bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new experimental system to study meiotic recurrent non-allelic homologous recombination in budding yeast
Authors: Sedam Hailey N. C. , Argueso Juan Lucas 
Published: June 2020

ABSTRACTIn humans,de novorecurrent copy number variations (CNVs) often arise during meiosis from non-allelic homologous recombination (NAHR) between low copy repeat elements (LCRs). These chromosomal rearrangements are responsible for a wide variety of genomic disorders involving duplication or deletion of dose-sensitive genes. The precise factors that steer meiotic cells toward this detrimental recombination pathway are not fully understood. To create a model for the investigation of LCR-mediated CNV mechanisms, we developed a diploid experimental system inSaccharomyces cerevisiae. We modified the right arm of chromosome V through the introduction of engineered LCRs: duplicated 5 to 35 kb segments of yeast DNA flanking single copy interstitial spacers, analogously to the meiotic NAHR substrates that exist in humans. Phenotypic markers, including a copy number reporter, were inserted within the interstitial spacer. Their segregation in the haploid meiotic progeny was used to phenotypically identity and classify recurrent CNV events. This system allowed us to measure the effects of LCR size on the frequency of meioticde novorecurrent CNV formation, and to determine the relative proportions of each of the three main NAHR classes: interhomolog, intersister, and intrachromatid. The frequency of CNV increased as the LCRs became larger, and interhomolog NAHR was overrepresented relative to the two other classes. We showed that this experimental system directly mimics the features ofde novorecurrent CNVs reported in human disease, thus it represents a promising tool for the discovery and characterization of conserved cellular factors and environmental exposures that can modulate meiotic NAHR.
Pupil dilation and the slow wave ERP reflect surprise about choice outcome resulting from intrinsic variability in decision confidence
Authors: de Gee Jan Willem , Correa Camile M.C. , Weaver Matthew , Donner Tobias H. , van Gaal Simon 
Published: June 2020

AbstractCentral to human and animal cognition is the ability to learn from feedback in order to optimize future rewards. Such a learning signal might be encoded and broadcasted by the brain’s arousal systems, including the noradrenergic locus coeruleus. Pupil responses and the positive slow wave component of event-related potentials reflect rapid changes in the arousal level of the brain. Here we ask whether and how these variables may reflect surprise: the mismatch between one’s expectation about being correct and the outcome of a decision, when expectations fluctuate due to internal factors (e.g., engagement). We show that during an elementary decision-task in the face of uncertainty both physiological markers of phasic arousal reflect surprise. We further show that pupil responses and slow wave ERP are unrelated to each other, and that prediction error computations depend on feedback awareness. These results further advance our understanding of the role of central arousal systems in decision-making under uncertainty.
Predicting range shifts of African apes under global change scenarios
Authors: Carvalho Joana S. , Graham Bruce , Bocksberger Gaёlle , Maisels Fiona , Williamson Elizabeth A. , Wich Serge , Sop Tenekwetche , Amarasekaran Bala , Bergl Richard A. , Boesch Christophe , Boesch Hedwige , Brncic Terry M. , Buys Bartelijntje , Chancellor Rebecca , Danquah Emmanuel , Doumbé Osiris A. , Galat-Luong Anh , Ganas Jessica , Gatti Sylvain , Ghiurghi Andrea , Goedmakers Annemarie , Granier Nicolas , Hakizimana Dismas , Haurez Barbara , Head Josephine , Herbinger Ilka , Hillers Annika , Jones Sorrel , Manasseh Eno-Nku , McCarthy Maureen S. , Morgan Bethan J. , Nixon Stuart , Nkembi Louis , Normand Emmanuelle , Olson Sarah H. , Payne Leon , Petre Charles-Albert , Piel Alex K. , Pintea Lilian , Plumptre Andrew J. , Rundus Aaron , Serckx Adeline , Stewart Fiona A. , Sunderland-Groves Jacqueline , Tagg Nikki , Todd Angelique , Vosper Ashley , Wenceslau José Francisco Carminatti , Wessling Erin G. , Willie Jacob , Kühl Hjalmar 
Published: June 2020

ABSTRACTAimModelling African great ape distribution has until now focused on current or past conditions, whilst future scenarios remain scarcely explored. Using an ensemble forecasting approach, we predicted changes in taxon-specific distribution under future scenarios of climate, land-use and human population changes.LocationSub-Saharan AfricaMethodsWe compiled occurrence data on African ape populations from the IUCN A.P.E.S. database and extracted relevant human-, climate- and habitat-related predictors representing current and future (2050) conditions to predict taxon-specific distribution under a best- and a worst-case scenario, using ensemble forecasting. Given the large effect on model predictions, we further tested algorithm sensitivity by consideringdefaultandnon-defaultmodelling options. The latter included interactions between predictors and polynomial terms in correlative algorithms.ResultsThe future distributions of gorilla and bonobo populations are likely to be directly determined by climate-related variables. In contrast, future chimpanzee distribution is influenced mostly by anthropogenic variables. Both our modelling approaches produced similar model accuracy, although a slight difference in the magnitude of range change was found forGorilla beringei beringei, G. gorilla diehli, andPan troglodytes schweinfurthii. On average, a decline of 50% of the geographic range (non-default; or 55%default) is expected under the best scenario if no dispersal occurs (57%non-defaultor 58%defaultin worst scenario). However, new areas of suitable habitat are predicted to become available for most taxa if dispersal occurs (81% or 103% best, 93% or 91% worst,non-defaultanddefault, respectively), except forG. b. beringei.Main ConclusionsDespite the uncertainty in predicting the precise proportion of suitable habitat by 2050, both modelling approaches predict large range losses for all African apes. Thus, conservation planners urgently need to integrate land-use planning and simultaneously support conservation and climate change mitigation measures at all decision-making levels both in range countries and abroad.
Custom-designed, degradation-resistant messenger RNAs in yeast
Authors: Franklin Ana L. , Macfadden Andrea , Kieft Jeffrey S. , Hesselberth Jay R. , Chapman Erich G. 
Published: June 2020

ABSTRACTStructured RNA elements that protect RNA transcripts from 5’→3’ degradation are becoming useful research tools. Here we show that exonuclease-resistant RNA structures (xrRNAs) from Flaviviruses can be used to protect heterologous messenger RNAs (mRNAs) from 5’→3’ degradation in budding yeast. Installation of xrRNAs ahead of a downstream internal ribosome entry site (IRES) leads to the accumulation of partially-degraded mRNAs that are substrates for cap-independent translation of a LacZ reporter, yielding a 30-fold increase in measured β-galactosidase activity. Additionally, by monitoring the translation of dual-luciferase reporters we show that xrRNA sequences do not interfere with the progression of an elongating ribosome. Combined these data indicate that xrRNA elements can be used in creative ways to stabilize RNAs with potentially useful applications.
Significant non-existence of sequences in genomes and proteomes
Authors: Koulouras Grigorios , Frith Martin C. 
Published: June 2020

AbstractNullomers are minimal-length oligomers absent from a genome or proteome. Although research has shown that artificially synthesized nullomers have deleterious effects, there is still a lack of a strategy for the prioritisation and classification of non-occurring sequences as potentially malicious or benign. In this work, by using Markovian models with multiple-testing correction, we reveal significant absent oligomers which are statistically expected to exist. This strongly suggests that their absence is due to negative selection. We survey genomes and proteomes covering the diversity of life, and find thousands of significant absent sequences. Common significant nullomers are often mono- or dinucleotide tracts, or palindromic. Significant viral nullomers are often restriction sites, and may indicate unknown restriction motifs. Surprisingly, significant mammal genome nullomers are often present, but rare, in other mammals, suggesting that they are suppressed but not completely forbidden. Significant human nullomers are rarely present in human viruses, indicating viral mimicry of the host. More than 1/4 of human proteins are one substitution away from containing a significant nullomer. We provide a web-based, interactive database of significant nullomers across genomes and proteomes.
Patterns of genetic variation in a prairie wildflower,Silphium integrifolium, suggest a non-prairie origin and locally adaptive variation
Authors: Raduski Andrew R. , Herman Adam , Pogoda Cloe , Dorn Kevin M. , Van Tassel David L. , Kane Nolan , Brandvain Yaniv 
Published: June 2020

AbstractPremiseUnderstanding the relationship between genetic structure and geography provides information about a species’ evolutionary history and can be useful to breeders interested in de novo domestication. The North American prairie is especially interesting because of its relatively recent origin and subsequent dramatic fragmentation and degradation.Silphium integrifoliumis an iconic perennial American prairie wildflower targeted for domestication as an oilseed crop. Germplasm in the existing breeding program is derived from accessions collected in restricted geographic regions. We present the first application of population genetic data in this species to address the following goals (1) improve breeding programs by characterizing genetic structure and (2) identify the species geographic origin and potential targets and drivers of selection during range expansion.MethodsWe developed a reference transcriptome as a genotyping reference for samples from throughout the species range. Population genetic analyses were used to describe the distribution of genetic variation and demographic modeling was used to characterize potential processes that shaped variation. Outlier scans for selection and associations with environmental variables were used to identify loci linked to putative targets and drivers of selection.Key resultsGenetic variation partitions samples into three geographic clusters. Patterns of variation and demographic modeling suggest that the species origin is in the American southeast. Breeding program accessions are from the region with lowest observed genetic variation.ConclusionsThis iconic prairie species did not originate within the modern prairie. Breeding programs can be improved by including accessions from outside of the germplasm founding region, which has relatively little variation. The geographic structuring coupled with the identified targets and drivers of adaptation can guide collecting efforts towards populations with beneficial agronomic traits.
Adult Stem Cells and Niche Cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development
Authors: Reilein Amy , Kogan Helen V. , Misner Rachel , Park Karen Sophia , Kalderon Daniel 
Published: June 2020

SummaryAdult stem cell function relies on the prior development of appropriate numbers and spatial organization of stem cells and supportive niche cells. Drosophila Follicle Stem Cells (FSCs) present a favorable paradigm for understanding those developmental processes. About sixteen FSCs in an adult germarium produce transit-amplifying Follicle Cells (FCs) from their posterior face and quiescent Escort Cells (ECs) to their anterior. Both ECs and FCs also act as niche cells. Here we show that adult ECs, FSCs and FCs derive from common precursors intermingled with germline cells during pupal development, with progeny of a single precursor commonly including ECs and FSCs, FSCs and FCs, or all three adult cell types. Precursors posterior to germline cells become the first FCs and engulf a largely naked germline cyst projected out of the germarium to form the first egg chamber and set up a key posterior signaling center for regulating adult FSC behavior.
Photoperiodic Effects on Monoamine Signaling & Gene Expression Throughout Development in the Serotonin & Dopamine Systems
Authors: Siemann Justin K. , Williams Piper , Malik Turnee N. , Jackson Chad , Green Noah H. , Emeson Ronald , Levitt Pat , McMahon Douglas G. 
Published: June 2020

AbstractPhotoperiod or the duration of daylight has been implicated as a risk factor in the development of mood disorders. The dopamine and serotonin systems are impacted by photoperiod and are consistently associated with affective disorders. Hence, we evaluated, at multiple stages of postnatal development, the expression of key dopaminergic (TH) and serotonergic (Tph2, SERT,andPet-1) genes, and midbrain monoamine content in mice raised under control Equinox (LD 12:12), Short winter-like (LD 8:16), or Long summerlike (LD 16:8) photoperiods. Focusing in early adulthood, we evaluated the midbrain levels of these serotonergic genes, and also assayed these gene levels in the dorsal raphe nucleus (DRN) with RNAScope. Mice that developed under Short photoperiods demonstrated elevated midbrainTHexpression levels, specifically during perinatal development compared to mice raised under Long photoperiods, and significantly decreased serotonin and dopamine content throughout the course of development. In adulthood, Long photoperiod mice demonstrated decreased midbrainTph2andSERTexpression levels and reducedTph2levels in the DRN compared Short photoperiod mice. Thus, evaluating gene x environment interactions in the dopaminergic and serotonergic systems during multiple stages of development may lead to novel insights into the underlying mechanisms in the development of affective disorders.
Intestinal transkingdom analysis on the impact of antibiotic perturbation in health and critical illness
Authors: Haak Bastiaan W. , Argelaguet Ricard , Kinsella Cormac M. , Kullberg Robert F.J. , Lankelma Jacqueline M. , Hakvoort Theodorus B.M. , Hugenholtz Floor , Kostidis Sarantos , Giera Martin , de Jonge Wouter J. , Schultz Marcus J. , van Gool Tom , van der Poll Tom , de Vos Willem M. , van den Hoek Lia , Wiersinga W. Joost 
Published: June 2020

AbstractBacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, and protozoa, are closely interlinked with the bacterial microbiota and their host, yet their collective role during antibiotic perturbation and critical illness remains to be elucidated. Here, multi-omics factor analysis (MOFA), a novel computational strategy to systematically integrate viral, fungal and bacterial sequence data, we describe the functional impact of exposure to broad-spectrum antibiotics in healthy volunteers and critically ill patients. We observe that a loss of the anaerobic intestinal environment is directly correlated with an overgrowth of aerobic pathobionts and their corresponding bacteriophages, as well as an absolute enrichment of opportunistic yeasts capable of causing invasive disease. These findings further illustrate the complexity of transkingdom interactions within the intestinal environment, and show that modulation of the bacterial component of the microbiome has implications extending beyond this kingdom alone.
Chasing the origin of SARS-CoV-2 in Canada’s COVID-19 cases: A genomics study
Authors: Sjaarda Calvin P , Rustom Nazneen , Huang David , Perez-Patrigeon Santiago , Hudson Melissa L , Wong Henry , Guan T Hugh , Ayub Muhammad , Soares Claudio N , Colautti Robert I , Evans Gerald A , Sheth Prameet M 
Published: June 2020

AbstractThe emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.
The neural dynamics underlying prioritisation of task-relevant information
Authors: Grootswagers Tijl , Robinson Amanda K. , Shatek Sophia M. , Carlson Thomas A. 
Published: June 2020

AbstractThe human brain prioritises relevant sensory information to perform different tasks. Enhancement of task-relevant information requires flexible allocation of attentional resources, but it is still a mystery how this is operationalised in the brain. We investigated how attentional mechanisms operate in situations where multiple stimuli are presented in the same location and at the same time. In two experiments, participants performed a challenging two-back task on different types of visual stimuli that were presented simultaneously and superimposed over each other. Using electroencephalography and multivariate decoding, we analysed the effect of attention on the neural responses to each individual stimulus. Whole brain neural responses contained considerable information about both the attended and unattended stimuli, even though they were presented simultaneously and represented in overlapping receptive fields. As expected, attention increased the decodability of stimulus-related information contained in the neural responses, but this effect was evident earlier for stimuli that were presented at smaller sizes. Our results show that early neural responses to stimuli in fast-changing displays contain remarkable information about the sensory environment but are also modulated by attention in a manner dependent on perceptual characteristics of the relevant stimuli. Stimuli, code, and data for this study can be found athttps://osf.io/7zhwp/.
Factors Associated with Hospitalization and Disease Severity in a Racially and Ethnically Diverse Population of COVID-19 Patients
Authors: Mendy Angelico , Apewokin Senu , Wells Anjanette A. , Morrow Ardythe L. 
Published: June 2020

ABSTRACTBackgroundThe coronavirus disease (COVID-19) first identified in Wuhan in December 2019 became a pandemic within a few months of its discovery. The impact of COVID-19 is due to both its rapid spread and its severity, but the determinants of severity have not been fully delineated.ObjectiveIdentify factors associated with hospitalization and disease severity in a racially and ethnically diverse cohort of COVID-19 patients.MethodsWe analyzed data from COVID-19 patients diagnosed at the University of Cincinnati health system from March 13, 2020 to May 31, 2020. Severe COVID-19 was defined as admission to intensive care unit or death. Logistic regression modeling adjusted for covariates was used to identify the factors associated with hospitalization and severe COVID-19.ResultsAmong the 689 COVID-19 patients included in our study, 29.2% were non-Hispanic White, 25.5% were non-Hispanic Black, 32.5% were Hispanic, and 12.8% were of ‘Other’ race/ethnicity. About 31.3% of patients were hospitalized and 13.2% had severe disease. In adjusted analyses, the sociodemographic factors associated with hospitalization and/or disease severity included older age, non-Hispanic Black or Hispanic race/ethnicity (compared non-Hispanic White), and smoking. The following comorbidities: diabetes, hypercholesterolemia, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, cardiovascular diseases, osteoarthritis, and vitamin D deficiency, were associated with hospitalization and/or disease severity. Hematological disorders such as anemia, coagulation disorders, and thrombocytopenia were associated with higher odds of both hospitalization and disease severity.ConclusionThis study confirms race and ethnicity as predictors of severe COVID-19 and identifies clinical risk factors not previously reported such a vitamin D deficiency, hypercholesterolemia, osteoarthritis, and anemia.
Ultra-fast one-step RT-PCR protocol for the detection of SARS-CoV-2
Authors: Asghari Ehsan , Höving Anna , van Heijningen Paula , Kiel Annika , Krahlemann-Köhler Angela , Lütkemeyer Melanie , Storm Jonathan , Vollmer Tanja , Knabbe Cornelius , Kaltschmidt Barbara , de Vos Gert , Kaltschmidt Christian 
Published: June 2020

AbstractThe COVID-19 pandemic resulted in lockdowns all over the world thus affecting nearly all aspects of social life and also had a huge impact on global economies. Since vaccines and therapies are still not available for the population, prevention becomes desperately needed. One important aspect for prevention is the identification and subsequent isolation of contagious specimens. The currently used methods for diagnostics are time consuming and also hindered by the limited availability of reagents and reaction costs, thus presenting a bottle neck for prevention of COVID-19 spread. Here, we present a new ultra-fast test method which is ten times faster than conventional diagnostic tests using real time quantitative PCR (RT-qPCR). In addition, this ultra-fast method is easy to handle as well as cost effective. We translated published SARS-CoV-2 testing protocols from the Centers of Disease Control and Prevention (Atlanta, Georgia, USA) and the Charité Berlin (Germany) to the NEXTGENPCR (NGPCR) machine and combined it with a fluorescence-based endpoint measurement. Fluorescence was measured with a commercial blue light scanner. We confirmed the NEXTGENPCR results with commercially available positive controls. In addition, we isolated RNA from SARS-CoV-2 infected patients and achieved similar results to clinical RT-qPCR assays. Here, we could show correlation between the results obtained by NEXTGENPCR and conventional RT-qPCR.
The effect of reopening policy on COVID-19 related cases and deaths
Authors: Zhou Qiyao 
Published: June 2020

AbstractBy May 29, 2020, all 50 states in the United States had reopened their economies to some extent after the coronavirus lockdown. Although there are many debates about whether states reopened their economies too early, no study has examined this effect quantitatively. This paper takes advantage of the daily cases, deaths, and test data at the state level, and uses the synthetic control method to address this question. I find that reopening the economy caused an additional 2000 deaths in the 6 states (Alabama, Colorado, Georgia, Mississippi, Tennessee, and Texas) that reopened before May 1stby three weeks after reopening. It also increased daily confirmed cases by 40%, 52%, and 53% after the first, second, and third week of reopening, respectively. Moreover, contrary to scientists’ prescription that expanding tests is a necessary condition for reopening, these states witnessed a decline in daily tests by 17%, 47%, and 31% after the first, second, and third week of reopening, respectively.