bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functions of the High Mobility Group Protein, Abf2p, in Mitochondrial DNA Segregation, Recombination and Copy Number in Saccharomyces cerevisiae
Authors: Zelenaya-Troitskaya Olga , Newman Scott M , Okamoto Koji , Perlman Philip S , Butow Ronald A 
Published: February 2021

Abstract
Previous studies have established that the mitochondrial high mobility group (HMG) protein, Abf2p, of Saccharomyces cerevisiae influences the stability of wild-type (ρ+) mitochondrial DNA (mtDNA) and plays an important role in mtDNA organization. Here we report new functions for Abf2p in mtDNA transactions. We find that in homozygous Δabf2 crosses, the pattern of sorting of mtDNA and mitochondrial matrix protein is altered, and mtDNA recombination is suppressed relative to homozygous ABF2 crosses. Although Abf 2p is known to be required for the maintenance of mtDNA in ρ+ cells growing on rich dextrose medium, we find that it is not required for the maintenance of mtDNA in ρ− cells grown on the same medium. The content of both ρ+ and ρ− mtDNAs is increased in cells by 50–150% by moderate (two- to threefold) increases in the ABF2 copy number, suggesting that Abf2p plays a role in mtDNA copy control. Overproduction of Abf 2p by ≥10-fold from an ABF2 gene placed under control of the GAL1 promoter, however, leads to a rapid loss of ρ+ mtDNA and a quantitative conversion of ρ+ cells to petites within two to four generations after a shift of the culture from glucose to galactose medium. Overexpression of Abf2p in ρ− cells also leads to a loss of mtDNA, but at a slower rate than was observed for ρ+ cells. The mtDNA instability phenotype is related to the DNA-binding properties of Abf 2p because a mutant Abf 2p that contains mutations in residues of both HMG box domains known to affect DNA binding in vitro, and that binds poorly to mtDNA in vivo, complements Δabf2 cells only weakly and greatly lessens the effect of overproduction on mtDNA instability. In vivo binding was assessed by colocalization to mtDNA of fusions between mutant or wild-type Abf 2p and green fluorescent protein. These findings are discussed in the context of a model relating mtDNA copy number control and stability to mtDNA recombination.
The fluffy Gene of Neurospora crassa Encodes a Gal4p-Type C6 Zinc Cluster Protein Required for Conidial Development
Authors: Bailey Lori A , Ebbole Daniel J 
Published: February 2021

Abstract
Neurospora crassa fluffy (fl) mutants are unable to produce macroconidia. We cloned the fl gene to determine its role in regulating conidiation. A cosmid clone containing fl was identified by complementation. The sequence of fl revealed that it encodes a Gal4p-type C6 zinc cluster protein with greatest similarity to the N. crassa NIT4 protein that regulates genes required for nitrate utilization. Analysis of several fl mutant alleles demonstrated that null mutants are blocked in the budding phase of development required to produce conidiophores. fl mRNA is transiently induced just prior to the developmental commitment to budding growth. This timing of fl expression is consistent with a role for FL protein in activation of the previously characterized conidiation-specific (con) genes, con-6 and con-10. These data suggest that FL acts as a developmentally regulated transcription factor required for conidiophore morphogenesis.
High-Efficiency Transformation of Chlamydomonas reinhardtii by Electroporation
Authors: Shimogawara Kosuke , Fujiwara Shoko , Grossman Arthur , Usuda Hideaki 
Published: February 2021

Abstract
We have established a high-efficiency method for transforming the unicellular, green alga Chlamydomonas reinhardtii by electroporation. Electroporation of strains CC3395 and CC425, cell wall-less mutants devoid of argininosuccinate lyase (encoded by ARG7), in the presence of the plasmid pJD67 (which contains ARG7) was used to optimize conditions for the introduction of exogenous DNA. The conditions that were varied included osmolarity, temperature, concentration of exogenous DNA, voltage and capacitance. Following optimization, the maximum transformation frequency obtained was 2 × 105 transformants per μg of DNA; this frequency is two orders of magnitude higher than obtained with the current standard method using glass beads to introduce exogenous DNA. The electroporation procedure described in this article is of general utility, and makes it feasible to isolate genes by direct complementation of Chlamydomonas reinhardtii mutants.
Mapping of Drosophila Mutations Using Site-Specific Male Recombination
Authors: Chen Bin , Chu Tehyen , Harms Emily , Gergen J Peter , Strickland Sidney 
Published: February 2021

Abstract
Although recombination does not usually occur in the male Drosophila germline, site-specific recombination can be induced at the ends of P elements. This finding suggested that male recombination could be used to map Drosophila mutations. In this article, we describe the general method and its application to the mapping of two EMS-induced female-sterile mutations, grauzone and cortex. Within two months, the grauzone gene was mapped relative to seven different P-element insertion sites, and cortex was mapped relative to 23 different P-elements. The results allowed us to map grauzone to a region of about 50 kb, and cortex distal to the chromosomal region 33E. These experiments demonstrate that P-element-induced site-specific male recombination is an efficient and general method to map Drosophila autosomal mutations.
Molecular and Behavioral Analysis of Four period Mutants in Drosophila melanogaster Encompassing Extreme Short, Novel Long, and Unorthodox Arrhythmic Types
Authors: Hamblen Melanie J , White Neal E , Emery Philip T J , Kaiser Kim , Hall Jeffrey C 
Published: February 2021

AbstractOf the mutationally defined rhythm genes in Drosophila melanogaster, period (per) has been studied the most. We have molecularly characterized three older per mutants—perT, perClk, and per04—along with a novel long-period one (perSLIH). Each mutant is the result of a single nucleotide change. perT, perClk, and perSLIH are accounted for by amino acid substitutions; per04 is altered at a splice site acceptor and causes aberrant splicing. perSLIH exhibits a long period of 27 hr in constant darkness and entrains to light/dark (L/D) cycles with a later-than-normal evening peak of locomotion. perSLIH males are more rhythmic than females. perSLIH's clock runs faster at higher temperatures and slower at lower ones, exhibiting a temperature-compensation defect opposite to that of perLong. The per-encoded protein (PER) in the perT mutant cycles in L/D with an earlier-than-normal peak; this peak in perSLIH is later than normal, and there was a slight difference in the PER timecourse of males vs. females. PER in per04 was undetectable. Two of these mutations, perSLIH and perClk, lie within regions of PER that have not been studied previously and may define important functional domains of this clock protein.
Spectra of Spontaneous Frameshift Mutations at the hisD3052 Allele of Salmonella typhimurium in Four DNA Repair Backgrounds
Authors: DeMarini David M , Shelton Melissa L , Abu-Shakra Amal , Szakmary Akos , Levine Jessie G 
Published: February 2021

Abstract
To characterize the hisD3052 −1 frameshift allele of Salmonella typhimurium, we analyzed ~6000 spontaneous revertants (rev) for a 2-base deletion hotspot within the sequence (CG)4, and we sequenced ~500 nonhotspot rev. The reversion target is a minimum of 76 bases (nucleotides 843–918) that code for amino acids within a nonconserved region of the histidinol dehydrogenase protein. Only 0.4–3.9% were true rev. Of the following classes, 182 unique second-site mutations were identified: hotspot, complex frameshifts requiring ΔuvrB + pKM101 (TA98-specific) or not (concerted), 1-base insertions, duplications, and nonhotspot deletions. The percentages of hotspot mutations were 13.8% in TA1978 (wild type), 24.5% in UTH8413 (pKM101), 31.6% in TA1538 (ΔuvrB), and 41.0% in TA98 (ΔuvrB, pKM101). The ΔuvrB allele decreased by three times the mutant frequency (MF, rev/108 survivors) of duplications and increased by about two times the MF of deletions. Separately, the ΔuvrB allele or pKM101 plasmid increased by two to three times the MF of hotspot mutations; combined, they increased this MF by five times. The percentage of 1-base insertions was not influenced by either ΔuvrB or pKM101. Hotspot deletions and TA98-specific complex frameshifts are inducible by some mutagens; concerted complex frameshifts and 1-base insertions are not; and there is little evidence for mutagen-induced duplications and nonhotspot deletions. Except for the base substitutions in TA98-specific complex frameshifts, all spontaneous mutations of the hisD3052 allele are likely templated. The mechanisms may involve (1) the potential of direct and inverted repeats to undergo slippage and misalignment and to form quasi-palindromes and (2) the interaction of these sequences with DNA replication and repair proteins.
Genetic Polymorphism and Natural Selection in the Malaria Parasite Plasmodium falciparum
Authors: Escalante Ananias A , Lal Altaf A , Ayala Francisco J 
Published: February 2021

AbstractWe have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the G↔C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.
Genes Expressed in the Ring Gland, the Major Endocrine Organ of Drosophila melanogaster
Authors: Harvie Peter D , Filippova Maria , Bryant Peter J 
Published: February 2021

Abstract
We have used an enhancer-trap approach to begin characterizing the function of the Drosophila endocrine system during larval development. Five hundred and ten different lethal PZ element insertions were screened to identify those in which a reporter gene within the P element showed strong expression in part or all of the ring gland, the major site of production and release of developmental hormones, and which had a mutant phenotype consistent with an endocrine defect. Nine strong candidate genes were identified in this screen, and eight of these are expressed in the lateral cells of the ring gland that produce ecdysteroid molting hormone (EC). We have confirmed that the genes detected by these enhancer traps are expressed in patterns similar to those detected by the reporter gene. Two of the genes encode proteins, protein kinase A and calmodulin, that have previously been implicated in the signaling pathway leading to EC synthesis and release in other insects. A third gene product, the translational elongation factor EF-1α F1, could play a role in the translational regulation of EC production. The screen also identified the genes couch potato and tramtrack, previously known from their roles in peripheral nervous system development, as being expressed in the ring gland. One enhancer trap revealed expression of the gene encoding the C subunit of vacuolar ATPase (V-ATPase) in the medial cells of the ring gland, which produce the juvenile hormone that controls progression through developmental stages. This could reveal a function of V-ATPase in the response of this part of the ring gland to adenotropic neuropeptides. However, the gene identified by this enhancer trap is ubiquitously expressed, suggesting that the enhancer trap is detecting only a subset of its control elements. The results show that the enhancer trap approach can be a productive way of exploring tissue-specific genetic functions in Drosophila.
Mapping the Genome of a Model Protochordate. I. A Low Resolution Genetic Map Encompassing the Fusion/Histocompatibility (Fu/HC) Locus of Botryllus schlosseri
Authors: De Tomaso Anthony W , Saito Yasunori , Ishizuka Katharine J , Palmeri Karla J , Weissman Irving L 
Published: February 2021

Abstract
The colonial protochordate, Botryllus schlosseri, undergoes a genetically defined, natural transplantation reaction when the edges of two growing colonies interact. Peripheral blood vessels of each colony touch and will either fuse together to form a common vasculature between the colonies, or reject each other in an active blood-based inflammatory process in which the interacting vessels are cut off and the two colonies no longer interact. Previous studies have demonstrated that allorecognition in Botryllus is principally controlled by a single Mendelian locus named the fusion/histocompatibility (Fu/HC) locus, with multiple codominantly expressed alleles. However, identification and cloning of this locus has been difficult. We are taking a genomic approach in isolating this locus by creating a detailed genetic linkage map of the 725 Mbp Botryllus genome using DNA polymorphisms (primarily identified as AFLPs) as molecular genetic markers. DNA polymorphisms are identified in inbred laboratory strains of Fu/HC defined Botryllus, and their segregation and linkage is analyzed in a series of defined crosses. Using bulk segregant analysis, we have focused our mapping efforts on the Fu/HC region of the genome, and have generated an initial map which delineates the Fu/HC locus to a 5.5 cM region.
Maximum Likelihood Estimation of Population Growth Rates Based on the Coalescent
Authors: Kuhner Mary K , Yamato Jon , Felsenstein Joseph 
Published: February 2021

Abstract
We describe a method for co-estimating 4Neμ (four times the product of effective population size and neutral mutation rate) and population growth rate from sequence samples using Metropolis-Hastings sampling. Population growth (or decline) is assumed to be exponential. The estimates of growth rate are biased upwards, especially when 4Neμ is low; there is also a slight upwards bias in the estimate of 4Neμ itself due to correlation between the parameters. This bias cannot be attributed solely to Metropolis-Hastings sampling but appears to be an inherent property of the estimator and is expected to appear in any approach which estimates growth rate from genealogy structure. Sampling additional unlinked loci is much more effective in reducing the bias than increasing the number or length of sequences from the same locus.
Testing for Epistasis Between Deleterious Mutations
Authors: West S A , Peters A D , Barton N H 
Published: February 2021

Abstract
Determining the way in which deleterious mutations interact in their effects on fitness is crucial to numerous areas in population genetics and evolutionary biology. For example, if each additional mutation leads to a greater decrease in log fitness than the last (synergistic epistasis), then the evolution of sex and recombination may be favored to facilitate the elimination of deleterious mutations. However, there is a severe shortage of relevant data. Three relatively simple experimental methods to test for epistasis between deleterious mutations in haploid species have recently been proposed. These methods involve crossing individuals and examining the mean and/or skew in log fitness of the offspring and parents. The main aim of this paper is to formalize these methods, and determine the most effective way in which tests for epistasis could be carried out. We show that only one of these methods is likely to give useful results: crossing individuals that have very different numbers of deleterious mutations, and comparing the mean log fitness of the parents with that of their offspring. We also reconsider experimental data collected on Chlamydomonas moewussi using two of the three methods. Finally, we suggest how the test could be applied to diploid species.
Proposed Genetic Nomenclature Rules for Tetrahymena thermophila, Paramecium primaurelia and Paramecium tetraurelia
Authors:   The Seventh International Meeting on Ciliate Molecular Biology Genetics Nomenclature Committee, Allen Sally Lyman , Altschuler Marsha I , Bruns Peter J , Cohen Jean , Doerder F Paul , Gaertig Jacek , Gorovsky Martin , Orias Eduardo , Turkewitz Aaron 
Published: February 2021

Abstract
The genetics of the ciliated protozoa Tetrahymena thermophila and certain species of Paramecium (P. primaurelia and P. tetraurelia) have reached a level of maturity such that rules for genetic nomenclature for micronuclear and macronuclear genetics need to be clarified for workers in the field as well as for other geneticists. After a short introduction, the rules follow.
Single-Strand DNA-Specific Exonucleases in Escherichia coli: Roles in Repair and Mutation Avoidance
Authors: Viswanathan Mohan , Lovett Susan T 
Published: February 2021

Abstract
Mutations in the genes encoding single-strand DNA-specific exonucleases (ssExos) of Escherichia coli were examined for effects on mutation avoidance, UV repair, and conjugational recombination. Our results indicate complex and partially redundant roles for ssExos in these processes. Although biochemical experiments have implicated RecJ exonuclease, Exonuclease I (ExoI), and Exonuclease VII (ExoVII) in the methyl-directed mismatch repair pathway, the RecJ− ExoI− ExoVII− mutant did not exhibit a mutator phenotype in several assays for base substitution mutations. If these exonucleases do participate in mismatch excision, other exonucleases in E. coli can compensate for their loss. Frameshift mutations, however, were stimulated in the RecJ− ExoI− ExoVII− mutant. For acridine-induced frameshifts, this mutator effect was due to a synergistic effect of ExoI− and ExoVII− mutations, implicating both ExoI and ExoVII in avoidance of frameshift mutations. Although no single exonuclease mutant was especially sensitive to UV irradiation, the RecJ− ExoVII− double mutant was extremely sensitive. The addition of an ExoI− mutation augmented this sensitivity, suggesting that all three exonucleases play partially redundant roles in DNA repair. The ability to inherit genetic markers by conjugation was reduced modestly in the ExoI− RecJ− mutant, implying that the function of either ExoI or RecJ exonucleases enhances RecBCD-dependent homologous recombination.
Prevalence of Memory-Related Diagnoses Among U.S. Older Adults With Early Symptoms of Cognitive Impairment
Authors: Qian Yuting , Chen Xi , Tang Diwen , Kelley Amy S , Li Jing 
Published: February 2021

Abstract

Background
Early diagnosis of cognitive impairment may confer important advantages. Yet the prevalence of memory-related diagnoses among older adults with early symptoms of cognitive impairment is unknown.

Methods
A retrospective, longitudinal cohort design using 2000–2014 Health and Retirement Survey–Medicare linked data. We leveraged within-individual variation to examine the relationship between incident cognitive impairment and receipt of diagnosis among 1225 individuals aged 66 or older. Receipt of a memory-related diagnosis was determined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Incident cognitive impairment was defined as the first assessment wherein the participant’s modified Telephone Interview for Cognitive Status score was less than 12.

Results
The unadjusted prevalence of memory-related diagnosis at cognitive impairment was 12.0%. Incident cognitive impairment was associated with a 7.3% (95% confidence interval [CI], 5.6% to 9.0%; p &lt; .001) higher adjusted probability of any memory-related diagnosis overall, yielding 9.8% adjusted prevalence of diagnosis. The increase in likelihood of diagnosis associated with cognitive decline was significantly higher among non-Hispanic Whites than non-Hispanic Blacks (8.2% vs −0.7%), and among those with at least a college degree than those with a high school diploma or less (17.4% vs 6.8% vs 1.6%). Those who were younger, had below-median wealth, or without a partner had lower probability of diagnosis than their counterparts.

Conclusions
We found overall low prevalence of early diagnosis, or high rate of underdiagnosis, among older adults showing symptoms of cognitive impairment, especially among non-Whites and socioeconomically disadvantaged subgroups. Our findings call for targeted interventions to improve the rate of early diagnosis, especially among vulnerable populations.
The Effect of Frailty on Walking Recovery After Hip Fracture: A Secondary Analysis of the Community Ambulation Project
Authors: Mangione Kathleen K , Craik Rebecca L , Kenny Anne , Memaj Arteid , Miller Melissa F , Chen Menki , Weingart Molly , Orwig Denise , Magaziner Jay 
Published: February 2021

Abstract

Background
The impact of frailty on walking recovery after hip fracture has not been reported. We describe the prevalence of frailty approximately 3 months after hip fracture, and identify the impact of baseline frailty on ambulation recovery.

Methods
Data from the Community Ambulation Project, that examined the effects of 2 multicomponent home exercise programs on 6-minute walk test in participants post hip fracture, were used to reconstruct the 5-item frailty phenotype. We detailed the prevalence of frailty by subgroup and assessed the comparability between frailty groups for the categorical variable of achieving 300 m in 6-minute walk test (community ambulation threshold), and the continuous variable of total distance in 6-minute walk test before and after 16 weeks of intervention.

Results
Of the 210 participants, 9% were nonfrail, 59% were prefrail, and 32% were frail. The odds of a nonfrail participant achieving the 300-m threshold were 14.4 (95% CI: 2.4–87.6) times the odds of a frail participant, while a prefrail participant’s odds were 6.1 (95% CI: 1.3–28.4) times after controlling for treatment group and baseline walking distance. The nonfrail participants had an increase of 92.1 m from baseline to 16 weeks, the prefrail had a 50.8 m increase, and the frail group had the smallest increase of 36.6 m (p &lt; .001 for all).

Conclusions
Prefrailty and frailty were highly prevalent in this sample of community-dwelling survivors of a recent hip fracture. Gains in walking distance and attaining a level of community ambulation were affected significantly by the level of baseline frailty.