bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Contributions To Health Literacy
Authors: Fawns-Ritchie Chloe , Davies Gail , Hagenaars Saskia P , Deary Ian J 
Published: April 2019

AbstractHigher health literacy is associated with higher cognitive function and better health. Despite its wide use in medical research, no study has investigated the genetic contributions to health literacy. Using 5,783 English Longitudinal Study of Ageing (ELSA) participants (mean age=65.49, SD=9.55) who had genotyping data and had completed a health literacy test at wave 2 (2004-2005), we carried out a genome-wide association study (GWAS) of health literacy. We estimated the proportion of variance in health literacy explained by all common single nucleotide polymorphisms (SNPs). Polygenic profile scores were calculated using summary statistics from GWAS of 21 cognitive and health measures. Logistic regression was used to test whether polygenic scores for cognitive and health-related traits were associated with having adequate, compared to limited, health literacy. No SNPs achieved genome-wide significance for association with health literacy. The proportion of variance in health literacy accounted for by common SNPs was 8.5% (SE=7.2%). Greater odds of having adequate health literacy were associated with a 1SD higher polygenic score for general cognitive ability (OR=1.34, 95% CI 1.26-1.42), verbal-numerical reasoning (OR=1.30, 1.23-1.39), and years of schooling (OR=1.29, 1.21-1.36). Reduced odds of having adequate health literacy were associated with higher polygenic profiles for poorer self-rated health (OR=0.92, 0.87-0.98) and schizophrenia (OR=0.91, 0.85-0.96). The well-documented associations between health literacy, cognitive function and health may partly be due to shared genetic aetiology. Larger studies are required to obtain accurate estimates of SNP-based heritability, and to discover specific health literacy-associated genetic variants.
A three-years assessment of Ixodes ricinus-borne pathogens in a French peri-urban forest
Authors: Lejal Emilie , Marsot Maud , Chalvet-Monfray Karine , Cosson Jean-François , Moutailler Sara , Vayssier-Taussat Muriel , Pollet Thomas 
Published: April 2019

AbstractBackgroundIxodes ricinus is the predominant tick species in Europe and the primary pathogen vector for both humans and animals. These ticks are frequently involved in the transmission of Borrelia burgdorferi sensu lato, the causative agents of Lyme borreliosis. While much more is known about I. ricinus tick-borne pathogen composition, information about temporal tick-borne pathogen patterns remain scarce. These data are crucial for predicting seasonal/annual patterns which could improve understanding and prevent tick-borne diseases.MethodsWe examined tick-borne pathogen (TBPs) dynamics in I. ricinus collected monthly in a peri-urban forest over three consecutive years. In total, 998 nymphs were screened for 31 pathogenic species using high-throughput microfluidic real-time PCR.ResultsWe detected DNA from Anaplasma phagocytophilum (5.3%), Rickettsia helvetica (4.5%), Borrelia burgdorferi s.l. (3.7%), Borrelia miyamotoi (1.2%), Babesia venatorum (1.5%) and Rickettsia felis (0.1%). Among all analysed ticks, 15.9% were infected by at least one of these microorganisms, and 1.3% were co-infected. Co-infections with B. afzeli/B. garinii and B. garinii/B. spielmanii were significantly over-represented. Moreover, significant variations in seasonal and/or inter-annual prevalence were observed for several pathogens (R. helvetica, B. burgdorferi s.l., B. miyamotoi, and A. phagocytophilum).ConclusionsAnalysing TBPs prevalence in monthly sampled tick over three years allowed us to assess seasonal and inter-annual fluctuations of the prevalence of TBPs known to circulate in the sampled area, but also to punctually detect less common species. All these data emphasize that sporadic tick samplings are not sufficient to determine TBPs prevalence and that regular monitoring is necessary.
Inhibiting TG2 sensitizes lung cancer to radiotherapy through interfering TOPOIIα-mediated DNA repair
Authors: Lei Xiao , Liu Zhe , Cao Kun , Chen Yuanyuan , Cai Jianming , Gao Fu , Yang Yanyong 
Published: April 2019

AbstractRadiotherapy is an indispensable strategy for lung cancer, however, treatment failure or reoccurrence is often found in patients due to the developing radioresistance. Novel approaches are required for radiosensitizing to improve the therapeutic efficacy. In present study, we found that transglutaminase 2 (TG2) confers radioresistance in non-small cell lung cancer (NSCLC) cells through regulating TOPOIIα and promoting DNA repair. Our data showed that TG2 inhibitor or knockdown increased NSCLC radiosensitivity in vivo and in vitro. We found that TG2 translocated into nucleus and located to DSB sites, surprisingly, knockdown TG2 or glucosamine inhibited the phosphorylation of ATM, ATR and DNA-Pkcs. Through IP-MS assay and functional experiments, we identified that TOPOIIα as an downstream factor of TG2. Moreover, we found that TGase domain account for the interaction with TOPOIIα. Finally, we found that TG2 expression was correlated with poor survival in lung adenocarcinoma instead of squamous cell carcinoma. In conclusion, we demonstrated that inhibiting TG2 sensitize NSCLC to IR through interfere TOPOIIα mediated DNA repair, suggesting TG2 as a potential radiosensitizing target in NSCLC.
Decoys and dilution: the impact of incompetent hosts on prevalence of Chagas disease
Authors: Zahid Mondal Hasan , Kribs Christopher M. 
Published: April 2019

AbstractBiodiversity is commonly believed to reduce risk of vector-borne zoonoses. However, researchers already showed that the effect of biodiversity on disease transmission is not that straightforward. This study focuses on the effect of biodiversity, specifically on the effect of the decoy process (additional hosts distracting vectors from their focal host), on reducing infections of vector-borne diseases in humans. Here, we consider the specific case of Chagas disease and use mathematical population models to observe the impact on human infection of the proximity of chickens, which are incompetent hosts for the parasite but serve as a preferred food source for vectors. We consider three cases as the distance between the two host populations varies: short (when farmers bring chickens inside the home to protect them from predators), intermediate (close enough for vectors with one host to detect the presence of the other host type), and far (separate enclosed buildings such as a home and hen-house). Our analysis shows that the presence of chickens reduces parasite prevalence in humans only at an intermediate distance under the condition that the vector birth rate from feeding on chickens is sufficiently low.
A New European Species of The Opportunistic Pathogenic GenusSaksenaea–S. dorisiaeSp. Nov.
Authors: Labuda Roman , Bernreiter Andreas , Hochenauer Doris , Schüller Christoph , Kubátová Alena , Strauss Joseph , Wagner Martin 
Published: April 2019

AbstractA new speciesSaksenaea dorisiae(Mucoromycotina, Mucorales), recently isolated from a water sample originating from a private well in a rural area of Serbia (Europe), is described and illustrated. The new taxon is well supported by phylogenetic analysis of the internal transcribed spacer region (ITS), domains D1 and D2 of the 28S rRNA gene (LSU), and translation elongation factor-1α gene (TEF-1α), and it is resolved in a clade withS. oblongisporaandS. trapezispora. This fungus is characteristic by its moderately slow growth at 15 and 37°C, sparse rhizoids, conical-shaped sporangia and short-cylindrical sporangiospores.S. dorisiaeis a member of the opportunistic pathogenic genus often involved in severe human and animal mucormycoses encountered in tropical and subtropical regions. Despite its sensitivity to several conventional antifungals (terbinafine and ciclopirox), the fungus is potentially causing clinically challenging infections. This is the first novel taxon of the genusSaksenaeadescribed from the moderately continental climate area of Europe.
Sagittal abdominal diameter and waist circumference are equally good as identifiers of cardiometabolic risk
Authors: Møller Grith , Ritz Christian , Kjølbæk Louise , Vuholm Stine , Korndal Sanne Kellebjerg , Larsen Thomas Meinert , Pedersen Oluf , Saris Wim , Astrup Arne , Lauritzen Lotte , Kristensen Mette , Lind Mads Vendelbo 
Published: April 2019

AbstractBackgroundBody mass index (BMI) and waist circumference (WC) are commonly used markers of cardiometabolic risk. However, sagittal abdominal diameter (SAD) has been proposed to be a better marker of intra-abdominal obesity compared to WC and might better associate with metabolic disturbances in high-risk populations. The objective of this study was to compare SAD, WC, and BMI as determinants of an adverse metabolic phenotype.MethodAnthropometric and metabolic measures of 1516 overweight or obese individuals with features of the metabolic syndrome were included to examine differences between SAD, WC and BMI as measures of an adverse metabolic phenotype. Multiple linear regression and logistic regression models were used to investigate the association between SAD, WC, and BMI and markers of metabolic syndrome, insulin resistance, blood lipids, and low grade inflammation.ResultsBoth SAD and WC correlated with BMI, but as BMI increased, SAD proportionately estimated higher abdominal adiposity compared to WC (slope = 0.0037 (0.0029; 0.0046), p<0.0001). We did not find major differences between SAD, WC and BMI in explained variance in models with the different markers of metabolic risk. Furthermore, we did not find differences between SAD and WC in the ability to identify individuals with metabolic syndrome according to the International Diabetes Federation (IDF) cut-offs, but a few differences from BMI were indicated but mostly before adjustments. Moreover, the differences between SAD and WC associations were not modified by sex or degree of adiposity, but identification of individuals with a metabolic phenotype was generally better in women.ConclusionThese data indicate that SAD and WC are equally good indicators of an adverse metabolic phenotype. Thus, from a public health perspective choice of anthropometric measure may depend only on what is the most practical method in a given situation.
Specific Disruption of EstablishedP. aeruginosaBiofilms Using Polymer-Attacking Enzymes
Authors: Kovach Kristin N. , Fleming Derek , Rumbaugh Kendra P. , Gordon Vernita D. 
Published: April 2019

AbstractBiofilms are communities of bacteria embedded in an extracellular matrix of self-produced polymeric substances. This polymer matrix lends the bacteria protection against a wide array of chemical and mechanical stresses that they may experience in their environment, which might be a location in the human body in the case of a biofilm infection, or a surface immersed in fluid in an industrial setting. Breaking down the matrix network renders biofilms more susceptible to physical disruption and to treatments. Different species of bacteria, and different strains within the same species, produce different types of matrix polymers – this suggests that targeting specific polymers for disruption may be more effective than non-specific approaches to disrupting biofilm matrices. In this study, we treatedPseudomonas aeruginosabiofilms with enzymes that are specific to different matrix polymers. We used bulk rheology to measure the resulting alteration in biofilm mechanics, and scanning electron microscopy to visualize the alteration in the matrix network upon treatment. Different lab strains ofP. aeruginosaform biofilms that can be dominated by one of three main extracellular polysaccharides: Psl, alginate, and Pel, which binds electrostatically to extracellular DNA in the matrix. We applied enzymes to biofilms dominated by different extracellular polysaccharides and found that, for biofilms grownin vitro, the effect of enzymatic treatment is maximized when the enzyme is specific to a dominant matrix polymer – for such a case, specifically-matched enzymatic treatment tends to: reduce yield strain and yield stress; reduce or eliminate long-range structure and shorten or eliminate connecting network fibers in the biofilm as seen under scanning electron microscopy; and increase the rate of biofilm drying, most likely due to increased diffusivity as a result of network compromise. However, forex vivobiofilms grown in murine wounds, we find that generic glycoside hydrolases have more profound disruptive effects than specifically-matched enzymes, even though they had no measurable effect for biofilms grownin vitro. This highlights the importance of the environment in which the biofilms are grown, the need to take this into account when developing treatments for biofilms, and the possibility that effective approaches to eradicating biofilms in environmental or industrial settings may need to be very different from effective treatments of infection.
Evolutionary contingency’s impact on laboratory evolution ofEscherichia coliunder fluctuating environments
Authors: Pechuan Ximo , Biro Daniel , Lambros Maryl , Bergman Aviv 
Published: April 2019

1AbstractThe adaptation of biological organisms to fluctuating environments is one major determinant of their structural and dynamical complexity. Organisms have evolved devoted adaptations to ensure the robust performance of physiological functions under environmental fluctuations. To further our understanding of particular adaptation strategies to different environmental fluctuations, we perform laboratory evolution experiments ofEscherichia coliunder three temperature fluctuation regimes alternating between 15°C and 43°C. Two of these regimes are determined by the population’s growth, while the third regime switches stochastically. To address evolutionary contingencies, the experiments are performed on two lineages departing from different genetic backgrounds. The two lineages display distinct evolutionary trajectories, demonstrating dependency on the starting strain’s genetic background. Several genes exhibit a high degree of parallelism, suggesting their potential adaptive nature. The growth increase of the representative clones from each final population relative to their ancestor at 15°C and 43°C demonstrated no correlation between both temperatures, insinuating an absence of a strong trade-off between these two temperatures. Some had a growth rate decrease at 15°C unless exposed to a 43°C epoch, indicating some degree of internalization of the structure of the environment fluctuations. The phenotypic response of the evolved clones at 15°C and 43°C was assessed by a phenotype array method. The resulting responses reveal a general tendency to move closer to the phenotypic response of our starting strains at the optimum of 37°C. This observation expands the documented restorative responses, even when facing complex environmental conditions.2Author SummaryLaboratory evolution experiments have been widely employed to test hypotheses from evolutionary theory. To assess the dynamics of adaptation under environmental fluctuations, we evolved 24Escherichia colipopulations under different regimes of temperature switching between 15°C and 43°C for about 600 generations. At the final point of the evolution experiment, the evolved populations were genome sequenced and clones were isolated and sequenced for phenotypic characterization. Fitness measurements revealed adaptation to both environmental conditions and some strains internalized the environmental fluctuation. Array phenotypic measurements showed that the majority of evolved strains tended to restore the phenotypic signature of the perturbed environments to that of the optimal temperature condition. This observation expands the documented restorative responses, even when facing complex environmental conditions.
Prediction of antiviral drugs against African Swine Fever Viruses based on protein-protein interaction analysis
Authors: Zhu Zhaozhong , Fan Yunshi , Cai Zena , Zhang Zheng , Lu Congyu , Jiang Taijiao , Zhang Gaihua , Peng Yousong 
Published: April 2019

AbstractThe African swine fever virus (ASFV) has severely influenced the swine industry of the world. Unfortunately, there is no effective antiviral drug or vaccine against the virus until now. Identification of new anti-ASFV drugs is urgently needed. Here, an up-to-date set of protein-protein interactions (PPIs) between ASFV and swine were curated by integration of PPIs from multiple sources. Thirty-two swine proteins were observed to interact with ASFVs and were defined as AIPs. They were found to play a central role in the swine PPI network, with significant larger degree, betweenness and smaller shortest path length than other swine proteins. Some of AIPs also interacted with several other viruses and could be taken as potential targets of drugs for broad-spectrum effect, such as HSP90AB1. Finally, the antiviral drugs which targeted AIPs and ASFV proteins were predicted. Several drugs with either broad-spectrum effect or high specificity on AIPs were identified, such as Polaprezinc. This work could not only deepen our understanding towards the ASFV-swine interactions, but also help for the development of effective antiviral drugs against the ASFVs.
Homeostasis in the Central Dogma of Molecular Biology: the importance of mRNA instability
Authors: Pérez-Ortín José E. , Tordera Vicente , Chávez Sebastián 
Published: April 2019

AbstractCell survival requires the control of biomolecule concentration, i.e. biomolecules should approach homeostasis. With information-carrying macromolecules, the particular concentration variation ranges depend on each type: DNA is not buffered, but mRNA and protein concentrations are homeostatically controlled, which leads to the ribostasis and proteostasis concepts. In recent years, we have studied the particular features of mRNA ribostasis and proteostasis in the model organismS. cerevisiae. Here we extend this study by comparing published data from three other model organisms:E. coli, S. pombeand cultured human cells. We describe how mRNA ribostasis is less strict than proteostasis. A constant ratio appears between the average decay and dilution rates during cell growth for mRNA, but not for proteins. We postulate that this is due to a trade-off between the cost of synthesis and the response capacity. This compromise takes place at the transcription level, but is not possible at the translation level as the high stability of proteins,versusthat of mRNAs, precludes it. We hypothesize that the middle-place role of mRNA in theCentral Dogmaof Molecular Biology and its chemical instability make it more suitable than proteins for the fast changes needed for gene regulation.Graphical Abstract
Different Whole-Brain Functional Connectivity Correlates of Reactive-Proactive Aggression and Callous-Unemotional Traits in Disruptive Children and Adolescents
Authors: Werhahn Julia E , Mohl Susanna , Willinger David , Smigielski Lukasz , Roth Alexander , Naaijen Jilly , Mulder Leandra M , Glennon Jeffrey C , Hoekstra Pieter J , Dietrich Andrea , Deters Renee Kleine , Aggensteiner Pascal M , Holz Nathalie E , Baumeister Sarah , Banaschewski Tobias , Saam Melanie C , Schulze Ulrike M E , Lythgoe David J , Sethi Arjun , Craig Michael , Mastroianni Mathilde , Sagar-Ouriaghli Ilyas , Santosh Paramala J , Rosa Mireia , Bargallo Nuria , Castro-Fornieles Josefina , Arango Celso , Penzol Maria J , Zwiers Marcel P , Franke Barbara , Buitelaar Jan K , Walitza Susanne , Brandeis Daniel 
Published: April 2019

AbstractBackgroundDisruptive behavior in children and adolescents can manifest itself in reactive (RA) and proactive (PA) aggression and is modulated by callous-unemotional (CU) traits and comorbidity. Research on aggression subtype-specific neural correlates is limited and the role of comorbid symptoms largely neglected.MethodsThe current multi-center study extended previous efforts by investigating unrestricted resting state functional connectivity (rsFC) alterations. The large sample (n = 207) of children and adolescents aged 8 – 18 years (mean age = 13.30 ± 2.60 years) included 118 cases with disruptive behavior (80 diagnosed with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were added as covariates. We measured changes in global and local voxel-to-voxel rsFC using functional magnetic resonance imaging at 3T (mean acquisition time = 8 min 25 sec).ResultsCompared to controls, cases demonstrated altered rsFC including frontal areas when anxiety but not ADHD symptoms were considered. Within cases, RA and PA scores related to changes in global and local rsFC in central gyrus and precuneus previously linked to aggression-related impairments. CU trait severity correlated with global rsFC alterations including inferior and middle temporal gyrus implicated in empathy, emotion, and reward-related activity. Importantly, most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety problems were also accounted for.ConclusionsThe current study clarifies that distinct though overlapping brain connectivity measures can disentangle differing manifestations of aggressive behavior. Moreover, our results highlight the importance of considering comorbid symptoms for detecting aggression-related rsFC alterations.
Gene-level heritability analysis explains the polygenic architecture of cancer
Authors: Fanfani Viola , Citi Luca , Harris Adrian L. , Pezzella Francesco , Stracquadanio Giovanni 
Published: April 2019

AbstractGenome-wide association studies (GWAS) have found hundreds of single nucleotide polymorphisms (SNPs) associated with increased risk of cancer. However, the amount of heritable risk explained by these variants is limited, thus leaving most of cancer heritability unexplained.Recent studies have shown that genomic regions associated with specific biological functions explain a large proportion of the heritability of many traits. Since cancer is mostly triggered by aberrant genes function, we hypothesised that SNPs located in protein-coding genes could explain a significant proportion of cancer heritability.To perform this analysis, we developed a new method, called Bayesian Gene HERitability Analysis (BAGHERA), to estimate the heritability explained by all the genotyped SNPs and by those located in protein coding genes directly from GWAS summary statistics.By applying BAGHERA to the 38 cancers reported in the UK Biobank, we identified 1, 146 genes explaining a significant amount of cancer heritability. We found these genes to be tumour suppressors directly involved in the hallmark processes controlling the transformation from normal to cancer cell; moreover, these genes also harbour somatic driver mutation for many tumours, suggesting a two-hit model underpinning tumorigenesis.Our study provides new evidence for a functional role of SNPs in cancer and identifies new targets for risk assessment and patients’ stratification.