bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supergene potential of a selfish centromere
Authors: Finseth Findley , Brown Keely , Demaree Andrew , Fishman Lila 
Published: June 2022

Selfishly evolving centromeres bias their transmission by exploiting the asymmetry of female meiosis and preferentially segregating to the egg. Such female meiotic drive systems have the potential to be supergenes, with multiple linked loci contributing to drive costs or enhancement. Here, we explore the supergene potential of a selfish centromere (
D
) in
Mimulus guttatus
, which was discovered in the Iron Mountain (IM) Oregon population. In the nearby Cone Peak population,
D
is still a large, non-recombining and costly haplotype that recently swept, but shorter haplotypes and mutational variation suggest a distinct population history. We detected
D
in five additional populations spanning more than 200 km; together, these findings suggest that selfish centromere dynamics are widespread in
M. guttatus
. Transcriptome comparisons reveal elevated differences in expression between driving and non-driving haplotypes within, but not outside, the drive region, suggesting large-scale
cis
effects of
D
's spread on gene expression. We use the expression data to refine linked candidates that may interact with drive, including Nuclear Autoantigenic Sperm Protein (NASP
SIM3
), which chaperones the centromere-defining histone CenH3 known to modify
Mimulus
drive. Together, our results show that selfishly evolving centromeres may exhibit supergene behaviour and lay the foundation for future genetic dissection of drive and its costs.

This article is part of the theme issue ‘Genomic architecture of supergenes: causes and evolutionary consequences’.
Network-based multi-omics integration reveals metabolic at-risk profile within treated HIV-infection
Authors: Mikaeloff Flora , Gelpi Marco , Benfeitas Rui , Knudsen Andreas D. , Vestad Beate , Høgh Julie , Hov Johannes R. , Benfield Thomas , Murray Daniel , Giske Christian G , Mardinoglu Adil , Trøseid Marius , Nielsen Susanne D. , Neogi Ujjwal 
Published: June 2022

AbstractMultiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PLWHART). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic and metabolomic, and fecal 16s microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PLWHART. Through network analysis and similarity network fusion (SNF), we identified three groups of PLWHART (SNF-1 to 3). The PLWHART at SNF-2 (45%) was a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4+ T-cell counts than the other two clusters. However, the healthy-like and severe at-risk group had a similar metabolic profile differing from HC, with dysregulation of amino acid metabolism. At the microbiome profile, the healthy-like group had a lower α-diversity, a lower proportion of MSM, and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in Prevotella, with a high proportion of men who have sex with men (MSM) confirming the influence of sexual orientation on the microbiome profile The multi-omics integrative analysis reveals a complex microbial interplay by microbiome-derived metabolites in PLWHART. PLWHART those are severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their metabolic profile.SignificanceThe network and factorization-based integrative analysis of plasma metabolomics, lipidomics, and microbiome profile identified three different diseases’ state -omics phenotypes within PLWHART driven by metabolomics, lipidomics, and microbiome that a single omics or clinical feature could not explain. The severe at-risk group has a dysregulated metabolic profile that potentiates metabolic diseases that could be barriers to healthy aging. The at-risk group may benefit from personalized medicine and lifestyle intervention to improve their metabolic profile.
Cdh5-lineage independent origin of dermal lymphatic vessels revealed by temporally restricted lineage tracing
Authors: Zhang Yan , Ortsäter Henrik , Martinez-Corral Ines , Mäkinen Taija 
Published: June 2022

AbstractThe developmental origins of lymphatic endothelial cells (LECs) have been under intense research after a century-long debate. Although previously thought to be of solely venous endothelial origin, additional sources of LECs were recently identified in multiple tissues in mice. Here, we investigated the regional differences in the origin(s) of the dermal lymphatic vasculature by lineage tracing using the pan-endothelial Cdh5-CreERT2 line. Tamoxifen-induced labeling of blood ECs at E9.5, prior to initiation of lymphatic development, traced the majority of dermal LECs but with lower efficiency in the lumbar compared with cervical skin. By contrast, when used at E9.5 but not at E11.5, 4-hydroxytamoxifen, the active metabolite of tamoxifen that provides a tighter window of Cre activity, revealed low labeling frequency of LECs, and lymphvasculogenic clusters in the lumbar skin in particular. Temporally restricted lineage tracing thus reveals contribution of LECs of Cdh5-lineage independent origin to dermal lymphatic vasculature. Our results further highlight the Cre induction strategy as a critical parameter in defining the temporal window for stage-specific lineage tracing during early developmental stages of rapid tissue differentiation.
Genetic conflicts between sex chromosomes drive expansion and loss of sperm nuclear basic protein genes in Drosophila
Authors: Chang Ching-Ho , Malik Harmit S. 
Published: June 2022

AbstractMany animal species employ short, positively charged proteins, called sperm nuclear basic proteins (SNBPs) or protamines, for tighter packaging of genomes in sperm. SNBP repertoires differ dramatically across animal lineages and signatures of rapid evolution have been reported in mammals. Both sperm competition and meiotic drive between sex chromosomes have been proposed as causes of SNBP innovation. We used a phylogenomic approach to investigate SNBP diversification and its underlying causes in Drosophila species. We found unambiguous signatures of positive selection in most SNBP genes except for genes essential for male fertility in D. melanogaster. Unexpectedly, evolutionarily young SNBP genes are more likely to encode essential functions for fertility than ancient, conserved SNBP genes like CG30056, which we found is dispensable for male fertility despite universal retention in Drosophila species. We found 19 independent amplification events involving eight SNBP genes that occurred preferentially on sex chromosomes in 78 Drosophila species. Conversely, we found that otherwise-conserved SNBP genes were lost in the montium group of Drosophila species, coincident with an X-Y chromosomal fusion. Furthermore, SNBP genes that became linked to sex chromosomes via chromosomal fusions are prone to degenerate or relocate back to autosomes. We hypothesize that SNBP genes ancestrally encoded by autosomes suppress meiotic drive, whereas sex-chromosomal SNBP expansions directly participate in meiotic drive. X-Y fusions in the montium group render autosomal SNBPs dispensable by making X-versus-Y meiotic drive obsolete or costly. We conclude that SNBP rapid evolution is driven by genetic conflicts between sex chromosomes during spermatogenesis in Drosophila species.
The incubation period for monkeypox cases confirmed in the Netherlands, May 2022
Authors: Miura Fuminari , van Ewijk Catharina Else , Backer Jantien A. , Xiridou Maria , Franz Eelco , de Coul Eline Op , Brandwagt Diederik , van Cleef Brigitte , van Rijckevorsel Gini , Swaan Corien , van den Hof Susan , Wallinga Jacco 
Published: June 2022

AbstractIn May 2022 outbreaks of monkeypox have been reported in countries where the monkeypox virus is not endemic. We estimate the incubation period for monkeypox, using the reported time of exposure and symptom onset for 18 confirmed cases detected in the Netherlands up to 31st May 2022. The mean incubation period was 8.5 days, ranging from 4.2 to 17.3 days (5th to 95th percentiles). These findings underpin 21 days for monitoring or quarantining of case contacts.
A new Oprm1-Cre mouse line enables detailed molecular characterization of μ-opioid receptor cell types
Authors: Mengaziol Juliet , Dunn Amelia D. , Crues-Muncunill Jordi , Eacret Darrell , Chen Chongguang , Bland Kathryn , Liu-Chen Lee-Yuan , Ehrlich Michelle E. , Blendy Julie A. 
Published: June 2022

AbstractKey targets of both the therapeutic and abused properties of opioids are μ-opioid receptors (MORs). Despite years of research investigating the biochemistry and signal transduction pathways associated with MOR activation, we do not fully understand the cellular mechanisms underlying opioid addiction. Given that addictive opioids such as morphine, oxycodone, heroin, and fentanyl all activate MORs, and current therapies such as naloxone and buprenorphine block this activation, the availability of tools to mechanistically investigate opioid-mediated cellular and behavioral phenotypes are necessary. Therefore, we derived, validated, and applied a novel MOR-specific Cre mouse line, inserting the Cre coding sequence into the MOR 3’UTR to generate a bicistronic gene. As intended, there were no differences in behavioral responses to morphine when compared to wild type mice, nor are there any alterations in Oprm1 gene expression or receptor density. To assess Cre recombinase activity, MOR-Cre mice were crossed with the floxed GFP-reporters, RosaLSLSun1-sfGFP or RosaLSL-GFP-L10a. The latter allowed for cell type specific RNA sequencing via TRAP (Translating Ribosome Affinity Purification) of striatal MOR+ neurons following opioid withdrawal. This new tool will facilitate the study of opioid biology under varying conditions.
Human norovirus efficiently replicates in differentiated 3D-human intestinal enteroids
Authors: Mirabelli Carmen , Santos-Ferreira Nanci , Gillilland Merritt G. , Cieza Roberto J. , Colacino Justin A. , Sexton Jonathan Z. , Taube Stefan , Rocha-Pereira Joana , Wobus Christiane E. 
Published: June 2022

AbstractHuman norovirus (HNoV) accounts for one fifth of all acute viral gastroenteritis worldwide and an economic burden of ∼$60 billion globally. The lack of treatment options against HNoV is in part due to the lack of cultivation systems. Recently, a model of infection in biopsies-derived human intestinal enteroids (HIE) has been described: 3D-HIE are first dispersed in 2D-monolayers and differentiated prior to infection, resulting in a labor-intensive, time-consuming procedure. Here, we present an alternative protocol for HNoV infection of 3D-HIE. We found that 3D-HIE differentiate as efficiently as 2D-monolayers. In addition, immunofluorescence-based quantification of UEA-1, a lectin that stains the villus brush border, revealed that over 90% of differentiated 3D-HIE spontaneously undergo polarity inversion, allowing for viral infection without the need for microinjection. Infection with HNoV GII.4-positive stool samples attained a fold-increase over inoculum of ∼2 Log10 at 2 days post infection or up to 3.5 Log10 when ruxolitinib, a JAK1/2-inhibitor, was added. Treatment of GII.4-infected 3D-HIE with the polymerase inhibitor 2’-C-Methylcytidine (2CMC), other antivirals, or with a HNoV-neutralizing antibody showed a reduction in viral infection, suggesting that 3D-HIE are an excellent platform to test anti-infectives. The host response to HNoV was then investigated by RNA sequencing in infected versus uninfected 3D-HIE, in the presence of ruxolitinib to focus on viral-associated signatures. The analysis revealed upregulated hormones and neurotransmitter signal transduction pathways and downregulated inflammatory pathways upon HNoV infection. Overall, 3D-HIE have proven to be a more robust model to study HNoV infection, screen antivirals and investigate host response to HNoV infection.ImportanceHuman norovirus (HNoV) clinical and socio-economic impact calls for immediate actions in the development of anti-infectives. Physiologically-relevant in vitro models are hence needed to study HNoV biology, tropism and mechanism of viral-associated disease but also as a platform to identify antiviral agents. Biopsy-derived human intestinal enteroids are a biomimetic of the intestine and recently described as a model that supports HNoV infection. The established protocol is time-consuming and labor-intensive. Therefore, we sought to develop a simplified and robust alternative model of infection in 3D enteroids that undergo differentiation and spontaneous polarity inversion. Advantages of this model are the shorter experimental time, better infection yield and spatial integrity of the intestinal epithelium. This model is potentially suitable for the study of pathogens that infect intestinal cells from the apical surface but also for unraveling the interactions between intestinal epithelium and indigenous bacteria of the human microbiome.
SARS-CoV-2 type I Interferon modulation by nonstructural proteins 1 and 2
Authors: Lacasse Émile , Dubuc Isabelle , Gudimard Leslie , Gravel Annie , Allaeys Isabelle , Boilard Éric , Flamand Louis 
Published: June 2022

AbstractSince the beginning of the COVID-19 pandemic, enormous efforts were devoted to understanding how SARS-CoV-2 escapes the antiviral response. Yet, modulation of type I interferons (IFNs) by this virus is not completely understood. Using in vitro and in vivo approaches, we have characterized the type I IFN response during SARS-CoV-2 infection as well as immune evasion mechanisms. The transcriptional and translational expression of IFNs, cytokines and chemokines were measured in lung homogenates of Wuhan-like, Beta, and Delta SARS-CoV-2 K18-ACE2 transgenic mice. Using in vitro experiments, we measured SARS-CoV-2 and its non-structural proteins 1 and 2 (Nsp1-2) to modulate expression of IFNβ and interferon-stimulated genes (ISG). Our data show that infection of mice with Wuhan-like virus induces robust expression of Ifna and Ifnb1 mRNA and limited type I production. In contrast, Beta and Delta variant infected mice failed to activate and produce IFNα. Using in vitro systems, Ifnβ gene translation inhibition was observed using an Nsp1 expression vector. Conversely, SARS-CoV-2 and its variants induce robust expression of NF-κB-driven genes such as those encoding CCL2 ans CXCL10 chemokines. We also identified Nsp2 as an activator of NF-κB that partially counteracts the inhibitory actions of Nsp1. In summary, our work indicates that SARS-CoV-2 skews the antiviral response in favor of an NF-κB-driven inflammatory response, a hallmark of acute COVID-19, and that Nsp2 is partly responsible for this effect.ImportanceSeveral studies suggest that SARS-CoV-2 possess multiple mechanisms aimed shunting the type I interferon response. However, few studies have studied type I IFN modulation in the context of infection. Our work indicates that mice and human cells infected with SARS-CoV-2 produce sufficient type I IFN to activate an antiviral response, despite Nsp1 translational blockade of IFNΒ1 mRNA. In contrast to Wuhan-like virus, Beta and Delta variants failed to induce Ifna gene expression. Our work also showcases the importance of studying protein functions in the context of infection, as demonstrated by the partial antagonizing properties of the Nsp2 protein on the activities of Nsp1. Our studies also highlight that the innate immune response triggered by SARS-CoV-2 is chiefly driven by NF-κB responsive genes for which Nsp2 is partially responsible.
Media coverage and speculation about the impact of the COVID-19 pandemic on suicide: A content analysis of UK news
Authors: Marzano Lisa , Hawley Monica , Fraser Lorna , Lainez Yasmine , Marsh James , Hawton Keith 
Published: June 2022

AbstractObjectivesSince the start of the COVID-19 pandemic, there has been much concern and speculation about rises in suicide rates, despite evidence that suicides did not in fact increase in the first year of the pandemic in most countries with real-time suicide data. This public narrative is potentially harmful, as well as misleading, and is likely to be perpetuated by sensational news coverage.MethodWe conducted a systematic analysis of UK news coverage (including opinion pieces) on the impact of COVID-19 on suicidality, to examine the content and quality of such reporting as the pandemic developed, and as different coronavirus restrictions were imposed.ResultsWe identified 372 stories about COVID-19 and suicidality in online and print news between the first UK lockdown (March 2020) and May 2021 (when restrictions were significantly eased in the UK). Throughout this period, over a third of articles (39.2%) and headlines (41.4%) claimed or predicted a rise in suicide, often attributed to feelings of entrapment and poor mental health (especially amongst young people), and fueled by expert commentary and speculation. Almost a third of reports were rated as being of poor overall quality (116, 31.2%), and at least half included no signposting to help and support. However, reporting improved in phases of less stringent COVID-19 restrictions and over time, with later articles and headlines including fewer negative statements and predictions about rises in suicides, and greater reliance on academic evidence.ConclusionsAs the longer-term consequences of the pandemic develop, and other national and global events unfold, it is increasingly important that the media, and the wider community of experts shaping its narratives, strive for a positive and evidence-informed approach to news coverage of suicide.Strengths and Limitations of this StudyThis is the first systematic analysis of UK news coverage on the impact of COVID-19 on suicidality.Findings are based on a well-established, evidence-informed news monitoring database.However, this analysis cannot account for the impact of news coverage on different audiences, nor for its reachOur focus did not extend to broadcasts or other media formats.
Optical Control of Neuronal Activities with Photoswitchable Nanovesicles
Authors: Xiong Hejian , Alberto Kevin A. , Youn Jonghae , Taura Jaume , Morstein Johannes , Li Xiuying , Wang Yang , Trauner Dirk , Slesinger Paul A. , Nielsen Steven O. , Qin Zhenpeng 
Published: June 2022

ABSTRACTPrecise modulation of neuronal activity by neuroactive molecules is essential for understanding brain circuits and behavior. However, tools for highly controllable molecular release are lacking. Here, we developed a photoswitchable nanovesicle with azobenzene-containing phosphatidylcholine (azo-PC), coined ‘azosome’, for neuromodulation. Irradiation with 365 nm light triggers thetrans-to-cisisomerization of azo-PC, resulting in a disordered lipid bilayer with decreased thickness and cargo release. Irradiation with 455 nm light induces reverse isomerization and switches the release off. Real-time fluorescence imaging shows controllable and repeatable cargo release within seconds (< 3 s). Importantly, we demonstrate that SKF-81297, a dopamine D1-receptor agonist, can be released from the azosome to activate cultures of primary striatal neurons. Azosome shows promise in precise optical control over the molecular release and can be a valuable tool for molecular neuroscience studies.
New model of glucose-insulin regulation characterizes effects of physical activity and facilitates personalized treatment evaluation in children and adults with type 1 diabetes
Authors: Deichmann Julia , Bachmann Sara , Burckhardt Marie-Anne , Pfister Marc , Szinnai Gabor , Kaltenbach Hans-Michael 
Published: June 2022

AbstractAccurate treatment adjustment to physical activity (PA) remains a challenging problem in type 1 diabetes (T1D) management. Exercise-driven effects on glucose metabolism depend strongly on duration and intensity of the activity, and are highly variable between patients. In-silico evaluation can support the development of improved treatment strategies, and can facilitate personalized treatment optimization. This requires models of the glucose-insulin system that capture relevant exercise-related processes. We developed a model of glucose-insulin regulation that describes changes in glucose metabolism for moderate- to high-intensity PA of short and prolonged duration. In particular, we incorporated the insulin-independent increase in glucose uptake and production, including glycogen depletion, and the prolonged rise in insulin sensitivity. The model further includes meal absorption and insulin kinetics, allowing simulation of everyday scenarios. The model accurately predicts glucose dynamics for varying PA scenarios in a range of independent validation data sets, and full-day simulations with PA of different timing, duration and intensity agree with clinical observations. We personalized the model on data from a multi-day free-living study of children with T1D by adjusting a small number of model parameters to each child. To assess the use of the personalized models for individual treatment evaluation, we compared subject-specific treatment options for PA management in replay simulations of the recorded data with altered meal, insulin and PA inputs.Author summaryExercise represents a cornerstone of diabetes management. Yet, many people with type 1 diabetes restrain from exercising, since it increases the risk for hypoglycemia and requires adjusted insulin treatment. The effect of exercise on blood glucose levels depends on exercise duration and intensity, but also varies strongly between individuals, making accurate adjustment a challenge. Mathematical models can help to better understand exercise physiology and to devise new treatment strategies. Here, we propose a model of glucose-insulin regulation that captures the effects of exercise on glucose metabolism and personalize it to individual children with type 1 diabetes, allowing subject-specific treatment assessment.
Mutation of theDrosophilaserotonin transporter dSERT disrupts courtship and feeding and increases both daytime and nighttime sleep
Authors: Knapp Elizabeth M. , Kaiser Andrea , Arnold Rebecca C. , Sampson Maureen M. , Ruppert Manuela , Xu Li , Anderson Matthew I. , Bonanno Shivan L. , Scholz Henrike , Donlea Jeffrey M. , Krantz David E. 
Published: June 2022

AbstractThe Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organismDrosophila melanogaster, we developed new loss of function mutations inDrosophila SERT(dSERT).Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generateddSERTmutants show an increase in total sleep and altered sleep architecture. Differences in daytime vs. nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep.dSERTmutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs. Starvation did not overcome the sleep drive in the mutants. Additionally in males, but not femaledSERTmutants, the drive to mate also failed to overcome sleep drive.dSERTmay be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.Author SummaryMany medications used to treat depression and anxiety act by changing serotonin levels in the brain. Fruit flies also use serotonin and can be used as a model to study the brain. We have made a fly mutant for the serotonin transporter (SERT), which is the target of antidepressants in humans. The mutants sleep more, eat less, and have a decreased sex drive. These flies can be used to study the neuronal pathways by which serotonin regulates sleep, eating and sexual behaviors and may help us to understand the behavioral effects of antidepressants.