bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabinoid Receptor Activation on Haematopoietic Cells and Enterocytes Protects against Colitis
Authors: Becker William , Alrafas Haider Rasheed , Busbee Philip B , Walla Michael D , Wilson Kiesha , Miranda Kathryn , Cai Guoshuai , Putluri Vasanta , Putluri Nagireddy , Nagarkatti Mitzi , Nagarkatti Prakash S
Published: December 2020

Background and Aims

Cannabinoid receptor [CB] activation can attenuate inflammatory bowel disease [IBD] in experimental models and human cohorts. However, the roles of the microbiome, metabolome, and the respective contributions of haematopoietic and non-haematopoietic cells in the anti-colitic effects of cannabinoids have yet to be determined.

Methods

Female C57BL/6 mice were treated with either cannabidiol [CBD], Δ 9-tetrahydrocannabinol [THC], a combination of CBD and THC, or vehicle, in several models of chemically induced colitis. Clinical parameters of colitis were assessed by colonoscopy, histology, flow cytometry, and detection of serum biomarkers; single-cell RNA sequencing and qRT-PCR were used to evaluate the effects of cannabinoids on enterocytes. Immune cell transfer from CB2 knockout mice was used to evaluate the contribution of haematopoietic and non-haematopoietic cells to colitis protection.

Results

We found that THC prevented colitis and that CBD, at the dose tested, provided little benefit to the amelioration of colitis, nor when added synergistically with THC. THC increased colonic barrier integrity by stimulating mucus and tight junction and antimicrobial peptide production, and these effects were specific to the large intestine. THC increased colonic Gram-negative bacteria, but the anti-colitic effects of THC were independent of the microbiome. THC acted both on immune cells via CB2 and on enterocytes, to attenuate colitis.

Conclusions

Our findings demonstrate how cannabinoid receptor activation on both immune cells and colonocytes is critical to prevent colonic inflammation. These studies also suggest how cannabinoid receptor activation can be used as a preventive and therapeutic modality against colitis.
Weather Conditions Affect the Visitation Frequency, Richness and Detectability of Insect Flower Visitors in the Australian Alpine Zone
Authors: Goodwin Emma K , Rader Romina , Encinas-Viso Francisco , Saunders Manu E
Published: December 2020

Weather conditions, such as humidity, temperature, and wind speed, affect insect activity. Understanding how different taxa respond to varying environmental conditions is necessary to determine the extent to which environmental change may impact plant-pollinator networks. This is particularly important in alpine regions where taxa may be more susceptible to extreme climatic events and overall increases in temperature. We observed plant–flower visitor interactions in Australian alpine plant communities to determine 1) the structure of the plant-flower visitor community, and 2) how floral visitation and diversity of insect taxa varied according to environmental conditions and habitat type. Coleoptera and Diptera were the most dominant flower visitors in the visitation networks. Most insect orders were moderately generalized in their interactions, but Hymenoptera showed greater specialization (d′) at exposed sites compared to other insect orders. Importantly, insect orders behaved differently in response to changes in environmental conditions. Hymenoptera visitation increased with higher temperatures. Diptera was the only taxon observed actively moving between flowers under inclement conditions. Our results demonstrate the value in sampling across the spectrum of environmental conditions to capture the differences among flower visiting insect taxa in their responses to varying environmental conditions. A diversity of responses among insect taxa could facilitate community-level resilience to changing environmental conditions.
Exploring LGBTQ+ pedagogy in Japanese university classrooms
Authors: Lawrence Luke , Nagashima Yuzuko
Published: December 2020

Although ostensibly a free and open society, Japan is often seen to be lagging behind in terms of lesbian, gay, bisexual, transgender, queer, and other (LGBTQ+) rights and understanding of LGBTQ+ issues. This lack of understanding leads to a high degree of invisibility for LGBTQ+ members and a lack of inclusivity in educational curriculums. In this article, the authors document their explorations of introducing both explicit and implicit LGBTQ+ content into university English classes in Japan and their efforts to create a safe and inclusive classroom environment. After reporting on students’ reactions and feelings towards these activities, we recommend a varied approach to LGBTQ+ topics in the classroom that we hope will be of use to teachers not only in Japan, but around the world too.
A systematic review of general practice-based pharmacists’ services to optimize medicines management in older people with multimorbidity and polypharmacy
Authors: Hasan Ibrahim Ameerah S , Barry Heather E , Hughes Carmel M
Published: December 2020

Background

Few studies have evaluated roles of general practice-based pharmacists (PBPs), particularly in optimizing medicines management for older people with both multimorbidity and polypharmacy.

Objective

To explore the types and effectiveness of services provided by PBPs, either alone or in collaboration with other primary health care professionals, that sought to optimize medicines management for older people with multimorbidity and polypharmacy.

Methods

Eight electronic databases and three trial registries were searched for studies published in English until April 2020. Inclusion criteria were randomized controlled trials, non-randomized controlled trials and controlled before-and-after studies of services delivered by PBPs in primary care/general practice, for patients aged ≥65 years with both multimorbidity and polypharmacy that focused on a number of outcomes. The Cochrane risk of bias tool for randomized trials (RoB 1) and the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) assessment tool were used for quality assessment. A narrative synthesis was conducted due to study heterogeneity.

Results

Seven studies met inclusion criteria. All included studies employed PBP-led medication review accompanied by recommendations agreed and implemented by general practitioners. Other patient-level and practice-level interventions were described in one study. The limited available evidence suggested that PBPs, in collaboration with other practice team members, had mixed effects on outcomes focused on optimizing medicines management for older people. Most included studies were of poor quality and data to estimate the risk of bias were often missing.

Conclusion

Future high-quality studies are needed to test the effects of PBP interventions on a well-defined range of medicines management-related outcomes.
microeco: an R package for data mining in microbial community ecology
Authors: Liu Chi , Cui Yaoming , Li Xiangzhen , Yao Minjie
Published: December 2020

A large amount of sequencing data is produced in microbial community ecology studies using the high-throughput sequencing technique, especially amplicon-sequencing-based community data. After conducting the initial bioinformatic analysis of amplicon sequencing data, performing the subsequent statistics and data mining based on the operational taxonomic unit and taxonomic assignment tables is still complicated and time-consuming. To address this problem, we present an integrated R package-‘microeco’ as an analysis pipeline for treating microbial community and environmental data. This package was developed based on the R6 class system and combines a series of commonly used and advanced approaches in microbial community ecology research. The package includes classes for data preprocessing, taxa abundance plotting, venn diagram, alpha diversity analysis, beta diversity analysis, differential abundance test and indicator taxon analysis, environmental data analysis, null model analysis, network analysis and functional analysis. Each class is designed to provide a set of approaches that can be easily accessible to users. Compared with other R packages in the microbial ecology field, the microeco package is fast, flexible and modularized to use and provides powerful and convenient tools for researchers. The microeco package can be installed from CRAN (The Comprehensive R Archive Network) or github (https://github.com/ChiLiubio/microeco).
Metabolic engineering of Saccharomyces cerevisiae for production of β-carotene from hydrophobic substrates
Authors: Fathi Zahra , Tramontin Larissa Ribeiro Ramos , Ebrahimipour Gholamhossein , Borodina Irina , Darvishi Farshad
Published: December 2020

β-Carotene is a yellow–orange–red pigment used in food, cosmetics and pharmacy. There is no commercial yeast-based process for β-carotene manufacturing. In this work, we engineered the baker's yeast Saccharomyces cerevisiae by expression of lipases and carotenogenic genes to enable the production of β-carotene on hydrophobic substrates. First, the extracellular lipase (LIP2) and two cell-bound lipases (LIP7 and LIP8) from oleaginous yeast Yarrowia lipolytica were expressed either individually or in combination in S. cerevisiae. The engineered strains could grow on olive oil and triolein as the sole carbon source. The strain expressing all three lipases had ∼40% lipid content per dry weight. Next, we integrated the genes encoding β-carotene biosynthetic pathway, crtI, crtYB and crtE from Xanthophyllomyces dendrorhous. The resulting engineered strain bearing the lipases and carotenogenic genes reached a titer of 477.9 mg/L β-carotene in yeast peptone dextrose (YPD) medium supplemented with 1% (v/v) olive oil, which was 12-fold higher than an analogous strain without lipases. The highest β-carotene content of 46.5 mg/g DCW was obtained in yeast nitrogen base (YNB) medium supplemented with 1% (v/v) olive oil. The study demonstrates the potential of applying lipases and hydrophobic substrate supplementation for the production of carotenoids in S. cerevisiae.
A Blind Spot in the Use of the Weibull Function for Modeling Diameter Distributions
Authors: Goodwin Adrian Norman
Published: December 2020

Diameter distribution models based on probability density functions are integral to many forest growth and yield systems, where they are used to estimate product volumes within diameter classes. The three-parameter Weibull function with a constrained nonnegative lower bound is commonly used because of its flexibility and ease of fitting. This study compared Weibull and reverse Weibull functions with and without a lower bound constraint and left-hand truncation, across three large unthinned plantation cohorts in which 81% of plots had negatively skewed diameter distributions. Near-optimal lower bounds for the unconstrained Weibull function were negative for negatively skewed data, and the left-truncated Weibull using these bounds was 14.2% more accurate than the constrained Weibull, based on the Kolmogorov-Smirnov statistic. The truncated reverse Weibull fit dominant tree distributions 23.7% more accurately than the constrained Weibull, based on a mean absolute difference statistic. This work indicates that a blind spot may have developed in plantation growth modeling systems deploying constrained Weibull functions, and that left-truncation of unconstrained functions could substantially improve model accuracy for negatively skewed distributions.
SNP-adjacent super enhancer network mediates enhanced osteogenic differentiation of MSCs in ankylosing spondylitis
Authors: Yu Wenhui , Chen Keng , Ye Guiwen , Wang Shan , Wang Peng , Li Jinteng , Zheng Guan , Liu Wenjie , Lin Jiajie , Su Zepeng , Che Yunshu , Ye Feng , Ma Mengjun , Xie Zhongyu , Shen Huiyong
Published: December 2020

Ankylosing spondylitis (AS) is a rheumatic disease with pathological osteogenesis that causes bony ankylosis and even deformity over time. Mesenchymal stem cells (MSCs) are multipotent stem cells that are the main source of osteoblasts. We previously demonstrated that enhanced osteogenic differentiation of MSCs from AS patients (ASMSCs) is related to pathological osteogenesis in AS. However, the more concrete mechanism needs further exploration. Super enhancers (SEs) are dense clusters of stitched enhancers that control cell identity determination and disease development. Single-nucleotide polymorphisms (SNPs) regulate the formation and interaction of SEs and denote genes accounting for AS susceptibility. Via integrative analysis of multiomic data, including histone 3 lysine 27 acetylation (H3K27ac), chromatin immunoprecipitation sequencing (ChIP-seq), SNPs and RNA sequencing (RNA-seq) data, we discovered a transcription network mediated by AS SNP-adjacent SEs (SASEs) in ASMSCs and identified key genes, such as Toll-like receptor 4 (TLR4), interleukin 18 receptor 1 (IL18R1), insulin-like growth factor binding protein 4 (IGFBP4), transportin 1 (TNPO1) and proprotein convertase subtilisin/kexin type 5 (PCSK5), which are pivotal in osteogenesis and AS pathogenesis. The SASE-regulated network modulates the enhanced osteogenic differentiation of ASMSCs by synergistically activating the PI3K-Akt, NF-kappaB and Hippo signaling pathways. Our results emphasize the crucial role of the SASE-regulated network in pathological osteogenesis in AS, and the preferential inhibition of ASMSC osteogenic differentiation by JQ1 indicates that SEs may be attractive targets in future treatment for new bone formation in AS.
Postsurgical Treatment in Pediatric Patients With Crohn’s Disease: Physician Practice
Authors: Magen-Rimon Ramit , Garah Jamal , Rosen Irit , Shaoul Ron
Published: December 2020

The aim of this study was to evaluate the implementation of the pediatric Crohn’s disease postsurgical guidelines using an online questionnaire among North American, European, Middle Eastern, Australian, and New Zealand pediatric gastroenterologists. We found high variability in practice and low adherence to guidelines.
Mycoplasma genitalium infections can comprise a mixture of both fluoroquinolone-susceptible and fluoroquinolone-resistant strains
Authors: Sweeney Emma L , Lowry Kym , Bletchly Cheryl , Nimmo Graeme R , Whiley David M
Published: December 2020

Background

Mycoplasma genitalium was recently added to the CDC’s antimicrobial resistance threats ‘watch list’, as it has rapidly become resistant to mainstay treatments. In Australia, treatment failure with fluoroquinolones remain commonplace, even when Sanger sequencing fails to identify evidence of resistance mutations.

Methods

Suspecting that Sanger sequencing may miss low-load mixed infections, we applied three additional PCR-based approaches (allele-specific primer-based PCR, probe-based PCR and amplicon deep sequencing) to detect mutations associated with fluoroquinolone susceptibility/resistance. We focused on resistance mutations at amino acid positions 83 and 87 of parC, as these were previously shown to be common in Australia.

Results

Our results showed evidence of mixtures of fluoroquinolone-susceptible and -resistant strains in up to 27/423 samples (6.4%). These included 1 sample that was indicated to be mixed by Sanger sequencing and all three additional PCR methods, 6 samples detected by two or more of the additional PCRs but not by Sanger sequencing and finally 20 samples that were detected by only one of the additional PCR methods. A key question was whether Sanger sequencing failed to detect fluoroquinolone resistance in any samples; overall, we observed that Sanger sequencing failed to detect fluoroquinolone resistance in up to 3.8% (16/423) of samples.

Conclusions

The presence of mixed susceptibility infections may have important implications for clinical patient management and stresses the need for appropriate detection of resistance and selection of antimicrobials to ensure appropriate treatment of M. genitalium infections.
Dynamics of creatinine estimated glomerular filtration rate using one or more antiretrovirals that inhibit creatinine tubular secretion
Authors: Perez Elias Maria Jesus , Alejos Belen , Gutierrez Maria Mar , Crespo Manuel , De Los Santos Gil Ignacio , Ribera Esteve , Galindo Maria Jose , Lozano Fernando , Payeras Cifre Antonio , Boix Vicente , Montero-Alonso Marta , Sanz José , De La Torre Lima Javier , Palacios Rosario , De La Fuente Moral Sara , Martinez Esteban ,   the Codar Study Group, Callau Pilar , Cajal Ramon y , Moreno Ana , Casado Jose Luis , Sanchez Javier Martinez , Ayerbe Cristina Gómez , Vizcarra Pilar , del Campo Santos , Negredo Eugenia , Campos Isabel , Puig Jordi , Ribera Esteban , Torrella Ariadna , Planas Bibiana , Knobel Hernando , Ferrando Ramon , Crespo Manuel , Ocampo Antonio , Sanz José , de los Santos Ignacio , Moreno Alfonso , Díaz Alberto , Carbonero Luz Martin , de la Torre Javier , De Lomas Jose María Garcia , Reina Mercedes Rivas , Santos Jesús , González Domenech Carmen María , Gutierrez Ma Mar , Montero Marta , Cuéllar Sandra , Tasias María , Castro Iván , Boix Vicente , Payeras Antonio , Ryan Pablo , Torralba Miguel , Aznar Esther , Esteban Herminia , de Miguel Marta , Gonzalez Patricia , Yllescas María
Published: December 2020

Background

Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known.

Methods

Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient’s characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses.

Results

The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR [adjusted median difference (±SD) –3.5 ± 1.6 (95% CI –6.6 to –0.3), P = 0.047], and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent [adjusted OR 3.233 (95% CI 1.343–7.782), P = 0.009], with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390).

Conclusions

Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.
Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients
Authors: Falcone Marco , Menichetti Francesco , Cattaneo Dario , Tiseo Giusy , Baldelli Sara , Galfo Valentina , Leonildi Alessandro , Tagliaferri Enrico , Di Paolo Antonello , Pai Manjunath P
Published: December 2020

Background

Avibactam is a β-lactamase inhibitor that is combined with aztreonam against Enterobacterales co-expressing serine- and metallo-β-lactamases (MBL). Optimal dosing of aztreonam with avibactam is not well-defined in critically ill patients and contingent on ceftazidime/avibactam product labelling.

Objectives

To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA).

Methods

We conducted a prospective observational pharmacokinetic study. Five blood samples were collected around the fourth dose of aztreonam or ceftazidime/avibactam and assayed for all three drugs. Population pharmacokinetic (PK) analysis coupled with Monte Carlo simulations were used to create a dosing nomogram for aztreonam and ceftazidime/avibactam based on drug-specific pharmacodynamic (PD) targets.

Results

A total of 41 participants (59% male) median age of 75 years (IQR 63–79 years) were enrolled. They were critically ill (46%) with multiple comorbidities and complications including burns (20%). Population PK analysis identified higher volume of distribution and lower clearance (CL) compared with typical value expectations for aztreonam and ceftazidime/avibactam. Estimated glomerular filtration (eGFR) rate using the CKD-EPI equation predicted CL for all three drugs. The need for high doses of aztreonam and ceftazidime/avibactam above those in the existing product labels are not predicted by this analysis with the exception of ceftazidime/avibactam for patients with eGFR of 6–15 mL/min, in whom suboptimal PTA of ≤71% is predicted.

Conclusions

Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is <90 mL/min. These options should be tested prospectively.
Maternal and direct genetic parameters for tail length, tail lesions, and growth traits in pigs
Authors: Aikins-Wilson Sheila , Bohlouli Mehdi , König Sven
Published: December 2020

Tail length and tail lesions are the major triggers for tail biting in pigs. Against this background, 2 datasets were analyzed to estimate genetic parameters for tail characteristics and growth traits. Dataset 1 considered measurements for trait tail length (T-LEN) and for the growth traits birth weight (BW), weaning weight (WW), postweaning weight (PWW), and average daily gain (ADG) from 9,348 piglets. Piglets were born in the period from 2015 to 2018 and kept on the university Gießen research station. Dataset 2 included 4,943 binary observations from 1,648 pigs from the birth years 2016 to 2019 for tail lesions (T-LES) as indicators for nail necrosis, tail abnormalities, or tail biting. T-LES were recorded at 30 ± 7 d after entry for rearing (T-Les-1), at 50 ± 7 d after entry for rearing (end of the rearing period, T-LES-2), and 130 ± 20 d after entry for rearing (end of fattening period, T-LES-3). Genetic statistical model evaluation for dataset 1 based on Akaike’s information criterion and likelihood ration tests suggested multiple-trait animal models considering covariances between direct and maternal genetic effects. The direct heritability for T-LEN was 0.42 (±0.03), indicating the potential for genetic selection on short tails. The maternal genetic heritability for T-LEN was 0.05 (±0.04), indicating the influence of uterine characteristics on morphological traits. The negative correlation between direct and maternal effects for T-LEN of –0.35 (±0.13), as well as the antagonistic relationships (i.e., positive direct genetic correlations in the range from 0.03 to 0.40) between T-LEN with the growth traits BW, WW, PWW, and ADG, complicate selection strategies and breeding goal definitions. The correlations between direct effects for T-LEN and maternal effects for breeding goal traits, and vice versa, were positive but associated with a quite large SE. The heritability for T-LES when considering the 3 repeated measurements was 0.23 (±0.04) from the linear (repeatability of 0.30) and 0.21 (±0.06; repeatability of 0.29) from the threshold model. The breeding value correlations between T-LES-3 with breeding values from the repeatability models were quite large (0.74 to 0.90), suggesting trait lesion recording at the end of the rearing period. To understand all genetic mechanisms in detail, ongoing studies are focusing on association analyses between T-LEN and T-LES, and the identification of tail biting from an actor’s perspective.
The presence of multiple copies of the vitellogenin gene in Fenneropenaeus merguiensis (De Man, 1888) (Decapoda: Dendrobranchiata: Penaeidae): Evidence for gene expansion and functional diversification in shrimps
Authors: Zhao Jichen , Wang Wei , Wang Chenggui , Shi Lili , Wang Gang , Sun Chengbo , Chan Siuming F
Published: December 2020

Vitellogenin (Vg) is the precursor of egg yolk that provides nutrients to embryos of oviparous animals. We identified three Vg genes (FmVg1, FmVg2, and FmVg3) from the banana shrimp Fennerpenaeus merguiensis (De Man, 1888) (Penaeidae). The cDNAs ranged from 7,758 to 7,764 bp, and the encoded protein consisted of 2,553–2,585 amino acid residues. The genome structures of FmVg1, FmVg2, and FmVg3 were highly conserved, containing 15 exons and 14 introns. FmVg1-FmVg2, FmVg1-FmVg3, and FmVg2-FmVg3 shared a moderate 52.25%, 60.77%, and 56.45%, respectively. Phylogenetic analysis further revealed that the FmVg1 class vitellogenins are more conserved among the shrimps. The expression patterns of FmVg1, FmVg2, and FmVg3 were similar in the hepatopancreas at different ovarian developmental stages, whereas the expression trends between FmVg1 and FmVg2/3 in the ovary were remarkably different. During ontogenic development, the expression of these Vg genes all reached the highest levels at the post-larval stage. The three Vg genes also exhibited dynamic expression changes at different molting stages, with the highest expression level detected at the intermolt stage. Our study provides evidence that at least three copies of the Vg gene are present in the banana shrimp. These Vg genes are potentially involved in ovary maturation and larval development, and the divergence in their sequences, structures, and expression dynamics reflects their functional diversification in F. merguiensis. The expression of these Vg genes is therefore tightly regulated spatially and temporally. This is the first report for the molecular characterization of multiple vitellogenin genes in shrimps. Our results indicate that the vitellogenin gene is multi-functional and shows a non-sex specific expression pattern.
Measuring Systemic Risk Using Multivariate Quantile-Located ES Models
Authors: Garcia-Jorcano Laura , Sanchis-Marco Lidia
Published: December 2020

We examine the tail systemic risk between the global financial system and financial institutions that belong to different industry groups. Our main contribution is the development of a systemic risk measure Delta Quantile-Located Conditional Autoregressive Expected Shortfall, ΔQLMV−CoCARES. This new measure captures the extreme downside risk in terms of the ES of the system should both the financial system and the institution simultaneously be in distress. The evidence suggests that cross significant volatility and ES effects exist between the system and financial institutions. Furthermore, our measure presents better forecasting performance than standard or novel systemic risk measures based on VaR such as CoVaR or ΔQLMV−CoCAViaR and it is effective at predicting financial crises. We also develop a new systemic stress indicator SSIES based on ΔQLMV−CoCARES systemic risk measure which presents higher forecasting ability than other standard stress indicators.
Whole plastomes are not enough: phylogenomic and morphometric exploration at multiple demographic levels of the bee orchid clade Ophrys sect. Sphegodes
Authors: Bateman Richard M , Rudall Paula J , Murphy Alexander R M , Cowan Robyn S , Devey Dion S , Peréz-Escobar Oscar A
Published: December 2020

Plastid sequences have long dominated phylogeny reconstruction at all time depths, predicated on a usually untested assumption that they accurately represent the evolutionary histories of phenotypically circumscribed species. We combined detailed in situ morphometrics (124 plants) and whole-plastome sequencing through genome skimming (71 plants) in order to better understand species-level diversity and speciation in arguably the most challenging monophyletic group within the taxonomically controversial, pseudo-copulatory bee orchid genus Ophrys. Using trees and ordinations, we interpreted the data at four nested demographic levels—macrospecies, mesospecies, microspecies, and local population—seeking the optimal level for bona fide species. Neither morphological nor molecular discontinuities are evident at any level below macrospecies, the observed overlap among taxa suggesting that both mesospecies and microspecies reflect arbitrary division of a continuum of variation. Plastomes represent geographic location more strongly than taxonomic assignment and correlate poorly with morphology, suggesting widespread plastid capture and possibly post-glacial expansion from multiple southern refugia. As they are rarely directly involved in the speciation process, plastomes depend on extinction of intermediate lineages to provide phylogenetic signal and so cannot adequately document evolutionary radiations. The popular ‘ethological’ evolutionary model recognizes as numerous ‘ecological species’ (microspecies) lineages perceived as actively diverging as a result of density-dependent selection on very few features that immediately dictate extreme pollinator specificity. However, it is assumed rather than demonstrated that the many microspecies are genuinely diverging. We conversely envisage a complex four-dimensional reticulate network of lineages, generated locally and transiently through a wide spectrum of mechanisms, but each unlikely to maintain an independent evolutionary trajectory long enough to genuinely speciate by escaping ongoing gene flow. The frequent but localized microevolution that characterizes the Ophrys sphegodes complex is often convergent and rarely leads to macroevolution. Choosing between the contrasting ‘discontinuity’ and ‘ethology’ models will require next-generation sequencing of nuclear genomes plus ordination of corresponding morphometric matrices, seeking the crucial distinction between retained ancestral polymorphism—consistent with lineage divergence—and polymorphisms reflecting gene flow through ‘hybridization’—more consistent with lineage convergence.
An application of data visualization technique in Arabic literature and linguistics
Authors: Yi Fan , Mahmoudi Mohammad Reza , S Band Shahab
Published: December 2020

In this work, we intended to study and compare the traits of God in the Medinan and Meccan Qur'an’s Suras, based on statistics and data visualization. The entire verses of Qur’an were considered and the count of each beauty and divine glory trait was calculated, separately in Medinan and Meccan Suras. The frequencies of the divine glory, the beauty and total traits in Meccan, Medinan and total Suras were studied and compared using data visualization technique. The results indicated that for Medinan Suras, in divine glory traits, Hakem and Aziz, in beauty traits, Alim and Rahim, and totally, Alim, Rahim, and Hakem had the most uses; for Meccan Suras, in divine glory traits, Aziz and Hakim, in beauty traits, Rahman and Rahim, and totally, Rahman and Rahim had the most uses; and for total Suras, in divine glory traits, Hakem and Aziz, in beauty traits, Rahim, Rahman, and Alim, and totally, Rahim, Rahman, and Alim had the most uses. Moreover, the rates of using divine glory traits in Medinan and Meccan Suras (16.1% and 17.6%) and the rates of using beauty traits in Medinan and Meccan Suras (83.9% and 82.4%) significantly did not differ.
Feedback-limited accretion: variable luminosity from growing planets
Authors: Gárate M , Cuadra J , Montesinos M , Arévalo P
Published: December 2020

Planets form in discs of gas and dust around stars, and continue to grow by accretion of disc material while available. Massive planets clear a gap in their protoplanetary disc, but can still accrete gas through a circumplanetary disc. For high enough accretion rates, the planet should be detectable at infrared wavelengths. As the energy of the gas accreted on to the planet is released, the planet surroundings heat up in a feedback process. We aim to test how this planet feedback affects the gas in the coorbital region and the accretion rate itself. We modified the 2D code FARGO-AD to include a prescription for the accretion and feedback luminosity of the planet and use it to model giant planets on 10 au circular and eccentric orbits around a solar mass star. We find that this feedback reduces but does not halt the accretion on to the planet, although this result might depend on the near-coincident radial ranges where both recipes are implemented. Our simulations also show that the planet heating gives the accretion rate a stochastic variability with an amplitude $\Delta \dot{M}_p \sim 0.1 \dot{M}_p$. A planet on an eccentric orbit (e = 0.1) presents a similar variability amplitude, but concentrated on a well-defined periodicity of half the orbital period and weaker broad-band noise, potentially allowing observations to discriminate between both cases. Finally, we find that the heating of the co-orbital region by the planet feedback alters the gas dynamics, reducing the difference between its orbital velocity and the Keplerian motion at the edge of the gap, which can have important consequences for the formation of dust rings.
An ALMA/NOEMA survey of the molecular gas properties of high-redshift star-forming galaxies
Authors: Birkin Jack E , Weiss Axel , Wardlow J L , Smail Ian , Swinbank A M , Dudzevičiūtė U , An Fang Xia , Ao Y , Chapman S C , Chen Chian-Chou , da Cunha E , Dannerbauer H , Gullberg B , Hodge J A , Ikarashi S , Ivison R J , Matsuda Y , Stach S M , Walter F , Wang W-H , van der Werf P
Published: December 2020

We have used ALMA and NOEMA to study the molecular gas reservoirs in 61 ALMA-identified submillimetre galaxies (SMGs) in the COSMOS, UDS, and ECDFS fields. We detect 12CO ($J_{\rm up} =$ 2–5) emission lines in 50 sources, and [C i](3P1 − 3P0) emission in eight, at $z =$ 1.2–4.8 and with a median redshift of 2.9 ± 0.2. By supplementing our data with literature sources, we construct a statistical CO spectral line energy distribution and find that the 12CO line luminosities in SMGs peak at Jup ∼ 6, consistent with similar studies. We also test the correlations of the CO, [C i], and dust as tracers of the gas mass, finding the three to correlate well, although the CO and dust mass as estimated from the 3-mm continuum are preferable. We estimate that SMGs lie mostly on or just above the star-forming main sequence, with a median gas depletion timescale, tdep = Mgas/SFR, of 210 ± 40 Myr for our sample. Additionally, tdep declines with redshift across z ∼ 1–5, while the molecular gas fraction, μgas = Mgas/M*, increases across the same redshift range. Finally, we demonstrate that the distribution of total baryonic mass and dynamical line width, Mbaryon–σ, for our SMGs is consistent with that followed by early-type galaxies in the Coma cluster, providing strong support to the suggestion that SMGs are progenitors of massive local spheroidal galaxies. On the basis of this, we suggest that the SMG populations above and below an 870-μm flux limit of S870 ∼ 5 mJy may correspond to the division between slow and fast rotators seen in local early-type galaxies.
The Swift bulge survey: motivation, strategy, and first X-ray results
Authors: Bahramian A , Heinke C O , Kennea J A , Maccarone T J , Evans P A , Wijnands R , Degenaar N , in’t Zand J J M , Shaw A W , Rivera Sandoval L E , McClure S , Tetarenko A J , Strader J , Kuulkers E , Sivakoff G R
Published: December 2020

Very faint X-ray transients (VFXTs) are X-ray transients with peak X-ray luminosities (LX) of L$_X \lesssim 10^{36}$ erg s−1, which are not well understood. We carried out a survey of 16 deg2 of the Galactic Bulge with the Swift Observatory, using short (60 s) exposures, and returning every 2 weeks for 19 epochs in 2017–18 (with a gap from 2017 November to 2018 February, when the Bulge was in sun-constraint). Our main goal was to detect and study VFXT behaviour in the Galactic Bulge across various classes of X-ray sources. In this work, we explain the observing strategy of the survey, compare our results with the expected number of source detections per class, and discuss the constraints from our survey on the Galactic VFXT population. We detected 91 X-ray sources, 25 of which have clearly varied by a factor of at least 10. In total, 45 of these X-ray sources have known counterparts: 17 chromospherically active stars, 12 X-ray binaries, 5 cataclysmic variables (and 4 candidates), 3 symbiotic systems, 2 radio pulsars, 1 active galactic nuclei, and a young star cluster. The other 46 are of previously undetermined nature. We utilize X-ray hardness ratios, searches for optical/infrared counterparts in published catalogues, and flux ratios from quiescence to outburst to constrain the nature of the unknown sources. Of these 46, 7 are newly discovered hard transients, which are likely VFXT X-ray binaries. Furthermore, we find strong new evidence for a symbiotic nature of four sources in our full sample, and new evidence for accretion power in six X-ray sources with optical counterparts. Our findings indicate that a large subset of VXFTs is likely made up of symbiotic systems.
Multiwavelength analysis of low surface brightness galaxies to study possible dark matter signature
Authors: Bhattacharjee Pooja , Majumdar Pratik , Das Mousumi , Das Subinoy , Joarder Partha S , Biswas Sayan
Published: December 2020

Low surface brightness (LSB) galaxies have very diffuse, low surface density stellar discs that appear faint in optical images. They are very rich in neutral hydrogen (H i) gas, which extends well beyond the stellar discs. Their extended H i rotation curves and stellar discs indicate that they have very massive dark matter (DM) haloes compared to normal bright galaxies. Hence, LSB galaxies may represent valuable laboratories for the indirect detection of DM. In this paper, we search for weakly interacting massive particle annihilation signatures in four LSB galaxies and present an analysis of nearly 9 yr of data from the Fermi Large Area Telescope (Fermi-LAT). Above 500 MeV, no excess emission was detected from the LSB galaxies. We obtain constraints on the DM cross-section for different annihilation channels, for both individual and stacked targets. In addition to this, we use radio data from the Very Large Array radio telescope in order to derive DM constraints, following a multiwavelength approach. The constraints obtained from the four considered LSB galaxies are nearly three orders of magnitude weaker than the predicted limits for the thermal relic abundances and the combined limits achieved from Fermi-LAT observations of dwarf spheroidal galaxies. Finally, we discuss the possibility of detecting emission from LSB galaxies using the upcoming ground-based γ-ray and radio observatories, namely the Cherenkov Telescope Array and the Square Kilometre Array.
The Completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: measurement of the BAO and growth rate of structure of the emission line galaxy sample from the anisotropic power spectrum between redshift 0.6 and 1.1
Authors: de Mattia Arnaud , Ruhlmann-Kleider Vanina , Raichoor Anand , Ross Ashley J , Tamone Amélie , Zhao Cheng , Alam Shadab , Avila Santiago , Burtin Etienne , Bautista Julian , Beutler Florian , Brinkmann Jonathan , Brownstein Joel R , Chapman Michael J , Chuang Chia-Hsun , Comparat Johan , Bourboux Hélion du Mas des , Dawson Kyle S , de la Macorra Axel , Gil-Marín Héctor , Gonzalez-Perez Violeta , Gorgoni Claudio , Hou Jiamin , Kong Hui , Lin Sicheng , Nadathur Seshadri , Newman Jeffrey A , Mueller Eva-Maria , Percival Will J , Rezaie Mehdi , Rossi Graziano , Schneider Donald P , Tiwari Prabhakar , Vivek M , Wang Yuting , Zhao Gong-Bo
Published: December 2020

We analyse the large-scale clustering in Fourier space of emission line galaxies (ELG) from the Data Release 16 of the Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey. The ELG sample contains 173,736 galaxies covering 1,170 square degrees in the redshift range 0.6 < z < 1.1. We perform a BAO measurement from the post-reconstruction power spectrum monopole, and study redshift space distortions (RSD) in the first three even multipoles. Photometric variations yield fluctuations of both the angular and radial survey selection functions. Those are directly inferred from data, imposing integral constraints which we model consistently. The full data set has only a weak preference for a BAO feature (1.4σ). At the effective redshift zeff = 0.845 we measure $D_{\rm V}(z_{\rm eff})/r_{\rm drag} = 18.33_{-0.62}^{+0.57}$, with DV the volume-averaged distance and rdrag the comoving sound horizon at the drag epoch. In combination with the RSD measurement, at zeff = 0.85 we find $f\sigma _8(z_{\rm eff}) = 0.289_{-0.096}^{+0.085}$, with f the growth rate of structure and σ8 the normalisation of the linear power spectrum, $D_{\rm H}(z_{\rm eff})/r_{\rm drag} = 20.0_{-2.2}^{+2.4}$ and DM(zeff)/rdrag = 19.17 ± 0.99 with DH and DM the Hubble and comoving angular distances, respectively. These results are in agreement with those obtained in configuration space, thus allowing a consensus measurement of fσ8(zeff) = 0.315 ± 0.095, $D_{\rm H}(z_{\rm eff})/r_{\rm drag} = 19.6_{-2.1}^{+2.2}$ and DM(zeff)/rdrag = 19.5 ± 1.0. This measurement is consistent with a flat ΛCDM model with Planck parameters.
Crystal structure of a tick-borne flavivirus RNA-dependent RNA polymerase suggests a host adaptation hotspot in RNA viruses
Authors: Yang Jieyu , Jing Xuping , Yi Wenfu , Li Xiao-Dan , Yao Chen , Zhang Bo , Zheng Zhenhua , Wang Hanzhong , Gong Peng
Published: December 2020

The RNA-dependent RNA polymerases (RdRPs) encoded by RNA viruses represent a unique class of nucleic acid polymerases. RdRPs are essential in virus life cycle due to their central role in viral genome replication/transcription processes. However, their contribution in host adaption has not been well documented. By solving the RdRP crystal structure of the tick-borne encephalitis virus (TBEV), a tick-borne flavivirus, and comparing the structural and sequence features with mosquito-borne flavivirus RdRPs, we found that a region between RdRP catalytic motifs B and C, namely region B-C, clearly bears host-related diversity. Inter-virus substitutions of region B-C sequence were designed in both TBEV and mosquito-borne Japanese encephalitis virus backbones. While region B-C substitutions only had little or moderate effect on RdRP catalytic activities, virus proliferation was not supported by these substitutions in both virus systems. Importantly, a TBEV replicon-derived viral RNA replication was significantly reduced but not abolished by the substitution, suggesting the involvement of region B-C in viral and/or host processes beyond RdRP catalysis. A systematic structural analysis of region B-C in viral RdRPs further emphasizes its high level of structure and length diversity, providing a basis to further refine its relevance in RNA virus-host interactions in a general context.
Whole-brain radiotherapy with and without concurrent erlotinib in NSCLC with brain metastases: a multicenter, open-label, randomized, controlled phase III trial
Authors: Yang Zhenzhou , Zhang Yan , Li Rongqing , Yisikandaer Abulimiti , Ren Biyong , Sun Jianguo , Li Jianjun , Chen Long , Zhao Ren , Zhang Juying , Xia Xuefeng , Liao Zhongxing , Carbone David P
Published: December 2020

Background

Erlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non–small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial.

Methods

NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE).

Results

A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments.

Conclusion

Concurrent erlotinib with WBRT didn’t improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases.

Trial registration: Clinical trials.gov identifier: NCT01887795
Poststudy Point-of-Care Oral Fluid Testing in Human Immunodeficiency Virus-1 Vaccinees
Authors: Oganezova Karina , Fontana-Martinez Elvin J , Gothing Jon A , Pandit Alisha , Kwara Esther , Yanosick Katherine , Dragavon Joan , Goecker Erin A , Maenza Janine , Espy Nicole , Tomaka Frank , Lavreys Ludo , Allen Mary , D’Souza Patricia , Hural John , Coombs Robert W , Dolin Raphael , Seaman Michael S , Walsh Stephen R , Baden Lindsey R
Published: December 2020

Background

Experimental human immunodeficiency virus (HIV)-1 vaccines frequently elicit antibodies against HIV-1 that may react with commonly used HIV diagnostic tests, a phenomenon known as vaccine-induced seropositivity/seroreactivity (VISP/VISR). We sought to determine, under clinic conditions, whether a patient-controlled HIV test, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, detected HIV-1 vaccine-induced antibodies.

Methods

Plasma assessment of HIV-1 cross-reactivity was examined in end-of-study samples from 57 healthy, HIV-uninfected participants who received a candidate vaccine that has entered Phase 2B and 3 testing. We also screened 120 healthy, HIV-uninfected, unblinded HIV-1 vaccine participants with VISP/VISR for an assessment using saliva. These participants came from 21 different parent vaccine protocols representing 17 different vaccine regimens, all of which contained an HIV-1 envelope immunogen. OraQuick ADVANCE was compared with results from concurrent blood samples using a series of commercial HIV screening immunoassays.

Results

Fifty-seven unique participant plasma samples were assayed in vitro, and only 1 (1.8%) was reactive by OraQuick ADVANCE. None of the 120 clinic participants (0%; 95% confidence interval, 0% to 3.7%) tested positive by OraQuick ADVANCE, and all were confirmed to be uninfected by HIV-1 viral ribonucleic acid testing. One hundred eighteen of the 120 (98.3%) participants had a reactive HIV test for VISP/VISR: 77 (64%) had at least 1 reactive fourth-generation HIV-1 diagnostic test (P < .0001 vs no reactive OraQuick ADVANCE results), and 41 (34%) only had a reactive test by the less specific third-generation Abbott Prism assay.

Conclusions

These data suggest that this widely available patient-controlled test has limited reactivity to HIV-1 antibodies elicited by these candidate HIV-1 vaccines.