bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colibactin DNA damage signature indicates causative role in colorectal cancer
Authors: Dziubańska-Kusibab Paulina J. , Berger Hilmar , Battistini Federica , Bouwman Britta A. M. , Iftekhar Amina , Katainen Riku , Crosetto Nicola , Orozco Modesto , Aaltonen Lauri A. , Meyer Thomas F. 
Published: October 2019

AbstractColibactin, a potent genotoxin of Escherichia coli, causes DNA double strand breaks (DSBs) in human cells. We investigated if colibactin creates a particular DNA damage signature in infected cells by identifying DSBs in colon cells after infection with pks+ E.coli. Interestingly, genomic contexts of DSBs were enriched for AT-rich penta-/hexameric sequence motifs, exhibiting a particularly narrow minor groove width and extremely negative electrostatic potential. This corresponded with the binding characteristics of colibactin to double-stranded DNA, as elucidated by docking and molecular dynamics simulations. A survey of somatic mutations at the colibactin target sites of several thousand cancer genomes revealed significant enrichment of the identified motifs in colorectal cancers. Our work provides direct evidence for a role of colibactin in the etiology of human cancer.One sentence summaryWe identify a mutational signature of colibactin, which is significantly enriched in human colorectal cancers.
Ant cuticular hydrocarbons are heritable and associated with variation in colony productivity
Authors: Walsh Justin , Pontieri Luigi , d’Ettorre Patrizia , Linksvayer Timothy A. 
Published: October 2019

AbstractIn social insects, cuticular hydrocarbons function in nestmate recognition and also provide a waxy barrier against desiccation, but basic evolutionary genetic features, including the heritability of hydrocarbon profiles and how they are shaped by natural selection are largely unknown. We used a new pharaoh ant (Monomorium pharaonis) laboratory mapping population to estimate the heritability of individual cuticular hydrocarbons, genetic correlations between hydrocarbons, and fitness consequences of phenotypic variation in the hydrocarbons. Individual hydrocarbons had low to moderate estimated heritability, indicating that some compounds provide more information about genetic relatedness and can also better respond to natural selection. Strong genetic correlations between compounds are likely to constrain independent evolutionary trajectories, which is expected given that many hydrocarbons share biosynthetic pathways. Variation in cuticular hydrocarbons was associated with variation in colony productivity, with some hydrocarbons experiencing strong directional selection. Altogether, our study builds on our knowledge of the genetic architecture of the social insect hydrocarbon profile and demonstrates that hydrocarbon variation is shaped by natural selection.
Identification and biochemical characterization of a novel eukaryotic-like Ser/Thr kinase inE. coli
Authors: Rajagopalan Krithika , Dworkin Jonathan 
Published: October 2019

AbstractIn bacteria, signaling phosphorylation is thought to occur primarily on His and Asp residues. However, phosphoproteomic surveys in phylogenetically diverse bacteria over the past decade have identified numerous proteins that are phosphorylated on Ser and/or Thr residues. Consistently, genes encoding Ser/Thr kinases are present in many bacterial genomes such asE. coli, which encodes at least three Ser/Thr kinases. Here we identify a previously uncharacterized ORF,yegI, and demonstrate that it encodes a novel Ser/Thr kinase. YegI lacks several conserved residues including those important for Mg2+binding seen in other bacterial Ser/Thr kinases, suggesting that the consensus may be too stringent. We further find that YegI is a two-pass membrane protein with both N- and C-termini located intracellularly.
The role of environment, local adaptation and past climate fluctuation on the amount and distribution of genetic diversity in the teosinte in Mexico
Authors: Gasca-Pineda Jaime , Gutiérrez-Guerrero Yocelyn T. , Aguirre-Planter Erika , Eguiarte Luis E. 
Published: October 2019

AbstractWild maize, commonly known as teosinte, has a wide distribution in central Mexico and inhabits a wide range of environmental conditions. According to previous studies, the environment is a determinant factor for the amount and distribution of genetic diversity. In this study, we used a set of neutral markers to explore the influence of contemporary factors and historical environmental shifts on genetic diversity, including present and three historical periods. Using a set of 22 nuclear microsatellite loci, we genotyped 527 individuals from 29 localities. We found highly variable levels of genetic diversity (Z. m. parviglumis HE= 0.3646–0.7699;Z. m. mexicana HE= 0.5885–0.7671) and significant genetic structure among localities (averageDEST= 0.4332). Also, we recovered significant values of heterozygote deficiency (averageFIS= 0.1796) and variable levels of selfing (sg2=0.0–0.3090). The Bayesian assignment analysis yielded four genetic clusters dividing the sample into subspecies, that in turn, were separated into two clusters. Environmental conditions played a strong influence in the distribution of genetic diversity, as demographic analysis and changes in species range revealed by modeling analyses were consistent. We conclude that current genetic diversity in teosinte is the result of a mixture of local adaptation and genetic isolation along with historical environmental fluctuations.
MitoPlex: A Targeted Multiple Reaction Monitoring Assay for Quantification of a Curated Set of Mitochondrial Proteins
Authors: Stotland Aleksandr B. , Spivia Weston , Orosco Amanda , Andres Allen M. , Gottlieb Roberta A. , Van Eyk Jennifer E. , Parker Sarah J. 
Published: October 2019

SummaryMitochondria are the major source of cellular energy (ATP), as well as critical mediators of widespread functions such as cellular redox balance, apoptosis, and metabolic flux. Methods to quantify mitochondrial content are limited to low throughput immunoassays, measurement of mitochondrial DNA, or relative quantification by untargeted mass spectrometry. Here, we present a high throughput, reproducible and quantitative mass spectrometry multiple reaction monitoring based assay of 37 proteins critical to central carbon chain metabolism and overall mitochondrial function termed ‘MitoPlex’. We coupled this protein multiplex with a parallel analysis of the central carbon chain metabolites (218 metabolite assay) extracted in tandem from the same sample, be it cells or tissue. In tests of its biological applicability in cells and tissues, ‘MitoPlex plus metabolites’ indicated profound effects of HMG-CoA Reductase inhibition (e.g., statin treatment) on mitochondria of i) differentiating C2C12 skeletal myoblasts, as well as a clear opposite trend of statins to promote mitochondrial protein expression and metabolism in heart and liver, while suppressing mitochondrial protein and ii) aspects of metabolism in the skeletal muscle obtained from C57Bl6 mice. Our results not only reveal new insights into the metabolic effect of statins in skeletal muscle, but present a new high throughput, reliable MS-based tool to study mitochondrial dynamics in both cell culture and in vivo models.
The interplay between host community structure and pathogen life‐history constraints in driving the evolution of host‐range shifts
Authors: Okamoto Kenichi W. , Amarasekare Priyanga , Post David M. , Vasseur David A. , Turner Paul E. 
Published: October 2019

Abstract

The ability of pathogens and parasites to adaptively exploit novel hosts has contributed to their unparalleled diversification along the tree of life. Moreover, evolved host‐range shifts are of particular applied interest – for instance, zoonotic ‘spillovers’ towards humans motivate growing concern about emerging infectious diseases. Thus, identifying the constraints upon, and conditions conducive to, host switching by pathogens is critical to addressing pressing public health and agricultural problems, as well as to understand a major driver of biodiversity.

How do processes that structure host communities (such as among‐host competition) set the selective context for the evolution of pathogen host ranges, and how do these processes interact with trade‐offs constraining the evolution of a pathogen's ability to exploit its host?

Here, we develop a theoretical framework to understand how resource competition among hosts interacts with constraints on pathogen biology in driving host shifts. We characterize how antagonistic pleiotropy in the pathogen's ability to exploit hosts can counteract ecological selection towards host‐range shifts.

We find that although the effects of apparent competition on host‐range shifts are mediated through the ancestral pathogen's direct and indirect effects on the entire host community, the effects of exploitative competition on host‐range shifts are mediated through exploitative competition's effect on the previously unexploited host.

Finally, we show that even when changes in host community structure create conditions conducive to host switching, a general trade‐off between pathogen virulence and burst size can prevent pathogens from evolving seemingly adaptive patterns of host use. We illustrate how these constraints faced by pathogens shape the eco‐evolutionary interaction between pathogen evolution and host communities.

We discuss how our results inform predictions about the kinds of pathogen lineages likely to exhibit host‐range shifts, and the role of apparent versus direct competition in structuring host—pathogen communities over evolutionary time.

A free Plain Language Summary can be found within the Supporting Information of this article.
Distribution maps of cetacean and seabird populations in the North‐East Atlantic
Authors: Waggitt James J. , Evans Peter G. H. , Andrade Joana , Banks Alex N. , Boisseau Oliver , Bolton Mark , Bradbury Gareth , Brereton Tom , Camphuysen Cornelis Jan , Durinck Jan , Felce Tom , Fijn Ruben Christiaan , Garcia‐Baron Isabel , Garthe Stefan , Geelhoed Steve C. V. , Gilles Anita , Goodall Martin , Haelters Jan , Hamilton Sally , Hartny‐Mills Lauren , Hodgins Nicola , James Kathy , Jessopp Mark , Kavanagh Ailbhe S. , Leopold Mardik , Lohrengel Katrin , Louzao Maite , Markones Nele , Martínez-Cedeira Jose , Ó Cadhla Oliver , Perry Sarah L. , Pierce Graham J. , Ridoux Vincent , Robinson Kevin P. , Santos M. Begoña , Saavedra Camilo , Skov Henrik , Stienen Eric W. M. , Sveegaard Signe , Thompson Paul , Vanermen Nicolas , Wall Dave , Webb Andy , Wilson Jared , Wanless Sarah , Hiddink Jan Geert 
Published: October 2019

AbstractDistribution maps of cetaceans and seabirds at basin and monthly scales are needed for conservation and marine management. These are usually created from standardized and systematic aerial and vessel surveys, with recorded animal densities interpolated across study areas. However, distribution maps at basin and monthly scales have previously not been possible because individual surveys have restricted spatial and temporal coverage.This study develops an alternative approach consisting of: (a) collating diverse survey data to maximize spatial and temporal coverage, (b) using detection functions to estimate variation in the surface area covered (km2) among these surveys, standardizing measurements of effort and animal densities, and (c) developing species distribution models (SDM) that overcome issues with heterogeneous and uneven coverage.2.68 million km of survey data in the North‐East Atlantic between 1980 and 2018 were collated and standardized. SDM using Generalized Linear Models and General Estimating Equations in a hurdle approach were developed. Distribution maps were then created for 12 cetacean and 12 seabird species at 10 km and monthly resolution. Qualitative and quantitative assessment indicated good model performance.Synthesis and applications. This study provides the largest ever collation and standardization of diverse survey data for cetaceans and seabirds, and the most comprehensive distribution maps of these taxa in the North‐East Atlantic. These distribution maps have numerous applications including the identification of important areas needing protection, and the quantification of overlap between vulnerable species and anthropogenic activities. This study demonstrates how the analysis of existing and diverse survey data can meet conservation and marine management needs.
Exposure to Asian dust within a few days of delivery is associated with placental abruption in Japan: a case‐crossover study
Authors: Michikawa T , Yamazaki S , Shimizu A , Nitta H , Kato K , Nishiwaki Y , Morokuma S 
Published: October 2019

ObjectiveAsian dust is a natural phenomenon in which dust particles are transported from desert areas in China and Mongolia to East Asia. Short‐term exposure to Asian dust has been associated with cardiovascular disease through mechanisms such as systemic inflammation. Because inflammation is a potential trigger of placental abruption, exposure may also lead to abruption. We examined whether exposure to Asian dust was associated with abruption.DesignA bi‐directional, time‐stratified case‐crossover design.Setting and populationFrom the Japan Perinatal Registry Network database, we identified 3014 patients who delivered singleton births in hospitals in nine Japanese prefectures from 2009 to 2014 with a diagnosis of placental abruption.MethodsAsian dust levels were measured at Light Detection and Ranging monitoring stations, and these measurements were used to define the Asian dust days. As there was no information on the onset day of abruption, we assumed this day was the day before delivery (lag1).Main outcome measuresPlacental abruption.ResultsDuring the study period, the Asian dust days ranged from 15 to 71 days, depending on the prefecture. The adjusted odds ratio of placental abruption associated with exposure to Asian dust was 1.4 (95% confidence interval = 1.0, 2.0) for cumulative lags of 1–2 days. Even after adjustment for co‐pollutant exposures, this association did not change substantially.ConclusionsIn this Japanese multi‐area study, exposure to Asian dust was associated with an increased risk of placental abruption.Tweetable abstractExposure to environmental factors such as Asian dust may be a trigger of placental abruption.
Therapeutic Plasma Exchange in Neuromyelitis Optica Spectrum Disorders and Related Disorders in Resource‐Limited Settings: Outcomes in a Multiethnic Single‐Center Population
Authors: Ong Zhi Miin , Schee Jie Ping , Viswanathan Shanthi 
Published: October 2019

AbstractWe evaluated therapeutic plasma exchange (TPE) efficiency in treatment of a single relapse in steroid‐refractory patients with neuromyelitis optica spectrum disorders (NMOSD) in a multi‐ethnic resource‐limited setting. This was a historical cohort study on the clinical outcomes post‐TPE in a multiethnic cohort of 53 steroid‐refractory NMOSD patients at a single Malaysian tertiary center. Primary outcomes, assessed both pre‐ and post‐TPE, were Medical Research Council scale of muscle power, Modified Rankin Scale, Expanded Disability Status Scale (EDSS), and visual acuity. Secondary outcomes were ambulatory status and target neurological deficit (TND)‐based TPE response. Significant improvements in Medical Research Council, Modified Rankin Scale, EDSS, and visual acuity (P < 0.001) were observed at 1‐month post‐TPE with further improvement of EDSS at 6 months (EDSSΔ6) post‐TPE (P < 0.001). At 6 months post‐TPE, 87% of patients has successful TND‐based TPE response and 69.8% were ambulating without support. Patients with anti‐aquaporin 4 seronegativity (P = 0.004), myelitis and brainstem features at first relapse (P = 0.004), longer cord lesions (P = 0.030), higher pre‐TPE EDSS of ≥8 (P = 0.018) and delayed TPE initiation of >14 days (P = 0.047) were significantly associated with improved EDSSΔ6. TND‐based TPE response was significant in absence of cord atrophy (P = 0.030). TPE is an effective treatment for steroid‐refractory acute relapses of NMOSD in a multiethnic Malaysian population despite its resource‐limited setting. The predictive factors of EDSSΔ6 improvement were anti‐aquaporin 4 seronegativity, longer cord lesions, and higher pre‐TPE EDSS. Absence of cord atrophy was predictive of better TND‐based TPE response. Unexpectedly, our study showed that delayed TPE initiation of more than 14 days and up to 60 days may also be beneficial.
Genetic polymorphisms of ATG16L1 and IRGM genes in Malaysian patients with Crohn's disease
Authors: Kee Boon Pin , Ng Jin Guan , Ng Ching Ching , Hilmi Ida , Goh Khean Lee , Chua Kek Heng 
Published: October 2019

ObjectiveTo investigate the association between genetic polymorphisms in ATG16L1 and IRGM genes and the development of Crohn's disease (CD) in Malaysian patients.MethodsAltogether 335 participants were recruited, including 85 patients with CD and 250 unrelated healthy controls, and their informed consent was obtained. Genomic DNA was extracted via a conventional phenol‐chloroform extraction method. Six single nucleotide polymorphisms (SNPs) in ATG16L1 and IRGM genes were genotyped using TaqMan SNP genotyping assays. Associations between SNP and CD were determined using Fisher's exact test, odds ratio, and 95% confidence interval. Statistical power and the Hardy‐Weinberg equilibrium were also calculated.ResultsTwo SNPs (rs2241880 and rs6754677) in the ATG16L1 gene were significantly associated with the onset of CD in the Malaysian population. The A allele and homozygous A/A genotype of the rs2241880 A/G polymorphism were protective against CD in the overall Malaysian and Malay population. The G allele and homozygous G/G genotype of the rs6754677 G/A polymorphism were protective in the Indian population, whereas the homozygous A/A genotype showed a risk of developing CD. The homozygous G/G genotype of IRGM rs11747270 was significantly present in the controls. However, this significance was not observed in a race‐stratified analysis. All three ATG16L1 SNPs were associated with inflamed terminal ileum. IRGM rs4958847 and rs11747270 increased the risk of developing arthritis in patients with CD.ConclusionWe found a significant association between SNP, which are located in autophagy‐related genes, and CD in a Malaysian population.
Pregnancy outcome in women with gestational diabetes – A longitudinal study of changes in demography and treatment modalities
Authors: Moll Ulrika , Landin‐Olsson Mona , Nilsson Charlotta , Ursing Dag , Strevens Helena 
Published: October 2019

AbstractIntroductionGestational diabetes is on the rise and demographics are changing in many countries due to increased migration. Simultaneously, the treatment of gestational diabetes in our clinic has shifted towards metformin with substantially less insulin treatment. The aim was to study the impact of these changes on metabolic control and pregnancy outcome by comparing women diagnosed with gestational diabetes during 2012‐2013 and 2016‐2017.Material and methodsOur universal Oral Glucose Tolerance Test screening program for gestational diabetes diagnosed 199 women with singleton pregnancies during 2012‐2013 and 203 during 2016‐2017. Treatment and achieved metabolic control in the two different time periods were compared. Pregnancy outcome data related to gestational diabetes were retrieved from case notes and compared between the different time periods.ResultsWhen comparing results from 2016‐2017 with 2012‐2013 there was no difference in maternal weight or weight gain. There was a higher frequency of heredity (52.6 vs 35.4%; P = 0.001) and non‐Scandinavian ethnicity (46.5 vs 33.8%; P = 0.011).The frequency of smoking during pregnancy was significantly lower (2.6 vs 7.7%; P = 0.023) There was an improved metabolic control as measured by median glucose in 2016‐2017 compared with 2012‐2013 (5.8 vs 6.2 mmol/L; P < 0.001). Insulin was less frequently used in 2016‐2017 than in 2012‐2013 (32.5 vs 44.7%; P = 0.012). There was a significant increase in the use of metformin (14.8 vs 0%; P < 0.001). There were no differences regarding the frequency of large‐for‐gestational‐age infants (8.2% vs 7.3%; P = 0.762) or macrosomia (16.3 vs 15.1%; P = 0.745), median birthweight (3510 vs 3521; P = 0.879), frequency of cesarean section (28.1 vs 27.8%; P = 0.951) or Apgar scores at 10 minutes (10 [3‐10] vs 10 [7‐10]; P = 0.290).ConclusionsIn an increasing but changing population of gestational diabetes women in our region, with more hereditary and non‐Scandinavian origins, but with fewer smokers, metabolic control has improved with maintained favorable pregnancy outcomes, with more frequent use of metformin and substantially less use of insulin treatment.
Timing of delivery in women with diabetes: A population‐based study
Authors: Metcalfe Amy , Hutcheon Jennifer A. , Sabr Yasser , Lyons Janet , Burrows Jason , Donovan Lois E. , Joseph K. S. 
Published: October 2019

AbstractIntroductionWomen with diabetes, and their infants, have an increased risk of adverse events due to excess fetal growth. Earlier delivery, when fetuses are smaller, may reduce these risks. This study aimed to evaluate the week‐specific risks of maternal and neonatal morbidity/mortality to assist with obstetrical decision making.Material and methodsIn this population‐based cohort study, women with type 1 diabetes (n = 5889), type 2 diabetes (n = 9422) and gestational diabetes (n = 138 917) and a comparison group without diabetes (n = 2 553 243) who delivered a singleton infant at ≥36 completed weeks of gestation between 2004 and 2014 were identified from the Canadian Institute of Health Information Discharge Abstract Database. Multivariate logistic regression was used to determine the week‐specific rates of severe maternal and neonatal morbidity/mortality among women delivered iatrogenically vs those undergoing expectant management.ResultsFor all women, the absolute risk of severe maternal morbidity/mortality was low, typically impacting less than 1% of women, and there was no significant difference in gestational age‐specific severe maternal morbidity/mortality between iatrogenic delivery and expectant management among women with any form of diabetes. Among women with gestational diabetes, iatrogenic delivery was associated with an increased risk of neonatal morbidity/mortality compared with expectant management at 36 and 37 weeks’ gestation (76.7 and 27.8 excess cases per 1000 deliveries, respectively) and a lower risk of neonatal morbidity/mortality at 38, 39 and 40 weeks’ gestation (7.9, 27.3 and 15.9 fewer cases per 1000 deliveries, respectively). Increased risks of severe neonatal morbidity following iatrogenic delivery compared with expectant management were also observed for women with type 1 diabetes at 36 (98.3 excess cases per 1000 deliveries) and 37 weeks’ gestation (44.5 excess cases per 1000 deliveries) and for women with type 2 diabetes at 36 weeks’ gestation (77.9 excess cases per 1000 deliveries) weeks.ConclusionsThe clinical decision regarding timing of delivery is complex and contingent on maternal‐fetal wellbeing, including adequate glycemic control. This study suggests that delivery at 38, 39 or 40 weeks’ gestation may optimize neonatal outcomes among women with diabetes.