperativity (autoactivation). In mouse primary proximal tubular cells, [
3
H]gentamicin uptake was reduced by approximately 40% when the cells were coincubated with the OCT2 substrate metformin. The basolateral localization of OCT2 suggests that gentamicin can enter proximal tubular cells from the blood side, probably as part of a slow tubular secretion process that may influence intracellular drug concentrations and exposure time. Increased expression of OCT2 may explain the higher accumulation of gentamicin, thereby conferring an increased risk of renal toxicity in obese patients.
Basic Reproduction Number and Transmission Dynamics of Common Serogroups of Enterohemorrhagic Escherichia coli
Authors: Chen Shi , Sanderson Michael W. , Lee Chihoon , Cernicchiaro Natalia , Renter David G. , Lanzas Cristina 
Published: July 2016

ABSTRACT

Understanding the transmission dynamics of pathogens is essential to determine the epidemiology, ecology, and ways of controlling enterohemorrhagic
Escherichia coli
(EHEC) in animals and their environments. Our objective was to estimate the epidemiological fitness of common EHEC strains in cattle populations. For that purpose, we developed a Markov chain model to characterize the dynamics of 7 serogroups of enterohemorrhagic
Escherichia coli
(O26, O45, O103, O111, O121, O145, and O157) in cattle production environments based on a set of cross-sectional data on infection prevalence in 2 years in two U.S. states. The basic reproduction number (
R
0
) was estimated using a Bayesian framework for each serogroup based on two criteria (using serogroup alone [the O-group data] and using O serogroup, Shiga toxin gene[s], and intimin [
eae
] gene together [the EHEC data]). In addition, correlations between external covariates (e.g., location, ambient temperature, dietary, and probiotic usage) and prevalence/
R
0
were quantified.
R
0
estimates varied substantially among different EHEC serogroups, with EHEC O157 having an
R
0
of >1 (∼1.5) and all six other EHEC serogroups having an
R
0
of less than 1. Using the O-group data substantially increased
R
0
estimates for the O26, O45, and O103 serogroups (
R
0
> 1) but not for the others. Different covariates had distinct influences on different serogroups: the coefficients for each covariate were different among serogroups. Our modeling and analysis of this system can be readily expanded to other pathogen systems in order to estimate the pathogen and external factors that influence spread of infectious agents.

IMPORTANCE
In this paper we describe a Bayesian modeling framework to estimate basic reproduction numbers of multiple serotypes of Shiga toxin-producing
Escherichia coli
according to a cross-sectional study. We then coupled a compartmental model to reconstruct the infection dynamics of these serotypes and quantify their risk in the population. We incorporated different sensitivity levels of detecting different serotypes and evaluated their potential influence on the estimation of basic reproduction numbers.
Vitamin D Deficiency Does Not Result in a Breach of Host Defense in Murine Models of Pneumonia
Authors: Niederstrasser Julia , Herr Christian , Wolf Lisa , Lehr Claus M. , Beisswenger Christoph , Bals Robert 
Published: July 2016

ABSTRACT

Vitamin D (VitD) has a role in the regulation of calcium and phosphate metabolism and in addition impacts the activity of the immune system. VitD deficiency might be linked to increased susceptibility to respiratory tract infection. The aim of the present study was to characterize the impact of VitD deficiency on the susceptibility to bacterial infection in murine models. C57BL/6N mice were fed a diet with or without VitD for 10 weeks. The VitD-deficient or -sufficient mice were infected with
Pseudomonas aeruginosa
or
Streptococcus pneumoniae
. The colonization and inflammatory response in the lung were analyzed at defined time points. The serum 25-hydroxy-VitD concentration was significantly lower in mice on the VitD-deficient diet. In infection experiments with
Pseudomonas aeruginosa
or
Streptococcus pneumoniae
, no differences could be observed in the numbers of viable bacteria or in differential cell counts in the bronchoalveolar lavage fluids. Measurements of inflammatory cytokines (KC and interleukin-1β [IL-1β]) did not show significant differences between the groups. In conclusion, VitD-deficient animals did not show significantly increased susceptibility to infection or an altered course of infection. The immune systems of humans and mice likely respond differently to VitD. Murine models are likely not appropriate for drawing conclusions on the role of VitD in human pulmonary host defense.
Tryptophan Codon-Dependent Transcription in Chlamydia pneumoniae during Gamma Interferon-Mediated Tryptophan Limitation
Authors: Ouellette Scot P. , Rueden Kelsey J. , Rucks Elizabeth A. 
Published: July 2016

ABSTRACT

In evolving to an obligate intracellular niche,
Chlamydia
has streamlined its genome by eliminating superfluous genes as it relies on the host cell for a variety of nutritional needs like amino acids. However,
Chlamydia
can experience amino acid starvation when the human host cell in which the bacteria reside is exposed to interferon gamma (IFN-γ), which leads to a tryptophan (Trp)-limiting environment via induction of the enzyme indoleamine-2,3-dioxygenase (IDO). The stringent response is used to respond to amino acid starvation in most bacteria but is missing from
Chlamydia
. Thus, how
Chlamydia
, a Trp auxotroph, responds to Trp starvation in the absence of a stringent response is an intriguing question. We previously observed that
C. pneumoniae
responds to this stress by globally increasing transcription while globally decreasing translation, an unusual response. Here, we sought to understand this and hypothesized that the Trp codon content of a given gene would determine its transcription level. We quantified transcripts from
C. pneumoniae
genes that were either rich or poor in Trp codons and found that Trp codon-rich transcripts were increased, whereas those that lacked Trp codons were unchanged or even decreased. There were exceptions, and these involved operons or large genes with multiple Trp codons: downstream transcripts were less abundant after Trp codon-rich sequences. These data suggest that ribosome stalling on Trp codons causes a negative polar effect on downstream sequences. Finally, reassessing previous
C. pneumoniae
microarray data based on codon content, we found that upregulated transcripts were enriched in Trp codons, thus supporting our hypothesis.
Small RNAs Repress Expression of Polysaccharide Utilization Loci of Gut Bacteroides Species
Authors: Comstock Laurie E. 
Published: July 2016

ABSTRACT

Bacteroides
species can metabolize numerous plant polysaccharides and host glycans present in the mammalian gut. The regulatory systems governing the induction of particular polysaccharide utilization loci when the cognate glycan is present are known, but how expression is repressed when a higher-priority glycan is present is largely unknown. In this issue of the
Journal of Bacteriology
, Cao et al. (J. Bacteriol. 198:2410–2418, 2016,
http://dx.doi.org/10.1128/JB.00381-16
) reveal a conserved mechanism in
Bacteroides
whereby antisense small RNAs (sRNA) repress expression of genes involved in utilization of host glycans.
Fossil DNA persistence and decay in marine sediment over hundred-thousand-year to million-year time scales
Authors: Kirkpatrick John B. , Walsh Emily A. , D’Hondt Steven 
Published: July 2016

Abstract
DNA in marine sediment contains both fossil sequences and sequences from organisms that live in the sediment. The demarcation between these two pools and their respective rates of turnover are generally unknown. We address these issues by comparing the total extractable DNA pool to the fraction of sequenced chloroplast DNA (cpDNA) in sediment from two sites in the Bering Sea. We assume that cpDNA is a tracer of non-reproducing fossil DNA. Given &gt;150,000 sequence reads per sample, cpDNA is easily detectable in the shallowest samples but decays with depth, suggesting that sequencing-based richness assessments of communities in deep subseafloor sediment are relatively unaffected by fossil DNA. The initial decrease in cpDNA reads suggests that most cpDNA decays within 100–200 k.y. of deposition. However, cpDNA from a few phylotypes, including some that match fossil diatoms, are present throughout the cored sediment, ranging in age to 1.4 Ma. The relative fraction of sequences composed by cpDNA decreases non-linearly with increasing sediment age, suggesting that detectable cpDNA becomes more recalcitrant with age. This can be explained by biological activity decreasing with sediment age and/or by preferential long-term survival of only the most thoroughly protected DNA. The association of cpDNA reads with published records of siliceous microfossils, including diatom spores, at the same sites suggests that microfossils may help to preserve DNA. This DNA may be useful for studies of paleoenvironmental conditions and biological evolution on time scales that approach or exceed 1 m.y.
Paradigm shift in determining Neoproterozoic atmospheric oxygen
Authors: Blamey Nigel J.F. , Brand Uwe , Parnell John , Spear Natalie , Lécuyer Christophe , Benison Kathleen , Meng Fanwei , Ni Pei 
Published: July 2016

Abstract
We present a new and innovative way of determining the oxygen level of Earth’s past atmosphere by directly measuring inclusion gases trapped in halite. After intensive screening using multiple depositional, textural/fabric, and geochemical parameters, we determined that tectonically undisturbed cumulate, chevron, and cornet halite inclusions may retain atmospheric gas during crystallization from shallow saline, lagoonal, and/or saltpan brine. These are the first measurements of inclusion gas for the Neoproterozoic obtained from 815 ± 15–m.y.–old Browne Formation chevron halite of the Officer Basin, southwest Australia. The 31 gas measurements afford us a direct glimpse of the composition of the mid- to late Neoproterozoic atmosphere and register an average oxygen content of 10.9%. The measured pO2 puts oxygenation of Earth’s paleoatmosphere ∼100–200 m.y. ahead of current models and proxy studies. It also puts oxygenation of the Neoproterozoic atmosphere in agreement with time of diversification of eukaryotes and in advance of the emergence of marine animal life.
Empirical constraints on shock features in monazite using shocked zircon inclusions
Authors: Erickson Timmons M. , Cavosie Aaron J. , Pearce Mark A. , Timms Nicholas E. , Reddy Steven M. 
Published: July 2016

Abstract
Shock deformation microstructures in monazite have been systematically characterized for the first time in grains from the Vredefort impact structure in South Africa. Electron backscatter diffraction mapping has identified 12 unique orientations of monazite deformation twins, including 7 orientations that have not previously been described in experiments or nature. Other shock features include planar deformation bands and strain-free neoblasts, which have been shown to date deformation. Shock-twinned zircon inclusions within the deformed monazite require pressures of 20 GPa, thus providing critical empirical constraints on formation conditions, confirming a hypervelocity impact origin of the monazite microstructures. The Vredefort monazite grains described here represent the first case of using shocked mineral inclusions to empirically calibrate shock microstructures formed in the host mineral. These results conclusively establish monazite as a recorder of shock deformation, and highlight its use in identifying and dating impact structures.
The answers are blowin’ in the wind: Ultra-distal ashfall zircons, indicators of Cretaceous super-eruptions in eastern Gondwana
Authors: Barham M. , Kirkland C.L. , Reynolds S. , O’Leary M.J. , Evans N.J. , Allen H. , Haines P.W. , Hocking R.M. , McDonald B.J. , Belousova E. , Goodall J. 
Published: July 2016

Abstract
An Early Cretaceous siliceous large igneous province (SLIP) that developed on the eastern margin of Gondwana produced some of the most voluminous siliceous volcaniclastic deposits known globally. We report U-Pb ages and trace-element and Hf-isotopic signatures of detrital zircons from the Madura Shelf (onshore Bight Basin), Western Australia. These zircons include a geochemically distinct 106 Ma component with age and Hf characteristics that match SLIP volcanics some 2300 km distant in eastern Australia. This young subpopulation shows limited grain abrasion, which contrasts with older detrital components that are stratigraphically persistent. Regional detrital zircon provenance demonstrates that sediment routing systems were disconnected in the eastern and western Bight Basin, negating terrestrial transport mechanisms as a possible vector of the zircons from the SLIP to their recovered position. Palynology indicates that the 106 Ma zircons are syn-depositional, and we interpret them as being significantly transported in an eruption plume. Given the grain size and distance from source, such distal zircon emplacement suggests previously undocumented 106 Ma super-eruptions. The 106 Ma zircons likely reflect Southern Hemisphere winter eruptions when tropospheric polar easterly winds would have been favored across southeastern Australia.
Vigorous deep-sea currents cause global anomaly in sediment accumulation in the Southern Ocean
Authors: Dutkiewicz Adriana , Müller R. Dietmar , Hogg Andrew McC. , Spence Paul 
Published: July 2016

Abstract
The vigorous current systems in the Southern Ocean play a key role in regulating the Earth’s oceans and climate, with the record of long-term environmental change mostly contained in deep-sea sediments. However, the well-established occurrence of widespread regional disconformities in the abyssal plains of the Southern Ocean attests to extensive erosion of deep-sea sediments during the Quaternary. We show that a wide belt of rapid sedimentation rates (&gt;5.5 cm/k.y.) along the Southeast Indian Ridge (SEIR) is a global anomaly and occurs in a region of low surface productivity bounded by two major disconformity fields associated with the Kerguelen Plateau to the east and the Macquarie Ridge to the west. Our high-resolution numerical ocean circulation model shows that the disconformity fields occur in regions of intense bottom-current activity where current speeds reach 0.2 m/s and are favorable for generating intense nepheloid layers. These layers are transported toward and along the SEIR to regions where bottom-current velocities drop to &lt;0.03 m/s and fine particles settle out of suspension, consistent with focusing factors significantly greater than 1. We suggest that the anomalous accumulation of sediment along an 8000-km-long segment of the SEIR represents a giant succession of contourite drifts that is a major extension of the much smaller contourite east of Kerguelen Plateau and has occurred since 3–5 Ma based on the age of the oldest crust underlying the deposit. These inferred contourite drifts provide exceptionally valuable drilling targets for high-resolution climatic investigations of the Southern Ocean.
Exploring the impact of early life factors on inequalities in risk of overweight in UK children: findings from the UK Millennium Cohort Study
Authors: Massion Samuel , Wickham Sophie , Pearce Anna , Barr Ben , Law Catherine , Taylor-Robinson David 
Published: July 2016

BackgroundOverweight and obesity in childhood are socially patterned, with higher prevalence in more disadvantaged populations, but it is unclear to what extent early life factors attenuate the social inequalities found in childhood overweight/obesity.MethodsWe estimated relative risks (RRs) for being overweight (combining with obesity) at age 11 in 11 764 children from the UK Millennium Cohort Study (MCS) according to socio-economic circumstances (SEC). Early life risk factors were explored to assess if they attenuated associations between SECs and overweight.Results28.84% of children were overweight at 11 years. Children of mothers with no academic qualifications were more likely to be overweight (RR 1.72, 95% CI 1.48 to 2.01) compared to children of mothers with degrees and higher degrees. Controlling for prenatal, perinatal, and early life characteristics (particularly maternal pre-pregnancy overweight and maternal smoking during pregnancy) reduced the RR for overweight to 1.44, 95% CI 1.23 to 1.69 in the group with the lowest academic qualifications compared to the highest.ConclusionsWe observed a clear social gradient in overweight 11-year-old children using a representative UK sample. Moreover, we identified specific early life risk factors, including maternal smoking during pregnancy and maternal pre-pregnancy overweight, that partially account for the social inequalities found in childhood overweight. Policies to support mothers to maintain a healthy weight, breastfeed and abstain from smoking during pregnancy are important to improve maternal and child health outcomes, and our study provides some evidence that they may also help to address the continuing rise in inequalities in childhood overweight.
Neonatal thyroid-stimulating hormone concentration and psychomotor development at preschool age
Authors: Trumpff Caroline , De Schepper Jean , Vanderfaeillie Johan , Vercruysse Nathalie , Van Oyen Herman , Moreno-Reyes Rodrigo , Tafforeau Jean , Vandevijvere Stefanie 
Published: July 2016

ObjectiveThyroid hormones are essential for normal brain development. The aim of this study is to assess if high concentration of thyroid stimulating hormone (TSH) that is below the clinical threshold (5–15 mIU/L) at neonatal screening is linked to psychomotor development impairments in the offspring at preschool age.DesignA total of 284 Belgian preschool children 4–6 years old and their mothers were included in the study. The children were randomly selected from the total list of neonates screened in 2008, 2009 and 2010 by the Brussels newborn screening centre. The sampling was stratified by gender and TSH range (0.45–15 mIU/L). Infants with congenital hypothyroidism (>15 mIU/L), low birth weight and/or prematurity were excluded. Psychomotor development was assessed using the Charlop-Atwell scale of motor coordination. The iodine status of children was determined using median urinary iodine concentration. Socioeconomic, parental and child potential confounding factors were measured through a self-administered questionnaire.ResultsTSH level was not significantly associated with total motor score (average change in z-score per unit increase in TSH is 0.02 (−0.03, 0.07), p=0.351), objective motor score (p=0.794) and subjective motor score (p=0.124). No significant associations were found using multivariate regression model to control confounding factors.ConclusionsMild thyroid dysfunction in the newborn—reflected by an elevation of TSH that is below the clinical threshold (5–15 mIU/L)—was not associated with impaired psychomotor development at preschool age.
Psychological maladjustment and quality of life in adolescents with constipation
Authors: Ranasinghe Nishadi , Devanarayana Niranga Manjuri , Benninga Marc Alexander , van Dijk Marieke , Rajindrajith Shaman 
Published: July 2016

ObjectivesTo assess psychological maladjustment in adolescents with functional constipation.Study designWe conducted a cross-sectional survey in five schools. Adolescents aged between 13 and 18 years were included in the study. Validated questionnaires were used to collect bowel habits and demographic data, health-related quality of life (HRQoL) and psychological maladjustment. Rome III criteria were used to diagnose constipation.Results1697 adolescents were recruited (boys 779 (45.9%), mean age 15.06 years and SD 1.6 years). Prevalence of constipation was 6.7%, of whom 52 were boys (45.6%) and 62 were girls (54.4%). 38 adolescents (33.3%) with constipation and 230 controls (14.5%) had significant psychological maladjustment. Among seven different personality dimensions used to assess psychological maladjustment, children with constipation had significantly more deficits than controls in hostility and aggression (14.2 vs 12.6 in controls (mean difference 1.54, 95% CI (0.89 to 2.19) p<0.001), negative self-esteem (12.0 vs 10.5 in controls, mean difference 1.54 95% CI (0.96 to 2.06) p<0.001), negative self-adequacy (11.9 vs 9.8 controls, mean difference 2.07 95% CI (1.46 to 2.67) p<0.001), emotional unresponsiveness (12.9 vs 11.5 controls, mean difference 1.44 95% CI (0.84 to 2.04) p<0.001), emotional instability (17.1 vs 15.6, mean difference 1.53 95% CI (0.86 to 2.2) p<0.001) and negative world view (12.1 vs 10.2 controls, mean difference 1.91 95% CI (1.24 to 2.59) p<0.001). The total HRQoL of adolescents with constipation was lower than controls (70.6 vs 79.0 mean difference 9.48 95% CI (1.4 to 6.7) p<0.05).ConclusionA significant proportion of children with constipation are suffering from psychological maladjustment.
Is coffee consumption associated with a lower risk of hyperuricaemia or gout? A systematic review and meta-analysis
Authors: Zhang Yi , Yang Tuo , Zeng Chao , Wei Jie , Li Hui , Xiong Yi-lin , Yang Ye , Ding Xiang , Lei Guanghua 
Published: July 2016

ObjectivesTo examine the associations of coffee consumption with the serum uric acid (SUA) level, hyperuricaemia (HU) and gout.DesignSystematic review and meta-analysis.Data sources and study eligibility criteriaA comprehensive literature search up to April 2015, using PubMed and EMBASE databases, was conducted to identify the observational researches that examined the associations of coffee consumption with the SUA level, HU and gout. The standard mean difference (SMD), OR, relative risk (RR) and their corresponding 95% CIs for the highest and the lowest categories of coffee intake were determined.ResultsA total of 11 observational studies (6 cross-sectional, 3 cohort and 2 case–control studies) were included in this systematic review and meta-analysis. The combined SMD suggested that there was no significant difference between the highest and the lowest coffee intake categories in terms of the SUA level (SMD=−0.09, 95% CI −0.23 to 0.05; p=0.21). Meanwhile, the overall multivariable adjusted OR for HU showed no significant difference between the highest and the lowest coffee intake categories (OR=0.84, 95% CI 0.65 to 1.09; p=0.20). However, the overall multivariable adjusted RR for gout showed a significant inverse association between coffee consumption and the incidence of gout (RR=0.43, 95% CI 0.31 to 0.59, p<0.001).ConclusionsCurrent evidences are insufficient to validate the association between coffee consumption and a lower risk of HU. Owing to the limited number of studies, the available data show that coffee consumption may be associated with a lower risk of incident gout. Further well-designed prospective researches and randomised controlled trials are therefore needed to elaborate on these issues.