bluuebunny/crossref_metadata_2025_split huggingface dataset:
A picture is worth a thousand words: exploring the roles of caregivers and the home environment of ventricular assist device patients
Authors: Abshire Martha A. , Bidwell Julie T. , Pavlovic Noelle , DeGroot Lyndsay , Mammos Dimitra , Larsen Luke , Bautista Svetlana , Davidson Patricia M. 
Published: April 2021

Abstract

Aims
Caregivers of persons living with ventricular assist devices (VADs) are integrally involved in both medical and non-medical care. We sought to understand tasks caregivers perform after surgical recovery, ways the home is adapted for those tasks, and presence of home safety hazards.

Methods and results
We conducted semi-structured interviews with persons living with a VAD and their caregivers. Pictures were taken of areas in the home where: (i) caregiving activities occurred, (ii) VAD or medical supplies were kept, and (iii) home adaptations were made for VAD care. Pictures were described in written detail and analysed. A qualitative descriptive approach was used for analysis. The sample consisted of 10 dyads, with mostly spousal relationships (60%) between male patients (60%) and female caregivers (80%). Three themes were identified: (i) Evolution of Caregiving and Support: Patients gain independence, but caregivers are still needed, (ii) Adapting the Home Environment: Changes are focused on functional needs, and (iii) Hidden Dangers: Illumination of safety concerns by photographs. Assistance with bathing, driveline care, and medication management were common caregiving tasks. Most home adaptations occurred in the bathroom and bedroom including sleeping recliners, shower chairs, removable shower heads, and hanging hooks to hold VAD equipment. Safety hazards included minimal space for safe ambulation, infection risk, and home-made adaptations to the environment.

Conclusions
These findings describe key home caregiving tasks, home adaptations, and safety concerns that require further education and support. Utilizing pictures may be a feasible method for assessing VAD teaching, caregiving needs, and identifying potential risks.
Functional Characterization of the Adenylyl Cyclase Gene sgs-1 by Analysis of a Mutational Spectrum in Caenorhabditis elegans
Authors: Moorman Celine , Plasterk Ronald H A 
Published: April 2021

Abstract
The sgs-1 (suppressor of activated Gαs) gene encodes one of the four adenylyl cyclases in the nematode C. elegans and is most similar to mammalian adenylyl cyclase type IX. We isolated a complete loss-of-function mutation in sgs-1 and found it to result in animals with retarded development that arrest in variable larval stages. sgs-1 mutant animals exhibit lethargic movement and pharyngeal pumping and (while not reaching adulthood) have a mean life span that is &gt;50% extended compared to wild type. An extensive set of reduction-of-function mutations in sgs-1 was isolated in a screen for suppressors of a neuronal degeneration phenotype induced by the expression of a constitutively active version of the heterotrimeric Gαs subunit of C. elegans. Although most of these mutations change conserved residues within the catalytic domains of sgs-1, mutations in the less-conserved transmembrane domains are also found. The sgs-1 reduction-of-function mutants are viable and have reduced locomotion rates, but do not show defects in pharyngeal pumping or life span.
Alterations of the Portal Protein, gpB, of Bacteriophage λ Suppress Mutations in cosQ, the Site Required for Termination of DNA Packaging
Authors: Wieczorek Douglas J , Didion Lisa , Feiss Michael 
Published: April 2021

Abstract
The cosQ site of bacteriophage λ is required for DNA packaging termination. Previous studies have shown that cosQ mutations can be suppressed in three ways: by a local suppressor within cosQ, an increase in the length of the λ chromosome, and missense mutations affecting the prohead’s portal protein, gpB. In the present work, revertants of a set of lethal cosQ mutants were screened for suppressors. Seven new cosQ suppressors affected gene B, which encodes the portal protein of the prohead. All seven were allelenonspecific suppressors of cosQ mutations. Experiments with several phages having two cosQ suppressors showed that the suppression effects were additive. Furthermore, these double suppressors had minimal effects on the growth of cosQ+ phages. These trans-acting suppressors affecting the portal protein are proposed to allow the mutant cosQ site to be more efficiently recognized, due to the slowing of the rate of translocation.
Naturally Occurring Indel Variation in the Brassica nigra COL1 Gene Is Associated With Variation in Flowering Time
Authors: Österberg Marita Kruskopf , Shavorskaya Oksana , Lascoux Martin , Lagercrantz Ulf 
Published: April 2021

Abstract
Previous QTL mapping identified a Brassica nigra homolog to Arabidopsis thaliana CO as a candidate gene affecting flowering time in B. nigra. Transformation of an A. thaliana co mutant with two different alleles of the B. nigra CO (Bni COa) homolog, one from an early-flowering B. nigra plant and one from a late one, did not show any differential effect of the two alleles on flowering time. The DNA sequence of the coding region of the two alleles was also identical, showing that nucleotide variation influencing flowering time must reside outside the coding region of Bni COa. In contrast, the nucleotide sequence of the B. nigra COL1 (Bni COL1) gene located 3.5 kb upstream of Bni COa was highly diverged between the alleles from early and late plants. One indel polymorphism in the Bni COL1 coding region, present in several natural populations of B. nigra, displayed a significant association with flowering time within a majority of these populations. These data indicate that a quantitative trait nucleotide (QTN) affecting flowering time is located within or close to the Bni COL1 gene. The intergenic sequence between Bni COL1 and Bni COa displayed a prominent peak of divergence 1 kb downstream of the Bni COL1 coding region. This region could contain regulatory elements for the downstream Bni COa gene. Our data suggest that a naturally occurring QTN for flowering time affects the function or expression of either Bni COL1 or Bni COa.
Comparative Analysis of Quantitative Trait Loci Controlling Glucosinolates, Myrosinase and Insect Resistance in Arabidopsis thaliana
Authors: Kliebenstein Daniel , Pedersen Deana , Barker Bridget , Mitchell-Olds Thomas 
Published: April 2021

Abstract
Evolutionary interactions among insect herbivores and plant chemical defenses have generated systems where plant compounds have opposing fitness consequences for host plants, depending on attack by various insect herbivores. This interplay complicates understanding of fitness costs and benefits of plant chemical defenses. We are studying the role of the glucosinolate-myrosinase chemical defense system in protecting Arabidopsis thaliana from specialist and generalist insect herbivory. We used two Arabidopsis recombinant inbred populations in which we had previously mapped QTL controlling variation in the glucosinolate-myrosinase system. In this study we mapped QTL controlling resistance to specialist (Plutella xylostella) and generalist (Trichoplusia ni) herbivores. We identified a number of QTL that are specific to one herbivore or the other, as well as a single QTL that controls resistance to both insects. Comparison of QTL for herbivory, glucosinolates, and myrosinase showed that T. ni herbivory is strongly deterred by higher glucosinolate levels, faster breakdown rates, and specific chemical structures. In contrast, P. xylostella herbivory is uncorrelated with variation in the glucosinolate-myrosinase system. This agrees with evolutionary theory stating that specialist insects may overcome host plant chemical defenses, whereas generalists will be sensitive to these same defenses.
Two-Generation Analysis of Pollen Flow Across a Landscape. IV. Estimating the Dispersal Parameter
Authors: Austerlitz Frédéric , Smouse Peter E 
Published: April 2021

Abstract
The distance of pollen movement is an important determinant of the neighborhood area of plant populations. In earlier studies, we designed a method for estimating the distance of pollen dispersal, on the basis of the analysis of the differentiation among the pollen clouds of a sample of females, spaced across the landscape. The method was based solely on an estimate of the global level of differentiation among the pollen clouds of the total array of sampled females. Here, we develop novel estimators, on the basis of the divergence of pollen clouds for all pairs of females, assuming that an independent estimate of adult population density is available. A simulation study shows that the estimators are all slightly biased, but that most have enough precision to be useful, at least with adequate sample sizes. We show that one of the novel pairwise methods provides estimates that are slightly better than the best global estimate, especially when the markers used have low exclusion probability. The new method can also be generalized to the case where there is no prior information on the density of reproductive adults. In that case, we can jointly estimate the density itself and the pollen dispersal distance, given sufficient sample sizes. The bias of this last estimator is larger and the precision is lower than for those estimates based on independent estimates of density, but the estimate is of some interest, because a meaningful independent estimate of the density of reproducing individuals is difficult to obtain in most cases.
Enhancement of Saccharomyces cerevisiae End-Joining Efficiency by Cell Growth Stage but Not by Impairment of Recombination
Authors: Karathanasis Elissa , Wilson Thomas E 
Published: April 2021

Abstract
Cells can repair DNA double-strand breaks by both homologous and nonhomologous mechanisms. To explore the basis of pathway utilization, we developed both plasmid and chromosomal yeast repair assays in which breaks are created with restriction endonucleases so that nonhomologous end-joining (NHEJ) competes with the single-strand annealing (SSA) recombination pathway, which we show acts with high efficiency via terminal direct repeats of only 28 bp and with reduced but measurable efficiency at 10 bp. The chromosomal assay utilizes a novel approach termed suicide deletion in which the endonuclease cleaves its own gene from the chromosome, thereby ending the futile cleavage cycle that otherwise prevents detection of simple-religation events. Eliminating SSA as a possibility in either assay, either by removal of the direct repeat or by mutation of RAD52, increased the relative but not the absolute efficiency of NHEJ. In contrast, the apparent efficiency of NHEJ was specifically increased in the G1 stage of the haploid cell cycle, as well as by the glucose depletion-signaled transition to stationary phase. The combined results argue against a model in which pathway utilization is determined by a passive competition. Instead, they demonstrate an active regulation designed to optimize the likelihood of genome restoration based on cell state.
Formation of Large Palindromic DNA by Homologous Recombination of Short Inverted Repeat Sequences in Saccharomyces cerevisiae
Authors: Butler David K , Gillespie David , Steele Brandi 
Published: April 2021

Abstract
Large DNA palindromes form sporadically in many eukaryotic and prokaryotic genomes and are often associated with amplified genes. The presence of a short inverted repeat sequence near a DNA double-strand break has been implicated in the formation of large palindromes in a variety of organisms. Previously we have established that in Saccharomyces cerevisae a linear DNA palindrome is efficiently formed from a single-copy circular plasmid when a DNA double-strand break is introduced next to a short inverted repeat sequence. In this study we address whether the linear palindromes form by an intermolecular reaction (that is, a reaction between two identical fragments in a head-to-head arrangement) or by an unusual intramolecular reaction, as it apparently does in other examples of palindrome formation. Our evidence supports a model in which palindromes are primarily formed by an intermolecular reaction involving homologous recombination of short inverted repeat sequences. We have also extended our investigation into the requirement for DNA double-strand break repair genes in palindrome formation. We have found that a deletion of the RAD52 gene significantly reduces palindrome formation by intermolecular recombination and that deletions of two other genes in the RAD52-epistasis group (RAD51 and MRE11) have little or no effect on palindrome formation. In addition, palindrome formation is dramatically reduced by a deletion of the nucleotide excision repair gene RAD1.
General Statistics of Stochastic Process of Gene Expression in Eukaryotic Cells
Authors: Kuznetsov V A , Knott G D , Bonner R F 
Published: April 2021

Abstract
Thousands of genes are expressed at such very low levels (≤1 copy per cell) that global gene expression analysis of rarer transcripts remains problematic. Ambiguity in identification of rarer transcripts creates considerable uncertainty in fundamental questions such as the total number of genes expressed in an organism and the biological significance of rarer transcripts. Knowing the distribution of the true number of genes expressed at each level and the corresponding gene expression level probability function (GELPF) could help resolve these uncertainties. We found that all observed large-scale gene expression data sets in yeast, mouse, and human cells follow a Pareto-like distribution model skewed by many low-abundance transcripts. A novel stochastic model of the gene expression process predicts the universality of the GELPF both across different cell types within a multicellular organism and across different organisms. This model allows us to predict the frequency distribution of all gene expression levels within a single cell and to estimate the number of expressed genes in a single cell and in a population of cells. A random “basal” transcription mechanism for protein-coding genes in all or almost all eukaryotic cell types is predicted. This fundamental mechanism might enhance the expression of rarely expressed genes and, thus, provide a basic level of phenotypic diversity, adaptability, and random monoallelic expression in cell populations.
Maximal Power Tests for Detecting Defects in Meiotic Recombination
Authors: Milac Thomas I , Adler Frederick R , Smith Gerald R 
Published: April 2021

Abstract
We have determined the marker separations (genetic distances) that maximize the probability, or power, of detecting meiotic recombination deficiency when only a limited number of meiotic progeny can be assayed. We find that the optimal marker separation is as large as 30–100 cM in many cases. Provided the appropriate marker separation is used, small reductions in recombination potential (as little as 50%) can be detected by assaying a single interval in as few as 100 progeny. If recombination is uniformly altered across the genomic region of interest, the same sensitivity can be obtained by assaying multiple independent intervals in correspondingly fewer progeny. A reduction or abolition of crossover interference, with or without a reduction of recombination proficiency, can be detected with similar sensitivity. We present a set of graphs that display the optimal marker separation and the number of meiotic progeny that must be assayed to detect a given recombination deficiency in the presence of various levels of crossover interference. These results will aid the optimal design of experiments to detect meiotic recombination deficiency in any organism.
Saturation of DNA Mismatch Repair and Error Catastrophe by a Base Analogue in Escherichia coli
Authors: Negishi Kazuo , Loakes David , Schaaper Roel M 
Published: April 2021

Abstract
Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G · C → A · T and A · T → G · C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains.
Distribution of Nonrandom Associations Between Pairs of Protein Loci Along the Third Chromosome ofDrosophila melanogaster
Authors: Zapata Carlos , Núñez Concepción , Velasco Teresa 
Published: April 2021

AbstractThe within-chromosome distribution of gametic disequilibrium (GD) between protein loci, and the underlying evolutionary factors of this distribution, are still largely unknown. Here, we report a detailed study of GD between a large number of protein loci (15) spanning 87% of the total length of the third chromosome of Drosophila melanogaster in a large sample of haplotypes (600) drawn from a single natural population. We used a sign-based GD estimation method recently developed for multiallelic systems, which considerably increases both the statistical power and the accuracy of estimation of the intensity of GD. We found that strong GD between pairs of protein loci was widespread throughout the chromosome. In total, 22% of both the pairs of alleles and pairs of loci were in significant GD, with mean intensities (as measured by D′ coefficients) of 0.43 and 0.31, respectively. In addition, strong GD often occurs between loci that are far apart. By way of illustration, 32% of the allele pairs in significant GD occurred within pairs of loci separated by effective frequencies of recombination (EFRs) of 15–20 cM, the mean D′ value being 0.49. These observations are in sharp contrast with previous studies showing that GD between protein loci is rarely found in natural populations of outcrossing species, even between very closely linked loci. Interestingly, we found that most instances of significant interallelic GD (68%) involved functionally related protein loci. Specifically, GD was markedly more frequent between protein loci related by the functions of hormonal control, molybdenum control, antioxidant defense system, and reproduction than between loci without known functional relationship, which is indicative of epistatic selection. Furthermore, long-distance GD between functionally related loci (mean EFR 9 cM) suggests that epistatic interactions must be very strong along the chromosome. This evidence is hardly compatible with the neutral theory and has far-reaching implications for understanding the multilocus architecture of the functional genome. Our findings also suggest that GD may be a useful tool for discovering networks of functionally interacting proteins.
Genetic Differentiation in the African Malaria Vector,Anopheles gambiaes.s., and the Problem of Taxonomic Status
Authors: Gentile Gabriele , della Torre Alessandra , Maegga Bertha , Powell Jeffrey R , Caccone Adalgisa 
Published: April 2021

AbstractOf the seven recognized species of the Anopheles gambiae complex, A. gambiae s.s. is the most widespread and most important vector of malaria. It is becoming clear that, in parts of West Africa, this nominal species is not a single panmictic unit. We found that the internal transcribed spacer (ITS) of the X-linked rDNA has two distinct sequences with three fixed nucleotide differences; we detected no heterozygotes at these three sites, even in areas of sympatry of the two ITS types. The intergenic spacer (IGS) of this region also displays two distinct sequences that are in almost complete linkage disequilibrium with the distinct ITS alleles. We have designated these two types as S/type I and M/type II. These rDNA types correspond at least partly to the previously recognized chromosomal forms. Here we expand the geographic range of sampling to 251 individuals from 38 populations. Outside of West Africa, a single rDNA type, S/type I, corresponds to the Savanna chromosomal form. In West Africa, both types are often found in a single local sample. To understand if these findings might be due to unusual behavior of the rDNA region, we sequenced the same region for 46 A. arabiensis, a sympatric sibling species. No such distinct discontinuity was observed for this species. Autosomal inversions in one chromosome arm (2R), an insecticide resistance gene on 2L, and this single X-linked region indicate at least two genetically differentiated subpopulations of A. gambiae. Yet, rather extensive studies of other regions of the genome have failed to reveal genetic discontinuity. Evidently, incomplete genetic isolation exists within this single nominal species.
Historical Intensity of Natural Selection for Resistance to Tuberculosis
Authors: Lipsitch Marc , Sousa Alexandra O 
Published: April 2021

Abstract
Infections have long been thought to exert natural selection on humans. Infectious disease resistance is frequently invoked as a mechanism shaping human genetic diversity, but such hypotheses have rarely been quantitatively evaluated with direct measures of disease-related mortality. Enhancement of genetically determined resistance to tuberculosis by natural selection has been proposed as a factor explaining the decline of tuberculosis in Europe and North America in the period 1830–1950 (before the advent of antimicrobial chemotherapy) and the apparently reduced susceptibility of Europeans and their descendants to tuberculosis infection and/or disease. We used Swedish vital statistics from 1891 to 1900 to estimate that individuals who escaped mortality from pulmonary tuberculosis (PTB) during the European tuberculosis epidemic would have enjoyed a fitness advantage of 7–15% per generation compared to individuals who were susceptible to PTB mortality; individuals with 50% protection would have had a selection coefficient of 4–7%/generation. Selection during the peak of the European TB epidemic could have substantially reduced the frequency of already rare alleles conferring increased susceptibility to PTB mortality, but only if the phenotypic effects of these alleles were very large. However, if resistant alleles were rare at the beginning of this period, 300 years would not have been long enough for such selection to increase their frequency to epidemiologically significant levels. Reductions in the frequency of rare susceptibility alleles could have played at most a small part in the decline of the epidemic in the century preceding 1950. Natural selection by PTB deaths during the European TB epidemic alone cannot account for the presently low level of TB disease observed among Europeans and their descendants just prior to the appearance of antibiotic treatment.