bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic consequences of being a dwarf: do evolutionary changes in life-history traits influence gene flow patterns in populations of the world’s smallest goldenrod?
Authors: Sakaguchi Shota , Nagano Atsushi J , Yasugi Masaki , Kudoh Hiroshi , Ishikawa Naoko , Ito Motomi
Published: April 2020

Background and Aims

Contrasting life-history traits can evolve through generations of dwarf plant ecotypes, yet such phenotypic changes often involve decreased plant size and reproductive allocation, which can configure seed dispersal patterns and, subsequently, population demography. Therefore, evolutionary transitions to dwarfism can represent good study systems to test the roles of life-history traits in population demography by comparing genetic structure between related but phenotypically divergent ecotypes.

Methods

In this study, we examined an ecotypic taxon pair of the world’s smallest goldenrod (stem height 2.6 cm) in alpine habitats and its closely related lowland taxon (30–40 cm) found on Yakushima Island, Japan. Genetic variation in chloroplast DNA sequences, nuclear microsatellites and genome-wide single-nucleotide polymorphisms were used to investigate 197 samples from 16 populations, to infer the population genetic demography and compare local genetic structure of the ecotypes.

Key Results

We found a pronounced level of genetic differentiation among alpine dwarf populations, which were much less geographically isolated than their lowland counterparts. In particular, several neighbouring dwarf populations (located ~500 m apart) harboured completely different sets of chloroplast haplotypes and nuclear genetic clusters. Demographic modelling revealed that the dwarf populations have not exchanged genes at significant levels after population divergence.

Conclusions

These lines of evidence suggest that substantial effects of genetic drift have operated on these dwarf populations. The low-growing stature and reduced fecundity (only 3.1 heads per plant) of the dwarf plants may have reduced gene flow and rare long-distance seed dispersal among habitat patches, although the effects of life-history traits require further evaluation using ecological approaches.
Symbol Digit Modalities Test: Greek Normative Data for the Oral and Written Version and Discriminative Validity in Patients with Multiple Sclerosis
Authors: Messinis Lambros , Bakirtzis Christos , Kosmidis Mary Helen , Economou Alexandra , Nasios Grigorios , Anyfantis Emmanouil , Konitsiotis Spiridon , Ntoskou Aikaterini , Peristeri Eleni , Dardiotis Efthymios , Grigoriadis Nikolaos , Gourzis Phillipos , Papathanasopoulos Panagiotis
Published: April 2020

Objectives

The purpose of this study was to generate normative data on the Symbol Digits Modalities Test (SDMT) for the written and oral versions in the Greek adult population. We also investigated the test’s validity in discriminating the performance of healthy adults from two groups of adults diagnosed with relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis.

Method

The sample consisted of 609 healthy men and women between the ages of 18 and 65. All participants were monolingual native Greek adult speakers. Each healthy participant was administered either the written (n = 460) or oral (n = 149) versions of the SDMT. Discriminant validity was examined by comparing 35 healthy participants who had completed the oral version of the SDMT to 35 age - and education-matched RRMS and SPMS patients.

Results

Linear regression models explained between 36% and 55% of the variance in the SDMT oral and written version scores. Age was the strongest predictor of difference in SDMT written and oral version performance, followed by education that also accounted for a further proportion of the SDMT variance. On the contrary, gender was found not to contribute significantly to the variance in the SDMT for either the written or the oral versions. As a result, age- and education-adjusted norms were generated. Regarding the tests discriminative validity, we found that both MS patient groups scored significantly lower than the healthy group.

Conclusions

This is the first study to provide comprehensive normative data for the SDMT in the adult population in Greece, impacting the future practice of neuropsychological assessment in this country.
A venous mechanism of ventriculomegaly shared between traumatic brain injury and normal ageing
Authors: Aso Toshihiko , Sugihara Genichi , Murai Toshiya , Ubukata Shiho , Urayama Shin-ichi , Ueno Tsukasa , Fujimoto Gaku , Thuy Dinh Ha Duy , Fukuyama Hidenao , Ueda Keita
Published: April 2020

Recently, age-related timing dissociation between the superficial and deep venous systems has been observed; this was particularly pronounced in patients with normal pressure hydrocephalus, suggesting a common mechanism of ventriculomegaly. Establishing the relationship between venous drainage and ventricular enlargement would be clinically relevant and could provide insight into the mechanisms underlying brain ageing. To investigate a possible link between venous drainage and ventriculomegaly in both normal ageing and pathological conditions, we compared 225 healthy subjects (137 males and 88 females) and 71 traumatic brain injury patients of varying ages (53 males and 18 females) using MRI-based volumetry and a novel perfusion-timing analysis. Volumetry, focusing on the CSF space, revealed that the sulcal space and ventricular size presented different lifespan profiles with age; the latter presented a quadratic, rather than linear, pattern of increase. The venous timing shift slightly preceded this change, supporting a role for venous drainage in ventriculomegaly. In traumatic brain injury, a small but significant disease effect, similar to idiopathic normal pressure hydrocephalus, was found in venous timing, but it tended to decrease with age at injury, suggesting an overlapping mechanism with normal ageing. Structural bias due to, or a direct causative role of ventriculomegaly was unlikely to play a dominant role, because of the low correlation between venous timing and ventricular size after adjustment for age in both patients and controls. Since post-traumatic hydrocephalus can be asymptomatic and occasionally overlooked, the observation suggested a link between venous drainage and CSF accumulation. Thus, hydrocephalus, involving venous insufficiency, may be a part of normal ageing, can be detected non-invasively, and is potentially treatable. Further investigation into the clinical application of this new marker of venous function is therefore warranted.
Prenatal stress enhances NNK-induced lung tumors in A/J mice
Authors: Ito Tomoaki , Saeki Harumi , Guo Xin , Sysa-Shah Polina , Coulter Jonathan , Tamashiro Kellie L K , Lee Richard S , Orita Hajime , Sato Koichi , Ishiyama Shun , Hulbert Alicia , Smith William E , Peterson Lisa A , Brock Malcolm V , Gabrielson Kathleen L
Published: April 2020

Children born to women who experience stress during pregnancy have an increased risk of cancer in later life, but no previous animal studies have tested such a link. We questioned whether prenatal stress (PS) in A/J mice affected the development of lung tumors after postnatal response to tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Timed-bred A/J mice were randomly assigned on gestation day 12.5 to PS by restraint for 5 consecutive days or control (no restraint). Adult offspring of control and stressed pregnancies were all treated with three NNK injections (50 mg/kg every other day) and euthanized 16 weeks later to examine their lungs. Compared with controls, PS dams exhibited significantly increased levels of plasma corticosterone, increased adrenal weights and decreased fetus weights without fetal loss. Prenatally stressed litters had a significantly higher neonatal death rate within first week of life, and surviving male and female offspring developed lung epithelial proliferations with increase multiplicity, increased area and aggressive morphology. PS also induced more advanced atypical adenomatous hyperplasia lesions. We found no difference in lung NNK-derived methyl DNA adducts, but PS did significantly enhance CD3+ T cell and Foxp3+ T cell tumor infiltration. PS significantly increases multiplicity, area of NNK-induced lung tumors and advanced morphology. PS did not affect production of NNK-derived methyl DNA adducts but did increase lymphocytic infiltration of lung tumors. To our knowledge, this is the first animal model of PS with evaluation of cancer development in offspring.
Antimicrobial Use in US Hospitals: Comparison of Results From Emerging Infections Program Prevalence Surveys, 2015 and 2011
Authors: Magill Shelley S , O’Leary Erin , Ray Susan M , Kainer Marion A , Evans Christopher , Bamberg Wendy M , Johnston Helen , Janelle Sarah J , Oyewumi Tolulope , Lynfield Ruth , Rainbow Jean , Warnke Linn , Nadle Joelle , Thompson Deborah L , Sharmin Shamima , Pierce Rebecca , Zhang Alexia Y , Ocampo Valerie , Maloney Meghan , Greissman Samantha , Wilson Lucy E , Dumyati Ghinwa , Edwards Jonathan R ,   Emerging Infections Program Hospital Prevalence Survey Team, Frank Linda , Godine Deborah , Martin Brittany , Parker Erin , Pasutti Lauren , Friedman Sarabeth , Jones Annika , Kosmicki Tabetha , Fisher James , Maslar Amber , Meek James , Melchreit Richard , Badrun Farzana , Fiore Anthony , Fridkin Scott K , Morabit Susan L , Perry Lewis A , Perlmutter Rebecca , Vaeth Elisabeth , Gross Annastasia , Harper Jane , Pattee Brittany , Rahmathullah Nabeelah , Baumbach Joan , Sievers Marla , Concannon Cathleen , Felsen Christina , Gellert Anita , Samper Monika , Beard Raphaelle H , Lawson Patricia , Muleta Daniel , Reed Vicky P
Published: April 2020

Background

In the 2011 US hospital prevalence survey of healthcare-associated infections and antimicrobial use 50% of patients received antimicrobial medications on the survey date or day before. More hospitals have since established antimicrobial stewardship programs. We repeated the survey in 2015 to determine antimicrobial use prevalence and describe changes since 2011.

Methods

The Centers for Disease Control and Prevention’s Emerging Infections Program sites in 10 states each recruited ≤25 general and women’s and children’s hospitals. Hospitals selected a survey date from May–September 2015. Medical records for a random patient sample on the survey date were reviewed to collect data on antimicrobial medications administered on the survey date or day before. Percentages of patients on antimicrobial medications were compared; multivariable log-binomial regression modeling was used to evaluate factors associated with antimicrobial use.

Results

Of 12 299 patients in 199 hospitals, 6084 (49.5%; 95% CI, 48.6–50.4%) received antimicrobials. Among 148 hospitals in both surveys, overall antimicrobial use prevalence was similar in 2011 and 2015, although the percentage of neonatal critical care patients on antimicrobials was lower in 2015 (22.8% vs 32.0% [2011]; P = .006). Fluoroquinolone use was lower in 2015 (10.1% of patients vs 11.9% [2011]; P < .001). Third- or fourth-generation cephalosporin use was higher (12.2% vs 10.7% [2011]; P = .002), as was carbapenem use (3.7% vs 2.7% [2011]; P < .001).

Conclusions

Overall hospital antimicrobial use prevalence was not different in 2011 and 2015; however, differences observed in selected patient or antimicrobial groups may provide evidence of stewardship impact.
Clinical Predictors of Liver Fibrosis Presence and Progression in Human Immunodeficiency Virus–Associated Nonalcoholic Fatty Liver Disease
Authors: Fourman Lindsay T , Stanley Takara L , Zheng Isabel , Pan Chelsea S , Feldpausch Meghan N , Purdy Julia , Aepfelbacher Julia , Buckless Colleen , Tsao Andrew , Corey Kathleen E , Chung Raymond T , Torriani Martin , Kleiner David E , Hadigan Colleen M , Grinspoon Steven K
Published: April 2020

Background

Nonalcoholic fatty liver disease (NAFLD) affects more than one-third of people living with human immunodeficiency virus (HIV). Nonetheless, its natural history is poorly understood, including which patients are most likely to have a progressive disease course.

Methods

We leveraged a randomized trial of the growth hormone–releasing hormone analogue tesamorelin to treat NAFLD in HIV. Sixty-one participants with HIV-associated NAFLD were randomized to tesamorelin or placebo for 12 months with serial biopsies.

Results

In all participants with baseline biopsies (n = 58), 43% had hepatic fibrosis. Individuals with fibrosis had higher NAFLD Activity Score (NAS) (mean ± standard deviation [SD], 3.6 ± 2.0 vs 2.0 ± 0.8; P < .0001) and visceral fat content (mean ± SD, 284 ± 91 cm2 vs 212 ± 95 cm2; P = .005), but no difference in hepatic fat or body mass index. Among placebo-treated participants with paired biopsies (n = 24), 38% had hepatic fibrosis progression over 12 months. For each 25 cm2 higher visceral fat at baseline, odds of fibrosis progression increased by 37% (odds ratio, 1.37 [95% confidence interval, 1.03–2.07]). There was no difference in baseline NAS between fibrosis progressors and nonprogressors, though NAS rose over time in the progressor group (mean ± SD, 1.1 ± 0.8 vs −0.5 ± 0.6; P < .0001).

Conclusions

In this longitudinal study of HIV-associated NAFLD, high rates of hepatic fibrosis and progression were observed. Visceral adiposity was identified as a novel predictor of worsening fibrosis. In contrast, baseline histologic characteristics did not relate to fibrosis progression.
Genome-wide analysis of short interspersed nuclear elements provides insight into gene and genome evolution in citrus
Authors: Meng Haijun , Feng Jiancan , Bai Tuanhui , Jian Zaihai , Chen Yanhui , Wu Guoliang
Published: April 2020

Short interspersed nuclear elements (SINEs) are non-autonomous retrotransposons that are highly abundant, but not well annotated, in plant genomes. In this study, we identified 41,573 copies of SINEs in seven citrus genomes, including 11,275 full-length copies. The citrus SINEs were distributed among 12 families, with an average full-length rate of 0.27, and were dispersed throughout the chromosomes, preferentially in AT-rich areas. Approximately 18.4% of citrus SINEs were found in close proximity (≤1 kb upstream) to genes, indicating a significant enrichment of SINEs in promoter regions. Citrus SINEs promote gene and genome evolution by offering exons as well as splice sites and start and stop codons, creating novel genes and forming tandem and dispersed repeat structures. Comparative analysis of unique homologous SINE-containing loci (HSCLs) revealed chromosome rearrangements in sweet orange, pummelo, and mandarin, suggesting that unique HSCLs might be valuable for understanding chromosomal abnormalities. This study of SINEs provides us with new perspectives and new avenues by which to understand the evolution of citrus genes and genomes.
Impact of angiotensin receptor blockers on mortality after hospitalization for symptomatic lower extremity artery disease
Authors: Lapébie François-Xavier , Bura-Rivière Alessandra , Lacroix Philippe , Constans Joël , Boulon Carine , Messas Emmanuel , Aboyans Victor , Ferrières Jean , Bongard Vanina
Published: April 2020

Aims

The objective was to assess the association between angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) prescription at discharge in patients hospitalized for symptomatic lower extremity artery disease (LEAD) and 1-year mortality.

Methods and results

The COPART registry is a multicentre, prospective, observational, cohort study which includes consecutive patients hospitalized for symptomatic LEAD in four French academic centres. All-cause mortality during a 1-year follow-up after hospital discharge was compared between patients with ARB, patients with ACEI and patients without ARB or ACEI. Analyses were performed using Cox models. As a sensitivity analysis, a propensity score (PS)-matching analysis was carried out. Among 1981 patients, 421 had ARB (21.3%), 766 ACEI (38.7%), and 794 no ACEI/ARB (40.1%) at discharge. During the 1-year follow-up, incidence rates for mortality were 12.6/100 person-years [95% confidence interval (CI) 9.7–16.1] for patients with ARB, 15.8/100 person-years (95% CI 13.4–18.6) for patients with ACEI and 19.8/100 person-years for patients without ACEI/ARB (95% CI 17.2–22.8). In a multivariate Cox model, ARB at discharge was associated with decreased mortality compared with no ACEI/ARB, hazard ratio (HR) 0.68 (95% CI 0.49–0.95), and with ACEI, HR 0.69 (95% CI 0.49–0.97). These results are consistent with those obtained by the Cox analyses in the PS-matched sample: HR 0.68 (95% CI 0.47–0.98) for patients with ARB compared with no ARB.

Conclusion

Angiotensin receptor blockers at discharge after hospitalization for symptomatic LEAD is associated with a better survival compared with ACEI or no ACEI/ARB.
Dysferlin links excitation–contraction coupling to structure and maintenance of the cardiac transverse–axial tubule system
Authors: Hofhuis Julia , Bersch Kristina , Wagner Stefan , Molina Cristina , Fakuade Funsho E , Iyer Lavanya M , Streckfuss-Bömeke Katrin , Toischer Karl , Zelarayán Laura C , Voigt Niels , Nikolaev Viacheslav O , Maier Lars S , Klinge Lars , Thoms Sven
Published: April 2020

Aims

The multi-C2 domain protein dysferlin localizes to the T-Tubule system of skeletal and heart muscles. In skeletal muscle, dysferlin is known to play a role in membrane repair and in T-tubule biogenesis and maintenance. Dysferlin deficiency manifests as muscular dystrophy of proximal and distal muscles. Cardiomyopathies have been also reported, and some dysferlinopathy mouse models develop cardiac dysfunction under stress. Generally, the role and functional relevance of dysferlin in the heart is not clear. The aim of this study was to analyse the effect of dysferlin deficiency on the transverse–axial tubule system (TATS) structure and on Ca2+ homeostasis in the heart.

Methods and results

We studied dysferlin localization in rat and mouse cardiomyocytes by immunofluorescence microscopy. In dysferlin-deficient ventricular mouse cardiomyocytes, we analysed the TATS by live staining and assessed Ca2+ handling by patch-clamp experiments and measurement of Ca2+ transients and Ca2+ sparks. We found increasing co-localization of dysferlin with the L-type Ca2+-channel during TATS development and show that dysferlin deficiency leads to pathological loss of transversal and increase in longitudinal elements (axialization). We detected reduced L-type Ca2+-current (ICa,L) in cardiomyocytes from dysferlin-deficient mice and increased frequency of spontaneous sarcoplasmic reticulum Ca2+ release events resulting in pro-arrhythmic contractions. Moreover, cardiomyocytes from dysferlin-deficient mice showed an impaired response to β-adrenergic receptor stimulation.

Conclusions

Dysferlin is required for TATS biogenesis and maintenance in the heart by controlling the ratio of transversal and axial membrane elements. Absence of dysferlin leads to defects in Ca2+ homeostasis which may contribute to contractile heart dysfunction in dysferlinopathy patients.
Outcomes in patients with cardiac amyloidosis and implantable cardioverter-defibrillator
Authors: Kim Eun-Jeong , Holmes Benjamin B , Huang Shi , Lugo Ricardo , Al Aboud Asad , Goodman Stacey , Hung Rebecca R , Slosky David , Stevenson William G , Michaud Gregory F , John Roy M
Published: April 2020

Aims

Cardiac amyloidosis (CA) is associated with increased mortality due to arrhythmias, heart failure, and electromechanical dissociation. However, the role of an implantable cardioverter-defibrillator (ICD) remains unclear. We conducted case-control study to assess survival in CA patients with and without a primary prevention ICD and compared outcomes to an age, sex, and device implant year-matched non-CA group with primary prevention ICD.

Methods and results

There were 91 subjects with CA [mean age= 71.2 ± 10.2, female 22.0%, 49 AL with Mayo Stage 2.9 ± 1.0, 41 transthyretin amyloidosis (ATTR), 1 other] followed by Vanderbilt Amyloidosis centre. Patients with ICD (n = 23) were compared with those without (n = 68) and a non-amyloid group with ICD (n = 46). All subjects with ICD had implantation for primary prevention. Mean left ventricular ejection fraction was 36.2% ± 14.4% in CA with ICD, 41.0% ± 10.6% in CA without ICD, and 33.5% ± 14.4% in non-CA patients. Over 3.5 ± 3.1 years, 6 (26.1%) CA, and 12 (26.1%) non-CA subjects received ICD therapies (P = 0.71). Patients with CA had a significantly higher mortality (43.9% vs. 17.4%, P = 0.002) compared with the non-CA group. Mean time from device implantation to death was 21.8 months in AL and 22.8 months in ATTR patients. There was no significant difference in mortality between CA patients who did and did not receive an ICD (39.0% vs. 46.0%, P = 0.59).

Conclusions

Despite comparable event rates patients with CA had a significantly higher mortality and ICDs were not associated with longer survival. With the emergence of effective therapy for AL amyloidosis, further study of ICD is needed in this group.
Mortality and cardiac resynchronization therapy with or without defibrillation in primary prevention
Authors: Gras Matthieu , Bisson Arnaud , Bodin Alexandre , Herbert Julien , Babuty Dominique , Pierre Bertrand , Clementy Nicolas , Fauchier Laurent
Published: April 2020

Aims 

Cardiac resynchronization therapy with (CRTD) or without (CRTP) defibrillator is recommended in selected patient with systolic chronic heart failure and wide QRS. There is no guideline firmly indicating choice between CRTP and CRTD in primary prevention, particularly in older patients.

Methods and results 

Based on the French administrative hospital-discharge database, information was collected from 2010 to 2017 for all patients implanted with CRTP or CRTD in primary prevention. Outcome analyses were undertaken in the total study population and in propensity-matched samples. During follow-up (913 days, SD 841, median 701, IQR 151–1493), 45 697 patients were analysed (CRTP 19 266 and CRTD 26 431). Incidence rate (%patient/year) of all-cause mortality was higher in CRTP patients (11.6%) than in CRTD patients (6.8%) [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.63–1.76, P < 0.001]. After propensity-matched analyses, mortality of patients over 75 years old with non-ischaemic cardiomyopathy (NICM) was not different with CRTP and CRTD (HR 0.93, 95% CI 0.80–1.09, P = 0.39). The CRTP patients under 75 years old with NICM had a higher mortality than CRTD patients (HR 1.22, 95% CI 1.03–1.45, P = 0.02). Mortality rate was also higher with CRTP than with CRTD irrespectively of age in patients with ischaemic cardiomyopathy (ICM) (<75 years old: HR 1.22, 95% CI 1.08–1.37, P = 0.01; ≥75 years old: HR 1.13, 95% CI 1.04–1.22, P = 0.003).

Conclusion 

In this real-life study, CRTD was associated with a significantly lower all-cause mortality than CRTP in patients with ICM and in patients with NICM under 75 years old. Patients over 75 years old with NICM did not have lower mortality with primary prevention CRTD implantation.
Engaging adolescents in developing health education interventions: a multidisciplinary pilot project
Authors: Psaroudakis Irene , Quattrone Filippo , Tavoschi Lara , De Vita Erica , Cervia Silvia , Biancheri Rita , Lopalco Pietro Luigi
Published: April 2020

Adolescents engagement is fundamental to develop dedicated educational interventions. We piloted non-standard sociological methodology to assess risk perception, information sources and perceived educational needs of a group of Italian adolescents focusing on three infectious diseases. Three high-school classes students participated in a World Café event. A thematic analysis was performed. Participants showed lack of knowledge on diseases prevention. Family and school were key health information sources and social media considered unreliable. Future interventions preferences included interactive and informal sessions. We showed the utility of non-standard sociological methods to assess health knowledge among adolescents and enhance the design of dedicated interventions.
Increased temperatures alter viable microbial biomass, ammonia oxidizing bacteria and extracellular enzymatic activities in Antarctic soils
Authors: Barnard Sebastian , Van Goethem Marc W , de Scally Storme Z , Cowan Don A , van Rensburg Peet Jansen , Claassens Sarina , Makhalanyane Thulani P
Published: April 2020

The effects of temperature on microorganisms in high latitude regions, and their possible feedbacks in response to change, are unclear. Here, we assess microbial functionality and composition in response to a substantial temperature change. Total soil biomass, amoA gene sequencing, extracellular activity assays and soil physicochemistry were measured to assess a warming scenario. Soil warming to 15°C for 30 days triggered a significant decrease in microbial biomass compared to baseline soils (0°C; P < 0.05) after incubations had induced an initial increase. These changes coincided with increases in extracellular enzymatic activity for peptide hydrolysis and phenolic oxidation at higher temperatures, but not for the degradation of carbon substrates. Shifts in ammonia-oxidising bacteria (AOB) community composition related most significantly to changes in soil carbon content (P < 0.05), which gradually increased in microcosms exposed to a persistently elevated temperature relative to baseline incubations, while temperature did not influence AOBs. The concentration of soil ammonium (NH4+) decreased significantly at higher temperatures subsequent to an initial increase, possibly due to higher conversion rates of NH4+ to nitrate by nitrifying bacteria. We show that higher soil temperatures may reduce viable microbial biomass in cold environments but stimulate their activity over a short period.
Continuous chromosome-scale haplotypes assembled from a single interspecies F1 hybrid of yak and cattle
Authors: Rice Edward S , Koren Sergey , Rhie Arang , Heaton Michael P , Kalbfleisch Theodore S , Hardy Timothy , Hackett Peter H , Bickhart Derek M , Rosen Benjamin D , Ley Brian Vander , Maurer Nicholas W , Green Richard E , Phillippy Adam M , Petersen Jessica L , Smith Timothy P L
Published: April 2020

Background

The development of trio binning as an approach for assembling diploid genomes has enabled the creation of fully haplotype-resolved reference genomes. Unlike other methods of assembly for diploid genomes, this approach is enhanced, rather than hindered, by the heterozygosity of the individual sequenced. To maximize heterozygosity and simultaneously assemble reference genomes for 2 species, we applied trio binning to an interspecies F1 hybrid of yak (Bos grunniens) and cattle (Bos taurus), 2 species that diverged nearly 5 million years ago. The genomes of both of these species are composed of acrocentric autosomes.

Results

We produced the most continuous haplotype-resolved assemblies for a diploid animal yet reported. Both the maternal (yak) and paternal (cattle) assemblies have the largest 2 chromosomes in single haplotigs, and more than one-third of the autosomes similarly lack gaps. The maximum length haplotig produced was 153 Mb without any scaffolding or gap-filling steps and represents the longest haplotig reported for any species. The assemblies are also more complete and accurate than those reported for most other vertebrates, with 97% of mammalian universal single-copy orthologs present.

Conclusions

The high heterozygosity inherent to interspecies crosses maximizes the effectiveness of the trio binning method. The interspecies trio binning approach we describe is likely to provide the highest-quality assemblies for any pair of species that can interbreed to produce hybrid offspring that develop to sufficient cell numbers for DNA extraction.
Exact and approximate reflection/transmission responses from a layer containing vertical fractures
Authors: Jin Song , Stovas Alexey
Published: April 2020

Analyses of vertical fractures are of great interest in characterizing the fluid flow and minimum in situ stress direction in reservoirs. Long-wavelength equivalent orthorhombic (ORT) media typically characterize the anisotropy induced by a set of vertical parallel fractures or two sets of vertical and mutually orthogonal fractures embedded into a transversely isotropic medium with a vertical symmetry axis (VTI). Reflection and transmission (R/T) responses quantify wave amplitude variations in 1-D media and help to reveal the model property enclosing the heterogeneity. Conventionally, the R/T responses are analysed for an interface bounded by two half-spaces. However, for a plane wave travelling through a subsurface layer, the wave scattering effects at the top and bottom of the layer interact with each other. For a continuous infinite ORT space cut in two halves along the horizontal symmetry plane, we focus on the plane wave R/T responses from an ORT layer that is placed between the two halves, where the azimuths of the vertical symmetry plane in the layer and in the upper and lower half-spaces are identical. The R/T coefficient modelling method can be found in many publications for the ORT layer with an arbitrary finite thickness. We decompose the exact R/T coefficients into series expansions that correspond to different orders of intrabed multiples in the ORT layer. Under the weak-contrast assumption for the ORT half-spaces and the ORT layer, we use the anisotropic background medium to obtain the first-order R/T coefficient approximations and second-order reflectivity approximations. There is no constraint for the middle layer thickness in the obtained first-order reflectivity approximations. In the proposed first-order transmissivity approximations and second-order reflectivity approximations, the layer thickness is assumed to be thin to obtain appropriate approximations for a few wave modes. The isotropic background medium is also considered for weakly anisotropic models to obtain simpler approximations that facilitate parametric analyses. For the ORT layer with its thickness much smaller than the propagating wave's wavelength, the influences of the layer thickness on R/T coefficients can be inspected conveniently from the derived approximations. Particularly, the R/T coefficients are analysed for the model which would be a homogeneous VTI medium, if the vertical parallel fractures were absent from the middle layer. Numerical tests demonstrate that the proposed R/T coefficient approximations perform well for the thin ORT layer. The approximation accuracy decreases when the thin layer thickness increases.
Protein–protein interaction network with machine learning models and multiomics data reveal potential neurodegenerative disease-related proteins
Authors: Yu Xinjian , Lai Siqi , Chen Hongjun , Chen Ming
Published: April 2020

Research of protein–protein interaction in several model organisms is accumulating since the development of high-throughput experimental technologies and computational methods. The protein–protein interaction network (PPIN) is able to examine biological processes in a systematic manner and has already been used to predict potential disease-related proteins or drug targets. Based on the topological characteristics of the PPIN, we investigated the application of the random forest classification algorithm to predict proteins that may cause neurodegenerative disease, a set of pathological changes featured by protein malfunction. By integrating multiomics data, we further showed the validity of our machine learning model and narrowed down the prediction results to several hub proteins that play essential roles in the PPIN. The novel insights into neurodegeneration pathogenesis brought by this computational study can indicate promising directions for future experimental research.
Impaired mitochondrial–endoplasmic reticulum interaction and mitophagy in Miro1-mutant neurons in Parkinson’s disease
Authors: Berenguer-Escuder Clara , Grossmann Dajana , Antony Paul , Arena Giuseppe , Wasner Kobi , Massart François , Jarazo Javier , Walter Jonas , Schwamborn Jens C , Grünewald Anne , Krüger Rejko
Published: April 2020

Mitochondrial Rho GTPase 1 (Miro1) protein is a well-known adaptor for mitochondrial transport and also regulates mitochondrial quality control and function. Furthermore, Miro1 was associated with mitochondrial-endoplasmic reticulum (ER) contact sites (MERCs), which are key regulators of cellular calcium homeostasis and the initiation of autophagy. Impairments of these mechanisms were linked to neurodegeneration in Parkinson’s disease (PD). We recently revealed that PD fibroblasts harboring Miro1 mutations displayed dysregulations in MERC organization and abundance, affecting mitochondrial homeostasis and clearance. We hypothesize that mutant Miro1 impairs the function of MERCs and mitochondrial dynamics, altering neuronal homeostasis and integrity in PD. PD skin fibroblasts harboring the Miro1-R272Q mutation were differentiated into patient-derived neurons. Live-cell imaging and immunocytochemistry were used to study mitophagy and the organization and function of MERCs. Markers of autophagy or mitochondrial function were assessed by western blotting. Quantification of organelle juxtapositions revealed an increased number of MERCs in patient-derived neurons. Live-cell imaging results showed alterations of mitochondrial dynamics and increased sensitivity to calcium stress, as well as reduced mitochondrial clearance. Finally, western blot analysis indicated a blockage of the autophagy flux in Miro1-mutant neurons. Miro1-mutant neurons display altered ER-mitochondrial tethering compared with control neurons. This alteration likely interferes with proper MERC function, contributing to a defective autophagic flux and cytosolic calcium handling capacity. Moreover, mutant Miro1 affects mitochondrial dynamics in neurons, which may result in disrupted mitochondrial turnover and altered mitochondrial movement.
Lipid storage patterns in marine copepods: environmental, ecological, and intrinsic drivers
Authors: Cavallo Alessandro , Peck Lloyd S
Published: April 2020

Seasonality of food supply is a major driver of physiological and ecological adaptations of marine zooplankton. High-latitude marine copepods accumulate lipids for maintenance and reproductive maturation during the food-depleted winter period. The relationship between latitude and lipid storage in copepods is well established, but it is influenced by many factors, such as trophic position, sex, and depth distribution. In this study, the influence of latitude and collection depth, trophic level, sex, and the presence or absence of dormancy on the relative amount and composition of lipids stored was assessed by analysing published data. Our analyses confirmed higher lipid contents (expressed as % dry weight) in high-latitude species, and in deep-dwelling tropical copepods compared to shallow-living ones. Contrary to our original hypothesis, carnivorous and herbivorous copepods had similar lipid levels. Copepod species that undergo dormancy had higher levels of wax ester and were more common at polar and temperate latitudes. Lastly, adult male and female copepods did not significantly differ in the amount of lipids they store, suggesting that the portion of male reproductive investment, which may depend on lipid stores, has been underestimated. Taken together, these results both confirm some previously reported trends and refute others.
Genomic Epidemiology of Invasive Methicillin-Resistant Staphylococcus aureus Infections Among Hospitalized Individuals in Ontario, Canada
Authors: Guthrie Jennifer L , Teatero Sarah , Hirai Sotaro , Fortuna Alex , Rosen Daniel , Mallo Gustavo V , Campbell Jennifer , Pelude Linda , Golding George , Simor Andrew E , Patel Samir N , McGeer Allison , Fittipaldi Nahuel ,   Ontario CNISP Hospital Investigators, Delport Johan , Evans Gerald , Hota Susy , Katz Kevin , Lemieux Camille , Mertz Dominik , Science Michelle , Thampi Nisha
Published: April 2020

Background

Prevention and control of methicillin-resistant Staphylococcus aureus (MRSA) infections remain challenging. In-depth surveillance integrating patient and isolate data can provide evidence to better inform infection control and public health practice.

Methods

We analyzed MRSA cases diagnosed in 2010 (n = 212) and 2016 (n = 214) by hospitals in Ontario, Canada. Case-level clinical and demographic data were integrated with isolate characteristics, including antimicrobial resistance (AMR), classic genotyping, and whole-genome sequencing results.

Results

Community-associated MRSA (epidemiologically defined) increased significantly from 23.6% in 2010 to 43.0% in 2016 (P < .001). The MRSA population structure changed over time, with a 1.5× increase in clonal complex (CC)8 strains and a concomitant decrease in CC5. The clonal shift was reflected in AMR patterns, with a decrease in erythromycin (86.7% to 78.4%, P = .036) and clindamycin resistance (84.3% to 47.9%, P < .001) and a >2-fold increase in fusidic acid resistance (9.0% to 22.5%, P < .001). Isolates within both CC5 and CC8 were relatively genetically diverse. We identified 6 small genomic clusters—3 potentially related to transmission in healthcare settings.

Conclusions

Community-associated MRSA is increasing among hospitalized individuals in Ontario. Clonal shifting from CC5 to CC8 has impacted AMR. We identified a relatively high genetic diversity and limited genomic clustering within these dominant CCs.
Nonalcoholic Fatty Liver Disease and the Development of Metabolic Comorbid Conditions in Patients With Human Immunodeficiency Virus Infection
Authors: Krahn Thomas , Martel Myriam , Sapir-Pichhadze Ruth , Kronfli Nadine , Falutz Julian , Guaraldi Giovanni , Lebouche Bertrand , Klein Marina B , Wong Philip , Deschenes Marc , Ghali Peter , Sebastiani Giada
Published: April 2020

Background

Cardiovascular and liver disease are main causes of death in people with human immunodeficiency virus (HIV) (PWH). In HIV-uninfected patients, nonalcoholic fatty liver disease (NAFLD) is associated with incident metabolic complications. We investigated the effect of NAFLD on development of metabolic comorbid conditions in PWH.

Methods

We included PWH undergoing a screening program for NAFLD using transient elastography. NAFLD was defined as a controlled attenuation parameter ≥248 dB/m with exclusion of other liver diseases. Incident diabetes, hypertension, dyslipidemia, and chronic kidney disease were investigated using survival analysis and Cox proportional hazards.

Results

The study included 485 HIV-monoinfected patients. During a median follow-up of 40.1 months (interquartile range, 26.5–50.7 months), patients with NAFLD had higher incidences of diabetes (4.74 [95% confidence interval, 3.09–7.27] vs 0.87 [.42–1.83] per 100 person-years) and dyslipidemia (8.16 [5.42–12.27] vs 3.99 [2.67–5.95] per 100 person-years) than those without NAFLD. With multivariable analysis, NAFLD was an independent predictor of diabetes (adjusted hazard ratio, 5.13; 95% confidence interval, 2.14–12.31) and dyslipidemia (2.35; 1.34–4.14) development.

Conclusions

HIV-monoinfected patients with NAFLD are at higher risk of incident diabetes and dyslipidemia. Early referral strategies and timely management of metabolic risk may improve outcomes.
A Simple and Sensitive Dispersive Micro-Solid-Phase Extraction Coupled with High-Performance Liquid Chromatography for Quantification of Honokiol and Magnolol in Complex Matrices
Authors: Chu Chu , Li Jing , Wang Shan , Weng Lvnan , Jiang Luyi , Zhang Huan , Liu Caijing , Yan Jizhong
Published: April 2020

Background

Honokiol and magnolol were considered as markers for the analysis of Cortex Magnoliae Officinalis, its related Chinese Patent Medicines and their metabolites. However, the determination of these two analytes in a water-soluble sample is difficult and therefore requires a more efficient method.

Objective

To develop a sensitive method for the determination of honokiol and magnolol in a water-soluble sample for better quality control of Cortex Magnoliae Officinalis and its related Chinese Patent Medicines.

Method

In this work, a combination of dispersive micro-solid-phase extraction (DMSPE) and high-performance liquid chromatography (HPLC) has been developed for simultaneous preconcentration and determination of honokiol and magnolol in complex bio-samples. Several experimental factors affecting the extraction efficiency were optimized by single factor test.

Results

Under the optimized extraction conditions, the proposed method exhibited good linearity of not less than 0.9998, satisfactory precision with relative standard deviation of less than 1.3%, and acceptable mean recoveries of 97.3% and 101.5% for honokiol and magnolol, respectively. Furthermore, the method exhibits extremely high sensitivity with detection limits of 0.0097 and 0.0231 ng/mL, which is even more sensitive than those methods developed by MS.

Conclusions

The method established in this study is fast, economic, accurate, easy to operate, and importantly well suited to the extraction and analysis of honokiol and magnolol in a real complex sample matrix.
Crystal structure of adenylate kinase from an extremophilic archaeon Aeropyrum pernix with ATP and AMP
Authors: Shibanuma Yoshinori , Nemoto Naoki , Yamamoto Norifumi , Sampei Gen-Ichi , Kawai Gota
Published: April 2020

The crystal structure of an adenylate kinase from an extremophilic archaeon Aeropyrum pernix was determined in complex with full ligands, ATP-Mg2+ and AMP, at a resolution of 2.0 Å. The protein forms a trimer as found for other adenylate kinases from archaea. Interestingly, the reacting three atoms, two phosphorus and one oxygen atoms, were located almost in line, supporting the SN2 nucleophilic substitution reaction mechanism. Based on the crystal structure obtained, the reaction coordinate was estimated by the quantum mechanics calculations combined with molecular dynamics. It was found that the reaction undergoes two energy barriers; the steps for breaking the bond between the oxygen and γ-phosphorus atoms of ATP to produce a phosphoryl fragment and creating the bond between the phosphoryl fragment and the oxygen atom of the β-phosphate group of ADP. The reaction coordinate analysis also suggested the role of amino-acid residues for the catalysis of adenylate kinase.
NGTS J214358.5−380102 – NGTS discovery of the most eccentric known eclipsing M-dwarf binary system
Authors: Acton Jack S , Goad Michael R , Raynard Liam , Casewell Sarah L , Jackman James A G , Alexander Richard D , Anderson David R , Bayliss Daniel , Bryant Edward M , Burleigh Matthew R , Belardi Claudia , Cooke Benjamin F , Eigmüller Philipp , Gill Samuel , Jenkins James S , Lendl Monika , Louden Tom , McCormac James , Moyano Maximiliano , Nielsen Louise D , Tilbrook Rosanna H , Udry Stéphane , Watson Christopher A , West Richard G , Wheatley Peter J , Vines Jose I
Published: April 2020

We present the discovery of NGTS J214358.5–380102, an eccentric M-dwarf binary discovered by the Next-Generation Transit Survey (NGTS). The system period of 7.618 d is greater than many known eclipsing M-dwarf binary systems. Its orbital eccentricity of $0.323^{+0.0014}_{-0.0037}$ is large relative to the period and semimajor axis of the binary. Global modelling of photometry and radial velocities indicates stellar masses of MA = $0.426 ^{+0.0056}_{-0.0049}$ M⊙, MB = $0.455 ^{+0.0058}_{-0.0052}$ M⊙ and stellar radii RA = $0.461 ^{+0.038}_{-0.025}$ R⊙, RB = $0.411 ^{+0.027}_{-0.039}$ R⊙, respectively. Comparisons with stellar models for low-mass stars show that one star is consistent with model predictions whereas the other is substantially oversized. Spectral analysis of the system suggests a primary of spectral type M3V, consistent with both modelled masses and radii, and with spectral energy distribution fitting of NGTS photometry. As the most eccentric eclipsing M-dwarf binary known, NGTS J214358.5–380102 provides an interesting insight into the strength of tidal effects in the circularization of stellar orbits.
The dynamics of the γ Vel cluster and nearby Vela OB2 association
Authors: Armstrong Joseph J , Wright Nicholas J , Jeffries R D , Jackson R J
Published: April 2020

The kinematics of low-mass stars in nearby OB associations can provide clues about their origins and evolution. Combining the precise positions, proper motions, and parallaxes given in the second Gaia Data Release with radial-velocity measurements obtained with the Hermes spectrograph at the Anglo-Australian Telescope, we have an opportunity to study in detail the kinematics of low-mass stars belonging to the nearby γ Vel cluster and the Vela OB2 association it is projected against. The presence of lithium is used to confirm the youth of our targets. We separate our sample into the cluster and association populations based on the Gaia-ESO Survey membership probabilities their parallaxes, and kinematics. We find strong evidence for expansion in the OB association population with at least 4σ significance along all three axes, though the expansion is notably anisotropic. We discuss these results in the context of cluster and association dispersal theories.
First cosmology results using type Ia supernovae from the Dark Energy Survey: the effect of host galaxy properties on supernova luminosity
Authors: Smith M , Sullivan M , Wiseman P , Kessler R , Scolnic D , Brout D , D’Andrea C B , Davis T M , Foley R J , Frohmaier C , Galbany L , Gupta R R , Gutiérrez C P , Hinton S R , Kelsey L , Lidman C , Macaulay E , Möller A , Nichol R C , Nugent P , Palmese A , Pursiainen M , Sako M , Swann E , Thomas R C , Tucker B E , Vincenzi M , Carollo D , Lewis G F , Sommer N E , Abbott T M C , Aguena M , Allam S , Avila S , Bertin E , Bhargava S , Brooks D , Buckley-Geer E , Burke D L , Carnero Rosell A , Carrasco Kind M , Costanzi M , da Costa L N , De Vicente J , Desai S , Diehl H T , Doel P , Eifler T F , Everett S , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Glazebrook K , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hartley W G , Hollowood D L , Honscheid K , James D J , Krause E , Kuehn K , Kuropatkin N , Lima M , MacCrann N , Maia M A G , Marshall J L , Martini P , Melchior P , Menanteau F , Miquel R , Paz-Chinchón F , Plazas A A , Romer A K , Roodman A , Rykoff E S , Sanchez E , Scarpine V , Schubnell M , Serrano S , Sevilla-Noarbe I , Suchyta E , Swanson M E C , Tarle G , Thomas D , Tucker D L , Varga T N , Walker A R ,   (DES Collaboration)
Published: April 2020

We present improved photometric measurements for the host galaxies of 206 spectroscopically confirmed type Ia supernovae discovered by the Dark Energy Survey Supernova Program (DES-SN) and used in the first DES-SN cosmological analysis. For the DES-SN sample, when considering a 5D (z, x1, c, α, β) bias correction, we find evidence of a Hubble residual ‘mass step’, where SNe Ia in high-mass galaxies (>1010M⊙) are intrinsically more luminous (after correction) than their low-mass counterparts by $\gamma =0.040\pm 0.019$ mag. This value is larger by 0.031 mag than the value found in the first DES-SN cosmological analysis. This difference is due to a combination of updated photometric measurements and improved star formation histories and is not from host-galaxy misidentification. When using a 1D (redshift-only) bias correction the inferred mass step is larger, with $\gamma =0.066\pm 0.020$ mag. The 1D−5D γ difference for DES-SN is $0.026\pm 0.009$ mag. We show that this difference is due to a strong correlation between host galaxy stellar mass and the x1 component of the 5D distance-bias correction. Including an intrinsic correlation between the observed properties of SNe Ia, stretch and colour, and stellar mass in simulated SN Ia samples, we show that a 5D fit recovers γ with −9 mmag bias compared to a +2 mmag bias for a 1D fit. This difference can explain part of the discrepancy seen in the data. Improvements in modelling correlations between galaxy properties and SN is necessary to ensure unbiased precision estimates of the dark energy equation of state as we enter the era of LSST.