bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ribosomal Protein Insufficiency and the Minute Syndrome in Drosophila: A Dose-Response Relationship
Authors: Sæbøe-Larssen Stein , Lyamouri May , Merriam John , Oksvold Morten P , Lambertsson Andrew 
Published: February 2021

Abstract
Minutes comprise &gt;50 phenotypically similar mutations scattered throughout the genome of Drosophila, many of which are identified as mutations in ribosomal protein (rp) genes. Common traits of the Minute phenotype are short and thin bristles, slow development, and recessive lethality. By mobilizing a P element inserted in the 5′ UTR of M(3)95A, the gene encoding ribosomal protein S3 (RPS3), we have generated two homozygous viable heteroalleles that are partial revertants with respect to the Minute phenotype. Molecular characterization revealed both alleles to be imprecise excisions, leaving 40 and 110 bp, respectively, at the P-element insertion site. The weaker allele (40 bp insert) is associated with a ~15% decrease in RPS3 mRNA abundance and displays a moderate Minute phenotype. In the stronger allele (110 bp insert) RPS3 mRNA levels are reduced by ~60%, resulting in an extreme Minute phenotype that includes many morphological abnormalities as well as sterility in both males and females due to disruption of early gametogenesis. The results show that there is a correlation between reduced RPS3 mRNA levels and the severity of the Minute phenotype, in which faulty differentiation of somatic tissues and arrest of gametogenesis represent the extreme case. That heteroalleles in M(3)95A can mimic the phenotypic variations that exist between different Minute/rp-gene mutations strongly suggests that all phenotypes primarily are caused by reductions in maximum protein synthesis rates, but that the sensitivity for reduced levels of the individual rp-gene products is different.
Radiation-Induced Chromosome Aberrations in Saccharomyces cerevisiae: Influence of DNA Repair Pathways
Authors: Friedl Anna A , Kiechle Markus , Fellerhoff Barbara , Eckardt-Schupp Friederike 
Published: February 2021

Abstract
Radiation-induced chromosome aberrations, particularly exchange-type aberrations, are thought to result from misrepair of DNA double-strand breaks. The relationship between individual pathways of break repair and aberration formation is not clear. By electrophoretic karyotyping of single-cell clones derived from irradiated cells, we have analyzed the induction of stable aberrations in haploid yeast cells mutated for the RAD52 gene, the RAD54 gene, the HDF1(=YKU70) gene, or combinations thereof. We found low and comparable frequencies of aberrational events in wildtype and hdf1 mutants, and assume that in these strains most of the survivors descended from cells that were in G2 phase during irradiation and therefore able to repair breaks by homologous recombination between sister chromatids. In the rad52 and the rad54 strains, enhanced formation of aberrations, mostly exchange-type aberrations, was detected, demonstrating the misrepair activity of a rejoining mechanism other than homologous recombination. No aberration was found in the rad52 hdf1 double mutant, and the frequency in the rad54 hdf1 mutant was very low. Hence, misrepair resulting in exchange-type aberrations depends largely on the presence of Hdf1, a component of the nonhomologous end-joining pathway in yeast.
DNA Sequence Analysis of Spontaneous Mutagenesis in Saccharomyces cerevisiae
Authors: Kunz Bernard A , Ramachandran Karthikeyan , Vonarx Edward J 
Published: February 2021

Abstract
To help elucidate the mechanisms involved in spontaneous mutagenesis, DNA sequencing has been applied to characterize the types of mutation whose rates are increased or decreased in mutator or antimutator strains, respectively. Increased spontaneous mutation rates point to malfunctions in genes that normally act to reduce spontaneous mutation, whereas decreased rates are associated with defects in genes whose products are necessary for spontaneous mutagenesis. In this article, we survey and discuss the mutational specificities conferred by mutator and antimutator genes in the budding yeast Saccharomyces cerevisiae. The implications of selected aspects of the data are considered with respect to the mechanisms of spontaneous mutagenesis.
Topical Reversion at the HIS1 Locus of Saccharomyces cerevisiae • A Tale of Three Mutants
Authors: von Borstel R C , Savage Elizabeth A , Wang Qi , Hennig Ursula G G , Ritzel R Gary , Lee Grace S-F , Hamilton Michael D , Chrenek Micah A , Tomaszewski Robert W , Higgins John A , Tenove Christopher J , Liviero Lucia , Hastings Philip J , Korch Christopher T , Steinberg C M 
Published: February 2021

Abstract
Mutants of the HIS1 locus of the yeast Saccharomyces cerevisiae are suitable reporters for spontaneous reversion events because most reversions are topical, that is, within the locus itself. Thirteen mutations of his1-1 now have been identified with respect to base sequence. Revertants of three mutants and their spontaneous reversion rates are presented: (1) a chain termination mutation (his1-208, née his1-1) that does not revert by mutations of tRNA loci and reverts only by intracodonic suppression; (2) a missense mutation (his1-798, née his1-7) that can revert by intragenic suppression by base substitutions of any sort, including a back mutation as well as one three-base deletion; and (3) a −1 frameshift mutation (his1-434, née his1-19) that only reverts topically by +1 back mutation, +1 intragenic suppression, or a −2 deletion. Often the +1 insertion is accompanied by base substitution events at one or both ends of a run of A's. Missense suppressors of his1-798 are either feeders or nonfeeders, and at four different locations within the locus, a single base substitution encoding an amino acid alteration will suffice to turn the nonfeeder phenotype into a feeder phenotype. Late-appearing revertants of his1-798 were found to be slowly growing leaky mutants rather than a manifestation of adaptive mutagenesis. Spontaneous revertants of his1-208 and his1-434 produced no late-arising colonies.
Isolation and Characterization of Fission Yeast sns Mutants Defective at the Mitosis-to-Interphase Transition
Authors: Matynia Anna , Mueller Ulrich , Ong Ngoctuyen , Demeter Janos , Granger Aaron L , Hinata Kaede , Sazer Shelley 
Published: February 2021

Abstractpim1-d1ts was previously identified in a visual screen for fission yeast mutants unable to complete the mitosis-to-interphase transition. pim1+ encodes the guanine nucleotide exchange factor (GEF) for the spi1 GTPase. Perturbations of this GTPase system by either mutation or overproduction of its regulatory proteins cause cells to arrest with postmitotic condensed chromosomes, an unreplicated genome, and a wide medial septum. The septation phenotype of pim1-d1ts was used as the basis for a more extensive screen for this novel class of sns (septated, not in S-phase) mutants. Seventeen mutants representing 14 complementation groups were isolated. Three strains, sns-A3, sns-A5, and sns-A6, representing two different alleles, are mutated in the pim1+ gene. Of the 13 non-pim1ts sns complementation groups, 11 showed genetic interactions with the spi1 GTPase system. The genes mutated in 10 sns strains were synthetically lethal with pim1-d1, and six sns strains were hypersensitive to overexpression of one or more of the known components of the spi1 GTPase system. Epistasis analysis places the action of the genes mutated in nine of these strains downstream of pim1+ and the action of one gene upstream of pim1+. Three strains, sns-A2, sns-B1, and sns-B9, showed genetic interaction with the spi1 GTPase system in every test performed. sns-B1 and sns-B9 are likely to identify downstream targets, whereas sns-A2 is likely to identify upstream regulators of the spi1 GTPase system that are required for the mitosis-to-interphase transition.
Physical Mapping of the liguleless Linkage Group in Sorghum bicolor Using Rice RFLP-Selected Sorghum BACs
Authors: Zwick Michael S , Islam-Faridi M Nurul , Czeschin Don G , Wing Rod A , Hart Gary E , Stelly David M , Price H James 
Published: February 2021

Abstract
Physical mapping of BACs by fluorescent in situ hybridization (FISH) was used to analyze the liguleless (lg-1) linkage group in sorghum and compare it to the conserved region in rice and maize. Six liguleless-associated rice restriction fragment length polymorphism (RFLP) markers were used to select 16 homeologous sorghum BACs, which were in turn used to physically map the liguleless linkage group in sorghum. Results show a basic conservation of the liguleless region in sorghum relative to the linkage map of rice. One marker which is distal in rice is more medial in sorghum, and another marker which is found within the linkage group in rice is on a different chromosome in sorghum. BACs associated with linkage group I hybridize to chromosome It, which was identified by using FISH in a sorghum cytogenetic stock trisomic for chromosome I (denoted It), and a BAC associated with linkage group E hybridized to an unidentified chromosome. Selected BACs, representing RFLP loci, were end-cloned for RFLP mapping, and the relative linkage order of these clones was in full agreement with the physical data. Similarities in locus order and the association of RFLP-selected BAC markers with two different chromosomes were found to exist between the linkage map of the liguleless region in maize and the physical map of the liguleless region in sorghum.
Identification of Chromosomal Regions Involved in decapentaplegic Function in Drosophila
Authors: Nicholls Russell E , Gelbart William M 
Published: February 2021

Abstract
Signaling molecules of the transforming growth factor β (TGF-β) family contribute to numerous developmental processes in a variety of organisms. However, our understanding of the mechanisms which regulate the activity of and mediate the response to TGF-β family members remains incomplete. The product of the Drosophila decapentaplegic (dpp) locus is a well-characterized member of this family. We have taken a genetic approach to identify factors required for TGF-β function in Drosophila by testing for genetic interactions between mutant alleles of dpp and a collection of chromosomal deficiencies. Our survey identified two deficiencies that act as maternal enhancers of recessive embryonic lethal alleles of dpp. The enhanced individuals die with weakly ventralized phenotypes. These phenotypes are consistent with a mechanism whereby the deficiencies deplete two maternally provided factors required for dpp's role in embryonic dorsal-ventral pattern formation. One of these deficiencies also appears to delete a factor required for dpp function in wing vein formation. These deficiencies remove material from the 54F-55A and 66B-66C polytene chromosomal regions, respectively. As neither of these regions has been previously implicated in dpp function, we propose that each of the deficiencies removes a novel factor or factors required for dpp function.
Bayesian Inference of Genetic Parameters and Selection Response for Litter Size Components in Pigs
Authors: Blasco A , Sorensen D , Bidanel J P 
Published: February 2021

Abstract
Three contemporary lines were formed from the progeny of 50 French Large White sows. In the first line, gilts were selected for ovulation rate at puberty. In the second line, they were selected for prenatal survival of the first two parities, corrected for ovulation rate. The control constituted the third line. Ovulation rate at puberty was analyzed using an animal model with a batch effect. Prenatal survival was analyzed with a repeatability animal model that included batch and parity effects. Flat priors were used to represent vague previous knowledge about parity and batch effects. Additive and residual effects were represented assuming that they were a priori normally distributed. Variance components were assumed to follow either uniform or inverted chi-square distributions, a priori. The use of different priors did not affect the results substantially. Heritabilities for ovulation rate ranged from 0.32 to 0.39, and from 0.11 to 0.16 for prenatal survival, depending on the prior used. The mean of the marginal posterior distribution of response to four generations of selection ranged from 0.38 to 0.40 ova per generation, and from 1.1 to 1.3% of the mean survival rate for average survival per generation.
Quantitative Trait Loci Affecting Differences in Floral Morphology Between Two Species of Monkeyflower (Mimulus)
Authors: Bradshaw H D , Otto Kevin G , Frewen Barbara E , McKay John K , Schemske Douglas W 
Published: February 2021

AbstractConspicuous differences in floral morphology are partly responsible for reproductive isolation between two sympatric species of monkeyflower because of their effect on visitation of the flowers by different pollinators. Mimulus lewisii flowers are visited primarily by bumblebees, whereas M. cardinalis flowers are visited mostly by hummingbirds. The genetic control of 12 morphological differences between the flowers of M. lewisii and M. cardinalis was explored in a large linkage mapping population of F2 plants (n = 465) to provide an accurate estimate of the number and magnitude of effect of quantitative trait loci (QTLs) governing each character. Between one and six QTLs were identified for each trait. Most (9/12) traits appear to be controlled in part by at least one major QTL explaining ≥25% of the total phenotypic variance. This implies that either single genes of individually large effect or linked clusters of genes with a large cumulative effect can play a role in the evolution of reproductive isolation and speciation.
Yeast dom34 Mutants Are Defective in Multiple Developmental Pathways and Exhibit Decreased Levels of Polyribosomes
Authors: Davis Luther , Engebrecht JoAnne 
Published: February 2021

Abstract
The DOM34 gene of Saccharomyces cerevisiae is similar togenes found in diverse eukaryotes and archaebacteria. Analysis of dom34 strains shows that progression through the G1 phase of the cell cycle is delayed, mutant cells enter meiosis aberrantly, and their ability to form pseudohyphae is significantly diminished. RPS30A, which encodes ribosomal protein S30, was identified in a screen for high-copy suppressors of the dom34Δ growth defect. dom34Δ mutants display an altered polyribosome profile that is rescued by expression of RPS30A. Taken together, these data indicate that Dom34p functions in protein translation to promote G1 progression and differentiation. A Drosophila homolog of Dom34p, pelota, is required for the proper coordination of meiosis and spermatogenesis. Heterologous expression of pelota in dom34Δ mutants restores wild-type growth and differentiation, suggesting conservation of function between the eukaryotic members of the gene family.
Regulation of Yeast Glycogen Metabolism and Sporulation by Glc7p Protein Phosphatase
Authors: Ramaswamy Nadja T , Li Li , Khalil Miriam , Cannon John F 
Published: February 2021

Abstract
Glc7p is an essential serine/threonine type 1 protein phosphatase (PP1) from the yeast Saccharomyces cerevisiae, which has a role in many processes including cell cycle progression, sporulation, glycogen accumulation, translation initiation, and glucose repression. Two hallmarks of PP1 enzymes are very high amino acid sequence conservation and association of the catalytic subunit with a variety of noncatalytic, regulatory subunits. We tested the hypothesis that PP1 sequence conservation was the result of each PP1 residue playing a role in multiple intermolecular interactions. Analysis of 24 glc7 mutants, isolated primarily by their glycogen accumulation traits, revealed that every mutated Glc7p residue altered many noncatalytic subunit affinities and conferred unselected sporulation traits to various degrees. Furthermore, quantitative analysis showed that Glc7p affinity for the glycogen-binding noncatalytic subunit Gac1p was not the only parameter that determines the glycogen accumulation by a glc7 mutant. Sds22p is one Glc7p noncatalytic subunit that is essential for mitotic growth. Surprisingly, several mutant Glc7p proteins had undetectable affinity for Sds22p, yet grew apparently normally. The characterization of glc7 diploid sporulation revealed that Glc7p has at least two meiotic roles. Premeiotic DNA synthesis was undetectable in glc7 mutants with the poorest sporulation. In the glc7 diploids examined, expression of the meiotic inducer IME1 was proportional to the glc7 diploid sporulation frequency. Moreover, IME1 hyperexpression could not suppress glc7 sporulation traits. The Glc7p/Gip1p holoenzyme may participate in completion of meiotic divisions or spore packaging because meiotic dyads predominate when some glc7 diploids sporulate.
Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates
Authors: Konuma Takahiro , Ogawa Kotaro , Okada Yukinori 
Published: February 2021

Abstract
Approaches toward new therapeutics using disease genomics, such as genome-wide association study (GWAS), are anticipated. Here, we developed Trans-Phar [integration of transcriptome-wide association study (TWAS) and pharmacological database], achieving in silico screening of compounds from a large-scale pharmacological database (L1000 Connectivity Map), which have inverse expression profiles compared with tissue-specific genetically regulated gene expression. Firstly we confirmed the statistical robustness by the application of the null GWAS data and enrichment in the true-positive drug–disease relationships by the application of UK-Biobank GWAS summary statistics in broad disease categories, then we applied the GWAS summary statistics of large-scale European meta-analysis (17 traits; naverage = 201 849) and the hospitalized COVID-19 (n = 900 687), which has urgent need for drug development. We detected potential therapeutic compounds as well as anisomycin in schizophrenia (false discovery rate (FDR)-q = 0.056) and verapamil in hospitalized COVID-19 (FDR-q = 0.068) as top-associated compounds. This approach could be effective in disease genomics-driven drug development.
Human Intestinal Macrophages Are Involved in the Pathology of Both Ulcerative Colitis and Crohn Disease
Authors: Dharmasiri Suranga , Garrido-Martin Eva M , Harris Richard J , Bateman Adrian C , Collins Jane E , Cummings J R Fraser , Sanchez-Elsner Tilman 
Published: February 2021

Abstract

Background
Intestinal macrophages are key immune cells in the maintenance of intestinal immune homeostasis and have a role in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms by which macrophages exert a pathological influence in both ulcerative colitis (UC) and Crohn disease (CD) are not yet well understood.

Methods
We purified intestinal macrophages from gastrointestinal mucosal biopsies (patients with UC, patients with CD, and healthy donors) and analyzed their transcriptome by RNA sequencing and bioinformatics, confirming results with quantitative polymerase chain reaction and immunohistochemistry.

Results
Compared with those of healthy donors, intestinal macrophages in patients with UC and with CD showed cellular reprograming of 1287 and 840 dysregulated genes, respectively (false discovery rate ≤ 0.1). The UC and CD intestinal macrophages showed an activated M1 inflammatory phenotype and the downregulation of genes engaged in drug/xenobiotic metabolism. Only macrophages from CD showed, concomitant to an M1 phenotype, a significant enrichment in the expression of M2 and fibrotic and granuloma-related genes. For the first time, we showed (and validated by quantitative polymerase chain reaction and immunohistochemistry) that intestinal macrophages in patients with IBD present both M1 and M2 features, as recently described for tumor-associated macrophages, that affect key pathways for IBD pathology, represented by key markers such as MMP12 (fibrosis), CXCL9 (T-cell attraction), and CD40 (T-cell activation).

Conclusions
Our data support the therapeutic targeting of macrophages to maintain remission in IBD but also indicate that a shift toward an M2 program—as proposed by some reports—may not limit the recruitment and activation of T cells because M2 features do not preclude M1 activation in patients with UC or CD and could exacerbate M2-related CD-specific features such as fibrosis and the formation of granulomas.
The 3-step approach for the treatment of multisegmental thoraco-abdominal aortic pathologies
Authors: Berger Tim , Kreibich Maximilian , Rylski Bartosz , Kondov Stoyan , Fagu Albi , Beyersdorf Friedhelm , Siepe Matthias , Czerny Martin 
Published: February 2021

Abstract

OBJECTIVES
The goal of this study was to describe our 3-step approach to treat multisegmental thoraco-abdominal aortic disease due to aortic dissection and to present our initial clinical results.

METHODS
Nine patients with multisegmental thoraco-abdominal aortic pathology due to aortic dissection underwent our 3-step approach, which consisted of total aortic arch replacement via the frozen elephant trunk technique, thoracic endovascular aortic repair for distal extension down to the level of the thoraco-abdominal transition and, finally, open thoraco-abdominal aortic replacement for the remaining downstream aortic segments. We assessed their baseline and aortic characteristics, previous aortic procedures, intraoperative details, clinical outcomes and follow-up data.

RESULTS
The median age was 58 (42–66) years; 4 patients (44%) presented connective tissue disease. Eight patients (89%) had undergone previous aortic surgery for aortic dissection. In-hospital mortality was 0% (n = 0). None suffered symptomatic spinal cord injury or disabling stroke. During the follow-up period, 1 patient died of acute biliary septic shock 6 months after thoraco-abdominal aortic replacement.

CONCLUSIONS
The 3-step approach to treat multisegmental thoraco-abdominal aortic pathology due to aortic dissection, which involves applying both open and endovascular techniques, is associated with an excellent clinical outcome and low perioperative risk. Distal shifting of the disease process through the thoracic endovascular aortic repair extension—and thereby necessitating limited open thoraco-abdominal aortic repair—seems to be the major factor enabling these favourable results.

IRB approval
IRB approval was obtained (No. 425/15) from the institutional review board of the University of Freiburg.
The Complement Pathway Is Activated in People With Human Immunodeficiency Virus and Is Associated With Non-AIDS Comorbidities
Authors: Vujkovic-Cvijin Ivan , Sortino Ornella , Verheij Eveline , Wit Ferdinand W , Kootstra Neeltje A , Sellers Brian , Schim van der Loeff Maarten , Belkaid Yasmine , Reiss Peter , Sereti Irini 
Published: February 2021

Abstract
Unbiased plasma proteomics in a matched case-control study of treated people with human immunodeficiency virus (PWH) revealed the complement cascade as being among the top pathways enriched in PWH. Specific complement components, namely C5, associated significantly with non-AIDS comorbidity prevalence, and did so more strongly than previously established predictive biomarkers.