bluuebunny/crossref_metadata_2025_split huggingface dataset:
HPCA1 is required for systemic ROS and calcium cell-to-cell signaling and plant acclimation to stress
Authors: Fichman Yosef , Zandalinas Sara I , Peck Scott , Luan Sheng , Mittler Ron 
Published: March 2022

ABSTRACTAs multicellular organisms, plants constantly balance and coordinate many metabolic, physiological, and molecular responses between different cell types and tissues. This process is essential for plant development, growth, and response to different environmental cues. Because plants lack a nervous system, they transmit different signals over long distances via cell-to-cell signaling. Recent studies revealed that reactive oxygen species (ROS), produced by respiratory burst oxidase homologs (RBOHs) at the apoplast play a key role in cell-to-cell signaling. A state of enhanced ROS production by one cell is thereby sensed by a neighboring cell, causing it to produce ROS, creating a continuous chain of cell-to-cell ROS accumulation termed the ‘ROS wave’. This process was found to mediate systemic signals throughout the plant and is required for plant acclimation to different stresses. Although RBOHs were found to produce ROS essential for this process, the identity of the receptor(s) perceiving the apoplastic ROS signal is currently unknow. Here we reveal that the leucine-rich-repeat receptor-like kinase HPCA1 (H2O2-induced Ca2+increases 1) acts as a central ROS receptor required for the propagation of cell-to-cell ROS signals, systemic signaling in response to different biotic and abiotic stresses, and plant acclimation to stress. We further report that HPCA1 is required for systemic calcium signals, but not systemic membrane depolarization responses, and identify key calcium-dependent signal transduction proteins involved in this process. Our findings reveal that HPCA1 plays a key role in mediating and coordinating systemic cell-to-cell ROS and calcium signals that are required for plant acclimation to stress.
A chromosome-level assembly of the “Cascade” hop (Humulus lupulus) genome uncovers signatures of molecular evolution and improves time of divergence estimates for the Cannabaceae family
Authors: Padgitt-Cobb Lillian K , Pitra Nicholi J , Matthews Paul D , Henning John A , Hendrix David A 
Published: March 2022

SummaryWe present a chromosome-level assembly of the Cascade hop (Humulus lupulus L. var. lupulus) genome. The hop genome is large (2.8 Gb) and complex, and early attempts at assembly resulted in fragmented assemblies. Recent advances have made assembly of the hop genome more tractable, transforming the extent of investigation that can occur.The chromosome-level assembly of Cascade was developed by scaffolding the previously-reported Cascade assembly generated with PacBio long-read sequencing, and polishing with Illumina short-read DNA sequencing. We developed gene models and repeat annotations, and used a controlled bi-parental mapping population to identify significant sex-associated markers. We assess molecular evolution in gene sequences, gene family expansion and contraction, and time divergence using Bayesian inference.We identified the putative sex chromosome in the female genome based on significant sex-associated markers from the bi-parental mapping population. While the estimate of repeat content (~64%) is similar to the hemp genome, syntenic blocks in hop contain a greater percentage of LTRs. Hop is enriched for disease resistance-associated genes in syntenic gene blocks and expanded gene families.The Cascade chromosome-level assembly will inform cultivation strategies and serve to deepen our understanding of the hop genomic landscape, benefiting hop researchers and the Cannabaceae genomics community.
Zinc as a non-hormonal contraceptive: a better alternative to the copper intrauterine device (IUD)
Authors: Shankie-Williams Kirsten , Lindsay Laura , Murphy Chris , Dowland Samson 
Published: March 2022

AbstractLong-acting and reversible contraceptives (LARC) are the most widely used form of female contraception worldwide, however they have significant side-effects that often result in early removal. Most LARCs are hormonal, but the use of exogenous hormones is not suitable for all women and causes side-effects in many others. The copper IUD (CuIUD) is the only non-hormonal LARC, but a large proportion of users suffer severe side effects. This study proposes the use of zinc as a suitable alternative to the CuIUD.A rat intrauterine device (IUD) model was established to test the efficacy of a zinc IUD (ZnIUD) against a CuIUD, and a control nylon IUD. The IUD was surgically implanted into one uterine horn while the other remained untreated. Both the ZnIUD and CuIUD resulted in significantly fewer implantation sites compared to untreated horns. There was no significant difference between treated and untreated horns in the control nylon IUD group. Histological assessment revealed damage and inflammation in the endometrium of CuIUD treated horns, but only minor epithelial damage in ZnIUD treated horns, closely resembling the normal appearance of the control horns. This suggests ZnIUDs may not share the side-effect profile of the CuIUD. To test the long-term efficacy of the ZnIUD, rats had a ZnIUD surgically implanted into both horns and cohoused with males for 3 months. These rats mated regularly but did not get pregnant, confirming the long-term effectiveness of the ZnIUD. Reversibility of the ZnIUD was also established, as removal of the ZnIUD after 3 months resulted in no significant difference in the number of implantation sites between treated and untreated horns.This study demonstrated the contraceptive efficacy of zinc and its potential as a LARC. The ZnIUD had minimal histological impact on the endometrium compared to the current copper standard, indicating that IUDs containing zinc may offer highly effective contraception while causing fewer side effects.
Leaf nitrogen does not explain changes in soybean radiation-use efficiency in vegetative and early reproductive stages
Authors: La Menza Nicolás Cafaro , Arkebauer Timothy J. , Lindquist John L. , Monzon Juan Pablo , Knops Johannes M.H. , Graef George , Scoby David , Howard Réka , Rees Jennifer , Specht James E. , Grassini Patricio 
Published: March 2022

AbstractOntogenic changes in soybean radiation-use efficiency (RUE) have been attributed to variation in specific leaf nitrogen (SLN) based only on data collected during seed filling. We evaluated this hypothesis using data on leaf area, absorbed photosynthetically active radiation (APAR), aboveground dry matter (ADM), and plant nitrogen (N) concentration collected during the entire crop season from seven field experiments conducted in a stress-free environment. Each experiment included a full N treatment that received ample N fertilizer and a zero N treatment that relied on N fixation and soil N mineralization. We estimated RUE based on changes in ADM between sampling times and associated APAR, accounting for changes in biomass composition. The SLN and RUE exhibited different seasonal patterns: a bell-shaped pattern with a peak around the beginning of seed filling, and a convex pattern followed by an abrupt decline during late seed filling, respectively. The level of N supply influenced SLN more than RUEviachanges in leaf N concentration, with small changes in specific leaf weight. Changes in SLN explained the decline in RUE during seed filling but failed to predict changes in RUE in earlier stages. A simple approach based on phenological stages may give more realistic estimates of RUE before seed filling, improving crop growth and yield predictionviacrop models and remote sensing.HighlightChanges in radiation-use efficiency during soybean vegetative and early reproductive stages are not related to specific leaf nitrogen.
Multi-omic integrated curvature study on pan-cancer genomic data
Authors: Zhu Jiening , Tran Anh Phong , Deasy Joseph O. , Tannenbaum Allen 
Published: March 2022

AbstractIn this work, we introduce a new mathematical framework based on network curvature to extract significant cancer subtypes from multi-omics data. This extends our previous work that was based on analyzing a fixed single-omics data class (e,g, CNA, gene expression, etc.). Notably, we are able to show that this new methodology provided us with significant survival differences on Kaplan-Meier curves across almost every cancer that we considered. Moreover, the variances in Ollivier-Ricci curvature was explored to investigate its usefulness in network topology analysis as this curvature may be capturing subtle functional changes between various cancer subtypes.
Utilisation of Oxford Nanopore sequencing to generate six complete gastropod mitochondrial genomes as part of a biodiversity curriculum
Authors: De Vivo Mattia , Lee Hsin-Han , Huang Yu-Sin , Dreyer Niklas , Fong Chia-ling , de Mattos Felipe Monteiro Gomes , Jain Dharmesh , Wen Yung-Hui Victoria , Mwihaki John Karichu , Wang Tzi-Yuan , Machida Ryuji J. , Wang John , Chan Benny K. K. , Tsai Isheng Jason 
Published: March 2022

AbstractHigh-throughput sequencing has enabled genome skimming approaches to produce complete mitochondrial genomes (mitogenomes) for species identification and phylogenomics purposes. In particular, the portable sequencing device from Oxford Nanopore Technologies (ONT) has the potential to facilitate hands-on training from sampling to sequencing and interpretation of mitogenomes. In this study, we present the results from sampling and sequencing six gastropod mitogenomes (Aplysia argus, Cellana orientalis, Cellana toreuma, Conus ebraeus, Conus miles and Tylothais aculeata) from a graduate level biodiversity course. The students were able to produce mitochondrial genomes from sampling to annotation using existing protocols and programs. Approximately 4Gb of sequence was produced from 15 Flongle and two R9.4 Flowcells, averaging 235Mb and N50=4.4kb per Flowcell. Five of the six 14.1-18kb mitogenomes were circlised containing all 13 core protein coding genes. Additional Illumina sequencing reveal that the ONT assemblies were able to span over highly AT rich sequence in the control region that was otherwise missing in Illumina-assembled mitogenomes, but still contained a base error of one every 70.8-346.7bp with the majority occurring at homopolymer regions. Our findings suggest that ONT are portable and can be used to rapidly produce mitogenomes at low cost and tailored to genomics-based training in biodiversity research.
Study of aging using circuit tests and parametric analysis
Authors: Konishi Tomokazu , Yanai Shuichi , Endo Shogo 
Published: March 2022

AbstractMouse development and aging were investigated in 11 tests. The test data were parametrically analysed, normalized, and integrated using principal component analysis (PCA). Changes in the indexing items displayed two trends: power and accuracy in the trials. Power decreased monotonically with age, whereas accuracy peaked at 6 months. Features, such as fear or anxiety, could not have been measured. The noise level and sensitivity of each test were determined. In an open field test that involved a video recording of movement, the noise level was the lowest and the sensitivity was high. This test contributed the most to the PCA axes, and reproduced the two main directions.Significance StatementThe mathematical aspect may have been neglected in behavioural tests. Here, the circuit test data were objectively analysed by focusing on the data distributions during the aging of mice. The test results revealed two clear directions for the data: power, which was gradually reduced, and accuracy, which peaked at sixth months old. Compared with the open field test evaluated using video recordings, the other tests had higher noise levels and weaker signals. Other tests can be improved by using movie recordings and identifying appropriate items.
The role of hepatitis B virus surface protein in inducing Sertoli cell ferroptosis
Authors: Pan Chengshuang , xiangbin Kong , zhigang Wu , Fei Qianjin 
Published: March 2022

ABSTRACTHepatitis B virus infection could result in male infertility by inhibiting sperm function and viability. Sertoli cell death contributes to spermatogenesis impairment, which is associated with sperm defects and dysfunction. Ferroptosis-mediated cell death of Sertoli cells was found to contribute to spermatogenesis disorder and poor sperm quality. However, the effects of hepatitis B virus infection on ferroptosis of Sertoli cells remain to be elucidated. Human Sertoli cells were cultured in vitro with 25, 50, and 100 mg/mL of hepatitis B virus surface protein for 48 hours. Cell viability was measured with CCK-8. Levels of glutathione, malondialdehyde, iron, and m6A in human Sertoli cells were determined. Lipid peroxidation was assessed using C11-BODIPY. Luminescence analysis was performed to detect the binding of METTL3 and 3¢-UTR of TRIM37 containing the m6A motifs. Immunoprecipitation was applied to determine the relationship between TRIM37 and GPX4. qPCR and immunoblotting were performed to measure mRNA and protein levels. Hepatitis B virus surface protein exposure significantly increased TRIM37 expression, malondialdehyde level, and ferroptosis, and decreased cell viability and glutathione level of human Sertoli cells. TRIM37 silencing inhibits the effect of HBs exposure-regulated cell viability and ferroptosis in human Sertoli cells. TRIM37 inhibits GPX4 expression through ubiquitination. GPX4 overexpression inhibits the effect of TRIM37 on cell viability and ferroptosis in human Sertoli cells.Administration of ferroptosis inhibitor recovers the cell viability decreased by TRIM37. Mechanism study showed HBs increases the level of TRIM37 3’-UTR m6A by promoting the expression of METTL3, and the binding of m6A reader IGF2BP2 and TRIM37 3’-UTR promotes the stability of TRIM37 mRNA.HBs inhibit Sertoli cell viability by promoting ferroptosis of Sertoli cells through TRIM37-mediated ubiquitination of GPX4. The findings highlight the importance of TRIM37/GPX4 signaling in the ferroptosis of Sertoli cells.
Patterns of presentations of children to emergency departments across Europe and the impact of the COVID-19 pandemic: retrospective observational multinational study
Authors: Nijman Ruud G. , Honeyford Kate , Farrugia Ruth , Rose Katy , Bognar Zsolt , Buonsenso Danilo , Da Dalt Liviana , De Tisham , Maconochie Ian K. , Parri Niccolo , Roland Damian , Alfven Tobias , Aupiais Camille , Barrett Michael , Basmaci Romain , Borensztajn Dorine , Castanhinha Susana , Corrine Vasilico , Durnin Sheena , Fitzpatrick Paddy , Fodor Laszlo , Gomez Borja , Greber-Platzer Susanne , Guedj Romain , Hartshorn Stuart , Hey Florian , Jankauskaite Lina , Kohlfuerst Daniela , Kolnik Mojca , Lyttle Mark D , Mação Patrícia , Mascarenhas Maria Inês , Messahel Shrouk , Özkan Esra Akyüz , Pučuka Zanda , Reis Sofia , Rybak Alexis , Rinder Malin Ryd , Teksam Ozlem , Turan Caner , Thors Valtýr Stefánsson , Velasco Roberto , Bressan Silvia , Moll Henriette A , Oostenbrink Rianne , Titomanlio Luigi ,   in association with the REPEM network (Research in European Pediatric Emergency Medicine) as part of the EPISODES study group
Published: March 2022

AbstractBackgroundTo investigate the impact of the COVID-19 pandemic and infection prevention measures on children visiting emergency departments across Europe.MethodsRoutine health data were extracted retrospectively from electronic patient records of children aged <16 years, presenting to 38 emergency departments (ED) in 16 European countries for the period January 2018 – May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRR) were used to compare age groups, diagnoses and outcomes.FindingsReductions in pediatric ED attendances, hospital admissions and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (incidence rate ratio (IRR) 2·62, 95% CI 2·19 to 3·13) and in children aged >12 months (12-<24 months IRR 0·89, 95% CI 0·86 to 0·92; 2-<5years IRR 0·84, 95% CI 0·82 to 0·87; 5-<12 years IRR 0·74, 95% CI 0·72 to 0·76; 12-<16 years IRR 0·74, 95% CI 0·71 to 0·77; vs. age <12 months as reference group). The impact on pediatric intensive care admissions (IRR 1·30, 95% CI 1·16 to 1·45) was not as great as the impact on general admissions. Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1·10, 95% CI 1·08 to 1·12; emergent and very urgent triage IRR 1·53, 95% CI 1·49 to 1·57; vs. non-urgent triage category). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases.Interpretation:Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell.Funding:RGN was supported by National Institute of Health Research, award number ACL-2018-021-007.Trial registry:ISRCTN91495258
Plasma cell-free DNA as a prognostic biomarker in small cell lung cancer patients
Authors: Mondelo-Macía Patricia , García-González Jorge , Abalo Alicia , Mosquera-Presedo Manuel , López-López Rafael , León-Mateos Luis , Muinelo-Romay Laura , Díaz-Peña Roberto 
Published: March 2022

ABSTRACTBackgroundLack of biomarkers for treatment selection and monitoring in small-cell lung cancer (SCLC) patients with the limited therapeutic options, result in poor outcomes. Therefore, new prognostic biomarkers are needed to improve their management. The prognostic value of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) have been less explored in SCLC.MethodsWe quantified cfDNA in 46 SCLC patients at different times during therapy. Moreover, CTCs were analyzed in 21 patients before therapy onset using CellSearch® system. Both biomarkers were associated with patients’ outcomes and a prognostic model was developed.ResultsHigh cfDNA levels before therapy were associated with shorter progression-free survival and overall survival. Furthermore, changes in cfDNA levels between baseline and 3 weeks and cfDNA levels at progression disease were also associated with patients’ outcomes. Multivariate analyses confirmed the independence of cfDNA levels as a prognostic biomarker. Finally, the three-risk category prognostic model developed included ECOG Performance Status, gender and baseline cfDNA levels was associated with a higher risk of progression and death.ConclusionsWe confirmed the prognostic utility of cfDNA in SCLC patients before and during therapy. Our novel risk prognostic model in clinical practice will allow to identify patients who could benefit with actual therapies.
Structural visualization of the tubulin folding pathway directed by eukaryotic chaperonin TRiC
Authors: Gestaut Daniel , Zhao Yanyan , Park Junsun , Ma Boxue , Leitner Alexander , Collier Miranda , Pintilie Grigore , Roh Soung-Hun , Chiu Wah , Frydman Judith 
Published: March 2022

SUMMARYThe ATP-dependent ring-shaped chaperonin TRiC/CCT is essential for cellular proteostasis. To uncover why some eukaryotic proteins can only fold with TRiC assistance, we reconstituted the folding of β-tubulin using human Prefoldin and TRiC. We find unstructured β-tubulin is delivered by Prefoldin to the open TRiC chamber followed by ATP-dependent chamber closure. CryoEM resolves four near-atomic resolution structures containing progressively folded β-tubulin intermediates within the closed TRiC chamber, culminating in native tubulin. This substrate folding pathway appears closely guided by site-specific interactions with conserved regions in the TRiC chamber. Initial electrostatic interactions between the TRiC interior wall and both the folded tubulin N-domain and its C-terminal E-hook tail establish the native substrate topology, thus enabling C-domain folding. Disordered CCT C-termini within the chamber promote subsequent folding of tubulin Core and Middle domains and GTP-binding. Thus, TRiC’s chamber provides chemical and topological directives that shape the folding landscape of its obligate substrates.
Domestication in dry-cured meatPenicilliumfungi: convergent specific phenotypes and horizontal gene transfers without strong genetic subdivision
Authors: Lo Ying-Chu , Bruxaux Jade , Rodríguez de la Vega Ricardo C. , O’Donnell Samuel , Snirc Alodie , Coton Monika , Le Piver Mélanie , Le Prieur Stéphanie , Roueyre Daniel , Dupont Joëlle , Houbraken Jos , Debuchy Robert , Ropars Jeanne , Giraud Tatiana , Branca Antoine 
Published: March 2022

AbstractSome fungi have been domesticated for food production, with genetic differentiation between populations from food and wild environments, and food populations often acquiring beneficial traits through horizontal gene transfers (HGTs). Studying their adaptation to human-made substrates are of fundamental and applied importance, for understanding adaptation processes and for further strain improvement. We studied here the population structures and phenotypes of two distantly relatedPenicilliumspecies used for dry-cured meat production,P. nalgiovense, the most common species in the dry-cured meat food industry, andP. salamii, used locally by farms. Both species displayed low genetic diversity, lacking differentiation between strains isolated from dry-cured meat and those from other environments. Nevertheless, the strains collected from dry-cured meat within each species displayed slower proteolysis and lipolysis than their wild conspecifics, and those ofP. nalgiovensewere whiter. Phenotypically, the non-dry-cured meat strains were more similar to their sister species than to their conspecific dry-cured meat strains, indicating an evolution of specific phenotypes in dry-cured meat strains. A comparison of availablePenicilliumgenomes from various environments revealed HGTs, particularly betweenP. nalgiovenseandP. salamii(representing almost 1.5 Mb of cumulative length). HGTs additionally involvedP. biforme, also found in dry-cured meat products. We further detected positive selection based on amino-acid changes. Our findings suggest that selection by humans has shaped theP. salamiiandP. nalgiovensepopulations used for dry-cured meat production, which constitutes domestication. Several genetic and phenotypic changes were similar inP. salamii,P. nalgiovense,andP. biforme, indicating convergent adaptation to the same human-made environment. Our findings have implications for fundamental knowledge on adaptation and for the food industry: the discovery of different phenotypes and of two mating types paves the way for strain improvement by conventional breeding, to elucidate the genomic bases of beneficial phenotypes and to generate diversity.