bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of quercetin on exercise performance, physical activity and blood supply in a novel model of sustained hind-limb ischaemia
Authors: Phie J , Krishna S M , Kinobe R , Moxon J V , Andrade-Lima A , Morton S K , Lazzaroni S M , Huynh P , Golledge J 
Published: February 2021

Abstract

Background
There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia.

Methods
Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring.

Results
A sustained reduction in relative limb blood supply (P &lt; 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period.

Conclusion
These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD.
Cardiac rehabilitation and all-cause mortality in patients with heart failure: a retrospective cohort study
Authors: Buckley Benjamin J R , Harrison Stephanie L , Fazio-Eynullayeva Elnara , Underhill Paula , Sankaranarayanan Rajiv , Wright David J , Thijssen Dick H J , Lip Gregory Y H 
Published: February 2021

Abstract

Aims
Despite the benefits of exercise training in the secondary prevention of cardiovascular disease, there are conflicting findings for the impact of exercise-based cardiac rehabilitation (CR) on mortality for patients with heart failure (HF). The aim of this study was therefore to investigate the association of exercise-based CR with all-cause mortality, hospitalisation, stroke, and atrial fibrillation in patients with heart failure.

Methods and results
A retrospective cohort study was conducted which utilized a global federated health research network, primarily in the USA. Patients with a diagnosis of HF were compared between those with and without an electronic medical record of CR and/or exercise programmes within 6 months of an HF diagnosis. Patients with HF undergoing exercise-based CR were propensity score matched to HF patients without exercise-based CR by age, sex, race, comorbidities, medications, and procedures (controls). We ascertained 2-year incidence of all-cause mortality, hospitalization, stroke, and atrial fibrillation. Following propensity score matching, a total of 40 364 patients with HF were identified. Exercise-based CR was associated with 42% lower odds of all-cause mortality [odds ratio 0.58, 95% confidence interval (CI): 0.54–0.62], 26% lower odds of hospitalization (0.74, 95% CI 0.71–0.77), 37% lower odds of incident stroke (0.63, 95% CI 0.51–0.79), and 53% lower odds of incident atrial fibrillation (0.47, 95% CI 0.4–0.55) compared to controls, after propensity score matching. The beneficial association of CR and exercise on all-cause mortality was consistent across all subgroups, including patients with HFrEF (0.52, 95% CI 0.48–0.56) and HFpEF (0.65, 95% CI 0.60–0.71).

Conclusion
Exercise-based CR was associated with lower odds of all-cause mortality, hospitalizations, incident stroke, and incident atrial fibrillation at 2-year follow-up for patients with HF (including patients with HFrEF and HFpEF).
The Effect of Mismatch Repair and Heteroduplex Formation on Sexual Isolation in Bacillus
Authors: Majewski Jacek , Cohan Frederick M 
Published: February 2021

Abstract
In Bacillus transformation, sexual isolation is known to be an exponential function of the sequence divergence between donor and recipient. Here, we have investigated the mechanism under which sequence divergence results in sexual isolation. We tested the effect of mismatch repair by comparing a wild-type strain and an isogenic mismatch-repair mutant for the relationship between sexual isolation and sequence divergence. Mismatch repair was shown to contribute to sexual isolation but was responsible for only a small fraction of the sexual isolation observed. Another possible mechanism of sexual isolation is that more divergent recipient and donor DNA strands have greater difficulty forming a heteroduplex because a region of perfect identity between donor and recipient is required for initiation of the heteroduplex. A mathematical model showed that this heteroduplex-resistance mechanism yields an exponential relationship between sexual isolation and sequence divergence. Moreover, this model yields an estimate of the size of the region of perfect identity that is comparable to independent estimates for Escherichia coli. For these reasons, and because all other mechanisms of sexual isolation may be ruled out, we conclude that resistance to heteroduplex formation is predominantly responsible for the exponential relationship between sexual isolation and sequence divergence in Bacillus transformation.
Genetic Evaluation by Best Linear Unbiased Prediction Using Marker and Trait Information in a Multibreed Population
Authors: Wang T , Fernando R L , Grossman M 
Published: February 2021

Abstract
Genetic evaluation by best linear unbiased prediction (BLUP) requires modeling genetic means, variances, and covariances. This paper presents theory to model means, variances, and covariances in a multibreed population, given marker and breed information, in the presence of gametic disequilibrium between the marker locus (ML) and linked quantitative trait locus (MQTL). Theory and algorithms are presented to construct the matrix of conditional covariances between relatives (Gv) for the MQTL effects in a multibreed population and to obtain the inverse of Gv efficiently. Theory presented here accounts for heterogeneity of variances among pure breeds and for segregation variances between pure breeds. A numerical example was used to illustrate how the theory and algorithms can be used for genetic evaluation by BLUP using marker and trait information in a multibreed population.
Mapping Quantitative Trait Loci Using Multiple Families of Line Crosses
Authors: Xu Shizhong 
Published: February 2021

Abstract
To avoid a loss in statistical power as a result of homozygous individuals being selected as parents of a mapping population, one can use multiple families of line crosses for quantitative trait genetic linkage analysis. Two strategies of combining data are investigated: the fixed-model and the random-model strategies. The fixed-model approach estimates and tests the average effect of gene substitution for each parent, while the random-model approach treats each effect of gene substitution as a random variable and directly estimates and tests the variance of gene substitution. Extensive Monte Carlo simulations verify that the two strategies perform equally well, although the random model is preferable in combining data from a large number of families. Simulations also show that there may be an optimal sampling strategy (number of families vs. number of individuals per family) in which QTL mapping reaches its maximum power and minimum estimation error. Deviation from the optimal strategy reduces the efficiency of the method.
Patterns of Y and X Chromosome DNA Sequence Divergence During the Felidae Radiation
Authors: Slattery Jill Pecon , O'Brien Stephen J 
Published: February 2021

Abstract
The 37 species of modern cats have evolved from approximately eight phylogenetic lineages within the past 10 to 15 million years. The Felidae family has been described with multiple measures of morphologic and molecular evolutionary methods that serve as a framework for tracking gene divergence during brief evolutionary periods. In this report, we compare the mode and tempo of evolution of noncoding sequences of a large intron within Zfy (783 bp) and Zfx (854 bp), homologous genes located on the felid Y and X chromosomes, respectively. Zfy sequence variation evolves at about twice the rate of Zfx, and both gene intron sequences track feline hierarchical topologies accurately. As homoplasies are infrequent in patterns of nucleotide substitution, the Y chromosome sequence displays a remarkable degree of phylogenetic consistency among cat species and provides a highly informative glimpse of divergence of sex chromosome sequences in Felidae.
Substitutions in the Pheromone-Responsive Gβ Protein of Saccharomyces cerevisiae Confer a Defect in Recovery from Pheromone Treatment
Authors: Li E , Meldrum Eric , Stratton Holly F , Stone David E 
Published: February 2021

Abstract
The pheromone-responsive Gα protein of Saccharomyces cerevisiae, Gpa1p, stimulates an adaptive mechanism that downregulates the mating signal. In a genetic screen designed to identify signaling elements required for Gpa1p-mediated adaptation, a large collection of adaptive-defective (Adp−) mutants were recovered. Of the 49 mutants characterized thus far, approximately three-quarters exhibit a dominant defect in the negative regulation of the pheromone response. Eight of the dominant Adp− mutations showed tight linkage to the gene encoding the pheromone-responsive Gβ, STE4. Sequence analysis of the STE4 locus in the relevant mutant strains revealed seven novel STE4 alleles, each of which was shown to disrupt proper regulation of the pheromone response. Although the STE4 mutations had only minor effects on basal mating pathway activity, the mutant forms of Gβ dramatically affected the ability of the cell to turn off the mating response after exposure to pheromone. Moreover, the signaling activity of the aberrant Gβγ subunits was suppressed by G322E, a mutant form of Gpa1p that blocks the pheromone response by sequestering Gβγ, but not by E364K, a hyperadaptive form of Gpa1p. On the basis of these observations, we propose that Gpa1p-mediated adaptation involves the binding of an unknown negative regulator to Gβγ.
Transient and Heritable Mutators in Adaptive Evolution in the Lab and in Nature
Authors: Rosenberg Susan M , Thulin Carl , Harris Reuben S 
Published: February 2021

Abstract
Major advances in understanding the molecular mechanism of recombination-dependent stationary-phase mutation in Escherichia coli occurred this past year. These advances are reviewed here, and we also present new evidence that the mutagenic state responsible is transient. We find that most stationary-phase mutants do not possess a heritable stationary-phase mutator phenotype, although a small proportion of heritable mutators was found previously. We outline similarities between this well-studied system and several recent examples of adaptive evolution associated with heritable mutator phenotype in a similarly small proportion of survivors of selection in nature and in the lab. We suggest the following: (1) Transient mutator states may also be a predominant source of adaptive mutations in these latter systems, the heritable mutators being a minority (Rosenberg 1997); (2) heritable mutators may sometimes be a product of, rather than the cause of, hypermutation that gives rise to adaptive mutations.
Mutagenesis and More: umuDC and the Escherichia coli SOS Response
Authors: Smith Bradley T , Walker Graham C 
Published: February 2021

Abstract
The cellular response to DNA damage that has been most extensively studied is the SOS response of Escherichia coli. Analyses of the SOS response have led to new insights into the transcriptional and posttranslational regulation of processes that increase cell survival after DNA damage as well as insights into DNA-damage-induced mutagenesis, i.e., SOS mutagenesis. SOS mutagenesis requires the recA and umuDC gene products and has as its mechanistic basis the alteration of DNA polymerase III such that it becomes capable of replicating DNA containing miscoding and noncoding lesions. Ongoing investigations of the mechanisms underlying SOS mutagenesis, as well as recent observations suggesting that the umuDC operon may have a role in the regulation of the E. coli cell cycle after DNA damage has occurred, are discussed.
Early Effect of Inbreeding as Revealed by Microsatellite Analyses on Ostrea edulis Larvae
Authors: Bierne Nicolas , Launey Sophie , Naciri-Graven Yamama , Bonhomme François 
Published: February 2021

Abstract
This paper reports new experimental evidence on the effect of inbreeding on growth and survival in the early developmental phase of a marine bivalve, the flat oyster Ostrea edulis. Two crosses between full sibs were analyzed using four microsatellite markers. Samples of 96 individuals were taken just after spawning (day 1), at the end of the larval stage before metamorphosis (day 10) and at the postlarval stage (day 70). Significant departure from Mendelian expectation was observed at two loci in the first cross and two loci in the second. Departure from 1:1 segregation occured in one parent of the first cross at three loci and genotypic selection, which resulted in highly significant heterozygote excesses, was recorded at three out of four loci in cross C1 and at two out of three loci in cross C2. Across the four markers, there were similar significant excesses of multilocus heterozygosity, and significant multilocus heterozygosity–growth correlations were recorded for both crosses at all stages. These results suggest that microsatellite markers, often assumed to be neutral, cosegregated with fitness-associated genes, the number of which is estimated to be between 15 and 38 in the whole genome, and that there is a potentially high genetic load in Ostrea edulis genome. This load provides a genetic basis for heterosis in marine bivalves.
Factors Affecting Transposition of the Himar1 mariner Transposon in Vitro
Authors: Lampe David J , Grant Theresa E , Robertson Hugh M 
Published: February 2021

Abstract
Mariner family transposable elements are widespread in animals, but their regulation is poorly understood, partly because only two are known to be functional. These are particular copies of the Dmmar1 element from Drosophila mauritiana, for example, Mos1, and the consensus sequence of the Himar1 element from the horn fly, Haematobia irritans. An in vitro transposition system was refined to investigate several parameters that influence the transposition of Himar1. Transposition products accumulated linearly over a period of 6 hr. Transposition frequency increased with temperature and was dependent on Mg2+ concentration. Transposition frequency peaked over a narrow range of transposase concentration. The decline at higher concentrations, a phenomenon observed in vivo with Mos1, supports the suggestion that mariners may be regulated in part by “overproduction inhibition.” Transposition frequency decreased exponentially with increasing transposon size and was affected by the sequence of the flanking DNA of the donor site. A noticeable bias in target site usage suggests a preference for insertion into bent or bendable DNA sequences rather than any specific nucleotide sequences beyond the TA target site.
Intron Loss and Gain During Evolution of the Catalase Gene Family in Angiosperms
Authors: Frugoli Julia A , McPeek Mark A , Thomas Terry L , McClung C Robertson 
Published: February 2021

Abstract
Angiosperms (flowering plants), including both monocots and dicots, contain small catalase gene families. In the dicot, Arabidopsis thaliana, two catalase (CAT) genes, CAT1 and CAT3, are tightly linked on chromosome 1 and a third, CAT2, which is more similar to CAT1 than to CAT3, is unlinked on chromosome 4. Comparison of positions and numbers of introns among 13 angiosperm catalase genomic sequences indicates that intron positions are conserved, and suggests that an ancestral catalase gene common to monocots and dicots contained seven introns. Arabidopsis CAT2 has seven introns; both CAT1 and CAT3 have six introns in positions conserved with CAT2, but each has lost a different intron. We suggest the following sequence of events during the evolution of the Arabidopsis catalase gene family. An initial duplication of an ancestral catalase gene gave rise to CAT3 and CAT1. CAT1 then served as the template for a second duplication, yielding CAT2. Intron losses from CAT1 and CAT3 followed these duplications. One subclade of monocot catalases has lost all but the 5′-most and 3′-most introns, which is consistent with a mechanism of intron loss by replacement of an ancestral intron-containing gene with a reverse-transcribed DNA copy of a fully spliced mRNA. Following this event of concerted intron loss, the Oryza sativa (rice, a monocot) CAT1 lineage acquired an intron in a novel position, consistent with a mechanism of intron gain at proto-splice sites.
Medicinal plants from the Himalayan region for potential novel antimicrobial and anti-inflammatory skin treatments
Authors: Heinrich Michael , Jiang Haiping , Scotti Francesca , Booker Anthony , Walt Heinrich , Weckerle Caroline , Maake Caroline 
Published: February 2021

Abstract

Background and Objectives
Adequate treatment of wounds remains one of the major medical needs globally, most notably in the regions with poor or limited access to health care. In many local and traditional systems of medicine, plants are often widely used for treating infected wounds.

Aim and objectives
The overarching aim of this project was selection of potential species for use in a future treatment by combining with plant resources with aspects of antimicrobial photodynamic therapy (aPDT). Specifically, we focussed on species used locally in the Himalayan region for the treatment of skin disorders and then assessed the existing pharmacological evidence for key species based on the published evidence available.

Methods
Database searches were performed to identify relevant publications describing local and traditional uses of plants in the Himalayan region of Bhutan, PR China, India, Nepal and Pakistan. Using the Global Biodiversity Information Facility (GBIF), species were researched in terms of their distribution including in different climatic regions, focussing on species mostly found in higher climatic zones (based on the Köppen–Geiger climate classification). For species used in three or more countries and restricted to the higher altitudes, data on safety, pharmacology, as it relates to dermatological conditions, and phytochemistry were retrieved.

Key findings
The study identified a total of 606 species that are used in the treatment of various skin conditions often associated with infections reported in 84 articles. Common weeds like Ageratum conyzoides and Bidens pilosa, widely used and cultivated species like Centealla asiatiaca and Prunus armenica were excluded. This ultimately led to the identification of a core group of five widely used species restricted to the Himalayan region (Cedrus deodara, Nardostachys jatamansi, Pinus wallichiana, Pinus roxburghii and Valeriana jatamansi).

Conclusions
Here we apply a novel approach comprising an assessment of the published information on the use of medicinal plants (i.e. local and traditional knowledge) in the context of their potential to be used in a biomedical form of clinical treatment – aPDT. Then, once sustainable sourcing based on access and benefit-sharing arrangements is in place, these species are investigated for their potential in wound treatment. Ultimately, the goal is to develop a new baseline for primary health care in some of the regions of the world with poor or limited access to health care.
Absolute parameters of young stars: V puppis
Authors: Budding E , Love T , Blackford M G , Banks T , Rhodes M J 
Published: February 2021

ABSTRACT
New spectrometric data on V Pup are combined with satellite photometry [HIPPARCOS and recent Transiting Exoplanet Survey Satellite (TESS)] to allow a revision of the absolute parameters with increased precision. We find: M1 = 14.0 ± 0.5, M2 = 7.3 ± 0.3 (M⊙); R1 = 5.48 ± 0.18, R2 = 4.59 ± 0.15 (R⊙); T1 26 000 ± 1000, T2 24 000 ± 1000 (K), age 5 ± 1 (Myr), photometric distance 320 ± 10 (pc). The TESS photometry reveals low-amplitude (∼0.002 mag) variations of the β Cep kind, consistent with the deduced evolutionary condition and age of the optical primary. This fact provides independent support to our understanding of the system as in a process of Case A type interactive evolution that can be compared with μ1 Sco. The ∼10 M⊙ amount of matter shed by the overluminous present secondary must have been mostly ejected from the system rather than transferred, thus taking angular momentum out of the orbit and keeping the pair in relative close proximity. New times of minima for V Pup have been studied and the results compared with previous analyses. The implied variation of period is consistent with the Case A evolutionary model, though we offer only a tentative sketch of the original arrangement of this massive system. We are not able to confirm the previously reported cyclical variations having a 5.47-yr period with the new data, though a direct comparison between the HIPPARCOS and TESS photometry points to the presence of third light from a star that is cooler than those of the close binary, as mentioned in previous literature.
Star formation in ‘the Brick’: ALMA reveals an active protocluster in the Galactic centre cloud G0.253+0.016
Authors: Walker Daniel L , Longmore Steven N , Bally John , Ginsburg Adam , Diederik Kruijssen J M , Zhang Qizhou , Henshaw Jonathan D , Lu Xing , Alves João , Barnes Ashley T , Battersby Cara , Beuther Henrik , Contreras Yanett A , Gómez Laura , Ho Luis C , Jackson James M , Kauffmann Jens , Mills Elisabeth A C , Pillai Thushara 
Published: February 2021

ABSTRACT
G0.253+0.016, aka ‘the Brick’, is one of the most massive (&gt;105 M⊙) and dense (&gt;104 cm−3) molecular clouds in the Milky Way’s Central Molecular Zone. Previous observations have detected tentative signs of active star formation, most notably a water maser that is associated with a dust continuum source. We present ALMA Band 6 observations with an angular resolution of 0.13 arcsec (1000 AU) towards this ‘maser core’ and report unambiguous evidence of active star formation within G0.253+0.016. We detect a population of eighteen continuum sources (median mass ∼2 M⊙), nine of which are driving bi-polar molecular outflows as seen via SiO (5–4) emission. At the location of the water maser, we find evidence for a protostellar binary/multiple with multidirectional outflow emission. Despite the high density of G0.253+0.016, we find no evidence for high-mass protostars in our ALMA field. The observed sources are instead consistent with a cluster of low-to-intermediate-mass protostars. However, the measured outflow properties are consistent with those expected for intermediate-to-high-mass star formation. We conclude that the sources are young and rapidly accreting, and may potentially form intermediate- and high-mass stars in the future. The masses and projected spatial distribution of the cores are generally consistent with thermal fragmentation, suggesting that the large-scale turbulence and strong magnetic field in the cloud do not dominate on these scales, and that star formation on the scale of individual protostars is similar to that in Galactic disc environments.