bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dinophyceae use exudates as weapons against the parasiteAmoebophryasp. (Syndiniales)
Authors: Marc Long , Dominique Marie , Jeremy Szymczak , Jordan Toullec , Estelle Bigeard , Marc Sourisseau , Mickael Le Gac , Laure Guillou , Cécile Jauzein 
Published: January 2021

SummaryParasites of the genusAmoebophryasp. are important contributors to marine ecosystems and can be determining factors in the demise of blooms of Dinophyceae, including microalgae commonly responsible for toxic red tides. Yet they rarely lead to the total collapse of Dinophyceae blooms. The addition of resistant Dinophyceae (Alexandrium minutumorScrippsiella donghaienis) or their exudate into a well-established host-parasite culture (Scrippsiella acuminata-Amoebophryasp.) mitigated the success of the parasite and increased the survival of the sensitive host. Effect were mediated via water-borne molecules without the need of a physical contact. Severity of the anti-parasitic defenses fluctuated depending on the species, the strain and its concentration, but never totally prevented the parasite transmission. The survival time ofAmoebophryasp. free-living stages (dinospores) decreased in presence ofA. minutumbut not ofS. donghaienis. The progeny drastically decreased with both species. Integrity of the membrane of dinospores was altered byA. minutumwhich provided a first indication on the mode of action of these anti-parasitic molecules. These results demonstrate that extracellular defenses are an effective strategy against parasites that does not only protect the resistant cells but also have the potential to affect the whole surrounding community.
Essential oil composition ofCallistemon citrinus(Curtis) and its protective assessment towardsTribolium castaneum(Herbst) (Coleoptera: Tenebrionidae)
Authors: Ramachandran Maduraiveeran , Baskar Kathirvelu , Hashem Abeer , Abd_Allah Elsayed Fathi , Jayakumar Manickkam 
Published: January 2021

AbstractEssential oil (EO) was extracted fromCallistemon citrinusleaves by hydro-distillation. The extracted oil was analysed by GC and Mass Spectroscopy. Analysis report showed that the major constituent of the essential oil was eucalyptol (40.44%). The EO ofC. citrinusexhibited 100% fumigation toxicity (adult mortality) against adult and 95.8% larvicidal activity againstTribolium castaneumat 160 μL/L (12 hrs) and 320 μL/L (48 hrs), respectively. The effective concentration of 37.05 μL/L (adult) and 144.31 μL/L (larva) at 24 and 48 hrs respectively. A 100% repellent activity was observed at 20 μl for adult beetles and 93.3% for larvae ofT. castaneumat 20 μl after 24 h. Exposure toC. citrinusEO significantly reduced beetle fecundity, ovicidal activity, egg hatching, larvae survival, and emergence of adult. The effect of EO on detoxification enzymes ofT. castaneumadults was examined. Results indicated that the activity of detoxification enzymes drastically varied when compared with control. This EO had toxicant effects on all stages of the life ofT. castaneum. Hence it may be used as fumigant instead of the use of using synthetic chemical fumigants.
Covid19Risk.ai: An open source repository and online calculator of prediction models for early diagnosis and prognosis of Covid-19
Authors: Halilaj Iva , Chatterjee Avishek , van Wijk Yvonka , Wu Guangyao , van Eeckhout Brice , Oberije Cary , Lambin Philippe 
Published: January 2021

AbstractObjectiveThe current pandemic has led to a proliferation of predictive models being developed to address various aspects of COVID-19 patient care. We aimed to develop an online platform that would serve as an open source repository for a curated subset of such models, and provide a simple interface for included models to allow for online calculation. This platform would support doctors during decision-making regarding diagnoses, prognoses, and follow-up of COVID-19 patients, expediting the models’ transition from research to clinical practice.MethodsIn this proof-of-principle study, we performed a literature search in PubMed and WHO database to find suitable models for implementation on our platform. All selected models were publicly available (peer reviewed publications or open source repository) and had been validated (TRIPOD type 3 or 2b). We created a method for obtaining the regression coefficients if only the nomogram was available in the original publication. All predictive models were transcribed on a practical graphical user interface using PHP 8.0.0, and published online together with supporting documentation and links to the associated articles.ResultsThe open source websitehttps://covid19risk.ai/currently incorporates nine models from six different research groups, evaluated on datasets from different countries. The website will continue to be populated with other models related to COVID-19 prediction as these become available. This dynamic platform allows COVID-19 researchers to contact us to have their model curated and included on our website, thereby increasing the reach and real-world impact of their work.ConclusionWe have successfully demonstrated in this proof-of-principle study that our website provides an inclusive platform for predictive models related to COVID-19. It enables doctors to supplement their judgment with patient-specific predictions from externally-validated models in a user-friendly format. Additionally, this platform supports researchers in showcasing their work, which will increase the visibility and use of their models.
How to attract and retain health workers in rural areas of a fragile state: findings from a labour market survey in Guinea
Authors: Witter Sophie , Herbst Christopher H. , Smitz Marc , Balde Mamadou Dioulde , Magazi Ibrahim , Zaman Rashid U. 
Published: January 2021

AbstractMost countries face challenges attracting and retaining health staff in remote areas but this is especially acute in fragile and shock-prone contexts, like Guinea, where imbalances in staffing are high and financial and governance arrangements to address rural shortfalls are weak.The objective of this study was to understand how health staff could be better motivated to work and remain in rural, under-served areas in Guinea. In order to inform the policy dialogue on strengthening human resources for health, we conducted three nationally representative cross-sectional surveys, adapted from tools used in other fragile contexts.We found that the locational job preferences of health workers in Guinea are particularly influenced by opportunities for training, working conditions, and housing. Most staff are satisfied with their work and with supervision, however, financial aspects and working conditions are considered least satisfactory, and worrying findings include the high proportion of staff favouring emigration, their high tolerance of informal user payments, as well as their limited exposure to rural areas during training.Based on our findings, we highlight measures which could improve rural recruitment and retention in Guinea and similar settings. These include offering upgrading and specialization in return for rural service; providing greater exposure to rural areas during training; increasing recruitment from rural areas; experimenting with fixed term contracts in rural areas; and improving working conditions in rural posts. The development of incentive packages should be accompanied by action to tackle wider issues, such as reforms to training and staff management.
A nuclear pore sub-complex restricts the propagation of Ty retrotransposons by limiting their transcription
Authors: Bonnet Amandine , Chaput Carole , Palancade Benoit , Lesage Pascale 
Published: January 2021

ABSTRACTBeyond their canonical function in nucleocytoplasmic exchanges, nuclear pore complexes (NPCs) regulate the expression of protein-coding genes. Here, we have implemented transcriptomic and molecular methods to specifically address the impact of the NPC on retroelements, which are present in multiple copies in genomes. We report a novel function for the Nup84 complex, a core NPC building block, in specifically restricting the transcription of LTR-retrotransposons in yeast. Nup84 complex-dependent repression impacts bothCopiaandGypsyTy LTR-retrotransposons, all over theS. cerevisiaegenome. Mechanistically, the Nup84 complex restricts the transcription of Ty1, the most active yeast retrotransposon, through the tethering of the SUMO-deconjugating enzyme Ulp1 to NPCs. Strikingly, the modest accumulation of Ty1 RNAs caused by Nup84 complex loss-of-function is sufficient to trigger an important increase of Ty1 cDNA levels, resulting in massive Ty1 retrotransposition. Altogether, our studies expand our understanding of the complex interactions between retrotransposons and the NPC, and highlight the importance for the cells to keep retrotransposon under tight transcriptional control.AUTHOR SUMMARYRetroelements, which replicate by reverse transcription of their RNA into a cDNA that is integrated into the host genetic material, play an important role in the plasticity of eukaryotic genomes. The study of yeast retrotransposons has led to the identification of host factors that limit retroelement mobility, including components of the nuclear pore complex (NPC), most of them still awaiting mechanistic characterization. Here, we investigated the contribution of the Nup84 complex, a core NPC scaffold, to retrotransposon biology in budding yeast. Our findings uncover that the Nup84 complex restricts the transcription of phylogenetically-distinct Ty retroelements. By focusing on Ty1 retrotransposons, we provide evidence that repression by the Nup84 complex depends on the maintenance at the NPC of the SUMO-protease Ulp1, an essential enzyme of the SUMO pathway with multiple targets in the transcription machinery. We finally show that this transcriptional control is critical for genome dynamics, since a small increase in the accumulation of Ty1 RNAs leads to massive retrotransposition. Our data reveal that although relatively abundant, Ty transcripts are limiting for retrotransposition, underscoring the importance of a tight control of their expression. They also characterize a new non-canonical function of NPCs, confirming their connection with genome expression and stability.
MAVERICC: Efficient marker-free rescue of vaccinia virus recombinants byin vitroCRISPR-Cas9 engineering
Authors: Laudermilch Ethan , Chandran Kartik 
Published: January 2021

AbstractVaccinia virus (VACV)-based vectors are in extensive use as vaccines and cancer immunotherapies. VACV engineering has traditionally relied on homologous recombination between a parental viral genome and a transgene-bearing transfer plasmid, a highly inefficient process that necessitates the use of a selection or screening marker to isolate recombinants. Recent extensions of this approach have sought to enhance the recovery of transgene-bearing viruses through the use of CRISPR-Cas9 engineering to cleave the viral genome in infected cells. However, these methods do not completely eliminate the generation of WT viral progeny and thus continue to require multiple rounds of viral propagation and plaque purification. Here, we describe MAVERICC (marker-freevaccinia virusengineering of recombinants throughin vitroCRISPR/Cas9cleavage), a new strategy to engineer recombinant VACVs in a manner that overcomes current limitations. MAVERICC also leverages the CRISPR/Cas9 system but requires no markers and yields essentially pure preparations of the desired recombinants in a single step. We used this approach to rapidly introduce point mutations, insertions, and deletions at multiple locations in the VACV genome, both singly and in combination. The efficiency and versatility of MAVERICC make it an ideal choice for generating mutants and mutant libraries at arbitrarily selected locations in the viral genome to build complex VACV vectors, effect vector improvements, and facilitate the study of poxvirus biology.Graphical AbstractOverview of MAVERICC.Conceptual overview of the approach outlined in this manuscript. To make VACV recombinants, the parental virus is first purified and vDNA is isolated with phenol:chloroform extraction. This purified vDNA is then treated with Cas9 enzyme and sgRNAs that are directed to a specific locus in the VACV genome. The cleaved vDNA is then transfected into FWPV-infected BSC-40 cells along with a transfer amplicon containing an insertion or mutation of interest flanked by homologous sequences. Recombination is allowed to occur for 5-7 days, during which time the cleaved vDNA is healed by the transfer amplicon, thus editing the VACV genome, and packaged into infectious viral particles. Individual plaques are grown up and rVACVs are isolated after a single round of plaque purification. Image was created with Biorender.com.
A novel skeletal-specific adipogenesis pathway defines key origins and adaptations of bone marrow adipocytes with age and disease
Authors: Robles Hero , Zhang Xiao , Magee Kristann L. , Lorenz Madelyn R. , Wang Zhaohua , Harris Charles A. , Craft Clarissa S. , Scheller Erica L. 
Published: January 2021

SUMMARYBone marrow adipocytes (BMAs) accumulate with age and in diverse disease states. However, their age- and disease-specific origins and adaptations remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, we identified a novel, bone marrow-specific adipogenesis pathway using theAdipoqCre+/DTA+‘fat free’ mouse (FF), a model in whichAdipoq-Cre drives diphtheria toxin-induced cell death in all adiponectin-expressing cells. Adiponectin is highly expressed by BMAs, peripheral adipocytes, and a subset of bone marrow stromal progenitor cells with preadipocyte-like characteristics. Consistent with this, FF mice presented with uniform depletion of peripheral white and brown adipose tissues, in addition to loss of BMAs in canonical locations such as the tail vertebrae. However, unexpectedly, a distinctly localized subset of BMAs accumulated with age in FF mice in regions such as the femoral and tibial diaphysis that are generally devoid of bone marrow adipose tissue (BMAT). Ectopic BMAs in FF mice were defined by increased lipid storage and decreased expression of cytokines including hematopoietic support factorCxcl12and adipokines adiponectin, resistin, and adipsin. FF BMAs also displayed resistance to lipolytic stimuli including cold stress and β3-adrenergic agonist CL316,243. This was associated with reduced expression of adrenergic receptors and monoacylglycerol lipase. Global ablation of adiponectin-expressing cells regulated bone accrual in an age- and sex-dependent manner. High bone mass was present early in life and this was more pronounced in females. However, with age, both male and female FF mice had decreased cortical thickness and mineral content. In addition, unlike BMAs in healthy mice, expansion of ectopic BMAs in FF mice was inversely correlated with cortical bone volume fraction. Subcutaneous fat transplant and normalization of systemic metabolic parameters was sufficient to prevent ectopic BMA expansion in FF mice but did not prevent the initial onset of the high bone mass phenotype. Altogether, this defines a novel, secondary adipogenesis pathway that relies on recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress, resulting in expansion of BMAs specialized for lipid storage with compromised lipid mobilization and endocrine function within regions traditionally devoted to hematopoiesis. Our findings further distinguish BMAT from peripheral adipose tissues and contribute to our understanding of BMA origins and adaptation with age and disease.
Training level reveals a dynamic dialogue between stress and memory systems in birds
Authors: Lormant Flore , Ferreira Vitor Hugo Bessa , Lemarchand Julie , Cornilleau Fabien , Constantin Paul , Parias Céline , Bertin Aline , Lansade Léa , Leterrier Christine , Lévy Frédéric , Calandreau Ludovic 
Published: January 2021

AbstractIt is now well-accepted that memory is a dynamic process, and that stress and training level may influence which memory system an individual engages when solving a task. In this work, we investigated whether and how chronic stress impacts spatial and cue-based memories according to training level. To that aim, control and chronically stressed Japanese quail were trained in a task that could be solved using spatial and cue-based memory and tested for their memory performances after 5 and 15 training days (initial training and overtraining, respectively) and following an emotional challenge (exposure to an open field). While chronic stress negatively impacted spatial memory in chronically stressed birds after initial training, this impact was lowered after overtraining compared to control quail. Interestingly, the emotional challenge reinstated the differences in performance between the two groups, revealing that chronic stress/overtraining did not eliminate spatial memory. Differences caused by previous stressors can re-emerge depending on the more immediate psychological state of the individual. Contrary to spatial memory, cue-based memory was not impaired in any test occasion, confirming that this form of memory is resistant to chronic stress. Altogether these findings reveal a dynamic dialogue between stress, training, and memory systems in birds.
Weight loss response following lifestyle intervention associated with baseline gut metagenomic signature in humans
Authors: Diener Christian , Qin Shizhen , Zhou Yong , Patwardhan Sushmita , Tang Li , Lovejoy Jennifer , Magis Andrew T. , Price Nathan D. , Hood Leroy , Gibbons Sean M. 
Published: January 2021

AbstractWe report a weight-loss response analysis on a small cohort of individuals (N=25) selected from a larger population (N∼5,000) enrolled in a commercial scientific wellness program, which included healthy lifestyle coaching. Each individual had baseline data on blood metabolomics, blood proteomics, clinical labs, lifestyle questionnaires, and stool metagenomes. A subset of these participants (N=15) lost at least 10% of their body weight within a 6-12 month period and saw significant improvement in metabolic health markers (‘weight loss’ group), while another subset of individuals (N=10) undergoing the same lifestyle intervention showed no change in BMI over the same timeframe (‘no weight loss’ group). Only a single baseline blood analyte, a metabolite linked to fried food consumption, was (negatively) associated with weight loss, but a large number of baseline stool metagenomic features, including complex polysaccharide and protein degradation genes, stress-response genes, respiration-related genes, cell wall synthesis genes, and gut bacterial replication rates, were significantly associated with weight loss after explicitly controlling for baseline BMI. Together, these results provide a set of baseline gut microbiome functional features that are associated with weight loss outcomes.
Generation of PathogenicTPP1Mutations in Human Stem Cells as a Model for CLN2 Disease
Authors: Ma Li , Prada Adriana , Schmidt Michael , Morrow Eric M. 
Published: January 2021

AbstractNeuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an autosomal recessive neurodegenerative disorder generally with onset at 2 to 4 years of age and characterized by seizures, loss of vision, progressive motor and mental decline, and premature death. CLN2 disease is caused by loss-of-function mutations in the tripeptidyl peptidase 1 (TPP1) gene leading to deficiency in TPP1 enzyme activity. Approximately 60% of patients have one of two pathogenic variants (c.509-1G>C or c.622C>T [p.(Arg208*)]). In order to generate a human stem cell model of CLN2 disease, we used CRISPR/Cas9-mediated knock-in technology to introduce these mutations in a homozygous state into H9 human embryonic stem cells. Heterozygous lines of the c.622C>T (p.(Arg208*)) mutation were also generated, which included a heterozygous mutant with a wild-type allele and different compound heterozygous coding mutants resulting from indels on one allele. We describe the methodology that led to the generation of the lines and provide data on the initial validation and characterization of these CLN2 disease models. Notably, both mutant lines (c.509-1G>C and c.622C>T [p.(Arg208*)]) in the homozygous state were shown to have reduced or absent protein, respectively, and deficiency of TPP1 enzyme activity. These models, which we are making available for wide-spread sharing, will be useful for future studies of molecular and cellular mechanisms underlying CLN2 disease and for therapeutic development.
Burden is in the eye of the beholder: Sensitivity of yellow fever disease burden estimates to modeling assumptions
Authors: Perkins T. Alex , Huber John H. , Minh Quan Tran , Oidtman Rachel J. , Walters Magdalene K. , Siraj Amir S. , Moore Sean M. 
Published: January 2021

ABSTRACTGeographically stratified estimates of disease burden play an important role in setting priorities for the management of different diseases and for targeting interventions against a single disease. Such estimates involve numerous assumptions, which uncertainty about is not always well accounted for. We developed a framework for estimating the burden of yellow fever in Africa and evaluated its sensitivity to assumptions about the interpretation of serological data and choice of regression model. We addressed the latter with an ensemble approach, and we found that the former resulted in a nearly twentyfold difference in burden estimates (range of central estimates: 8.4×104-1.5×106deaths in 2021-2030). Even so, statistical uncertainty made even greater contributions to variance in burden estimates (87%). Combined with estimates that most infections go unreported (range of 95% credible intervals: 99.65-99.99%), our results suggest that yellow fever’s burden will remain highly uncertain without major improvements in surveillance.
Impaired performance of SARS-CoV-2 antigen-detecting rapid tests at elevated temperatures
Authors: Haage Verena , de Oliveira-Filho Edmilson Ferreira , Moreira-Soto Andres , Kühne Arne , Fischer Carlo , Sacks Jilian , Corman Victor Max , Müller Marcel A. , Drosten Christian , Drexler Jan Felix 
Published: January 2021

AbstractRapid antigen-detecting tests (Ag-RDTs) can complement molecular diagnostics for COVID-19. The recommended temperature for storage of SARS-CoV-2 Ag-RDTs ranges between 5-30°C. In many countries that would benefit from SARS-CoV-2 Ag-RDTs, mean temperatures exceed 30°C. We assessed analytical sensitivity and specificity of eleven commercially available SARS-CoV-2 Ag-RDTs using different storage and operational temperatures, including (i) long-term storage and testing at recommended conditions, (ii) recommended storage conditions followed by 10 minutes exposure to 37°C and testing at 37°C and (iii) 3 weeks storage followed by testing at 37°C. The limits of detection of SARS-CoV-2 Ag-RDTs under recommended conditions ranged from 8.2×105-7.9×107genome copies/ml of infectious SARS-CoV-2 cell culture supernatant. Despite long-term storage at recommended conditions, 10 minutes pre-incubation of Ag-RDTs and testing at 37°C resulted in about ten-fold reduced sensitivity for 46% of SARS-CoV-2 Ag-RDTs, including both Ag-RDTs currently listed for emergency use by the World Health Organization. After 3 weeks of storage at 37°C, 73% of SARS-CoV-2 Ag-RDTs exhibited about ten-fold reduced sensitivity. Specificity of SARS-CoV-2 Ag-RDTs using cell culture-derived human coronaviruses HCoV-229E and HCoV-OC43 was not affected by storage and testing at 37°C. In summary, short- and long-term exposure to elevated temperatures likely impairs sensitivity of several SARS-CoV-2 Ag-RDTs that may translate to false-negative test results at clinically relevant virus concentrations compatible with inter-individual transmission. Ensuring appropriate transport and storage conditions, and development of tests that are more robust across temperature fluctuations will be important for accurate use of SARS-CoV-2 Ag-RDTs in tropical settings.