bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRANSDIRE: data-driven direct reprogramming by a pioneer factor-guided trans-omics approach
Authors: Eguchi Ryohei , Hamano Momoko , Iwata Michio , Nakamura Toru , Oki Shinya , Yamanishi Yoshihiro 
Published: April 2022

AbstractMotivationDirect reprogramming involves the direct conversion of fully differentiated mature cell types into various other cell types while bypassing an intermediate pluripotent state (e.g. induced pluripotent stem cells). Cell differentiation by direct reprogramming is determined by two types of transcription factors (TFs): pioneer factors (PFs) and cooperative TFs. PFs have the distinct ability to open chromatin aggregations, assemble a collective of cooperative TFs and activate gene expression. The experimental determination of two types of TFs is extremely difficult and costly.ResultsIn this study, we developed a novel computational method, TRANSDIRE (TRANS-omics-based approach for DIrect REprogramming), to predict the TFs that induce direct reprogramming in various human cell types using multiple omics data. In the algorithm, potential PFs were predicted based on low signal chromatin regions, and the cooperative TFs were predicted through a trans-omics analysis of genomic data (e.g. enhancers), transcriptome data (e.g. gene expression profiles in human cells), epigenome data (e.g. chromatin immunoprecipitation sequencing data) and interactome data. We applied the proposed methods to the reconstruction of TFs that induce direct reprogramming from fibroblasts to six other cell types: hepatocytes, cartilaginous cells, neurons, cardiomyocytes, pancreatic cells and Paneth cells. We demonstrated that the methods successfully predicted TFs for most cell conversions with high accuracy. Thus, the proposed methods are expected to be useful for various practical applications in regenerative medicine.Availability and implementationThe source code and data are available at the following website: http://figshare.com/s/b653781a5b9e6639972bSupplementary informationSupplementary data are available at Bioinformatics online.
MitoVisualize: a resource for analysis of variants in human mitochondrial RNAs and DNA
Authors: Lake Nicole J , Zhou Lily , Xu Jenny , Lek Monkol 
Published: April 2022

Abstract

Summary
We present MitoVisualize, a new tool for analysis of the human mitochondrial DNA (mtDNA). MitoVisualize enables visualization of: (i) the position and effect of variants in mitochondrial transfer RNA and ribosomal RNA secondary structures alongside curated variant annotations, (ii) data across RNA structures, such as to show all positions with disease-associated variants or with post-transcriptional modifications and (iii) the position of a base, gene or region in the circular mtDNA map, such as to show the location of a large deletion. All visualizations can be easily downloaded as figures for reuse. MitoVisualize can be useful for anyone interested in exploring mtDNA variation, though is designed to facilitate mtDNA variant interpretation in particular.

Availability and implementation
MitoVisualize can be accessed via https://www.mitovisualize.org/. The source code is available at https://github.com/leklab/mito_visualize/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Comparing the maternal-fetal microbiome of humans and cattle: a translational assessment of the reproductive, placental, and fetal gut microbiomes
Authors: Hummel Gwendolynn L , Austin Kathleen , Cunningham-Hollinger Hannah C 
Published: April 2022

Abstract
Despite differences in gut physiology and morphology, both humans and cattle require a functional gut microbiome in early life. Evidence suggests that both species acquire gut microbes prior to birth, likely from a maternal source, indicating the use of similar mechanisms and timing for fetal gut colonization. Unlike mouse models, cattle share a similar gestation length, parity, and placental microbiome characteristics to humans. The large size of calves allow for contamination-protected sampling of the gut, vagina, and uterus, which would typically require invasive procedures in human cohorts. The ruminant placenta also exhibits a larger degree of separation between maternal and fetal physiology, necessitating a direct and explicit route by which microbes may access the fetal gut. These and other features permit cattle to act as a translational model for early gut colonization. However, cattle do not share similar placental morphology, gut function, or early immune system interactions with humans, creating barriers to their use as a biomedical model. Identifying similarities and differences between humans and cattle may outline the most important functions of the placental and fetal gut microbiomes, indicate the source of these microbes, and highlight the role of maternal or environmental influences upon fetal health across species.
Altered alpha and theta oscillations correlate with sequential working memory in Parkinson’s disease
Authors: Ye Zheng , Heldmann Marcus , Herrmann Lisa , Brüggemann Norbert , Münte Thomas F 
Published: April 2022

Abstract
Daily activities such as preparing a meal rely on the ability to arrange thoughts and actions in the right order. Patients with Parkinson’s disease have difficulties in sequencing tasks. Their deficits in sequential working memory have been associated with basal ganglia dysfunction. Here we demonstrate that altered parietal alpha and theta oscillations correlate with sequential working memory in Parkinson’s disease. We included 15 patients with Parkinson’s disease (6 women, mean age: 66.0 years), 24 healthy young (14 women, mean age: 24.1 years), and 16 older participants (7 women, mean age: 68.6 years). All participants completed a picture ordering task with scalp electroencephalogram (EEG) recording, where they arranged five pictures in a specific order and memorized them over a delay. When encoding and maintaining picture sequences, patients with Parkinson’s disease showed a lower baseline alpha peak frequency with higher alpha power than healthy young and older participants. Patients with a higher baseline alpha power responded more slowly for ordered trials. When manipulating picture sequences, patients with Parkinson’s disease showed a lower frequency of maximal power change for random versus ordered trials than healthy young and older participants. Healthy older participants showed a higher frequency of maximal power change than healthy young participants. Compared with patients with frequency of maximal power change in the alpha band (8–15 Hz), patients with frequency of maximal power change in the theta band (4–7 Hz) showed a higher ordering-related accuracy cost (random versus ordered) in the main task and tended to respond more slowly and less accurately in an independent working memory test. In conclusion, altered baseline alpha oscillations and task-dependent modulation of alpha and theta oscillations may be neural markers of poor sequential working memory in Parkinson’s disease.
Investigation of a Severe Acute Respiratory Syndrome Coronavirus 2 Delta (B.1.617.2) Variant Outbreak Among Residents of a Skilled Nursing Facility and Vaccine Effectiveness Analysis: Maricopa County, Arizona, June–July 2021
Authors: Dale Ariella P , Almendares Olivia , Howard Brandon J , Burnett Eleanor , Prasai Siru , Arons Melissa , Collins Jennifer , Duffy Nadezdha , Pandit Urvashi , Brady Shane , White Jessica R , Garrett Brenna , Kirking Hannah L , Sunenshine Rebecca , Tate Jacqueline E , Scott Sarah E 
Published: April 2022

Abstract

Background
Short-term rehabilitation units present unique infection control challenges because of high turnover and medically complex residents. In June 2021, the Maricopa County Department of Public Health was notified of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta outbreak in a skilled nursing facility short-term rehabilitation unit. We describe the outbreak and assess vaccine effectiveness (VE).

Methods
Facility electronic medical records were reviewed for residents who spent &gt; 1 night on the affected unit between June 10 and July 23, 2021, to collect demographics, SARS-CoV-2 test results, underlying medical conditions, vaccination status, and clinical outcomes. Coronavirus disease 2019 VE estimates using Cox proportional hazards models were calculated.

Results
Forty (37%) of 109 short-stay rehabilitation unit residents who met inclusion criteria tested positive for SARS-CoV-2. SARS-CoV-2-positive case-patients were mostly male (58%) and White (78%) with a median age of 65 (range, 27-92) years; 11 (27%) were immunocompromised. Of residents, 39% (10 cases, 32 noncases) received 2 doses and 9% (4 cases, 6 noncases) received 1 dose of messenger RNA (mRNA) vaccine. Among nonimmunocompromised residents, adjusted 2-dose primary-series mRNA VE against symptomatic infection was 80% (95% confidence interval, 15-95). More cases were hospitalized (33%) or died (38%) than noncases (10% hospitalized; 16% died).

Conclusions
In this large SARS-CoV-2 Delta outbreak in a high-turnover short-term rehabilitation unit, a low vaccination rate and medically complex resident population were noted alongside severe outcomes. VE of 2-dose primary-series mRNA vaccine against symptomatic infection was the highest in nonimmunocompromised residents. Health departments can use vaccine coverage data to prioritize facilities for assistance in preventing outbreaks.
Associations Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants and Risk of Coronavirus Disease 2019 (COVID-19) Hospitalization Among Confirmed Cases in Washington State: A Retrospective Cohort Study
Authors: Paredes Miguel I , Lunn Stephanie M , Famulare Michael , Frisbie Lauren A , Painter Ian , Burstein Roy , Roychoudhury Pavitra , Xie Hong , Mohamed Bakhash Shah A , Perez Ricardo , Lukes Maria , Ellis Sean , Sathees Saraswathi , Mathias Patrick C , Greninger Alexander , Starita Lea M , Frazar Chris D , Ryke Erica , Zhong Weizhi , Gamboa Luis , Threlkeld Machiko , Lee Jover , McDermot Evan , Truong Melissa , Nickerson Deborah A , Bates Daniel L , Hartman Matthew E , Haugen Eric , Nguyen Truong N , Richards Joshua D , Rodriguez Jacob L , Stamatoyannopoulos John A , Thorland Eric , Melly Geoff , Dykema Philip E , MacKellar Drew C , Gray Hannah K , Singh Avi , Peterson JohnAric M , Russell Denny , Torres Laura Marcela , Lindquist Scott , Bedford Trevor , Allen Krisandra J , Oltean Hanna N 
Published: April 2022

Abstract

Background
The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.

Methods
Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination.

Results
In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40–4.26), Beta (HR 2.85, 95% CI 1.56–5.23), Delta (HR 2.28 95% CI 1.56–3.34), or Alpha (HR 1.64, 95% CI 1.29–2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56–1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination.

Conclusions
Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.
Origin, evolution, breeding, and omics of Apiaceae: a family of vegetables and medicinal plants
Authors: Wang Xiao-Jing , Luo Qing , Li Tong , Meng Ping-Hong , Pu Yu-Ting , Liu Jie-Xia , Zhang Jian , Liu Hui , Tan Guo-Fei , Xiong Ai-Sheng 
Published: April 2022

Abstract
Many of the world’s most important vegetables and medicinal crops, including carrot, celery, coriander, fennel, and cumin, belong to the Apiaceae family. In this review, we summarize the complex origins of Apiaceae and the current state of research on the family, including traditional and molecular breeding practices, bioactive compounds, medicinal applications, nanotechnology, and omics research. Numerous molecular markers, regulatory factors, and functional genes have been discovered, studied, and applied to improve vegetable and medicinal crops in Apiaceae. In addition, current trends in Apiaceae application and research are also briefly described, including mining new functional genes and metabolites using omics research, identifying new genetic variants associated with important agronomic traits by population genetics analysis and GWAS, applying genetic transformation, the CRISPR-Cas9 gene editing system, and nanotechnology. This review provides a reference for basic and applied research on Apiaceae vegetable and medicinal plants.
Transcriptome analysis reveals the regulatory mechanism by whichMdWOX11suppresses adventitious shoot formation in apple
Authors: Mao Jiangping , Ma Doudou , Niu Chundong , Ma Xiaolong , Li Ke , Tahir Muhammad Mobeen , Chen Shiyue , Liu Xiuxiu , Zhang Dong 
Published: April 2022

AbstractAdventitious shoot (AS) regeneration accelerates plant reproduction and genetic transformation. WOX11 is involved in many biological processes, but its regulation of AS regeneration has not been reported. Here, we showed that the genotype and CK/IAA ratio of apple leaves were the key factors that affected their capacity for AS formation. Moreover, the expression level of MdWOX11 was negatively correlated with the capacity for AS formation. Phenotypic analysis of MdWOX11 transgenic plants showed that overexpression of MdWOX11 inhibited AS formation. Endogenous hormone analysis demonstrated that the contents of auxin (IAA), cytokinin (CK), and abscisic acid (ABA) were higher in MdWOX11-RNAi plants than in MdWOX11-OE transgenic plants. We used RNA sequencing to examine the transcriptional responses of genes in MdWOX11-RNAi and MdWOX11-OE transgenic apple plants at different AS stages. We identified 8066 differentially expressed genes and focused our analysis on those involved in the IAA, CK, ABA, and gibberellin (GA) hormone signaling pathways. The expression of genes related to the CK signaling pathway and shoot development was higher in GL-3 than in MdWOX11-OE transgenic plants during the callus and AS emergence stages. However, the expression of MdCKX5 was higher in MdWOX11-OE transgenic plants than in GL3 and MdWOX11-RNAi transgenic plants. Yeast one-hybrid (Y1H) assays, dual-luciferase reporter assays, and ChIP-qPCR showed that MdWOX11 binds to the promoter of MdCKX5, and a dual-luciferase reporter assay showed that MdWOX11 enhanced the promoter activity of MdCKX5. We concluded that MdCKX5 acts downstream of MdWOX11 to control AS formation, and we built a regulatory model of the suppression of AS formation by MdWOX11 in apple.
MYB308-mediated transcriptional activation of plasma membrane H+-ATPase 6 promotes iron uptake in citrus
Authors: Fan Zhengyan , Wu Yifang , Zhao Liuying , Fu Lina , Deng Lile , Deng Jiarui , Ding Dekuan , Xiao Shunyuan , Deng Xiuxin , Peng Shu’ang , Pan Zhiyong 
Published: April 2022

Abstract
Iron-deficiency chlorosis is a common nutritional disorder in crops grown on alkaline or calcareous soils. Although the acclimation mechanism to iron deficiency has been investigated, the genetic regulation of iron acquisition is still unclear. Here, by comparing the iron uptake process between the iron-poor-soil-tolerant citrus species Zhique (ZQ) and the iron-poor-soil-sensitive citrus species trifoliate orange (TO), we discovered that enhanced root H + efflux is crucial for the tolerance to iron deficiency in ZQ. The H+ efflux is mainly regulated by a plasma membrane-localized H+-ATPase, HA6, the expression of which is upregulated in plants grown in soil with low iron content, and significantly higher in the roots of ZQ than TO. Overexpression of the HA6 gene in the Arabidopsis thaliana aha2 mutant, defective in iron uptake, recovered the wild-type phenotype. In parallel, overexpression of the HA6 gene in TO significantly increased iron content of plants. Moreover, an iron deficiency-induced transcription factor, MYB308, was revealed to bind the promoter and activate the expression of HA6 in ZQ in yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays. Overexpression of MYB308 in ZQ roots significantly increased the expression level of the HA6 gene. However, MYB308 cannot bind or activate the HA6 promoter in TO due to the sequence variation of the corresponding MYB308 binding motif. Taking these results together, we propose that the MYB308 could activate HA6 to promote root H+ efflux and iron uptake, and that the distinctive MYB308-HA6 transcriptional module may be, at least in part, responsible for the iron deficiency tolerance in citrus.
Immunoendocrinology and Ecoimmunology in Brazilian Anurans
Authors: Gomes Fernando Ribeiro , Madelaire Carla Bonetti , Moretti Eduardo Hermógenes , Titon Stefanny Christie Monteiro , Assis Vania Regina 
Published: April 2022

AbstractThis paper reviews several aspects of immunoendocrinology and ecoimmunology in Brazilian species of anurans under investigation for more than a decade, including (1) patterns of annual covariation of circulating steroids, calling behavior and innate immunity, (2) endocrine and immune correlates of calling performance, (3) behavioral and physiological correlates of parasite load, (4) thermal sensitivity of immune function, and (5) endocrine and immunomodulation by experimental exposure to acute and chronic stressors, as well as to endocrine manipulations and simulated infections. Integrated results have shown an immunoprotective role of increased steroid plasma levels during reproductive activity in calling males. Moreover, a higher helminth parasite load is associated with changes in several behavioral and physiological traits under field conditions. We also found anuran innate immunity is generally characterized by eurythermy, with maximal performance observed in temperatures close to normal and fever thermal preferendum. Moreover, the aerobic scope of innate immune response is decreased at fever thermal preferendum. Experimental exposure to stressors results in increased corticosterone plasma levels and immune redistribution, with an impact on immune function depending on the duration of the stress exposure. Interestingly, the fate of immunomodulation by chronic stressors also depends in part on individual body condition. Acute treatment with corticosterone generally enhances immune function, while prolonged exposure results in immunosuppression. Still, the results of hormonal treatment are complex and depend on the dose, duration of treatment, and the immune variable considered. Finally, simulated infection results in complex modulation of the expression of cytokines, increased immune function, activation of the Hypothalamus-Pituitary-Interrenal axis, and decreased activity of the Hypothalamus-Pituitary-Gonadal axis, as well as reduced melatonin plasma levels, suggesting that anurans have a functional Immune-Pineal axis, homologous to that previously described for mammals. These integrated and complementary approaches have contributed to a better understanding of physiological mechanisms and processes, as well as ecological and evolutionary implications of anuran immunoendocrinology.
88 Effect of Increasing Levels of a Novel Consensus Bacterial 6-Phytase Variant on Ileal and Total Tract Digestibility of Nutrients in Diets Fed to Young Pigs
Authors: Espinosa Charmaine D , Velayudhan Deepak , Dersjant-Li Yueming , Stein Hans H 
Published: April 2022

Abstract
An experiment was conducted to test the hypothesis that increasing levels of phytase increases apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of nutrients in diets fed to young pigs. A negative control (NC) diet that was deficient (compared with NRC recommendation) in total Ca (-0.15%), standardized total tract digestible P (-0.16%), net energy (-33 kcal/kg), and standardized ileal digestible amino acids (average -0.02% unit) was formulated. Five additional diets were formulated by adding 250, 500, 1,000, 2,000 or 4,000 phytase units per kg of a novel consensus bacterial 6-phytase variant (PhyG) to the NC diet. All diets were based on corn, soybean meal, and canola meal. Eighteen ileal-cannulated pigs (17.81 ± 1.71 kg) were allotted to a 6 × 3 incomplete Latin square design with 6 diets and 3 periods. There were 3 pigs per diet in each period; therefore, there were nine replicate pigs per diet. Data were analyzed using the Mixed Procedure of SAS with diet as the fixed effect whereas pig and period were considered random effects. Linear and quadratic effects of PhyG on nutrient digestibility were determined using polynomial contrast statements. Linear (P &lt; 0.01) and quadratic (P &lt; 0.05) increases in AID of all individual amino acids (except Arg) were observed as dietary concentrations of PhyG increased (Table 1). Likewise, an increase (linear, P &lt; 0.01; quadratic, P &lt; 0.05) in ATTD of minerals in diets was observed as the concentration of PhyG increased in diets. Increasing levels of PhyG in diets also increased (linear, P &lt; 0.05) ATTD of gross energy. In conclusion, increasing levels of the novel phytase (PhyG) effectively increased ileal and total tract digestibility of nutrients by pigs.