bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Evolution of the Glutathione S-Transferase Family in the Bemisia tabaci Species Complex
Authors: Aidlin Harari Ofer , Santos-Garcia Diego , Musseri Mirit , Moshitzky Pnina , Patel Mitulkumar , Visendi Paul , Seal Susan , Sertchook Rotem , Malka Osnat , Morin Shai
Published: January 2020

The glutathione S-transferase (GST) family plays an important role in the adaptation of herbivorous insects to new host plants and other environmental constrains. The family codes for enzymes that neutralize reactive oxygen species and phytotoxins through the conjugation of reduced glutathione. Here, we studied the molecular evolution of the GST family in Bemisia tabaci, a complex of >35 sibling species, differing in their geographic and host ranges. We tested if some enzymes evolved different functionality, by comparing their sequences in six species, representing five of the six major genetic clades in the complex. Comparisons of the nonsynonymous to synonymous substitution ratios detected positive selection events in 11 codons of 5 cytosolic GSTs. Ten of them are located in the periphery of the GST dimer, suggesting a putative involvement in interactions with other proteins. Modeling the tertiary structure of orthologous enzymes, identified additional 19 mutations in 9 GSTs, likely affecting the enzymes’ functionality. Most of the mutation events were found in the environmentally responsive classes Delta and Sigma, indicating a slightly different delta/sigma tool box in each species. At a broader genomic perspective, our analyses indicated a significant expansion of the Delta GST class in B. tabaci and a general association between the diet breadth of hemipteran species and their total number of GST genes. We raise the possibility that at least some of the identified changes improve the fitness of the B. tabaci species carrying them, leading to their better adaptation to specific environments.
Can Green Algal Plastid Genome Size Be Explained by DNA Repair Mechanisms?
Authors: Smith David Roy
Published: January 2020

A major finding in organelle biology over the past decade is that land plant mitochondrial genomes, which are the largest among eukaryotes, can have a “Jekyll and Hyde” mutational pattern: low for synonymous sites, high for intergenic ones. This has led to the theory that double-strand breaks (DSBs) in the intergenic DNA of plant mitogenomes are repaired by inaccurate mechanisms, such as break-induced replication, which can result in large insertions and, thus, could explain why these genomes are so prone to expansion. But how universal is this theory? Can it apply to other giant organelle DNAs, such as the massive plastid DNAs (ptDNAs) of chlamydomonadalean green algae? Indeed, it can. Analysis of the expanded plastomes from two distinct isolates of the unicellular chlamydomonadalean Chlorosarcinopsis eremi uncovered exceptionally low rates of synonymous substitution in the coding regions but high substitution rates, including frequent indels, in the noncoding ptDNA, mirroring the trend from land plant mitogenomes. Remarkably, nearly all of the substitutions and indels identified in the noncoding ptDNA of C. eremi occur adjacent to or within short inverted palindromic repeats, suggesting that these elements are mutational hotspots. Building upon earlier studies, I propose that these palindromic repeats are predisposed to DSBs and that error-prone repair of these breaks is contributing to genomic expansion. Short palindromic repeats are a common theme among bloated plastomes, including the largest one on record, meaning that these data could have wide-reaching implications for our understanding of ptDNA expansion.
Surgical correction of coarctation of the aorta featuring an incomplete circle of Willis
Authors: Sonobe Aiko , Kato Hideyuki , Mathis Bryan J , Hiramatsu Yuji
Published: January 2020

Although devastating complications during simple coarctation of aorta repair now occur less frequently, some unique cases still require extra caution. Here, we report a case of coarctation of the aorta with a rare anomaly in the circle of Willis and an aberrant right subclavian artery, which required a thorough surgical strategy that prevented cerebral malperfusion.
Floating thrombus in the ascending aorta revealed by peripheral arterial embolism
Authors: Gueldich Majdi , Piscitelli Mariantonietta , Derbel Haytham , Boughanmi Khaoula , Bergoend Eric , Chanai Nora , Folliguet Thierry , Fiore Antonio
Published: January 2020

A floating thrombus in the ascending aorta is rarely found in clinical practice and is an uncommon cause of peripheral arterial embolization. When there is minimal atherosclerosis or a normal aorta, the management of such a lesion is poorly defined. Currently, there is no clear consensus concerning optimal treatment. Herein, we report 2 cases of ascending aortic thrombus that are complicated by a peripheral embolic event. Due to the risk of recurrent systemic embolism, particularly with strokes, surgical thrombectomy with ascending aortic wall replacements was performed. We believe that floating ascending aorta thrombus represents a serious source of systemic embolism and stroke. Surgical removal is easy to perform with good clinical outcomes. Conservative treatments such as anticoagulation or thromboaspiration may be considered in high-risk or inoperable patients.
Hospital adoption of multiple health information exchange approaches and information accessibility
Authors: Everson Jordan , Butler Evan
Published: January 2020

Objective

Hospital engagement in electronic health information exchange (HIE) has increased over recent years. We aimed to 1) determine the change in adoption of 3 types of information exchange: secure messaging, provider portals, and use of an HIE; and 2) to assess if growth in each approach corresponded to increased ability to access and integrate patient information from outside providers.

Methods

Panel analysis of all nonfederal, acute care hospitals in the United States using hospital- and year-fixed effects. The sample consisted of 1917 hospitals that responded to the American Hospital Association Information Technology Supplement every year from 2014 to 2016.

Results

Adoption of each approach increased by 9–15 percentage points over the study period. The average number of HIE approaches used by each hospital increased from 1.0 to 1.4. Adoption of each approach was associated with increased likelihood that providers routinely had necessary outside information of 4.2–12.7 percentage points and 4.5–13.3 percentage points increase in information integration. Secure messaging was associated with the largest increase in both. Adoption of 1 approach increased the likelihood of having outside information by 10.3 percentage points, while adopting a second approach further increased the likelihood by 9.5 percentage points. Trends in number of approaches and integration were similar.

Discussion/Conclusion

No single HIE tool provided high levels of usable, integrated health information. Instead, hospitals benefited from adopting multiple tools. Policy initiatives that reduce the complexity of enabling high value HIE could result in broader adoption of HIE and use of information to inform care.
Transposon-induced methylation of the RsMYB1 promoter disturbs anthocyanin accumulation in red-fleshed radish
Authors: Wang Qingbiao , Wang Yanping , Sun Honghe , Sun Liang , Zhang Li
Published: January 2020

Red-fleshed radish (Raphanus sativus L.) is a unique cultivar whose taproot is rich in anthocyanins beneficial to human health. However, the frequent occurrence of white-fleshed mutants affects the purity of commercially produced radish and the underlying mechanism has puzzled breeders for many years. In this study, we combined quantitative trait location by genome resequencing and transcriptome analyses to identify a candidate gene (RsMYB1) responsible for anthocyanin accumulation in red-fleshed radish. However, no sequence variation was found in the coding and regulatory regions of the RsMYB1 genes of red-fleshed (MTH01) and white-fleshed (JC01) lines, and a 7372 bp CACTA transposon in the RsMYB1 promoter region occurred in both lines. A subsequent analysis suggested that the white-fleshed mutant was the result of altered DNA methylation in the RsMYB1 promoter. This heritable epigenetic change was due to the hypermethylated CACTA transposon, which induced the spreading of DNA methylation to the promoter region of RsMYB1. Thus, RsMYB1 expression was considerably down-regulated, which inhibited anthocyanin biosynthesis in the white-fleshed mutant. An examination of transgenic radish calli and the results of a virus-induced gene silencing experiment confirmed that RsMYB1 is responsible for anthocyanin accumulation. Moreover, the mutant phenotype was partially eliminated by treatment with a demethylating agent. This study explains the molecular mechanism regulating the appearance of white-fleshed mutants of red-fleshed radish.
Genome-Wide Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population
Authors: Yasumizu Yoshiaki , Sakaue Saori , Konuma Takahiro , Suzuki Ken , Matsuda Koichi , Murakami Yoshinori , Kubo Michiaki , Palamara Pier Francesco , Kamatani Yoichiro , Okada Yukinori
Published: January 2020

Elucidation of natural selection signatures and relationships with phenotype spectra is important to understand adaptive evolution of modern humans. Here, we conducted a genome-wide scan of selection signatures of the Japanese population by estimating locus-specific time to the most recent common ancestor using the ascertained sequentially Markovian coalescent (ASMC), from the biobank-based large-scale genome-wide association study data of 170,882 subjects. We identified 29 genetic loci with selection signatures satisfying the genome-wide significance. The signatures were most evident at the alcohol dehydrogenase (ADH) gene cluster locus at 4q23 (PASMC = 2.2 × 10−36), followed by relatively strong selection at the FAM96A (15q22), MYOF (10q23), 13q21, GRIA2 (4q32), and ASAP2 (2p25) loci (PASMC < 1.0 × 10−10). The additional analysis interrogating extended haplotypes (integrated haplotype score) showed robust concordance of the detected signatures, contributing to fine-mapping of the genes, and provided allelic directional insights into selection pressure (e.g., positive selection for ADH1B-Arg48His and HLA-DPB1*04:01). The phenome-wide selection enrichment analysis with the trait-associated variants identified a variety of the modern human phenotypes involved in the adaptation of Japanese. We observed population-specific evidence of enrichment with the alcohol-related phenotypes, anthropometric and biochemical clinical measurements, and immune-related diseases, differently from the findings in Europeans using the UK Biobank resource. Our study demonstrated population-specific features of the selection signatures in Japanese, highlighting a value of the natural selection study using the nation-wide biobank-scale genome and phenotype data.
FAM46B is a prokaryotic-like cytoplasmic poly(A) polymerase essential in human embryonic stem cells
Authors: Hu Jia-Li , Liang He , Zhang Hong , Yang Ming-Zhu , Sun Wei , Zhang Peng , Luo Li , Feng Jian-Xiong , Bai Huajun , Liu Fang , Zhang Tianpeng , Yang Jin-Yu , Gao Qingsong , Long Yongkang , Ma Xiao-Yan , Chen Yang , Zhong Qian , Yu Bing , Liao Shuang , Wang Yongbo , Zhao Yong , Zeng Mu-Sheng , Cao Nan , Wang Jichang , Chen Wei , Yang Huang-Tian , Gao Song
Published: January 2020

Family with sequence similarity (FAM46) proteins are newly identified metazoan-specific poly(A) polymerases (PAPs). Although predicted as Gld-2-like eukaryotic non-canonical PAPs, the detailed architecture of FAM46 proteins is still unclear. Exact biological functions for most of FAM46 proteins also remain largely unknown. Here, we report the first crystal structure of a FAM46 protein, FAM46B. FAM46B is composed of a prominently larger N-terminal catalytic domain as compared to known eukaryotic PAPs, and a C-terminal helical domain. FAM46B resembles prokaryotic PAP/CCA-adding enzymes in overall folding as well as certain inter-domain connections, which distinguishes FAM46B from other eukaryotic non-canonical PAPs. Biochemical analysis reveals that FAM46B is an active PAP, and prefers adenosine-rich substrate RNAs. FAM46B is uniquely and highly expressed in human pre-implantation embryos and pluripotent stem cells, but sharply down-regulated following differentiation. FAM46B is localized to both cell nucleus and cytosol, and is indispensable for the viability of human embryonic stem cells. Knock-out of FAM46B is lethal. Knock-down of FAM46B induces apoptosis and restricts protein synthesis. The identification of the bacterial-like FAM46B, as a pluripotent stem cell-specific PAP involved in the maintenance of translational efficiency, provides important clues for further functional studies of this PAP in the early embryonic development of high eukaryotes.
Sources and severity of stress in a Southwestern police department
Authors: Padilla K E
Published: January 2020

Background

Policing is a stressful occupation. Most research examining police stress focuses solely on patrol officers, and often focuses on black and white officers only. Further, organizational sources of stress tend to be more important for police officers generally.

Aims

To explore sources and severity of stress in a predominately Hispanic, mid-sized, Southwestern police department.

Methods

A cross-sectional study of 147 police officers of all ranks was conducted. A modified version of the Police Stress Survey (PSS) was administered during daily briefings. Logistical regression models were utilized to examine predictors of stress based on gender, race/ethnicity, rank and tenure.

Results

Overall, occupational stressors proved more prominent than organizational stressors, contrary to previous research. Additionally, race/ethnicity was predictive of both total stress and occupational stress; rank was predictive of organizational stress; and tenure in law enforcement was predictive of occupational stress.

Conclusions

The sources of stress that impact police officers may be shifting as the climate surrounding law enforcement changes. What is stressful for officers depends on the race/ethnicity, rank and tenure of the officer within the organizational structure. Potential interventions designed to alleviate stress should be mindful of the variety of needs within any given department.
UK military women: mental health, military service and occupational adjustment
Authors: Jones N , Jones M , Greenberg N , Phillips A , Simms A , Wessely S
Published: January 2020

Background

Recently, the UK Armed Forces have revised the ground close combat role to include women.

Aims

To assess the potential mental health impact of this initiative we examined gender differences in deployment patterns, work strain, occupational factors, mental health, alcohol use and help-seeking following operational deployment.

Methods

The study was a secondary analysis of self-report survey data; 8799 men (88%) and 1185 women (12%) provided data. A sub-sample (47%, n = 4659) provided data concerning post-deployment help-seeking. The latter consisted of 408 women (8.8%) and 4251 men (91%).

Results

With the exception of alcohol misuse, which was significantly lower for women, women reported significantly more common mental disorder symptoms, subjective depression and self-harm. Women were significantly more likely to seek help from healthcare providers. Men were significantly more likely to have deployed operationally and for longer cumulative periods. Subjective work strain, but not job control, was significantly lower for women whose military careers were significantly shorter. Post-traumatic stress disorder (PTSD) symptom intensity was similar to men.

Conclusions

With the exception of PTSD and alcohol misuse, UK military women experience more mental health-related problems than military men. This finding was not related to the more arduous aspects of military service as women served for shorter times, deployed less and for shorter cumulative periods and were less likely to report work-related stress.
Impaired HDL cholesterol efflux capacity in systemic lupus erythematosus patients is related to subclinical carotid atherosclerosis
Authors: Sánchez-Pérez Hiurma , Quevedo-Abeledo Juan Carlos , de Armas-Rillo Laura , Rua--Figueroa Íñigo  , Tejera-Segura Beatriz , Armas-González Estefanía , Machado José David  , García-Dopico Jose A , Jimenez-Sosa Alejandro , Rodríguez--Lozano Carlos  , Díaz-González Federico , González-Gay Miguel A , Ferraz-Amaro Iván
Published: January 2020

Objectives

Lipid profiles appear to be altered in SLE patients due to disease activity and inflammation. Cholesterol efflux capacity (CEC) is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages. CEC has been linked to cardiovascular events in the general population and is impaired in SLE patients. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in SLE patients.

Methods

The present report is of a cross-sectional study that encompassed 418 individuals: 195 SLE patients and 223 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. Carotid intima-media thickness and carotid plaques were evaluated in SLE patients. A multivariable analysis was performed to study the relationship of CEC to SLE-related data, lipid profile and subclinical carotid atherosclerosis.

Results

CEC was downregulated in SLE patients [8.1  (4.2) % vs 16.9 (10.4) %, P = 0.004). This occurred independently of traditional cardiovascular risk factors, statin use or other variations in the lipid profile related to the disease. Traditional cardiovascular risk factors, both in patients and controls, and SLE-related data such as activity, severity or damage were not associated with CEC. After multivariable regression analysis including lipid profile–related molecules, CEC was inversely and independently associated with the presence of carotid plaques in SLE patients [odds ratio 0.87 (95% CI: 0.78, 0.97), P = 0.014].

Conclusion

CEC is impaired in SLE patients independently of other inflammation-related lipid profile modifications that occur during the disease. CEC is associated with carotid plaques in SLE patients.
Gender Difference in Willingness and Capacity for Deliberation
Authors: Afsahi Afsoun
Published: January 2020

This article examines the gender gap in deliberation, focusing on three facets: willingness to deliberate, capacity for deliberation, and facilitation techniques aimed at reducing the gender gap. It hypothesizes that women will be less willing to deliberate but more likely to engage in strictly defined desired deliberative behaviors. Relying on original survey and experimental data, this paper finds women to be more willing to deliberate. However, men’s negative deliberative behaviors—particularly cutting others off or dominating speech––undermine women’s efforts to be effective deliberators. Finally, the two innovative facilitation methods outlined in the article eliminate the gender gap.
Effect of elevated ozone, nitrogen availability and mesophyll conductance on the temperature responses of leaf photosynthetic parameters in poplar
Authors: Xu Yansen , Shang Bo , Feng Zhaozhong , Tarvainen Lasse
Published: January 2020

Although ozone (O3) concentration and nitrogen (N) availability are well known to affect plant physiology, their impacts on the photosynthetic temperature response are poorly understood. We addressed this knowledge gap by exposing seedlings of hybrid poplar clone ‘107’ (Populous euramericana cv. ‘74/76’) to elevated O3 (E-O3) and N availability variation in a factorial experiment. E-O3 decreased light-saturated net photosynthesis (Asat), mesophyll conductance (gm) and apparent maximum rate of carboxylation (Vcmax, based on intercellular CO2 concentration) but not actual Vcmax (based on chloroplast CO2 concentration) and increased respiration in light (Rd) at 25 °C. Nitrogen fertilization increased Asat, gm, Vcmax and the maximum rate of electron transport (Jmax) and reduced Rd at 25 °C and the activation energy of actual Vcmax. No E-O3 or E-O3 x N interaction effects on the temperature response parameters were detected, simplifying the inclusion of O3 impacts on photosynthesis in vegetation models. gm peaked at 30 °C, apparent Vcmax and Jmax at 32–33 °C, while the optimum temperatures of actual Vcmax and Jmax exceeded the measured temperature range (15–35 °C). Ignoring gm would, thus, have resulted in mistakenly attributing the decrease in Asat at high temperatures to reduced biochemical capacity rather than to greater diffusion limitation.
Streptomyces qinzhouensis sp. nov., a mangrove soil actinobacterium
Authors: Zhu Peng , Xu Youhou , Fu Jianjun , Liao Yongyan
Published: January 2020

A novel

Streptomyces

strain (SSL-25T) was isolated from mangrove soil sampled at QinzhouBay, PR China. The isolate was observed to be Gram-stain-positive and to form greyish-white aerial mycelia that differentiated into straight spore chains with smooth-surfaced spores on International

Streptomyces

Project 2 medium. The cell-wall peptidoglycan was determined to contain ll-diaminopimelicacid. The cell-wall sugars were glucose and mannose. The predominant menaquinones were MK-9 (H6), MK-9 (H8) and MK-9 (H4). The major polar lipids contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and several unidentified phospholipids. The predominant cellular fatty acids were C16:0, iso-C16:0 and summed feature 3 (C16:1ω7c/C16:1ω6c). The genome size of strain SSL-25T was 8.1 Mbp with a G+C content of 71.5 mol%. Phylogenetic analysis indicated that strain SSL-25T is closely related to

Streptomyces tsukubensis

NRRL 18488T (99.4 % sequence similarity). However, the digital DNA–DNA hybridization (39.8 %) and average nucleotide identity (91.3 %) values between them showed that it represents a distinct species. Furthermore, the results of morphological, physiological and biochemical tests allowed further phenotypic differentiation of strain SSL-25T from

S. tsukubensis

NRRL 18488T. Therefore, based on these results, it is concluded that strain SSL-25T represents a novel

Streptomyces

species, for which the name Streptomyces qinzhouensis sp. nov. is proposed. The type strain is SSL-25T (=CICC 11054T=JCM33585T).
Norway spruce deploys tissue specific canonical responses to acclimate to cold
Authors: Vergara Alexander , Haas Julia Christa , Stachula Paulina , Street Nathaniel Robert , Hurry Vaughan
Published: January 2020

Cold acclimation in plants is a complex phenomenon involving numerous stress-responsive transcriptional and metabolic pathways. Existing gene expression studies have primarily addressed short-term cold acclimation responses in herbaceous plants, while few have focused on perennial evergreens, such as conifers, that survive extremely low temperatures during winter. To characterize the transcriptome changes during cold acclimation inPicea abies(L.) H. Karst (Norway spruce), we performed RNA-Sequencing analysis of needles and roots subjected to a chilling progression (5 °C) followed by 10 days at freezing temperature (−5 °C). Comparing gene expression responses of needles againstArabidopsis thalianaL. (Arabidopsis) leaves, our results showed that early transient inductions were observed in both species but the transcriptional response of Norway spruce was delayed. Our results indicate that, similar to herbaceous species, Norway spruce principally utilizes early response transcription factors (TFs) that belong to theAPETALA2/ethylene-responsive element binding factor (AP2/ERF) superfamily and NACs. However, unique to the Norway spruce response was a large group of TFs that mounted a late transcriptional response to low temperature. A predicted regulatory network analysis identified key conserved TFs, including a root-specificbHLH101homolog and other members of the same family with a pervasive role in cold regulation, such as homologs ofICE1andAKS3and also homologs of the NAC (anac47andanac28) and AP2/ERF superfamilies (DREB2andERF3), providing new functional insights into cold stress response strategies in Norway spruce.

One sentence summary

Norway spruce shares elements of the cold regulon described in herbaceous species but has undescribed components that contribute to the cold tolerance of this evergreen coniferous species.
Estimating the rate of cell type degeneration from epigenetic sequencing of cell-free DNA
Authors: Caggiano Christa , Celona Barbara , Garton Fleur , Mefford Joel , Black Brian , Lomen-Hoerth Catherine , Dahl Andrew , Zaitlen Noah
Published: January 2020

Circulating cell-free DNA (cfDNA) in the bloodstream originates from dying cells and is a promising non-invasive biomarker for cell death. Here, we develop a method to accurately estimate the relative abundances of cell types contributing to cfDNA. We leverage the distinct DNA methylation profile of each cell type throughout the body. Decomposing the cfDNA mixture is difficult, as fragments from relevant cell types may only be present in a small amount. We propose an algorithm, CelFiE, that estimates cell type proportion from both whole genome cfDNA input and reference data. CelFiE accommodates low coverage data, does not rely on CpG site curation, and estimates contributions from multiple unknown cell types that are not available in reference data. In simulations we show that CelFiE can accurately estimate known and unknown cell type of origin of cfDNA mixtures in low coverage and noisy data. Simulations also demonstrate that we can effectively estimate cfDNA originating from rare cell types composing less than 0.01% of the total cfDNA. To validate CelFiE, we use a positive control: cfDNA extracted from pregnant and non-pregnant women. CelFiE estimates a large placenta component specifically in pregnant women (p= 9.1 × 10−5). Finally, we use CelFiE to decompose cfDNA from ALS patients and age matched controls. We find increased cfDNA concentrations in ALS patients (p= 3.0 × 10−3). Specifically, CelFiE estimates increased skeletal muscle component in the cfDNA of ALS patients (p= 2.6 × 10−3), which is consistent with muscle impairment characterizing ALS. Quantification of skeletal muscle death in ALS is novel, and overall suggests that CelFiE may be a useful tool for biomarker discovery and monitoring of disease progression.
vRNA-vRNA interactions in influenza A virus HA vRNA packaging
Authors: Miyamoto Sho , Muramoto Yukiko , Shindo Keiko , Fujita Yoko , Morikawa Takeshi , Tamura Ryoma , Gilmore Jamie L , Nakano Masahiro , Noda Takeshi
Published: January 2020

The genome of the influenza A virus is composed of eight single-stranded negative-sense RNA segments (vRNAs). The eight different vRNAs are selectively packaged into progeny virions. This process likely involves specific interactions among vRNAs via segment-specific packaging signals located in the 3’ and 5’ terminal coding regions of vRNAs. To identify vRNA(s) that interact with hemagglutinin (HA) vRNA during genome packaging, we generated a mutant virus, HA 5m2, which possessed five silent mutations in the 5’ packaging signal region of HA vRNA. The HA 5m2 virus had a specific defect in HA vRNA incorporation, which reduced the viral replication efficiency. After serial passaging in cells, the virus acquired additional mutations in the 5’ terminal packaging signal regions of both HA and PB2 vRNAs. These mutations contributed to recovery of viral growth and packaging efficiency of HA vRNA. A direct RNA-RNA interaction between the 5’ ends of HA and PB2 vRNAs was confirmedin vitro. Our results indicate that direct interactions of HA vRNA with PB2 vRNA via their packaging signal regions are important for selective genome packaging and enhance our knowledge on the emergence of pandemic influenza viruses through genetic reassortment.
fMRI-guided white matter connectivity in fluid and crystallized cognitive abilities in healthy adults
Authors: Gazes Yunglin , Sakhardande Jayant , Mensing Ashley , Razlighi Qolamreza , Ohkawa Ann , Pleshkevich Maria , Luo Linggang , Habeck Christian
Published: January 2020

This study examined within-subject differences among three fluid abilities that decline with age: reasoning, episodic memory and processing speed, compared with vocabulary, a crystallized ability that is maintained with age. The data were obtained from the Reference Ability Neural Network (RANN) study from which 221 participants had complete behavioral data for all 12 cognitive tasks, three per ability, along with fMRI and diffusion weighted imaging data. We used fMRI task activation to guide white matter tractography, and generated mean percent signal change in the regions associated with the processing of each ability along with diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), for each cognitive ability. Qualitatively brain regions associated with vocabulary were more localized and lateralized to the left hemisphere whereas the fluid abilities were associated with brain activations that were more distributed across the brain and bilaterally situated. Using continuous age, we observed smaller correlations between MD and age for white matter tracts connecting brain regions associated with the vocabulary ability than that for the fluid abilities, suggesting that vocabulary white matter tracts were better maintained with age. Furthermore, after multiple comparisons correction, the mean percent signal change for the episodic memory showed positive associations with behavioral performance, and the associations between MD and percent signal change differed by age such that, when divided into three age groups to further explore this interaction, only the oldest age group show a significant negative correlation between the two brain measures. Overall, the vocabulary ability may be better maintained with age due to the more localized brain regions involved, which places smaller reliance on long distance white matter tracts for signal transduction. These results support the hypothesis that functional activation and white matter structures underlying the vocabulary ability contribute to the ability’s greater resistance against aging.
Assessment of statistical methods from single cell, bulk RNA-seq and metagenomics applied to microbiome data
Authors: Calgaro Matteo , Romualdi Chiara , Waldron Levi , Risso Davide , Vitulo Nicola
Published: January 2020

Background

The correct identification of differentially abundant microbial taxa between experimental conditions is a methodological and computational challenge. Recent work has produced methods to deal with the high sparsity and compositionality characteristic of microbiome data, but independent benchmarks comparing these to alternatives developed for RNA-seq data analysis are lacking.

Results

Here, we compare methods developed for single cell, bulk RNA-seq, and microbiome data, in terms of suitability of distributional assumptions, ability to control false discoveries, concordance, and power. We benchmark these methods using 100 manually curated datasets from 16S and whole metagenome shotgun sequencing.

Conclusions

The multivariate and compositional methods developed specifically for microbiome analysis did not outperform univariate methods developed for differential expression analysis of RNA-seq data. We recommend a careful exploratory data analysis prior to application of any inferential model and we present a framework to help scientists make an informed choice of analysis methods in a dataset-specific manner.
Urban warming inverse contribution on risk of dengue transmission in the southeastern North America
Authors: Simon Lorena M. , Pinto-Ledezma Jesús N. , Dunn Robert R. , Rangel Thiago
Published: January 2020

Preventing diseases from becoming a problem where they are not is a common ground for disease ecology. The expectation for vector-borne diseases, especially those transmitted by mosquitos, is that warm and wet conditions favor vector traits increasing transmission potential. The advent of urbanization altering inner climate conditions hazards to increase mosquito’s transmission potential on “disease-free” cooler areas as a consequence of a warming urban heat island (UHI) effect.

We assessed the realism of the anticipated dengue transmission potential into the southern United States in a causal pathway with the ongoing UHI effect, vectors’ spatial distribution patterns, and exogenous environment; We also measured the climatic niche similarity between both dengue vectors species.

Our path model revealed that the UHI effect presents negative or no relation with dengue transmission potential. Instead, the surrounding non-urban temperature was rather suitable for the expected mosquitos’ transmission potential.

Both dengue vectors’ occurrence revealed to be more aggregated then expected by chance. These mosquitos’ density patterns were responsive to the warming effect of UHI-especiallyAedes Aegypti-but not a reliable predictor for the anticipated dengue transmission potential pattern. The climatic niches of both vectors are not equivalent. Although currently highly overlapped, there is a wide space of their climatic niche still to be filled.

Policy implications.We highlight that the warming UHI effect on urban sites is not congruent with the expected suitability for dengue transmission. Instead, non-urban areas would be a better focus for dengue hazards into the southern United States. Our study also highlights the need for including low scale temperature on further mosquito-borne disease transmission models and track vectors niche filling under anthropogenic changes.
Expanding the utility of sequence comparisons using data from whole genomes
Authors: Gosselin Sean , Fullmer Matthew S. , Feng Yutian , Gogarten Johann Peter
Published: January 2020

Whole genome comparisons based on Average Nucleotide Identities (ANI), and the Genome-to-genome distance calculator have risen to prominence in rapidly classifying taxa using whole genome sequences. Some implementations have even been proposed as a new standard in species classification and have become a common technique for papers describing newly sequenced genomes. However, attempts to apply whole genome divergence data to delineation of higher taxonomic units, and to phylogenetic inference have had difficulty matching those produced by more complex phylogenetics methods. We present a novel method for generating reliable and statistically supported phylogenies using established ANI techniques. For the test cases to which we applied the developed approach we obtained accurate results up to at least the family level. The developed method uses non-parametric bootstrapping to gauge reliability of inferred groups. This method offers the opportunity make use of whole-genome comparison data that is already being generated to quickly produce accurate phylogenies. Additionally, the developed ANI methodology can assist classification of higher order taxonomic groups.

Significance Statement

The average nucleotide identity (ANI) measure and its iterations have come to dominatein-silicospecies delimitation in the past decade. Yet the problem of gene content has not been fully resolved, and attempts made to do so contain two metrics which makes interpretation difficult at times. We provide a new single based ANI metric created from the combination of genomic content and genomic identity measures. Our results show that this method can handle comparisons of genomes with divergent content or identity. Additionally, the metric can be used to create distance based phylogenetic trees that are comparable to other tree building methods, while also providing a tentative metric for categorizing organisms into higher level taxonomic classifications.
Macrofaunal Diversity and Community Structure of the DeSoto Canyon and Adjacent Slope
Authors: Shantharam Arvind K. , Wei Chih-Lin , Silva Mauricio , Baco Amy R.
Published: January 2020

Macrofauna within the DeSoto Canyon, northern Gulf of Mexico (GOM), along the canyon wall and axis, and on the adjacent slope, were sampled along with sediment, terrain, and water mass parameters. Within the canyon, abundance and species richness decreased with depth, while evenness increased. Cluster analysis identified three depth-related groups within the canyon that conformed to previously established bathymetric boundaries: stations at 464 – 485 m, 669 – 1834 m, and > 2000 m. Abundance differed between depth groups. Species richness was lowest for the deepest group and evenness was lowest for the shallowest. Community structure within the canyon most related to fluorometry and oxygen saturation, combined with any of salinity, particulate organic carbon, sediment organic carbon, or slope.

Canyon wall abundances were higher than the canyon axis or adjacent slope. Community structure differed between all three habitat types. Ordination of community structure suggests a longitudinal pattern that potentially tracks with increasing sea-surface chlorophyll that occurs in the eastward direction across the northern GOM. Canyon and slope differences may result from seasonal water masses entrained by canyon topography characterized by high salinity, oxygen saturation, fluorometry, and turbidity. Higher fluorescence and turbidity in the canyon did not translate into higher sediment organic matter. Flushing along canyon wall channels and the canyon axis may explain the low organic matter. Differences in abundance and structure between the canyon wall and axis may result from microhabitat heterogeneity due to potential hydrocarbon seepage, organically enriched sediment deposits along channels, or remnant influence from the Deepwater Horizon blowout.
CluStrat: a structure informed clustering strategy for population stratification
Authors: Bose Aritra , Burch Myson C. , Chowdhury Agniva , Paschou Peristera , Drineas Petros
Published: January 2020

Genome-wide association studies (GWAS) have been extensively used to estimate the signed effects of trait-associated alleles. Recent independent studies failed to replicate the strong evidence of selection for height across Europe implying the shortcomings of standard population stratification correction approaches. Here, we present CluStrat, a stratification correction algorithm for complex population structure that leverages the linkage disequilibrium (LD)-induced distances between individuals. CluStrat performs agglomerative hierarchical clustering using the Mahalanobis distance and then applies sketching-based randomized ridge regression on the genotype data to obtain the association statistics. With the growing size of data, computing and storing the genome wide covariance matrix is a non-trivial task. We get around this overhead by computing the GRM directly using a connection between statistical leverage scores and the Mahalanobis distance. We test CluStrat on a large simulation study of discrete and admixed, arbitrarily-structured sub-populations identifying two to three-fold more true causal variants when compared to Principal Component (PC) based stratification correction methods while trading off for a slightly higher spurious associations. Applying CluStrat on WTCCC2 Parkinson’s disease (PD) data, we identified loci mapped to a host of genes associated with PD such as BACH2, MAP2, NR4A2, SLC11A1, UNC5C to name a few.

Availability and Implementation

CluStrat source code and user manual is available at:https://github.com/aritra90/CluStrat
Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer
Authors: Tejada-Martinez Daniela , de Magalhães João Pedro , Opazo Juan C.
Published: January 2020

Cetaceans are the longest-living species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases such cancer, although the underlying molecular bases of these remain unknown. The goal of this study was to investigate the role of natural selection in the evolution of 1077 tumour suppressor genes (TSGs) in cetaceans. We used a comparative genomic approach to analyse two sources of molecular variation in the form of dN/dS rates and gene copy number variation. We found a signal of positive selection in the ancestor of cetaceans within theCXCR2gene, an important regulator of DNA-damage, tumour dissemination, and immune system. Further, in the ancestor of baleen whales, we found six genes exhibiting positive selection relating to such diseases as breast carcinoma, lung neoplasm (ADAMTS8) and leukaemia (ANXA1). The TSG turnover rate (gene gain and loss) was almost 2.4-fold higher in cetaceans as compared to other mammals, and noticeably even faster in baleen whales. The molecular variants in TSGs found in baleen whales, combined with the faster gene turnover rate, could have favoured the evolution of their particular traits of anti-cancer resistance, gigantism and longevity. Additionally, we report 71 genes with duplications, of which 11 genes are linked to longevity (e.g.NOTCH3andSIK1) and are important regulators of senescence, cell proliferation and metabolism. Overall, these results provide evolutionary evidence that natural selection in tumour suppressor genes could act on species with large body sizes and extended life span, providing novel insights into the genetic basis of disease resistance.
WNT and inflammatory signaling distinguish human Fallopian tube epithelial cell populations
Authors: Rose Ian , Bidarimath Mallikarjun , Webster Alex , Godwin Andrew K. , Flesken-Nikitin Andrea , Nikitin Alexander Yu.
Published: January 2020

A substantial fraction of ovarian/extra-uterine high-grade serous carcinomas (HGSCs) likely originate in the distal region of the Fallopian tube’s epithelium (TE) before implanting/metastasizing to the ovary. Unfortunately, molecular and cellular mechanisms rendering preferential cancer susceptibility of the human distal TE remain insufficiently elucidated, largely due to limited primary human TE gene expression data. Here we report an in depth bioinformatic characterization of 34 primary TE cell mRNA-seq samples. These samples were prepared from the proximal and distal TE regions of 12 normal Fallopian tubes. TE cells were segregated based on their aldehyde dehydrogenase (ALDH) activity. As compared to the proximal TE, cells from the distal region form organoids with higher frequency and larger size during serial organoid formation assays. Consistent with enrichment for organoid-forming stem/progenitor cells, ALDH+ cells have greater WNT signaling activity. Comparative evaluation of proximal and distal TE cell population’s shows heightened inflammatory signaling in distal differentiated (ALDH-) TE. Furthermore, comparisons of proximal and distal TE cell populations finds that the distal TE express gene sets characteristic of four HGSC molecular sub-types, and that distal ALDH+ cell populations exhibit greater enrichment than their ALDH-counterparts. Taken together, our study shows that increased organoid forming capacity, WNT and inflammatory signaling, and HGSC signatures underlie the differences between distal and proximal regions of the human TE. These findings provide the basis for further mechanistic studies of distal TE susceptibility to the malignant transformation.
Improvement of phycocyanobilin synthesis for genetically encoded phytochrome-based optogenetics
Authors: Uda Youichi , Miura Haruko , Goto Yuhei , Aoki Kazuhiro
Published: January 2020

Optogenetics is a powerful technique using photoresponsive proteins, and light-inducible dimerization (LID) systems, an optogenetic tool, allow to manipulate intracellular signaling pathways. One of the red/far-red responsive LID system, phytochrome B (PhyB)-phytochrome interacting factor (PIF), has a unique property of controlling both association and dissociation by light on the second time scale, but PhyB requires a linear tetrapyrrole chromophore such as phytochromobilin or phycocyanobilin (PCB), and such chromophores are present only in higher plants and cyanobacteria. Here, we report that we further improved our previously developed PCB synthesis system (synPCB), and successfully established a stable cell line containing a genetically encoded PhyB-PIF LID system. First, four genes responsible for PCB synthesis, namely,PcyA,HO1,Fd, andFnr, were replaced with their counterparts derived from thermophilic cyanobacteria. Second, Fnr was truncated, followed by fusion with Fd to generate a chimeric protein, tFnr-Fd. Third, these genes were concatenated with P2A peptide cDNAs for polycistronic expression, resulting in an approximately 4-fold increase in PCB synthesis compared with the previous version. Finally, we incorporated PhyB-PIF and synPCB into drug inducible lentiviral and transposon vectors, which enabled us to induce PCB synthesis and PhyB-PIF LID system by doxycycline treatment. These tools provide a new opportunity to advance our understanding of the causal relationship between intracellular signaling and cellular functions.
Deep Learning Modelling of Androgen Receptor Responses to Prostate Cancer Therapies
Authors: Snow Oliver , Lallous Nada , Ester Martin , Cherkasov Artem
Published: January 2020

Gain-of-function mutations in human Androgen Receptor (AR) are amongst major causes of drug resistance in prostate cancer (PCa). Identifying mutations that cause resistant phenotype is of critical importance for guiding treatment protocols as well as for designing drugs that do not elicit adverse responses. However, experimental characterization of these mutations is time consuming and costly, and therefore predictive models are needed to anticipate resistant mutations and to guide drug discovery process. In this work, we leverage experimental data collected on 69 clinically observed and/or literature described AR mutants to train a deep neural network (DNN) to predict their responses to currently used and experimental AR anti-androgens. We demonstrate that the use of DNN provides more accurate prediction of the biological outcome (inhibition, activation, no-response) in AR mutant-drug pairs compared to other machine learning approaches and also allows the use of more general 2D descriptors. Finally, the developed approach was used to predict the effect of the latest AR inhibitor darolutamide on all reported AR mutants.