bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology
Authors: Karaba Andrew H , Zhou Weiqiang , Hsieh Leon L , Figueroa Alexis , Massaccesi Guido , Rothman Richard E , Fenstermacher Katherine Z J , Sauer Lauren , Shaw-Saliba Kathryn , Blair Paul W , Robinson Matthew L , Leung Sherry , Wesson Russell , Alachkar Nada , El-Diwany Ramy , Ji Hongkai , Cox Andrea L 
Published: April 2021

Abstract

Background
Several inflammatory cytokines are upregulated in severe coronavirus disease 2019 (COVID-19). We compared cytokines in COVID-19 versus influenza to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease.

Methods
Thirty-seven cytokines and chemokines were measured in plasma from 135 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was used to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was used to identify cytokines that mediate the effect of BMI and age on disease severity.

Results
Interleukin-18 (IL-18), IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were significantly increased in COVID-19 versus influenza patients, whereas granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), IFN-λ1, IL-10, IL-15, and monocyte chemoattractant protein 2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not in severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity.

Conclusions
These findings point to activation of fundamentally different innate immune pathways in severe acute respiratory syndrome coronavirus 2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.
Improving the Outcomes of Immunocompromised Patients With Coronavirus Disease 2019
Authors: Haidar Ghady , Mellors John W 
Published: April 2021

Abstract
Recent case studies have highlighted the fact that certain immunocompromised individuals are at risk for prolonged SARS-CoV-2 replication, intrahost viral evolution of multiply-mutated variants, and poor clinical outcomes. The immunologic determinants of this risk, the duration of infectiousness, and optimal treatment and prevention strategies in immunocompromised hosts are ill defined. Of additional concern is the widespread use of immunosuppressive medications to treat COVID-19, which may enhance and prolong viral replication in the context of immunodeficiency. We outline the rationale for 4 interrelated approaches to usher in an era of evidence-based medicine for optimal management of immunocompromised patients with COVID-19: multicenter pathogenesis and outcomes studies to relate the risk of severe disease to the type and degree of immunodeficiency, studies to evaluate immunologic responses to SARS-CoV-2 vaccines, studies to evaluate the efficacy of monoclonal antibodies for primary prophylaxis, and clinical trials of novel antiviral agents for the treatment of COVID-19.
On the Quantity and Quality of Girls: Fertility, Parental Investments and Mortality
Authors: Anukriti S , Bhalotra Sonia , Tam Eddy H F 
Published: April 2021

Abstract
Access to prenatal sex-detection technology in India has led to a phenomenal increase in abortion of girls. We find that it has also narrowed the gender gap in under-five mortality, consistent with surviving girls being more wanted than aborted girls. For every three aborted girls, one additional girl survived to age five. Mechanisms include moderation of son-biased fertility stopping and narrowing of gender gaps in parental investments. However, surviving girls are more likely to be born in lower-status families. Our findings have implications not only for counts of missing girls but also for the later life outcomes of girls.
Gender differences in the association between physical activity and obesity in adults with vision and hearing losses
Authors: Pardhan Shahina , Smith Lee , Davis Adrian , Bourne Rupert , Barnett Yvonne , Jacob Louis , Koyanagi Ai , Radzimiński Łukasz , Skalska Maria , Jastrzębska Joanna , Jastrzębski Zbigniew , López-Sánchez Guillermo F 
Published: April 2021

Abstract

Background
Physical inactivity is strongly associated with obesity, which in turn is a major risk factor for many non-communicable diseases. We examined associations between physical inactivity and obesity in Spanish adults with vision and hearing difficulties and explored differences between men and women.

Methods
Data from the Spanish National Health Survey 2017 were analyzed [n = 23 089 adults (15–103 years, mean age 53.4 ± 18.9 years, 45.9% men)]. Participants self-reported difficulties in seeing and hearing. Physical inactivity (exposure) was evaluated with the International Physical Activity Questionnaire Short Form. Obesity (outcome) was defined as body mass index ≥30 kg m−2 based on self-reported weight and height. The association between physical inactivity and obesity was assessed with multivariable logistic regression in people with difficulties seeing and hearing, adjusting for significant covariates.

Results
Multivariable logistic regression analyses showed that the association between physical inactivity and obesity was stronger in those with difficulty hearing (OR 1.778, 95% CI 1.215–2.602) compared with difficulty seeing (OR 1.375, 95% CI 1.076–1.756). Gender-stratified analyses showed significant association between physical inactivity and obesity in men who reported difficulty hearing (OR 2.319, 95% CI 1.441–3.735) and difficulty seeing (OR 1.556, 95% CI 1.079–2.244), but not in women.

Conclusions
A significant association between physical inactivity and obesity was observed in Spanish men with vision and hearing difficulties. Physical activity has an important role in the prevention of obesity in men with seeing and hearing difficulties. Active steps should be taken to encourage physical activity to reduce the risk of obesity in people with sensory impairments.
Survival of young, dense Betula ermanii stands after wildfire at top soil removal sites
Authors: Hayamizu Masato , Nakata Yasutaka , Torita Hiroyuki 
Published: April 2021

Abstract
A forest fire in a cool-temperate broadleaved forest in northern Japan, from 26 May to 19 June 2019, provided an opportunity to examine the post-fire dynamics of young, dense birch (Betula ermanii Cham.) stands that had previously undergone top soil removal through soil scarification. To characterize the post-fire responses (survival and resprouting) of birch trees, we set up two plots, 6 months after the fire. We investigated the trunk diameter at breast height and burn marks on the trunks (scorch height and bole charring percentage) of all B. ermanii trees in both plots. Survival and resprouting of each tree were monitored over a 10-month period (6 and 16 months after the fire). To quantify post-fire vegetation recovery of the forest floor, we manually mapped the dominant understory plant, dwarf bamboo (i.e. Sasa kurilensis (Rupr.) Makino et Shibata), from orthomosaic images obtained using an unmanned aircraft vehicle, and estimated the recovery rate in the second year after the fire. Additionally, the seedlings of woody species were counted in both plots. A logistic generalized linear model revealed that the size-dependent survival rates of the plants in each plots were similar in the first year after fire. All B. ermanii trees died without resprouting in the second year after the fire, indicating the lethal effects of fire on young birch trees in top soil removal sites. Moreover, a high recovery rate of dwarf bamboo over 2 years in both plots and limited woody seedling establishment of woody plants suggest that the fire resulted in the regeneration failure of young stands in the top soil removal sites. Based on these findings, we suggest that the vulnerability of young trees can lead to the rapid change in vegetation from young forest to dense dwarf bamboo cover after a fire.
Transvection in the Drosophila Abd-B Domain: Extensive Upstream Sequences Are Involved in Anchoring Distant cis-Regulatory Regions to the Promoter
Authors: Sipos László , Mihály József , Karch François , Schedl Paul , Gausz János , Gyurkovics Henrik 
Published: April 2021

Abstract
The Abd-B gene, one of the three homeotic genes in the Drosophila bithorax complex (BX-C), is required for the proper identity of the fifth through the eighth abdominal segments (corresponding to parasegments 10–14) of the fruitfly. The morphological difference between these four segments is due to the differential expression of Abd-B, which is achieved by the action of the parasegment-specific cisregulatory regions infra-abdominal-5 (iab-5), -6, -7 and -8. The dominant gain-of-function mutation Frontabdominal-7 (Fab-7) removes a boundary separating two of these cis-regulatory regions, iab-6 and iab-7. As a consequence of the Fab-7 deletion, the parasegment 12- (PS12-) specific iab-7 is ectopically activated in PS11. This results in the transformation of the sixth abdominal segment (A6) into the seventh (A7) in Fab-7 flies. Here we report that point mutations of the Abd-B gene in trans suppress the Fab-7 phenotype in a pairing-dependent manner and thus represent a type of transvection. We show that the observed suppression is the result of trans-regulation of the defective Abd-B gene by the ectopically activated iab-7. Unlike previously demonstrated cases of trans-regulation in the Abd-B locus, trans-suppression of Fab-7 is sensitive to heterozygosity for chromosomal rearrangements that disturb homologous pairing at the nearby Ubx locus. However, in contrast to Ubx, the transvection we observed in the Abd-B locus is insensitive to the allelic status of zeste. Analysis of different deletion alleles of Abd-B that enhance trans-regulation suggests that an extensive upstream region, different from the sequences required for transcription initiation, mediates interactions between the iab cis-regulatory regions and the proximal Abd-B promoter. Moreover, we find that the amount of DNA deleted in the upstream region is roughly proportional to the strength of trans-interaction, suggesting that this region consists of numerous discrete elements that cooperate in tethering the iab regulatory domains to Abd-B. Possible implications of the tethering complex for the regulation of Abd-B are discussed. In addition, we present evidence that the tenacity of trans-interactions in the Abd-B gene may vary, depending upon the tissue and stage of development.
Mutational Analysis of the Yeast DEAH-Box Splicing Factor Prp16
Authors: Hotz Hans-Rudolf , Schwer Beate 
Published: April 2021

Abstract
Prp16 is an essential yeast splicing factor that catalyzes RNA-dependent hydrolysis of nucleoside triphosphates. Prp16 is a member of the DEAH-box protein family, which is defined by six collinear sequence motifs. The importance of residues within four of the conserved motifs was assessed by alanine-scanning mutagenesis. Mutant alleles of PRP16 were tested for in vivo function by complementation of a Δprp16 null strain. In motif I (GETGSGKT), alanine substitutions at Gly-378, Lys-379, and Thr-380 were lethal, whereas replacement of the amino acids in positions 373–377 were viable. In the signature DEAH-box (motif II), Asp-473 and Glu-474 were essential, whereas the H476A mutant was viable. The S505A and T507A mutants in motif III (SAT) were viable. In motif VI (QRSGRAGRTAPG), mutants Q685A, R686A, G688A, R689A, and R692A were lethal, whereas G691A, P695A, and G696A supported growth. Instructive structure-function relationships were established by conservative substitutions at essential residues identified by alanine scan. Overexpression of nonviable alleles impaired the growth of wild-type PRP16 cells. Deletion analysis of the 1071-amino-acid Prp16 protein revealed that the N-terminal 204 amino acids and the C-terminal 100 residues were dispensable for PRP16 function in vivo. These studies provide an instructive framework for functional analysis of other DEAH-box splicing factors.
Meiotic Chromosome Morphology and Behavior in zip1 Mutants of Saccharomyces cerevisiae
Authors: Tung Kuei-Shu , Roeder G Shirleen 
Published: April 2021

Abstract
The yeast Zip1 protein (Zip1p) is a component of the central region of the synaptonemal complex (SC). Zip1p is predicted to form a dimer consisting of a coiled-coil domain flanked by globular domains. To analyze the organization of Zip1p within the SC, in-frame deletions of ZIP1 were constructed and analyzed. The results demonstrate that the C terminus but not the N terminus of Zip1p is required for its localization to chromosomes. Deletions in the carboxy half of the predicted coiled-coil region cause decreases in the width of the SC. Based on these results, a model for the organization of Zip1p within the SC is proposed. zip1 deletion mutations were also examined for their effects on sporulation, spore viability, crossing over, and crossover interference. The results demonstrate that the extent of synapsis is positively correlated with the levels of spore viability, crossing over, and crossover interference. In contrast, the role of Zip1p in synapsis is separable from its role in meiotic cell cycle progression. zip1 mutants display interval-specific effects on crossing over.
Sir- and Silencer-Independent Disruption of Silencing in Saccharomyces by Sas10p
Authors: Kamakaka Rohinton T , Rine Jasper 
Published: April 2021

AbstractA promoter fusion library of Saccharomyces cerevisiae genes was used to exploit phenotypes associated with altered protein dosage. We identified a novel gene, SAS10, by the ability of Sas10p, when overproduced, to disrupt silencing. The predicted Sas10p was 70,200 kD and strikingly rich in charged amino acids. Sas10p was exclusively nuclear in all stages of the cell cycle. Overproduction of Sas10p caused derepression of mating type genes at both HML and HMR, as well as of URA3, TRP1, and ADE2 when inserted near a telomere or at HMR or the rDNA locus. Repressed genes not associated with silenced chromatin were unaffected. Sas10p was essential for viability, and the termination point following Sas10p depletion was as large budded cells. Remarkably, Sas10p overproduction disrupted silencing even under conditions that bypassed the requirement for Sir proteins, ORC, and Rap1p in silencing. These data implied that Sas10p function was intimately connected with the structure of silenced chromatin.
Rate Variation of DNA Sequence Evolution in the Drosophila Lineages
Authors: Takano Toshiyuki S 
Published: April 2021

Abstract
Rate constancy of DNA sequence evolution was examined for three species of Drosophila, using two samples: the published sequences of eight genes from regions of the normal recombination rates and new data of the four AS-C (ac, sc, l'sc and ase) and ci genes. The AS-C and ci genes were chosen because these genes are located in the regions of very reduced recombination in Drosophila melanogaster and their locations remain unchanged throughout the entire lineages involved, yielding less effect of ancestral polymorphism in the study of rate constancy. The synonymous substitution pattern of the three lineages was found to be erratic in both samples. The dispersion index for replacement substitution was relatively high for the per, G6pd and ac genes. A significant heterogeneity was found in the number of synonymous substitutions in the three lineages between the two samples of genes with different recombination rates. This is partly due to a lack of the lineage effect in the D. melanogaster and Drosophila simulans lineages in the AS-C and ci genes in contrast to Akashi's observation of genes in regions of normal recombination. The higher codon bias in Drosophila yakuba as compared with D. melanogaster and D. simulans was observed in the four AS-C genes, which suggests change(s) in action of natural selection involved in codon usage on these genes. Fluctuating selection intensity may also be responsible for the observed locus-lineage interaction effects in synonymous substitution.
A Methylated Neurospora 5S rRNA Pseudogene Contains a Transposable Element Inactivated by Repeat-Induced Point Mutation
Authors: Margolin Brian S , Garrett-Engele Phillip W , Stevens Judith N , Fritz Deborah Y , Garrett-Engele Carrie , Metzenberg Robert L , Selker Eric U 
Published: April 2021

AbstractIn an analysis of 22 of the roughly 100 dispersed 5S rRNA genes in Neurospora crassa, a methylated 5S rRNA pseudogene, Ψ63, was identified. We characterized the Ψ63 region to better understand the control and function of DNA methylation. The 120-bp 5S rRNA-like region of Ψ63 is interrupted by a 1.9-kb insertion that has characteristics of sequences that have been modified by repeat-induced point mutation (RIP). We found sequences related to this insertion in wild-type strains of N. crassa and other Neurospora species. Most showed evidence of RIP; but one, isolated from the N. crassa host of Ψ63, showed no evidence of RIP. A deletion from near the center of this sequence apparently rendered it incapable of participating in RIP with the related full-length copies. The Ψ63 insertion and the related sequences have features of transposons and are related to the Fot1 class of fungal transposable elements. Apparently Ψ63 was generated by insertion of a previously unrecognized Neurospora transposable element into a 5S rRNA gene, followed by RIP. We name the resulting inactivated Neurospora transposon PuntRIP1 and the related sequence showing no evidence of RIP, but harboring a deletion that presumably rendered it defective for transposition, dPunt.
Repression of Hybrid Dysgenesis in Drosophila melanogaster by Combinations of Telomeric P-Element Reporters and Naturally Occurring P Elements
Authors: Ronsseray Stéphane , Marin Laurent , Lehmann Monique , Anxolabéhère Dominique 
Published: April 2021

Abstract
In Drosophila melanogaster, hybrid dysgenesis occurs in the germline of flies produced by crosses between females lacking P elements and males carrying 25–55 P elements. We have previously shown that a complete maternally inherited repression of P transposition in the germline (P cytotype) can be elicited by only two autonomous P elements located at the X chromosome telomere (cytological site 1A). We have tested whether P transgenes at 1A, unable to code for a P-repressor, may contribute to the repression of P elements. Females carrying a P-lacZ transgene at 1A [“P-lacZ(1A)”], crossed with P males, do not repress dysgenic sterility in their progeny. However, these P-lacZ(1A) insertions, maternally or paternally inherited, contribute to P-element repression when they are combined with other regulatory P elements. This combination effect is not seen when the P-lacZ transgene is located in pericentromeric heterochromatin or in euchromatin; however a P-w,ry transgene located at the 3R chromosome telomere exhibits the combination effect. The combination effect with the P-lacZ(1A) transgene is impaired by a mutant Su(var)205 allele known to impair the repression ability of the autonomous P elements at 1A. We hypothesized that the combination effect is due to modification of the chromatin structure or nuclear location of genomic P elements.
Genotype-Environment Interaction at Quantitative Trait Loci Affecting Sensory Bristle Number in Drosophila melanogaster
Authors: Gurganus Marjorie C , Fry James D , Nuzhdin Sergey V , Pasyukova Elena G , Lyman Richard F , Mackay Trudy F C 
Published: April 2021

Abstract
The magnitude of segregating variation for bristle number in Drosophila melanogaster exceeds that predicted from models of mutation-selection balance. To evaluate the hypothesis that genotype-environment interaction (GEI) maintains variation for bristle number in nature, we quantified the extent of GEI for abdominal and sternopleural bristles among 98 recombinant inbred lines, derived from two homozygous laboratory strains, in three temperature environments. There was considerable GEI for both bristle traits, which was mainly attributable to changes in rank order of line means. We conducted a genome-wide screen for quantitative trait loci (QTLs) affecting bristle number in each sex and temperature environment, using a dense (3.2-cM) marker map of polymorphic insertion sites of roo transposable elements. Nine sternopleural and 11 abdominal bristle number QTLs were detected. Significant GEI was exhibited by 14 QTLs, but there was heterogeneity among QTLs in their sensitivity to thermal and sexual environments. To further evaluate the hypothesis that GEI maintains variation for bristle number, we require estimates of allelic effects across environments at genetic loci affecting the traits. This level of resolution may be achievable for Drosophila bristle number because candidate loci affecting bristle development often map to the same location as bristle number QTLs.
The Genetic Basis of Drosophila sechellia's Resistance to a Host Plant Toxin
Authors: Jones Corbin D 
Published: April 2021

Abstract
Unlike its close relatives, Drosophila sechellia is resistant to the toxic effects of the fruit of its host plant, Morinda citrifolia. Using 15 genetic markers, I analyze the genetic basis of D. sechellia's resistance to this fruit's primary toxin, octanoic acid. D. sechellia's resistance is dominant in F1 hybrids between it and its sister species D. simulans. All chromosomes, except the Y and the dot fourth, carry genes affecting resistance. The third chromosome has the greatest effect and carries at least two factors. The X chromosome has an intermediate effect and harbors at least two genes, whereas the second chromosome carries at least one gene of weak effect. Thus, at least five loci are involved in this adaptation. However, I also identified large chromosome regions having no effect on resistance, suggesting that D. sechellia's resistance is neither very simple nor highly polygenic. Instead, resistance appears to have an oligogenic basis. D. sechellia's resistance to its host may contribute to ecological isolation between it and D. simulans.