bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Fast and Accessible Method for the Isolation of RNA, DNA, and Protein to Facilitate the Detection of SARS-CoV-2
Authors: Ponce-Rojas Jose Carlos , Costello Michael S. , Proctor Duncan A. , Kosik Kenneth S. , Wilson Maxwell Z. , Arias Carolina , Acosta-Alvear Diego 
Published: July 2020

AbstractManagement of the COVID-19 pandemic requires widespread SARS-CoV-2 testing. A main limitation for widespread SARS-CoV-2 testing is the global shortage of essential supplies, among these, RNA extraction kits. The need for commercial RNA extraction kits places a bottleneck on tests that detect SARS-CoV-2 genetic material, including PCR-based reference tests. Here we propose an alternative method we call PEARL (PrecipitationEnhancedAnalyteRetrievaL) that addresses this limitation. PEARL uses a lysis solution that disrupts cell membranes and viral envelopes while simultaneously providing conditions suitable for alcohol-based precipitation of RNA, DNA, and proteins. PEARL is a fast, low-cost, and simple method that uses common laboratory reagents and offers comparable performance to commercial RNA extraction kits. PEARL offers an alternative method to isolate host and pathogen nucleic acids and proteins to streamline the detection of DNA and RNA viruses, including SARS-CoV-2.
Trade-offs between sperm viability and immune protein expression in honey bee queens (Apis mellifera)
Authors: McAfee Alison , Chapman Abigail , Pettis Jeffery S , Foster Leonard J , Tarpy David R 
Published: July 2020

AbstractQueens of many social hymenoptera keep sperm alive within their specialized storage organ, the spermatheca, for years, defying the typical trade-off between lifespan and reproduction. However, whether honey bee queens experience a trade-off between reproduction and immunity is unknown, and the biochemical processes underlying sperm viability are poorly understood. Here, we survey quality metrics and viral loads of honey bee queens from nine genetic sources. Queens rated as ‘failed’ by beekeepers had lower sperm viability, fewer sperm, and higher levels of SBV and BQCV. Quantitative proteomics on N = 123 spermathecal fluid samples shows, after accounting for sperm count, health status, and apiary effects, five spermathecal fluid proteins significantly correlating with sperm viability: odorant binding protein (OBP)14, lysozyme, serpin 88Ea, artichoke, and heat-shock protein (HSP)10. The significant negative correlation of lysozyme—a conserved immune effector—with sperm viability is consistent with a reproduction vs. immunity trade-off in honey bee queens.
Neural signatures of vigilance decrements predict behavioural errors before they occur
Authors: Karimi-Rouzbahani Hamid , Woolgar Alexandra , Rich Anina N. 
Published: July 2020

AbstractThere are many monitoring environments, such as railway control, in which lapses of attention can have tragic consequences. Problematically, sustained monitoring for rare targets is difficult, with more misses and longer reaction times over time. What changes in the brain underpin these “vigilance decrements”? We designed a multiple-object monitoring (MOM) paradigm to examine how the neural representation of information varied with target frequency and time performing the task. Behavioural performance decreased over time for the rare target (monitoring) condition, but not for a frequent target (active) condition. This was mirrored in the neural results: there was weaker coding of critical information during monitoring versus active conditions. We developed new analyses that can predict behavioural errors from the neural data more than a second before they occurred. This paves the way for pre-empting behavioural errors due to lapses in attention and provides new insight into the neural correlates of vigilance decrements.
Single cell in vivo brain optogenetic stimulation by two-photon excitation fluorescence transfer
Authors: Tong Lei , Yuan Peng , Xue Yao , Chen Minggang , Chen Fuyi , Bewersdorf Joerg , Zhou Z. Jimmy , Grutzendler Jaime 
Published: July 2020

AbstractOptogenetic manipulation with single-cell resolution can be achieved by two-photon excitation; however, this frequently requires relatively high laser powers or holographic illumination. Here we developed a practical strategy to improve the efficiency of two-photon stimulation by positioning fluorescent proteins or small fluorescent molecules with high two-photon cross-sections in the vicinity of opsins. This generates a highly localized source of endogenous single-photon illumination that can be tailored to match the optimal opsin absorbance. Through neuronal and vascular stimulation in the live mouse brain, we demonstrate the utility of this technique to achieve more efficient opsin stimulation, without loss of cellular resolution. We also provide a theoretical framework for understanding the potential advantages and constrains of this methodology, with suggestions for future improvements. Altogether, this fluorescence transfer illumination method allows experiments difficult to implement in the live brain such as all-optical neural interrogation and control of regional cerebral blood flow.
Most-probable number based minimum duration of killing assay for determining the spectrum of rifampicin susceptibility in clinicalM. tuberculosisisolates
Authors: Vijay Srinivasan , Nhung Hoang Ngoc , Bao Nguyen Le Hoai , Thu Do Dang Anh , Trieu Le Pham Tien , Phu Nguyen Hoan , Thwaites Guy E. , Javid Babak , Thuong Nguyen T. T. 
Published: July 2020

AbstractAccurate antibiotic susceptibility testing is essential for successful tuberculosis treatment. Recent studies have highlighted the limitations of minimum inhibitory concentrations (MIC) based phenotypic susceptibility methods in detecting other aspects of antibiotic susceptibilities in bacteria. Duration and peak of antibiotic exposure, at or above the MIC required for killing the bacterial population, has emerged as another important factor for determining the antibiotic susceptibility. This is broadly defined as antibiotic tolerance. Antibiotic tolerance can further facilitate the emergence of antibiotic resistance. Currently there are limited methods to quantify antibiotic tolerance among clinicalM. tuberculosisisolates. In this study, we develop a most-probable number (MPN) based minimum duration of killing (MDK) assay to quantify the spectrum ofM. tuberculosisrifampicin susceptibility within subpopulations, based on time duration of rifampicin exposure required for killing the bacterial population. MDK90-99and MDK99.99defined as the minimum time duration of antibiotic exposure at or above MIC required for killing 90-99% and 99.99% of the initial (pre-treatment) bacterial population respectively. Results from the rifampicin MDK assay applied to 28 laboratory and clinicalM. tuberculosisisolates showed that there is variation in rifampicin susceptibility among isolates. Rifampicin MDK99/99.99time for isolates varied from less than 2 to 10 days. MDK duration was correlated with larger sub-populations ofM. tuberculosisfrom clinical isolates that were rifampicin tolerant. Our study demonstrates the utility of MDK assays to measure the variation in antibiotic tolerance among clinicalM. tuberculosisisolates and further expands clinically important aspects of antibiotic susceptibility testing.
Developmental models reveal the role of phenotypic plasticity in explaining genetic evolvability
Authors: Brun-Usan Miguel , Rago Alfredo , Thies Christoph , Uller Tobias , Watson Richard A. 
Published: July 2020

AbstractBiological evolution exhibits an extraordinary capability to adapt organisms to their environments. The explanation for this often takes for granted that random genetic variation produces at least some beneficial phenotypic variation for natural selection to act on. Such genetic evolvability could itself be a product of evolution, but it is widely acknowledged that the immediate selective gains of evolvability are small on short timescales. So how do biological systems come to exhibit such extraordinary capacity to evolve? One suggestion is that adaptive phenotypic plasticity makes genetic evolution find adaptations faster. However, the need to explain the origin of adaptive plasticity puts genetic evolution back in the driving seat, and genetic evolvability remains unexplained. To better understand the interaction between plasticity and genetic evolvability, we simulate the evolution of phenotypes produced by gene-regulation network-based models of development. First, we show that the phenotypic variation resulting from genetic and environmental change are highly concordant. This is because phenotypic variation, regardless of its cause, occurs within the relatively specific space of possibilities allowed by development. Second, we show that selection for genetic evolvability results in the evolution of adaptive plasticity andvice versa. This linkage is essentially symmetric but, unlike genetic evolvability, the selective gains of plasticity are often substantial on short, including within-lifetime, timescales. Accordingly, we show that selection for phenotypic plasticity is, in general, the most efficient and results in the rapid evolution of high genetic evolvability. Thus, without overlooking the fact that adaptive plasticity is itself a product of genetic evolution, this shows how plasticity can influence adaptive evolution and helps explain the genetic evolvability observed in biological systems.
Klebsiella pneumoniaereduces SUMOylation to limit host defence responses
Authors: Sá-Pessoa Joana , Przybyszewska Kornelia , Vasconcelos Filipe Nuno , Dumigan Amy , Frank Christian G. , Hobley Laura , Bengoechea Jose A. 
Published: July 2020

ABSTRACTKlebsiella pneumoniaeis an important cause of multidrug resistant infections worldwide. Understanding the virulence mechanisms ofK. pneumoniaeis a priority and timely to design new therapeutics. Here we demonstrate thatK. pneumoniaelimits the SUMOylation of host proteins in epithelial cells and macrophages (mouse and human) to subvert cell innate immunity. Mechanistically, in lung epithelial cellsKlebsiellaincreases the levels of the deSUMOylase SENP2 in the cytosol by affecting its K48-ubiquitylation and its subsequent degradation by the ubiquitin proteasome. This is dependent onKlebsiellapreventing the NEDDylation of the Cullin-1 subunit of the ubiquitin ligase complex E3-SCFβ-TrCP by exploiting the CSN5 deNEDDylase.Klebsiellainduces the expression of CSN5 in an EGFR-PI3K-AKT-ERK-GSK3β signalling pathway dependent manner. In macrophages, TLR4-TRAM-TRIF induced type-I IFN via IFNAR1-controlled signalling mediatesKlebsiella-triggered decrease in the levels of SUMOylation vialet-7miRNAs. Our results revealed the crucial role played byKlebsiellapolysaccharides, the capsule and the LPS O-polysaccharide, to decrease the levels of SUMO-conjugated proteins in epithelial cells and macrophages.Klebsiella-induced decrease in SUMOylation promotes infection by limiting the activation of inflammatory responses and increasing intracellular survival in macrophages.IMPORTANCEKlebsiella pneumoniaehas been singled out as an urgent threat to human health due to the increasing isolation of strains resistant to “last line” antimicrobials, narrowing the treatment options againstKlebsiellainfections. Unfortunately, at present, we cannot identify candidate compounds in late-stage development for treatment of multidrugKlebsiellainfections; this pathogen is exemplary of the mismatch between unmet medical needs and the current antimicrobial research and development pipeline. Furthermore, there is still limited evidence onK. pneumoniaepathogenesis at the molecular and cellular level in the context of the interactions between bacterial pathogens and their hosts. In this research, we have uncovered a sophisticated strategy employed byKlebsiellato subvert the activation of immune defences by controlling the modification of proteins. Our research may open opportunities to develop new therapeutics based on counteracting thisKlebsiella-controlled immune evasion strategy.
Stabilization of β-catenin promotes melanocyte specification at the expense of the Schwann cell lineage
Authors: Colombo Sophie , Petit Valérie , Wagner Roselyne Y , Champeval Delphine , Yajima Ichiro , Gesbert Franck , Davidson Irwin , Delmas Véronique , Larue Lionel 
Published: July 2020

AbstractThe canonical Wnt/β-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, β-catenin regulatesMitf-Mtranscription, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, while a small number of second wave melanocytes is derived from Schwann-cell precursors (SCPs). We investigated the influence of β-catenin in the development of melanocytes of the first and second waves by generating mice expressing a constitutively active form of β-catenin in cells expressing tyrosinase. Constitutive activation of β-catenin did not affect the development of truncal melanoblasts, but led to a marked hyperpigmentation of the paws. By activating β-catenin at various stages of development (E8.5-E11.5), we showed that the activation of β-catenin in bipotent SCPs favored melanoblast specification at the expense of Schwann cells in the limbs within a specific temporal window. In addition, hyperactivation of the Wnt/β-catenin pathway repressedFoxD3expression, which is necessary for Schwann cell development, throughMitf-Mactivation. In conclusion, β-catenin overexpression promotes SCP cell-fate decisions towards the melanocyte lineage.Summary statementActivation of β-catenin in bipotent Schwann-cell precursors during a specific developmental window, induces MITF and represses FoxD3 to promote melanoblast cell fate at the expense of Schwann cells in limbs.
Inactivated trivalent influenza vaccine is associated with lower mortality among Covid-19 patients in Brazil
Authors: Fink Günther , Orlova-Fink Nina , Schindler Tobias , Grisi Sandra , Ferrer Ana Paula , Daubenberger Claudia , Brentani Alexandra 
Published: July 2020

AbstractWe analyzed data from 92,664 clinically and molecularly confirmed Covid-19 cases in Brazil to understand the potential associations between influenza vaccination and Covid-19 outcomes. Controlling for health facility of treatment, comorbidities as well as an extensive range of sociodemographic factors, we show that patients who received a recent influenza vaccine experienced on average 8% lower odds of needing intensive care treatment (95% CIs [0.86, 0.99]), 18% lower odds of requiring invasive respiratory support (0.74, 0.88) and 17% lower odds of death (0.75, 0.89). Large scale promotion of influenza vaccines seems advisable, especially in populations at high risk of severe SARS-CoV-2 infection.One Sentence SummaryCovid-19 patients with recent influenza vaccination experience better health outcomes than non-vaccinated patients in Brazil.
Multimodal Recruitment for an Internet-Based Pilot Study of Ovulation and Menstruation (OM) Health
Authors: Mahalingaiah Shruthi , Cheng J. Jojo , Winter Michael , Rodriguez Erika , Fruh Victoria , Williams Anna , Nguyen MyMy , Madhavan Rashmi , Karanja Pascaline , McCrae Jill , Konanki Sai Charan , Lane Kevin J , Aschengrau Ann 
Published: July 2020

AbstractBackgroundMultimodal recruitment strategies are a novel way to increase diversity of research populations. However, these methods have not been previously applied to understanding the prevalence of menstrual disorders such as polycystic ovary syndrome (PCOS).MethodsWe conducted the Ovulation and Menstruation Health (OM) Pilot Study using an online survey platform to recruit 200 women from a clinical population, a community fair, and the Internet.ResultsWe recruited 438 women over 29 weeks between September 2017 and March 2018. After consent and eligibility determination, 345 enrolled, 278 started, and 247 completed the survey. Survey initiation and (completion) by recruitment location were 43 (28) from the clinic, 61(60) from a community fair, and 174 (159) from the internet. Among all participants, the mean (SD) age was 27 (6) years, body mass index was 26 kg/m2 (7), 79.7% had a college degree or higher, and 14.6% reported a physician diagnosis of PCOS. Race/ethnic distribution was 64.7% White, 11.8% Black, 7.7% Hispanic; and 5.9% Asian; 9.9% reported more than one race/ethnicity. The highest enrollment of Black race/ethnicity was in clinic (40.5%) compared to 1.6% in the community fair, and 8.3% using the internet. Survey completion rates were highest among those recruited from the internet (91.4%) and community fairs (98.4%), compared to in-clinic (65.1%).ConclusionMultimodal recruitment achieved target recruitment in a short time period, and established a racially diverse cohort to study ovulation and menstruation health. There was greater enrollment and completion rates among those recruited via the internet and community-fair.Key MessageThe Ovulation and Menstruation Health Pilot Study:
Designed to determine the population prevalence of PCOS using a survey instrument and pictorial tool to ascertain menstrual cycle characteristics and androgen excess, and serve as a platform for a future longitudinal cohort study.Enrolled participants from diverse backgrounds using an online adaptable platform for multimodal recruitment.Mode of recruitment was associated with race/ethnic diversity and completion of survey.
Single-cell transcriptional atlas of the Chinese horseshoe bat (Rhinolophus sinicus) provides insight into the cellular mechanisms which enable bats to be viral reservoirs
Authors: Ren Lili , Wu Chao , Guo Li , Yao Jiacheng , Wang Conghui , Xiao Yan , Pisco Angela Oliveira , Wu Zhiqiang , Lei Xiaobo , Liu Yiwei , Shi Leisheng , Han Lianlian , Zhang Hu , Xiao Xia , Zhong Jingchuan , Wu Hongping , Li Mingkun , Quake Stephen R. , Huang Yanyi , Wang Jianbin , Wang Jianwei 
Published: July 2020

AbstractBats are a major “viral reservoir” in nature and there is a great interest in not only the cell biology of their innate and adaptive immune systems, but also in the expression patterns of receptors used for cellular entry by viruses with potential cross-species transmission. To address this and other questions, we created a single-cell transcriptomic atlas of the Chinese horseshoe bat (Rhinolophus sinicus) which comprises 82,924 cells from 19 organs and tissues. This atlas provides a molecular characterization of numerous cell types from a variety of anatomical sites, and we used it to identify clusters of transcription features that define cell types across all of the surveyed organs. Analysis of viral entry receptor genes for known zoonotic viruses showed cell distribution patterns similar to that of humans, with higher expression levels in bat intestine epithelial cells. In terms of the immune system, CD8+ T cells are in high proportion with tissue-resident memory T cells, and long-lived effector memory nature killer (NK) T-like cells (KLRG1,GZMAandITGA4genes) are broadly distributed across the organs. Isolated lung primary bat pulmonary fibroblast (BPF) cells were used to evaluate innate immunity, and they showed a weak response to interferon β and tumor necrosis factor-α compared to their human counterparts, consistent with our transcriptional analysis. This compendium of transcriptome data provides a molecular foundation for understanding the cell identities, functions and cellular receptor characteristics for viral reservoirs and zoonotic transmission.
Population density and temperature influence the return on maternal investment in wild house mice
Authors: Auclair Yannick , Gerber Nina , König Barbara , Lindholm Anna K. 
Published: July 2020

AbstractIn mammals, reproduction is influenced by competitive stress, temperature and food availability and these factors might be crucial already during early life. Favourable early life environment and high maternal investment are expected to improve survival and reproduction. In mammals, maternal investment via lactation predicts offspring growth. As body mass is often associated with fitness consequences, females have the potential to influence offspring fitness through their level of investment, which might interact with effects of population density and temperature. Here, we investigate the relationship between pup body mass at day 13 (used as approximation for weaning mass) and individual reproductive parameters as well as longevity under natural variation in population density and temperatures. Further, we assess the extent to which mothers influence the body mass of their offspring until weaning. We analysed life data of 384 house mice (Mus musculus domesticus) from a free-living wild population that was not food limited. We found a complex effect of population density, temperature and maternal investment on life-history traits related to fitness: Shorter longevity with increasing pup body mass at day 13; delayed reproduction of heavier pups when raised at warmer temperatures; and increased lifetime reproductive success for heavier pups at high densities. House mice could use population density and temperature as cues for predicting future environmental conditions, allowing a mother to adjust her investment according to the environment in which offspring will breed in order to maximise fitness. This study highlights the importance of considering ecological conditions in combination with maternal effects.
Codon optimisation for maximising gene expression in multiple species and microbial consortia
Authors: Skelton David J. , Eland Lucy E. , Sim Martin , White Michael A. , Davenport Russell J. , Wipat Anil 
Published: July 2020

AbstractMotivationCodon optimisation, the process of adapting the codon composition of a coding sequence, is often used in synthetic biology to increase expression of a heterologous protein. Recently, a number of synthetic biology approaches that allow synthetic constructs to be deployed in multiple organisms have been published. However, so far, design tools for codon optimisation have not been updated to reflect these new approaches.ApproachWe designed an evolutionary algorithm (EA) to design coding sequences (CDSs) that encode a target protein for one or more target organisms, based on the Chimera average repetitive substring (ARS) metric — a correlate of gene expression. A parameter scan was then used to find optimal parameter sets. Using the optimal parameter sets, three heterologous proteins were repeatedly optimisedBacillus subtilis168 andEscherichia coliMG1655. The ARS scores of the resulting sequences were compared to the ARS scores of coding sequences that had been optimised for each organism individually (using Chimera Map).ResultsWe demonstrate that an EA is a valid approach to optimising a coding sequence for multiple organisms at once; both crossover and mutation operators were shown to be necessary for the best performance. In some scenarios, the EA generated CDSs that had higher ARS scores than CDSs optimised for the individual organisms, suggesting that the EA exploits the CDS design space in a way that Chimera Map does not.Availability and implementationThe implementation of the EA, with instructions, is available on GitHub:https://github.com/intbio-ncl/chimera_evolve.