bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conjugal DNA transfer in the maternally inherited symbiont of tsetse fliesSodalis glossinidius
Authors: Kendra Christopher G. , Keller Chelsea M. , Bruna Roberto E. , Pontes Mauricio H. 
Published: June 2020

AbstractStable associations between insects and bacterial species are widespread in nature. This is the case for many economically important insects, such as tsetse flies. Tsetse flies are the vectors ofTrypanosoma brucei, the etiological agent of African trypanosomiasis—a zoonotic disease that incurs a high socioeconomic cost in endemic regions. Populations of tsetse flies are often infected with the bacteriumSodalis glossinidius. Following infection,S. glossinidiusestablishes a chronic, stable association characterized by vertical (maternal) and horizontal (paternal) modes of transmission. Due to the stable nature of this association,S. glossinidiushas been long sought as a means for the implementation ofanti-Trypanosomaparatransgenesis in tsetse flies. However, the lack of tools for the genetic modification ofS. glossinidiushas hindered progress in this area. Here we establish thatS. glossinidiusis amenable to DNA uptake by conjugation. We show that conjugation can be used as a DNA delivery method to conduct forward and reverse genetic experiments in this bacterium. This study serves as an important step in the development of genetic tools forS. glossinidius. The methods highlighted here should guide the implementation of genetics for the study of the tsetse-Sodalisassociation and the evaluation ofS. glossinidius-based tsetse fly paratransgenesis strategies.ImportanceTsetse flies are the insect vectors ofT. brucei, the causative agent of African sleeping sickness—a zoonotic disease that inflicts a substantial economic cost to a broad region of sub-Saharan Africa. Notably, tsetse flies can be infected with the bacteriumS. glossinidiusto establish an asymptomatic chronic infection. This infection can be inherited by future generations of tsetse flies allowingS. glossinidiusto spread and persist within populations. To this effect,S. glossinidiushas been considered as a potential expression platform to create flies which reduceT. bruceistasis and lower overall parasite transmission to humans and animals. However, the efficient genetic manipulation ofS. glossinidiushas remained a technical challenge due to its complex growth requirements and uncharacterized physiology. Here we exploit a natural mechanism of DNA transfer among bacteria and develop an efficient technique to genetically manipulateS. glossinidiusfor future studies in reducing trypanosome transmission.
Reduced odor detection and hedonic changes in asymptomatic university students as SARS-CoV-2 emerged locally
Authors: Walsh-Messinger Julie , Kaouk Sahar , Manis Hannah , Kaye Rachel , Cecchi Guillermo , Meyer Pablo , Malaspina Dolores 
Published: June 2020

ABSTRACTAerosol droplets have emerged as the primary mode of SARS-Cov-2 transmission and can be spread by infectious asymptomatic/pre-symptomatic persons rendering indicators of latent viral infection essential. Olfactory impairment is now a recognized symptom of COVID-19 and is rapidly becoming one of the most reliable indicators of the disease. We compared olfaction data from asymptomatic students, who were assessed as SARS-CoV-2 was unknowingly spreading locally, to students tested prior to the arrival of the virus. This study was naturalistic by design as testing occurred in the context of four research studies, all of which used the same inclusion/exclusion criteria and the same protocol to objectively assess odor detection, identification, and hedonics with physiological tests. Data from students (Cohort II; N=22) with probable SARS-CoV-2 exposure were compared to students tested just prior to local virus transmission (Cohort I; N=25), and a normative sample of students assessed over the previous four years (N=272). Students in Cohort II demonstrated significantly reduced odor detection sensitivity compared to students in Cohort I (t=2.60; P=.01; d=0.77; CI, 0.17, 1.36), with a distribution skewed towards reduced detection sensitivity (D=0.38; P=.005). Categorically, the exposed group was significantly more likely to have hyposmia (OR=7.74; CI, 3.1, 19.40), particularly the subgroup assessed in the final week before campus closure (OR=13.61; CI, 3.40, 35.66;). The exposed cohort also rated odors as less unpleasant (P<.001, CLES=0.77). A limitation of our study is that participants were not tested for COVID-19 as testing was unavailable in the area. Objective measures of olfaction may detect olfactory impairment in asymptomatic persons who are otherwise unaware of smell loss. The development of cost-effective, objective olfaction tests that could be self-administered regularly could aid in early detection of SARS-CoV-2 exposure, which is vital to combatting this pandemic.
In-depth virological assessment of kidney transplant recipients with COVID-19
Authors: Benotmane Ilies , Vargas Gabriela Gautier , Wendling Marie-Josée , Perrin Peggy , Velay Aurélie , Bassand Xavier , Bedo Dimitri , Baldacini Clement , Sagnard Mylene , Bozman Dogan-Firat , Chiesa Margaux Della , Solis Morgane , Gallais Floriane , Cognard Noëlle , Olagne Jerome , Delagreverie Héloïse , Gontard Louise , Panaget Baptiste , Marx David , Heibel Francoise , Braun Laura , Moulin Bruno , Caillard Sophie , Fafi-Kremer Samira 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via RT-PCR and SARS-CoV-2 serology via ELISA and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study we examined hospitalized kidney transplant recipients with non-severe (n = 21) and severe (n =19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (p=0.0087) and mortality (p=0.024). All patients harbored antibodies the second week after symptom onset that persisted for two months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.
A novel comprehensive metric to assess COVID-19 testing outcomes: Effects of geography, government, and policy response
Authors: Kuster Anthony C. , Overgaard Hans J. 
Published: June 2020

AbstractTesting and case identification are key strategies in controlling the COVID-19 pandemic. Contact tracing and isolation are only possible if cases have been identified. The effectiveness of testing must be tracked, but a single comprehensive metric is not available to assess testing effectiveness, and no timely estimates of case detection rate are available globally, making inter-country comparisons difficult. The purpose of this paper was to propose a single, comprehensive metric, called the COVID-19 Testing Index (CovTI) scaled from 0 to 100, that incorporated several testing metrics. The index was based on case-fatality rate, test positivity rate, active cases, and an estimate of the detection rate. It used parsimonious modeling to estimate the true total number of COVID-19 cases based on deaths, testing, health system capacity, and government transparency. Publicly reported data from 188 countries and territories were included in the index. Estimates of detection rates aligned with previous estimates in literature (R2=0.97). As of June 3, 2020, the states with the highest CovTI included Iceland, Australia, New Zealand, Hong Kong, and Thailand, and some island nations. Globally, CovTI increased from April 20 to June 3 but declined in ca. 10% of countries. Bivariate analyses showed the average in countries with open public testing policies (59.7, 95% CI 55.6-63.8) were significantly higher than countries with no testing policy (30.2, 95% CI 18.1-42.3) (p<0.0001). A multiple linear regression model assessed the association of independent grouping variables with CovTI. Open public testing and extensive contact tracing were shown to significantly increase CovTI, after adjusting for extrinsic factors, including geographic isolation and centralized forms of government. This tool may be useful for policymakers to assess testing effectiveness, inform decisions, and identify model countries. It may also serve as a tool for researchers in analyses by combining it with other databases.
Essential epidemiological parameters of COVID-19 for clinical and mathematical modeling purposes: a rapid review and meta-analysis
Authors: Fonfría Eva S. , Vigo María Isabel , García-García David , Herrador Zaida , Navarro Miriam , Bordehore Cesar 
Published: June 2020

AbstractWe present a literature review and meta-analysis of relevant epidemiological parameters (24 for adults, 7 for children) of COVID-19. Standardization of these parameters is key to performing valid clinical and mathematical modeling, as well as forecasts, helping us to improve our understanding about the characteristics and impact of the pandemic.
Health Implications of the Nutritional Status of Indian Adults
Authors: Chaurasia Aalok Ranjan 
Published: June 2020

AbstractThis paper analyses the nutritional status of around 630 thousand Indian adults aged 20-49 years on the basis of their body mass index (BMI) in the context of the implications for the health of adults. The analysis reveals that Indian adults can be divided into 15 mutually exclusive groups on the basis of their nutritional status and individual and household characteristics which has implications not only for health policy and planning but also for productivity and economic growth. The problem of under nourished adults appears to be quite challenging in the poor and the poorest adults of the country living in households without a toilet whereas the problem of over weight and obesity among adults has been found to be largely confined to rich and the richest adults living in the urban areas.
Transcriptional response of human articular chondrocytes treated with fibronectin fragments: anin vitromodel of the osteoarthritis phenotype
Authors: Reed Kathleen S. M. , Ulici Veronica , Kim Cheeho , Chubinskaya Susan , Loeser Richard F. , Phanstiel Douglas H. 
Published: June 2020

SummaryObjectiveFibronectin is a matrix protein that is fragmented during cartilage degradation in osteoarthritis (OA). Treatment of chondrocytes with fibronectin fragments (FN-f) has been used to model OAin vitro, but the system has not been fully characterized. This study sought to define the transcriptional response of chondrocytes to FN-f, and directly compare it to responses traditionally observed in OA.DesignNormal human femoral chondrocytes isolated from tissue donors were treated with either FN-f or PBS (control) for 3, 6, or 18 hours. RNA-seq libraries were compared between time-matched FN-f and control samples in order to identify changes in gene expression over time. Differentially expressed genes were compared to a published OA gene set and used for pathway, transcription factor motif, and kinome analysis.ResultsFN-f treatment resulted in 1,224 differentially expressed genes over the time course. Genes that are up- or downregulated in OA were significantly up- (p < 0.00001) or downregulated (p < 0.0004) in response to FN-f. Early response genes were involved in proinflammatory pathways and their promoters were enriched for NF-κB-related motifs, whereas many late response genes were involved in ferroptosis, and their promoters were enriched for Jun-related motifs. Highly upregulated kinases included CAMK1G, IRAK2, and the uncharacterized kinase DYRK3, while growth factor receptors TGFBR2 and FGFR2 were downregulated.ConclusionsFN-f treatment of normal human articular chondrocytes recapitulated many key aspects of the OA chondrocyte phenotype. Thisin vitromodel is promising for future OA studies, especially considering its compatibility with genomics and genome-editing techniques.
Membrane Interactions of α-Synuclein Revealed by Multiscale Molecular Dynamics Simulations, Markov State Models, and NMR
Authors: Amos Sarah-Beth T. A. , Schwarz Thomas C. , Shi Jiye , Cossins Benjamin P. , Baker Terry S. , Taylor Richard J. , Konrat Robert , Sansom Mark S. P. 
Published: June 2020

Abstractα-Synuclein is a presynaptic protein that binds to cell membranes and is linked to Parkinson’s disease (PD). Whilst the normal function of remains α-synuclein remains uncertain, it is thought that oligomerization of the protein on the cell membrane contributes to cell damage. Knowledge of how α-synuclein binds to lipid bilayers is therefore of great interest as a likely first step in the molecular pathophysiology of PD, and may provide insight of the phenotype of PD-promoting mutations. We use coarse-grained and atomistic simulations in conjunction with NMR and cross-linking mass spectrometry studies of α-synuclein bound to anionic lipid bilayers to reveal a break in the helical structure of the NAC region, which may give rise to subsequent oligomer formation. Coarse-grained simulations of α-synuclein show that the interhelical region leads recognition and binding to both POPG and mixed composition bilayers and identifies important protein-lipid contacts, including those in the region between the two helices in the folded structure. We extend these simulations with all-atom simulations of the initial binding event to reveal details of the time-progression of lipid binding. We present secondary structure analysis that reveals points of possible β-strand formation in the structure, and investigate intramolecular contacts with simulations and mass-spectrometry crosslinking. Additionally we show how Markov state models can be used to investigate possible conformational changes of membrane bound α-synuclein in the NAC region, and we extract representative structures. These structural insights will aid the design and development of novel therapeutic approaches.
The mitochondrial carrier SFXN1 is critical for Complex III integrity and cellular metabolism
Authors: Acoba Michelle Grace , Selen Alpergin Ebru S. , Renuse Santosh , Fernández-del-Río Lucía , Lu Ya-Wen , Clarke Catherine F. , Pandey Akhilesh , Wolfgang Michael J. , Claypool Steven M. 
Published: June 2020

SUMMARYMitochondrial carriers (MC) mediate the passage of small molecules across the inner mitochondrial membrane (IMM) enabling regulated crosstalk between compartmentalized reactions. Despite MCs representing the largest family of solute carriers in mammals, most have not been subjected to a comprehensive investigation, limiting our understanding of their metabolic contributions. Here, we functionally characterized SFXN1, a member of the non-canonical, sideroflexin MC family. We find that SFXN1, an integral membrane protein in the IMM with an uneven number of transmembrane domains, is a novel TIM22 substrate. SFXN1 deficiency specifically impairs Complex III (CIII) biogenesis, activity, and assembly, compromising coenzyme Q levels. This CIII dysfunction is independent of one-carbon metabolism, the known primary role for SFXN1 as a mitochondrial serine transporter. Instead, SFXN1 supports CIII function by participating in heme and central carbon metabolism. Our findings highlight the multiple ways that SFXN1-based amino acid transport impacts mitochondrial and cellular metabolic efficiency.
Polymorphism and selection pressure of SARS-CoV-2 vaccine and diagnostic antigens: implications for immune evasion and serologic diagnostic performance
Authors: Dumonteil Eric , Herrera Claudia 
Published: June 2020

AbstractThe ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6-7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.
The role of trehalose 6-phosphate in shoot branching – local and non-local effects on axillary bud outgrowth in arabidopsis rosettes
Authors: Fichtner Franziska , Barbier Francois F. , Annunziata Maria G. , Feil Regina , Olas Justyna J. , Mueller-Roeber Bernd , Stitt Mark , Beveridge Christine A. , Lunn John E. 
Published: June 2020

SUMMARY- Trehalose 6-phosphate (Tre6P) is a sucrose signalling metabolite that has been implicated in regulation of shoot branching, but its precise role is not understood.- We expressed tagged forms of TREHALOSE-6-PHOSPHATE SYNTHASE1 (TPS1) to determine where Tre6P is synthesized in arabidopsis (Arabidopsis thaliana), and investigated the impact of localized changes in Tre6P levels, in axillary buds or vascular tissues, on shoot branching in wild-type and branching mutant backgrounds.- TPS1 is expressed in axillary buds and the subtending vasculature, as well as in the leaf and stem vasculature. Expression of a heterologous trehalose-6-phosphate phosphatase (TPP) to lower Tre6P in axillary buds strongly delayed bud outgrowth in long days and inhibited branching in short days. TPP expression in the vasculature also delayed lateral bud outgrowth and decreased branching. Increased Tre6P in the vasculature enhanced branching and was accompanied by higher expression ofFLOWERING LOCUS T(FT)and up-regulation of sucrose transporters. Increased vascular Tre6P levels enhanced branching inbranched1but not inftmutant backgrounds.- These results provide direct genetic evidence of a local role for Tre6P in regulation of axillary bud outgrowth within the buds themselves, and also connect Tre6P with systemic regulation of shoot branching via FT.
Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein
Authors: Toelzer Christine , Gupta Kapil , Yadav Sathish K.N. , Borucu Ufuk , Garzoni Frederic , Staufer Oskar , Capin Julien , Spatz Joachim , Fitzgerald Daniel , Berger Imre , Schaffitzel Christiane 
Published: June 2020

AbstractCOVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly and specifically bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Lipid metabolome remodeling is a key feature of coronavirus infection, with LA at its core. LA metabolic pathways are central to inflammation, immune modulation and membrane fluidity. Our structure directly links LA and S, setting the stage for interventions targeting LA binding and metabolic remodeling by SARS-CoV-2.One Sentence SummaryA direct structural link between SARS-CoV-2 spike and linoleic acid, a key molecule in inflammation, immune modulation and membrane fluidity.
QUANTITATIVE ETHNOMEDICINAL SURVEY OF SHRUBBY PLANTS, USED BY THE LOCAL COMMUNITIES OF DISTRICT LAHORE (PUNJAB), PAKISTAN
Authors: Shaheen Shabnum , Sarwar Sobia , Harun Nidaa , Khalid Sana , Hussain Khadim , Khan Farah 
Published: June 2020

AbstractBackgroundIndigenous knowledge of medicinal flora is a baseline for the production of plant based commercial drugs. Current study was planned to explore the ethnomedicinal uses of shrubs in traditional health-care system of District Lahore. This study also aimed to represent the conservation status of these natural resources which are decreasing day by day due to their overexploitation and deforestation.MethodsThe key informants were identified by employing the snowball technique. Data was collected by conducting semi-structured interviews with 103 informants from different localities (herbal markets, nurseries, gardens) of district Lahore. Collected data about medicinal shrubs were analysed on different data analyses parameters such as relative frequency of citation (RFC), use value (UV), informant consensus factor (ICF), fidelity level (FL) and relative importance (RI). In addition, SPSS 22 software was used for statistics analysis and interpretation of associations among different studied parameters.ResultsA total of 115 ethnomedicinal shrubs belonging to 50 families were reported to be used against different diseases. The study area was dominated by Fabaceae family (n=10). The RFC ranged from 0.02 (Deutzia scabraandEuonymus japonicus) to 0.85 (Rosa indica) while UV ranged from 0.01 (Cestrum diurnumandGarcinia aristata) to 0.23 (Jasminum grandiflorumandHamelia patens) and RI ranged from 0.16 (Garcinia aristata) to 43.73 (Tabernaemontana divaricata). MoreoverLawsonia inermis, Piper nigrum, Punica granatum, Rosa indicaandVitis viniferareported with 100% FL whereas maximum ICF were calculated by gastrointestinal diseases i.e., 0.45. On the basis of cluster analysis ethnomedicinal shrubs were categorized into two groups i.e., high valued and low valued. It was also found that most of the species in high valued group (n=29) were rare in study area due to their over exploitation. This study also documented 104 new use reports for ethnomedicinal shrubs.ConclusionsThis study documented significant indigenous knowledge about ethnomedicinal shrubs used by the local people of District Lahore. This knowledge could be worthwhile in discovering and developing new plant-based drugs. Apart from this, current study also revealed that most valuable medicinal species are declining in their number due to over usage and mismanagement. Conservation strategies for medicinal plants of District Lahore are highly recommended.
Prime editing is achievable in the tetraploid potato, but needs improvement
Authors: Veillet Florian , Kermarrec Marie-Paule , Chauvin Laura , Guyon-Debast Anouchka , Chauvin Jean-Eric , Gallois Jean-Luc , Nogué Fabien 
Published: June 2020

AbstractSince its discovery and first applications for genome editing in plants, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology has revolutionized plant research and precision crop breeding. Although the classical CRISPR-Cas9 system is highly useful for the introduction of targeted small mutations for knock-out applications, this system is mostly inefficient for the introduction of precise and predictable nucleotide substitutions. Recently, the prime editing (PE) technology has been developed in human cells, allowing the introduction of all kinds of mutations, including the simultaneous generation of nucleotide transitions and transversions. Therefore, this system holds great promises for the production of gain-of-function mutants and for the improvement of precision breeding in crops. In this study, we report on the successful use of prime editing in the tetraploid and highly heterozygous potato (Solanum tuberosum) with the introduction of simultaneous nucleotide transitions and transversions in theStALS1gene.