bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovering and prioritizing candidate resistance genes against soybean pests by integrating GWAS and gene coexpression networks
Authors: Almeida-Silva Fabricio , Venancio Thiago M. 
Published: May 2022

ABSTRACTSoybean is one of the most important legume crops worldwide. Soybean pests have considerable impact on crop yield. Here, we integrated publicly available genome-wide association studies and transcriptomic data to prioritize candidate resistance genes against the insects Aphis glycines and Spodoptera litura, and the nematode Heterodera glycines. We identified 171, 7, and 228 high-confidence candidate resistance genes against A. glycines, S. litura, and H. glycines, respectively. We found some overlap of candidate genes between insect species, but not between insects and H. glycines. Although 15% of the prioritized candidate genes encode proteins of unknown function, the vast majority of the candidates are related to plant immunity processes, such as transcriptional regulation, signaling, oxidative stress, recognition, and physical defense. Based on the number of resistance alleles, we selected the ten most promising accessions against each pest species in the soybean USDA germplasm. The most resistant accessions do not reach the maximum theoretical resistance potential, indicating that they might be further improved to increase resistance in breeding programs or through genetic engineering. Finally, the coexpression networks generated here are available in a user-friendly web application (https://soypestgcn.venanciogroup.uenf.br/) and an R/Shiny package (https://github.com/almeidasilvaf/SoyPestGCN) that serve as a public resource to explore soybean-pest interactions at the transcriptional level.
Comparative Insilco functional, structural and phylogenetic characterization of plant Mn-Superoxide Dismutase
Authors: Gangwar Rashmi 
Published: May 2022

AbstractThe environmental stress is jeopardizing the production as well as the survival of plants. This stress leads to the emergence of ROS, a toxic byproduct of several metabolic processes. To combat the ROS plant possess definite defense machinery, superoxide dismutase is one of the antioxidant enzymes responsible for effectively eradicating these ROS. Amongst several SOD, MnSOD is specialized in eliminating the ROS from mitochondria, a site for cellular energy production. In this study, the MnSOD from 16 plants was considered, and its physiochemical and structural properties were predicted using various computational tools. The physiochemical characterization reveals protein properties such as Mw, PI, AI, GRAVY, and II. The secondary structure and the motif analysis revealed these proteins’ functional characteristics. The 3D structure of several proteins was not available, so the SWISS model was used for the homology modeling. The quality of the predicted protein structures was verified using the Ramachandran Plot, VERIFY 3D, and PROCHECK under the SAVES server. These data would provide a foundation for structural and functional characterization of potential MnSOD yet to be characterized, which is expected to enhance the knowledge about its metal binding and catalytic efficiency for future applications.
Ventral forebrain organoids derived from individuals with schizophrenia recapitulate perturbed striatal gene expression dynamics of the donor’s brains
Authors: Sawada Tomoyo , Barbosa André , Araujo Bruno , McCord Alejandra E. , D’Ignazio Laura , Benjamin Kynon J. M. , Feltrin Arthur , Arora Ria , Brandtjen Anna C. , Kleinman Joel E. , Hyde Thomas M. , Weinberger Daniel R. , Paquola Apuā C. M. , Erwin Jennifer A. 
Published: May 2022

ABSTRACTSchizophrenia (SCZ) is a brain disorder originating during neurodevelopment with complex genetic and environmental etiologies. Despite decades of clinical evidence of altered striatal function in affected patients, its cellular and molecular underpinnings remain unclear. Here, to explore neurodevelopmental alterations in the striatum associated with SCZ, we established a method for the differentiation of iPS cells into ventral forebrain organoids. Given substantial genetic heterogeneity among individuals, which can obscure disease-associated phenotypes, we generated organoids from postmortem dural fibroblast-derived iPS cells of 3 patients and 4 healthy control individuals with nonoverlapping polygenic risk score (PRS) for SCZ and whose genotype and postmortem caudate transcriptomic data were profiled in the Brainseq neurogenomics consortium. Single cell RNA sequencing (scRNA-seq) analyses of the organoids revealed differences in developmental trajectory between SCZ cases and controls in which inhibitory neurons from patients exhibited accelerated maturation. Furthermore, we found a significant overlap of genes upregulated in the inhibitory neurons in SCZ organoids with upregulated genes in postmortem caudate tissues from patients with SCZ compared with control individuals, including the donors of our iPS cell cohort. Our findings suggest that striatal neurons in the patients with SCZ carry abnormalities that originated during early brain development and a ventral forebrain striatal organoid model can recapitulate those neurodevelopmental phenotypes in a dish.
Genomic correlates for migratory direction in a free-ranging cervid
Authors: Bonar Maegwin , Anderson Spencer J. , Anderson Charles R. , Wittemyer George , Northrup Joseph M. , Shafer Aaron B. A. 
Published: May 2022

AbstractAnimal migrations are some of the most ubiquitous and one of the most threatened ecological processes. A wide range of migratory behaviours occur in nature, and this behaviour is not uniform between and within species, where even individuals in the same population can exhibit differentiation. While the environment largely drives migratory behaviour, it is necessary to understand the genetic mechanisms influencing migration to elucidate the adaptive potential of migratory species to cope with novel conditions and adapt to environmental change. In this study, we identified genes associated with migratory traits by undertaking pooled genome-wide scans on a natural population of a facultatively migrating ungulate. We identified genomic regions associated with variation in migratory direction in the study population, including FTM1, a gene linked to the formation of lipids, and DPPA3, a gene linked to epigenetic modifications of the maternal line. Such a genetic basis for migratory traits can have implications on heritability of behaviour and the flexibility of individuals to change their behaviour in the face of stochastic changes in their environment.
p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression
Authors: Ghosh Monisankar , Saha Suchandrima , Li Jinyu , Montrose David C , Martinez Luis A. 
Published: May 2022

AbstractTumor suppression by p53 is known to involve cell autonomous and non-cell autonomous mechanisms. p53 has been shown to suppress tumor growth by modulating immune system functions, however, the mechanistic basis for this activity is not well understood. Here we report that p53 promotes the degradation of the DNA exonuclease TREX1, resulting in cytosolic dsDNA accumulation. We demonstrate that p53 requires the ubiquitin ligase TRIM24 to induce TREX1 ubiquitin-dependent degradation. The accumulation of cytosolic DNA due to p53’s suppression of TREX1 activates the cytosolic DNA sensor, cGAS and its downstream effectors STING/TBK1/IRF3 resulting in induction of Type I interferons. TREX1 overexpression sufficed to block WTp53 activation of the cGAS/STING pathway. WTp53 mediated induction of type I interferon (IFNB1) response could be suppressed by cGAS/STING knockout. We find that p53’s tumor suppressor activities are compromised by loss of signaling through the cGAS/STING pathway. Thus, our study reveals that p53 utilizes the cGAS/STING innate immune system pathway for both cell intrinsic and cell extrinsic tumor suppressor activities.
Developmental heterogeneity of embryonic neuroendocrine chromaffin cells and their maturation dynamics
Authors: Akkuratova Natalia , Faure Louis , Kameneva Polina , Kastriti Maria Eleni , Adameyko Igor 
Published: May 2022

AbstractDuring embryonic development, nerve-associated Schwann cell precursors (SCPs) give rise to chromaffin cells of the adrenal gland via the “bridge” transient stage, according to recent functional experiments and single cell transcriptomics data from humans and mice. However, currently existing data do not resolve the finest heterogeneity of developing chromaffin populations. Here we took advantage of deep SmartSeq2 transcriptomics sequencing to expand our collection of individual cells from developing murine sympatho-adrenal anlage and uncover the microheterogeneity of embryonic chromaffin cells and corresponding developmental paths. After improving our atlas of sympatho-adrenal development and performing experimental validations, we discovered that SCPs in the local nerve show high degree of microheterogeneity corresponding to early biases towards either Schwann or chromaffin terminal fates. Furthermore, we found that a post-”bridge” population of developing chromaffin cells gives rise to persisting immature chromaffin cells and the two terminal populations (adrenergic and noradrenergic) via diverging differentiation paths. Taken together, we provide a thorough identification of novel markers of adrenergic and noradrenergic populations in developing adrenal glands and report novel differentiation micro-paths leading to them.
ALDH9A1 Deficiency as a Source of Endogenous DNA Damage that Requires Repair by the Fanconi Anemia Pathway
Authors: Jung Moonjung , Ilyashov Isaac , Park Yeji , Donovan Frank X. , Ramanagoudr-Bhojappa Ramanagouda , Keahi Danielle , Durmaz Jordan A. , Choijilsuren Haruna B. , Goldfarb Audrey , Stein Mia , Kim Jungwoo , White Ryan R. , Sridhar Sunandini , Noonan Raymond , Wiley Tom , Carroll Thomas S. , Lach Francis P. , Auerbach Arleen D. , Miranda Ileana , Chandrasekharappa Settara C. , Smogorzewska Agata 
Published: May 2022

AbstractFanconi anemia (FA) pathway is required for the repair of DNA interstrand crosslinks (ICL). ICLs are caused by genotoxins, such as chemotherapeutic agents or reactive aldehydes. Inappropriately repaired ICLs contribute to hematopoietic stem cell (HSC) failure and tumorigenesis. While endogenous acetaldehyde and formaldehyde are known to induce HSC failure and leukemia in humans with FA, the effects of other toxic metabolites in FA pathogenesis have not been systematically investigated. Using a metabolism-focused CRISPR screen, we found that ALDH9A1 deficiency causes synthetic lethality in FA pathway-deficient cells. Combined deficiency of ALDH9A1 and FANCD2 causes genomic instability, apoptosis, and decreased hematopoietic colony formation.Fanca−/−Aldh9a1−/−mice exhibited an increased incidence of ovarian tumors. A suppressor CRISPR screen revealed that the loss of ATP13A3, a polyamine transporter, resulted in improved survival ofFANCD2−/−ALDH9A1−/−cells. These findings implicate high intracellular polyamines and the resulting 3-aminopropanal or acrolein in the pathogenesis of FA. In addition, we find that ALDH9A1 variants may be modifying disease onset in FA patients.Statement of SignificanceALDH9A1 deficiency is a previously unrecognized source of endogenous DNA damage. If not repaired by the Fanconi anemia pathway, such damage leads to increased genomic instability and tumorigenesis. Limiting substrates that accumulate when ALDH9A1 is absent can reduce aldehyde production and rescue synthetic lethality in the combined deficiency of ALDH9A1/FANCD2.
Effect of chemical modifications of tannins on their antibiofilm effect against Gram-negative and Gram-positive bacteria
Authors: Villanueva Xabier , Zhen Lili , Nunez Ares José , Vackier Thijs , Lange Heiko , Crestini Claudia , Steenackers Hans 
Published: May 2022

Abstract(1)BackgroundTannins have demonstrated antibacterial and antibiofilm activity, but the mechanisms of action are not completely elucidated. We are interested in understanding how to modulate the antibiofilm activity of tannins and in delineating the relationship between chemical determinants and antibiofilm activity.(2)Materials and methodsthe effect of five different naturally acquired tannins and their chemical derivatives on biofilm formation and planktonic growth of Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was determined in the Calgary biofilm device.(3)Resultsmost of the unmodified tannins exhibited specific antibiofilm activity against the assayed bacteria. The chemical modifications were found to alter the antibiofilm activity level and spectrum of the tannins, with the positive charge introducing C3NMe3Cl-0.5 derivatization shifting the anti-biofilm spectrum towards Gram-negative bacteria and C3NMe3Cl-0.1 and the acidifying CH3COOH derivatization shifting the spectrum towards Gram-positive bacteria. Also, the quantity of phenolic-OH groups per molecule has a weak impact on the anti-biofilm activity of the tannins.(4)Conclusionswe were able to modulate the antibiofilm activity of several tannins by specific chemical modifications, providing a first approach for fine tuning of their activity and spectrum.
Bacterial growth-promoting properties of pooled urine and individual urines from post-menopausal women with or without a urinary tract infection can vary substantially
Authors: Hogins Jacob , Fan Ethan , Seyan Zheyar , Kusin Sam , Christie Alana L. , Zimmern Philippe E. , Reitzer Larry 
Published: May 2022

ABSTRACTUrinary tract infections (UTIs), mostly caused by uropathogenic E. coli (UPEC), are common bacterial infections that affect a majority of women and often recur. Genomic and transcriptomic analyses have not identified a common set of virulence genes which has suggested conserved virulence functions instead of virulence genes, multiple virulence mechanisms, and complex host-pathogen interactions. One aspect of the host-pathogen interaction is rapid UPEC growth in urine in vivo. When bacteria are grown in pooled urine, an averaged urine is assumed to diminish individual variation. We grew a non-pathogenic and pathogenic E. coli strains in urine from individuals who never had a UTI, had a UTI history but no current infection, and had a UTI history with a current infection. Bacterial growth showed large variations in individual urines and pooled urine supported significantly more growth than predicted for never and history groups but not the current group. UPEC strains, but not the non-pathogenic strain, were resistant to urinary inhibitory factors e.g., antimicrobial peptides based on an indirect inoculation-density effect assay. Total nutrient content tended to be higher in current group urine than never and history group urine. We propose that pooling optimizes a nutrient mixture in never and history group urines, which are often studied, whereas urine from current group individuals appear to have a more optimal nutrient mixture. We conclude that pooled urine is not “an average urine”, and that the best comparisons of results between labs using pooled urine would also include results with a standardized synthetic urine.
Antigen testing for COVID-19 using image-based assessment of oral specimens
Authors: Shimozono Satoshi , Sugiyama Mayu , Kurokawa Hiroshi , Hama Hiroshi , Sato Masae , Morikawa Satoru , Kuwana Kumiko , Haga Kei , Takai-Todaka Reiko , Inaura Shunsuke , Matsumura Yuta , Masaki Hidekazu , Nemoto Naoto , Ando Ryoko , Kogure Takako , Tosaki Asako , Fukuyama Hidehiro , Saya Hideyuki , Nakagawa Taneaki , Morimoto Takuya , Nishihara Hiroshi , Katayama Kazuhiko , Miyawaki Atsushi 
Published: May 2022

SummaryWhile numerous diagnostic tests for COVID-19 have been developed for clinical and public health use, most of them provide binary or one-dimensional information on SARS-CoV-2 infection in pursuit of speed and ease of use. As their readouts are largely dependent on the specimen collection procedure, reliable diagnosis is still difficult. Here we report the development of a prototypical method for the immunocytochemical diagnosis of SARS-CoV-2 infection using oral specimens and fluorescent nanobodies against the viral spike and nucleocapsid proteins. Our cytological approach for the detection of SARS-CoV-2 infection was validated by our finding that at least half of SARS-CoV-2 RNAs in oral specimens were localized in the cellular fraction. Mapping antigens on sampled cells provided qualitative image data to which appropriate statistical texture analysis could be applied for the quantitative assessment of SARS-CoV-2 infectious status. A comprehensive comparative analysis revealed that oral cavity swabbing by medical workers provides specimens for COVID-19 diagnosis that yield comparable diagnostic accuracy as self-collected saliva specimens. Our diagnostic strategy may enable medical workers to acquire a wealth of information on virus–human cell interactions for multifaceted insight into COVID-19.
Quantifying factors that affect polygenic risk score performance across diverse ancestries and age groups for body mass index
Authors: Hui Daniel , Xiao Brenda , Dikilitas Ozan , Freimuth Robert R. , Irvin Marguerite R. , Jarvik Gail P. , Kottyan Leah , Kullo Iftikhar , Limdi Nita A. , Liu Cong , Luo Yuan , Namjou Bahram , Puckelwartz Megan J. , Schaid Daniel , Tiwari Hemant , Wei Wei-Qi , Verma Shefali , Kim Dokyoon , Ritchie Marylyn D. 
Published: May 2022

AbstractPolygenic risk scores (PRS) have led to enthusiasm for precision medicine. However, it is well documented that PRS do not generalize across groups differing in ancestry or sample characteristics e.g., age. Quantifying performance of PRS across different groups of study participants, using genome-wide association study (GWAS) summary statistics from multiple ancestry groups and sample sizes, and using different linkage disequilibrium (LD) reference panels may clarify factors limiting PRS transferability. To evaluate these factors in the PRS generation process, we generated body mass index (BMI) PRS (PRSBMI) in the Electronic Medical Records and Genomics network (N=75,661). Analyses were conducted in two ancestry groups (European and African) and three age ranges (adult, teenagers, and children). For PRSBMI calculations, we evaluated five LD reference panels and three GWAS summary statistics of varying sample size and ancestry. PRSBMI performance increased for both African and European ancestry individuals using cross-ancestry GWAS summary statistics compared to European-only summary statistics (6.3% and 3.7% relative R2 increase, respectively, pAfrican=0.038, pEuropean=6.26×10−4). The effects of LD reference panels were more pronounced in African ancestry study datasets. PRSBMI performance degraded in children; R2 was less than half of teenagers or adults. The effect of GWAS summary statistics sample size was small when modeled with the other factors. We also explored clinical comorbidities associated with the PRSBMI and identified associations with type 2 diabetes and coronary atherosclerosis. This study quantifies effects that ancestry, GWAS summary statistic sample size, and LD reference panel have on PRS performance, especially in cross-ancestry and age-specific analyses.
A Model-Based Strategy on COVID-19 Vaccine Roll-out in the Philippines
Authors: Escosio Rey Audie S. , Cawiding Olive R. , Hernandez Bryan S. , Mendoza Renier G. , Mendoza Victoria May P. , Mohammad Rhudaina Z. , Pilar-Arceo Carlene P.C. , Salonga Pamela Kim N. , Suarez Fatima Lois E. , Sy Polly W. , Vergara Thomas Herald M. , de los Reyes V Aurelio A. 
Published: May 2022

AbstractCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. Millions of people have fallen sick, and some have died due to this affliction that has spread across the globe. The current pandemic has disrupted normal day-to-day human life, causing a profound social and economic burden. Vaccination is an important control measure that could significantly reduce the incidence of cases and mortality if properly and efficiently distributed. In this work, an age-structured model of COVID-19 transmission, incorporating an unreported infectious compartment, is developed. Three age groups are considered, namely:young(0-19 years),adult(20-64 years), andelderly(65+ years). The transmission and reporting rates are determined for each group by utilizing the number of COVID-19 cases in the National Capital Region in the Philippines. Optimal control theory is employed to identify the best vaccine allocation to different age groups. Further, three different vaccination periods are considered to reflect phases of vaccination priority groups: the first, second, and third account for the inoculation of the elderly, adult and elderly, and all three age groups, respectively. This study could guide in making informed decisions in mitigating a population-structured disease transmission under limited resources.
Emotional dysregulation in childhood and disordered eating and self-harm in adolescence: Prospective associations and mediating pathways
Authors: Warne Naomi , Heron Jon , Mars Becky , Solmi Francesca , Biddle Lucy , Gunnell David , Hammerton Gemma , Moran Paul , Munafò Marcus , Penton-Voak Ian , Skinner Andy , Stewart Anne , Bould Helen 
Published: May 2022

AbstractBackgroundEmotional dysregulation may be a risk factor for disordered eating and self-harm in young people, but few prospective studies have assessed these associations long-term, or considered potential mediators. We examined prospective relationships between childhood emotional dysregulation and disordered eating and self-harm in adolescence; and social cognition, emotional recognition and being bullied as mediators.MethodsWe analysed Avon Longitudinal Study of Parents and Children data on 3453 males and 3481 females. We examined associations between emotional dysregulation at 7 years and any disordered eating and any self-harm at 16 years with probit regression models. We also assessed whether social cognition (7 years), emotional recognition (8 years) and bullying victimisation (11 years) mediated these relationships.ResultsEmotional dysregulation at age 7 years was associated with disordered eating (fully adjusted probit B (95% CI) = 0.082 (0.029, 0.134)) and self-harm (fully adjusted probit B (95% CI) = 0.093 (0.036, 0.150)) at age 16 years. There was no evidence of sex interactions or difference in effects between self-harm and disordered eating. Mediation models found social cognition was a key pathway to disordered eating (females 51.2%; males 27.0% of total effect) and self-harm (females 15.7%; males 10.8% of total effect). Bullying victimisation was an important pathway to disordered eating (females 17.1%; males 10.0% of total effect), but only to self-harm in females (15.7% of total effect). Indirect effects were stronger for disordered eating than self-harm.ConclusionsIn males and females, emotional dysregulation in early childhood is associated with disordered eating and self-harm in adolescence and may be a useful target for prevention and treatment. Mediating pathways appeared to differ by sex and outcome, but social cognition was a key mediating pathway for both disordered eating and self-harm.