bluuebunny/crossref_metadata_2025_split huggingface dataset:
VARIANCE AND COVARIANCE OF HOMOZYGOSITY IN A STRUCTURED POPULATION
Authors: Golding G B , Strobeck C 
Published: January 2021

ABSTRACT
The variance of homozygosity for a K-allele model with n partially isolated subpopulations is derived numerically using identity coefficients. The variance of homozygosity within a subpopulation is shown to depend strongly upon the migration rates between subpopulations but is not strongly influenced by the number of alleles possible at a locus. The variance of homozygosity within a subpopulation, given the value of expected homozygosity, is approximately equal to the value of the variance of homozygosity given by Stewart's formula for a single population. If the population is presumed to be panmictic, but is actually subdivided, and the gametes are sampled at random from the total population, the apparent variance of homozygosity depends on the number of alleles possible. With small migration rates and K large, the apparent variance of homozygosity is much smaller than in a single population with the same expected homozygosity. However, when K is small, the variance of homozygosity is approximately given by Stewart's formula. The transient behavior of the variance of homozygosity shows that a large number of generations may be required to approach equilibrium values.
FUNCTIONAL EFFECTS OF PGI ALLOZYMES IN ESCHERICHIA COLI
Authors: Dykhuizen Daniel E , Hartl Daniel L 
Published: January 2021

ABSTRACT
Five alleles representing three electromorphs of phosphoglucose isomerase (PGI) have been transferred from natural isolates of E. coli into the genetic background of E. coli K12 and examined for their effect on growth rate in chemostats limited for glucose or fructose. With glucose limitation, all alleles are selectively neutral or nearly neutral within the limit of resolution of the technique, whether the genetic background is nonmutant or whether it contains a deletion of the locus of glucose-6-phosphate dehydrogenase, the enzyme that provides an alternative metabolic pathway for the substrate of PGI. With fructose limitation, one of the naturally occurring alleles has a small but reproducible detrimental effect on growth rate. A kinetic difference in this detrimental allozyme, apparently relating to an inhibition constant, has been observed in some, but not all, lots of substrate, and a similar difference has also been noted in one of the rare electromorphs that could not be transferred into E. coli K12. These results support a model of genetic variation in which the alleles are neutral or nearly neutral in the prevailing environment but have a potential for selection that can be expressed under the appropriate conditions of environment or genetic background. This hypothesis is discussed in the context of allozyme polymorphisms observed in other organisms.
THE RESPONSE OF ENZYME POLYMORPHISMS TO DEVELOPMENTAL RATE SELECTION IN DROSOPHILA MELANOGASTER
Authors: Cavener Douglas R 
Published: January 2021

ABSTRACT
Two strains of Drosophila melanogaster derived from different geographical localities were subjected to selection for fast and slow developmental rate. Four enzyme polymorphisms were monitored for their response to such selection. Significant changes in allele frequencies were effected for the αGpdh and 6Pgd polymorphisms under fast developmental rate selection. The strain from Rhode Island exhibited a correlated change in body weight during developmental rate selection, whereas the Georgia strain did not.
VIRILITY DEFICIENCY AND THE SEX-RATIO TRAIT IN DROSOPHILA PSEUDOOBSCURA. II. MULTIPLE MATING AND OVERALL VIRILITY SELECTION
Authors: Wu Chung-I 
Published: January 2021

ABSTRACT
Previous studies on fitness components of Drosophila have shown the over-whelming importance of virility selection. In this study, virility selection is further partitioned into two components—one with respect to virgin females and the other with respect to nonvirgin females. The relative importance of the two components to the overall virility selection depends on the remating tendency of females which is investigated here. A theoretical model is then proposed to estimate virility selection under the condition of frequent female remating. The model is tested experimentally. When this model is applied to the Sex-Ratio system of D. pseudoobscura, Sex-Ratio males are found to suffer substantial virility reduction. The significance of this finding to the Sex-Ratio problem is discussed.
GENETIC MAPPING OF IS200 COPIES IN SALMONELLA TYPHIMURIM STRAIN LT2
Authors: Lam Stephen , Roth John R 
Published: January 2021

ABSTRACT
The wild-type Salmonella typhimurium strain LT2 contains six copies of the insertion sequence element IS200 which is unique to Salmonella. We have determined the chromosomal locations of all six copies of IS200 in strain LT2. This was done by mapping the positions of Tn10 elements inserted near each copy of IS200. Such Tn10 insertions were detected by Southern hybridization as IS200-containing restriction fragments with altered electrophoretic mobility. The copies are located at quite evenly spaced sites in the chromosome. Some are found in regions with many known genes; others are in regions with few known functions. There is no indication of a possible function for IS200. The method described here should be applicable to the mapping of IS elements in general.
HYPOMORPHIC LETHAL MUTATIONS AND THEIR IMPLICATIONS FOR THE INTERPRETATION OF LETHAL COMPLEMENTATION STUDIES IN DROSOPHILA
Authors: Nash David , Janca Frank C 
Published: January 2021

ABSTRACT
In a small region of the X chromosome of Drosophila melanogaster, we have found that a third of the mutations that appear to act as lethals in segmental haploids are viable in homozygous mutant individuals. These viable mutations fall into four complementation groups. The most reasonable explanation of these mutations is that they are a subset of functionally hypomorphic alleles of essential genes: hypomorphic mutations with activity levels above a threshold required for survival, but below twice that level, should behave in this manner. We refer to these mutations as "haplo-specific lethal mutations." In studies of autosomal lethals, haplo-specific lethal mutations can be included in lethal complementation tests without being identified as such. Accidental inclusion of disguised haplo-specific lethals in autosomal complementation tests will generate spurious examples of interallelic complementation.
An Open-Label, Randomized, Controlled, Crossover Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers
Authors: Goldenson Nicholas I , Fearon Ian M , Buchhalter August R , Henningfield Jack E 
Published: January 2021

Abstract

Introduction
This randomized, open-label, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to the usual brand (UB) cigarettes in 24 adult smokers.

Methods
At five study visits, subjects used either the JS in 59 mg/mL, JS 18 mg/mL (two visits), and JS 9 mg/mL (all tobacco-flavored) or smoked their UB cigarette first during a controlled puffing sequence (CPS) and then ad libitum (5 min) use sessions. Blood samples were taken at specified timepoints for 60 min in each session. The modified Product Evaluation Scale assessed subjective effects 30-min post-use in the CPS session.

Results
Maximum plasma nicotine concentration (Cmax-BL), total nicotine exposure (AUC0-60-BL), and rate of plasma nicotine rise were significantly lower for all JS products compared to subjects' UB cigarette in CPS and ad libitum use sessions. In both use sessions these PK parameters were significantly higher for JS 59 mg/mL compared to 18 and 9 mg/mL. Subjective measures of cigarette craving relief and “Enough Nicotine” for JS 59 mg/mL did not differ significantly from UB cigarettes, but JS 18 and 9 mg/mL were rated significantly lower than JS 59 mg/mL and UB cigarettes.

Conclusions
Nicotine exposure and subjective relief were directly related to JS nicotine concentration: higher nicotine concentrations gave rise to significantly greater plasma nicotine levels and relief from craving. Heavier and more dependent smokers may require the greater nicotine delivery of JS 59 mg/mL to successfully transition away from cigarettes.

Implications
It has been suggested that electronic nicotine delivery systems (ENDS) and other alternative nicotine delivery products that more closely mimic the nicotine pharmacokinetics (PK) of cigarettes may facilitate smokers transitioning away from cigarettes. We examined nicotine PK and subjective effects of JUUL System (JS) ENDS with three nicotine concentrations (59, 18 and 9 mg/mL) compared to combustible cigarettes. Nicotine delivery from JS ENDS was nicotine concentration dependent, with higher nicotine concentrations giving rise to higher nicotine exposure. These findings suggest that heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20 mg/mL to successfully transition away from cigarettes.
Proton density polarization of the doubly magic 40Ca core in 48Ca and EoS parameters
Authors: Zenihiro Juzo , Uesaka Tomohiro , Sagawa Hiroyuki , Yoshida Satoshi 
Published: January 2021

Abstract
The proton density polarization in ${\rm ^{48}Ca}$ by the eight neutrons added on the ${\rm ^{40}Ca}$ core is discussed. We adopt the proton density distributions determined by electron scattering and the neutron density distributions determined by proton elastic scattering in ${\rm ^{40}Ca}$ and ${\rm ^{48}Ca}$. As a measure of the proton density polarization effect due to the neutrons, a ratio $R$ of the peak values of the neutron density difference $\Delta\rho_{n,{\rm peak}}$ between ${\rm ^{48}Ca}$ and ${\rm ^{40}Ca}$ to the proton one $\Delta\rho_{p,{\rm peak}}$ is introduced and compared with the Hartree–Fock and Hartree calculations by non-relativistic and relativistic energy density functionals (EDFs), respectively. The value $R$ shows clear correlations with the symmetry energy parameters $J$ and $L$, but not with the isoscalar incompressibility $K_\infty$. The experimental value $R$ can be reproduced by theoretical calculations using the EDFs with $L=25$–50 MeV.
Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes
Authors: Jordaan Pierre , Dumotier Bérengère , Traebert Martin , Miller Paul E , Ghetti Andre , Urban Laszlo , Abi-Gerges Najah 
Published: January 2021

Abstract
Substantial efforts have been recently committed to develop coronavirus disease-2019 (COVID-19) medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. Although these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the proarrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low proarrhythmia risk, whereas Chloroquine and Azithromycin were associated with high risk. Hydroxychloroquine proarrhythmia risk changed to high with low level of K+, whereas high level of Mg2+ protected against proarrhythmic effect of high Hydroxychloroquine concentrations. Moreover, therapeutic concentration of Hydroxychloroquine caused no enhancement of elevated temperature-induced proarrhythmia. Polytherapy of Hydroxychloroquine plus Azithromycin and sequential application of these drugs were also found to influence proarrhythmia risk categorization. Hydroxychloroquine proarrhythmia risk changed to high when combined with Azithromycin at therapeutic concentration. However, Hydroxychloroquine at therapeutic concentration impacted the cardiac safety profile of Azithromycin and its proarrhythmia risk only at concentrations above therapeutic level. We also report that Hydroxychloroquine and Chloroquine, but not Azithromycin, decreased contractility while exhibiting multi-ion channel block features, and Hydroxychloroquine’s contractility effect was abolished by Azithromycin. Thus, this study has the potential to inform clinical studies evaluating repurposed therapies, including those in the COVID-19 context. Additionally, it demonstrates the translational value of the human cardiomyocyte contractility-based model as a key early discovery path to inform decisions on novel therapies for COVID-19, malaria, and inflammatory diseases.
Medications for gout and its comorbidities: mutual benefits?
Authors: Yoshida Kazuki , Choi Hyon K. , Solomon Daniel H. 
Published: January 2021

Purpose of review
To review recent literature with relevance to the management of multimorbid patients with gout, i.e., gout medication repurposed for comorbidities and vice versa.

Recent findings
Adding to the previous success of interleukin-1 inhibition, two trials on low-dose colchicine's role in cardiovascular disease (CVD) demonstrated potential benefits in patients with or without gout. In Colchicine Cardiovascular Outcomes Trial, a composite CVD endpoint was reduced by 23% among patients who had experienced a recent myocardial infarction. In Low-Dose Colchicine 2, the composite CVD endpoint was reduced 31% among those with stable coronary artery disease. Use of urate-lowering therapy (ULT) for renal protection in patients without gout produced null results. Allopurinol did not benefit the glomerular filtration rate in two trials (Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase and Preventing Early Renal Function Loss) among patients with chronic kidney disease (with or without hyperuricemia, but not gout). SGLT-2 inhibitors, a medication recommended for patients with diabetes and CVD, diabetic kidney disease, or heart failure, demonstrated a protective effect against gout flares in a secondary trial analysis and a large observational study.

Summary
The role of colchicine may expand beyond gout flare prevention to patients with existing CVD. The renal benefit of ULT among patients with gout remains unclear. SGLT-2 inhibitors may benefit diabetic patients who have gout as a comorbidity.
Prevalence, incidence and clinical features of SARS-CoV-2 infection in adult coeliac patients
Authors: Schiepatti Annalisa , Alimenti Eleonora , Maimaris Stiliano , Nicolardi Maria Luisa , Manzella La Barbera Francesca , Baiardi Paola , Biagi Federico 
Published: January 2021

Objectives
Data on SARS-CoV-2 disease (COVID-19) in adult coeliac disease (CD) are lacking. The aim of the present study is to evaluate the epidemiology and clinical features of COVID-19 in adult coeliac patients regularly followed-up at our centre since January 2015.

Methods
Data about general health status and clinical features of laboratory-confirmed COVID-19 were prospectively collected over the phone. Data about CD were retrospectively collected from clinical notes. Prevalence and incidence of COVID-19 were compared between the coeliac cohort and the figures in the general population of Lombardy, Northern Italy between 20 February to 5 June 2020 provided by the Italian National Institute of Health (Istituto Superiore di Sanità) and the Lombardy regional government.

Results
Nine out of 324 patients contracted COVID-19, thus resulting in a prevalence of 2.78% [95% confidence interval (CI) 0.98–4.58] and an incidence rate of 8.15/1000 person-month (95% CI 4.24–15.66). Prevalence of COVID-19 ascertained by means of nasal swab was 1.79% (95% CI 0.22–3.35) and the incidence rate 5.26/1000 person-month (95% CI 2.19–12.63), without difference from the general population. Clinical type of CD, age, sex, duration and adherence to a gluten-free diet, and mucosal healing did not differ between coeliac patients with and without COVID-19. None of the 9 patients with COVID-19 required hospitalization.

Conclusion
Patients with CD do not seem to carry an increased risk of COVID-19 compared to the general population and their disease course is mild.
Population Differentiation ofRhodobacteraceaeAlong Coral Compartments
Authors: Luo Danli , Wang Xiaojun , Feng Xiaoyuan , Tian Mengdan , Wang Sishuo , Tang Sen-Lin , Ang Put , Yan Aixin , Luo Haiwei 
Published: January 2021

AbstractCoral mucus, tissue and skeleton harbor compositionally different microbiota, but how these coral compartments shape the microbial evolution remains unexplored. Here, we focused on theRhodobacteraceae, which represents a significant but variable proportion (5-50%) of the coral microbiota. We sequenced 234 genomes constituting two divergent populations inhabiting a prevalent coral speciesPlatygyra acuta. One population diverged into two clades colonizing the mucus and skeleton respectively. We reconstructed the ancestral gene changing events that potentially drove the split, and found that the affected genes matched well with the distinct physicochemical features of the mucus and skeleton. Specifically, the mucus clade acquired functions involved in the utilization of coral osmolytes abundant in the mucus (e.g., methylamines, DMSP, taurine and L-proline), whereas the skeleton clade uniquely harbored traits that may promote adaptation to the low-energy and diurnally anoxic skeleton (e.g., sulfur oxidation and swimming motility). These between-clade genetic differences were largely supported by physiological assays. Expanded analyses by including relatives isolated from various marine environments suggest that the mucus and skeleton clades may have diversified in non-coral habitats, but they also consolidated a key role of distinct coral compartments in diversifying many of the above-mentioned traits. The second population varied only at a few dozen nucleotide sites across the whole genomes, and the Slatkin-Maddison test supported that dispersal limitation between coral compartments is another key mechanism driving microbial population differentiation. Collectively, our results suggest that different coral compartments represent ecologically distinct and microgeographically separate habitats that drive the evolution of the coral microbiota.
“Roles for ELMOD2 and Rootletin in Ciliogenesis”
Authors: Turn Rachel E. , Linnert Joshua , Gigante Eduardo D. , Wolfrum Uwe , Caspary Tamara , Kahn Richard A. 
Published: January 2021

AbstractELMOD2 is a GTPase activating protein (GAP) with uniquely broad specificity for ARF family GTPases. We previously showed that it acts with ARL2 in mitochondrial fusion and microtubule stability and with ARF6 during cytokinesis. Mouse embryonic fibroblasts deleted for ELMOD2 also displayed changes in cilia related processes including increased ciliation, multiciliation, ciliary morphology, ciliary signaling, centrin accumulation inside cilia, and loss of rootlets at centrosomes with loss of centrosome cohesion. Increasing ARL2 activity or overexpressing Rootletin reversed these defects, revealing close functional links between the three proteins. This was further supported by the findings that deletion of Rootletin yielded similar phenotypes, which were rescued upon increasing ARL2 activity but not ELMOD2 overexpression. Thus, we propose that ARL2, ELMOD2, and Rootletin all act in a common pathway that suppresses spurious ciliation and maintains centrosome cohesion. Screening a number of markers of steps in the ciliation pathway support a model in which ELMOD2, Rootletin, and ARL2 act downstream of TTBK2 and upstream of CP110 to prevent spurious release of CP110 and to regulate ciliary vesicle docking. These data thus provide evidence supporting roles for ELMOD2, Rootletin, and ARL2 in the regulation of ciliary licensing.
Profitability analysis of rice production: a microeconomic perspective from northern Ghana
Authors: Zakaria Abraham , Azumah Shaibu Baanni , Dagunga Gilbert , Appiah-Twumasi Mark 
Published: January 2021

PurposeThe purpose of this study is to estimate the profitability of rice production for irrigated and rain-fed farmers; determine the factors that influence farmers' decision to participate in irrigation and the impact of irrigation on rice farmers' profitability in northern Ghana.Design/methodology/approachUsing cross-sectional data collected from 543 rice farmers in northern Ghana, the study employed both non-parametric (cost benefit analysis) and parametric (endogenous switching regression) approaches to analyse the data.FindingsThe empirical results reveal a significant difference between the profits of irrigated (GHS 2442.30) and rain-fed farmers (GHS 576.20), as well as the cost-benefit ratios between irrigators (2.53) and rain-fed farmers (1.37). Also, participation in irrigation was found to be influenced by relatively small farm size and off-farm income; while profitability was influenced by membership in a farmer-based organization, access to agricultural extension services and perception of decreasing rainfall intensity. Irrigation also had a positive significant net impact on profitability of rice production.Research limitations/implicationsThe results provide justification for development partners and the government of Ghana through the “one-village-one-dam” policy, to invest in irrigation in northern Ghana in order to improve household welfare as well as build resilience for sustainable production systems.Originality/valueThis study is the first of its kind to provide a robust analysis of the difference in profits of rain-fed and irrigated rice farmers while estimating the determinants of Ghanaian farmers' choice of either of the regimes within a bias-corrected framework.
Influence of high-performance work systems on intrapreneurial behavior
Authors: Farrukh Muhammad , Khan Mohammad Saud , Raza Ali , Shahzad Imran Ahmed 
Published: January 2021

PurposeIn the past, a plethora of studies has investigated the organizational and individual outcomes of high-performance work systems (HPWS). However, less is known about the mechanism through which HPWS impacts employees’ behavior, particularly intrapreneurial behavior (IB). Drawing on the social exchange theory, this study aims to fill this gap by investigating the mediation effect of perceived organizational support (POS) on HPWS-IB linkages.Design/methodology/approachData were collected with the help of structured questionnaires from employees working in service industries such as banking and insurance.FindingsHPWS was conceptualized as a higher-order measurement model that includes four lower-order dimensions, namely, information sharing, decision-making participation, job security, training and development. Partial least squares structural equation modeling technique was used to test the hypothesized relationships. Results showed a positive and significant effect of HPWS on IB. Moreover, POS significantly mediated the HPWS-IB link.Originality/valueDespite an increasing number of studies on the role of human resource management (HRM) practices in enhancing innovation and creativity, there has not been enough research on how HPWS affects IB at the individual level in the presence of POS. Thus, this research is the first of its kind to investigate the mediating role of POS in HPWS-IB linkages in the Malaysian context.