bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVOLUTIONARY RELATIONSHIPS AMONG FIVE SUBSPECIES OF MUS MUSCULUS BASED ON RESTRICTION ENZYME CLEAVAGE PATTERNS OF MITOCHONDRIAL DNA
Authors: Yonekawa Hiromichi , Moriwaki Kazuo , Gotoh Osamu , Hayashi Jun-Ichi , Watanabe Junko , Miyashita Nobumoto , Petras Michael L , Tagashira Yusaku 
Published: April 2021

ABSTRACT
The intra- and intersubspecific genetic distances between five subspecies of Mus musculus were estimated from restriction enzyme cleavage patterns or maps of mitochondrial DNA (mtDNA). The European subspecies, M. m. domesticus and Asian subspecies, M. m. bactrianus, M. m. castaneus, M. m. molossinus and M. m. urbanus were examined. For each subspecies, except M. m. urbanus, at least two local races from widely separated localities were examined. Intrasubspecific heterogeneity was found in the mtDNA cleavage patterns of M. m. bactrianus and M. m. castaneus. M. m. molossinus and M. m. domesticus, however, revealed no intrasubspecific heterogeneity. Four of the subspecies had distinct cleavage patterns. The fifth, M. m. urbanus, had cleavage patterns identical to those of M. m. castaneus with several enzymes. Estimates of genetic distances between the various races and subspecies were obtained by comparing cleavage maps of the mtDNAs with various restriction enzymes. Nucleotide sequence divergences of mtDNA between local races were estimated to be less than 0.4% in M. m. bactrianus and less than 0.3% in M. m. castaneus. The times of divergence of both subspecies were calculated to be 0.1-0.2 × 106 years. These values suggest that the intrasubspecific divergence began some 0.1-0.2 × 106 years ago. On the other hand, nucleotide sequence divergences between European subspecies M. m. domesticus and Asian subspecies M. m. bactrianus and M. m. castaneus were 7.1% and 5.8%, respectively. The times of divergence were calculated to be 2.1-2.6 × 106 years. Further, the nucleotide sequence divergence and time of divergence between M. m. molossinus and the other two Asian subspecies were comparable to those between M. m. molossinus and M. m. domesticus (about 3% and 1 × 106 years, respectively). These results suggest that M. m. molossinus is situated in a unique evolutionary position among Asian subspecies.
ESTIMATION OF LINKAGE IN THE PRESENCE OF MULTIPLICATIVE VIABILITY EFFECTS
Authors: Clark Andrew G 
Published: April 2021

ABSTRACT
Log-linear analysis of contingency tables is applied to trihybrid backcross data to estimate linkage and viability. Whereas nonadditive viability differences perturb recombination estimates in the classical analysis, this statistical procedure yields maximum likelihood crossover frequency estimates in the presence of multiplicative viability effects. Other advantages of this method include: (1) estimation of viability effects of gene substitution at each locus, (2) estimation of asymptotic confidence intervals on recombination frequencies and viabilities, and (3) it tests the null hypothesis of no interference and no viability interactions. Extensions to cover more loci and to allow certain kinds of epistasis are easily made. Relative merits of the proposed and classical methods are discussed.
FATE MAPPING MULTI-FOCUS PHENOTYPES
Authors: Arnold Jonathan , Kankel Douglas R 
Published: April 2021

ABSTRACT
A central assumption used in the genetic fate mapping of anatomical sites responsible for certain mutationally induced abnormalities is that a single pair of bilaterally symmetric sites on the blastoderm gives rise to structures that control the expression of that abnormality. We report a new model that is not so constrained and test its efficacy in the analysis of several mutations that induce behavioral abnormalities.
ESTIMATING LEVELS OF GENE FLOW IN NATURAL POPULATIONS
Authors: Slatkin Montgomery 
Published: April 2021

ABSTRACT
The results from a simulation model of selection, mutation and genetic drift in a geographically subdivided population are presented. The infinite-alleles mutation model of Kimura and Crow (1964) is asumed, and both advantageous and deleterious mutations are considered. It is shown that the average frequency of an allele conditioned on the number of local populations it appears in—the conditional average frequency—is approximately independent of both the selection intensity and mutation rates assumed, but depends strongly on the overall level of gene flow. This result justifies the use of the conditional average frequency to obtain a rough estimate of the level of gene flow in a subdivided population. Data from 16 species are presented and discussed. There are large differences in the conditional average frequencies of different species, although there is some consistency within taxa. Some species apparently have high levels of gene flow and others, particularly salamanders, have low levels. Alternative explanations for the patterns found in the data are considered.
SCALING THRESHOLD CHARACTERS
Authors: Gianola Daniel , Norton H W 
Published: April 2021

ABSTRACT
A simple method of scaling ordered categorical responses having a joint distribution with an underlying normal variable is presented. Scores are developed that maximize heritability of the observed variate and that in the class of scores based on polychotomies: (1) maximize the correlation between score and the underlying genetic value to be predicted, and (2) minimize mean-square prediction error. Several examples suggest little is lost, in terms of heritability, by using equally spaced scores. The proposed scaling method discriminates among candidates for selection that would be tied if equally spaced scores are used and sometimes yields different rankings of candidates.
"FUNDAMENTAL THEOREM" FOR TWO LOCI
Authors: Turner John R G 
Published: April 2021

ABSTRACT
The change in mean fitness for two loci under selection can be described by four terms: (i) the variance of fitness, (ii) a weighted between-gamete covariance, (iii) a function of recombination, linkage disequilibrium and the slope of the surface of mean fitness on disequilibrium, and (iv) a function of these two parameters and the curvature of the surface. Independent derivations of this equation by different methods, although thought at one time to be in disagreement, give algebraically identical results.
DOUBLED HAPLOIDS FOR STUDYING THE INHERITANCE OF QUANTITATIVE CHARACTERS
Authors: Choo T M 
Published: April 2021

ABSTRACT
By using a doubled-haploid population derived from F2 plants, additive and additive x additive genetic variances, as well as the number of segregating genes, can be estimated. An F2-derived doubled-haploid population may contain almost 50%more of the best recombinant than an F1-derived population. However, the best recombinant occurs in the same frequency in the two populations when there is no linkage between genes. The difference in the frequency of the best recombinant between F2- and F3-derived populations is small. This implies that the doubled-haploid method using F2 plants provides only slightly less opportunity for recombination than the conventional breeding methods of selfpollinating crops. In the absence of additive epistasis, a weighted mean of recombination values can be estimated using an F2-derived population and its parental lines. When additive epistasis is present, it can be estimated from doubled-haploid populations derived from two backcrosses. Studies on the linkage of quantitative characters are needed for determining whether doubled haploids should be produced from F2 or from F1 plants in a breeding program.
The sialyl-O-acetylesterase NanS of Tannerella forsythia encompasses two catalytic modules with different regiospecificity for O7 and O9 of sialic acid
Authors: Albers Malena , Schröter Larissa , Belousov Sergej , Hartmann Maike , Grove Melanie , Abeln Markus , Mühlenhoff Martina 
Published: April 2021

Abstract
The periodontal pathogen Tannerella forsythia utilizes host sialic acids as a nutrient source. To also make O-acetylated sialyl residues susceptible to the action of its sialidase and sialic acid uptake system, Tannerella produces NanS, an O-acetylesterase with two putative catalytic domains. Here, we analyzed NanS by homology modeling, predicted a catalytic serine–histidine–aspartate triad for each catalytic domain and performed individual domain inactivation by single alanine exchanges of the triad nucleophiles S32 and S311. Subsequent functional analyses revealed that both domains possess sialyl-O-acetylesterase activity, but differ in their regioselectivity with respect to position O9 and O7 of sialic acid. The 7-O-acetylesterase activity inherent to the C-terminal domain of NanS is unique among sialyl-O-acetylesterases and fills the current gap in tools targeting 7-O-acetylation. Application of the O7-specific variant NanS-S32A allowed us to evidence the presence of cellular 7,9-di-O-acetylated sialoglycans by monitoring the gain in 9-O-acetylation upon selective removal of acetyl groups from O7. Moreover, we established de-7,9-O-acetylation by wild-type NanS as an easy and efficient method to validate the specific binding of three viral lectins commonly used for the recognition of (7),9-O-acetylated sialoglycans. Their binding critically depends on an acetyl group in O9, yet de-7,9-O-acetylation proved advantageous over de-9-O-acetylation as the additional removal of the 7-O-acetyl group eliminated ligand formation by 7,9-ester migration. Together, our data show that NanS gained dual functionality through recruitment of two esterase modules with complementary activities. This enables Tannerella to scavenge 7,9-di-O-acetylated sialyl residues and provides a novel, O7-specific tool for studying sialic acid O-acetylation.
Proteoglycan profiling of human, rat and mouse insulin-secreting cells
Authors: Nikpour Mahnaz , Nilsson Jonas , Persson Andrea , Noborn Fredrik , Vorontsov Egor , Larson Göran 
Published: April 2021

Abstract
Proteoglycans (PGs) are proteins with glycosaminoglycan (GAG) chains, such as chondroitin sulfate (CS) or heparan sulfate (HS), attached to serine residues. We have earlier shown that prohormones can carry CS, constituting a novel class of PGs. The mapping of GAG modifications of proteins in endocrine cells may thus assist us in delineating possible roles of PGs in endocrine cellular physiology. With this aim, we applied a glycoproteomic approach to identify PGs, their GAG chains and their attachment sites in insulin-secreting cells. Glycopeptides carrying GAG chains were enriched from human pancreatic islets, rat (INS-1 832/13) and mouse (MIN6, NIT-1) insulinoma cell lines by exchange chromatography, depolymerized with GAG lyases, and analyzed by nanoflow liquid chromatography tandem mass spectrometry. We identified CS modifications of chromogranin-A (CgA), islet amyloid polypeptide, secretogranin-1 and secretogranin-2, immunoglobulin superfamily member 10, and protein AMBP. Additionally, we identified two HS-modified prohormones (CgA and secretogranin-1), which was surprising, as prohormones are not typically regarded as HSPGs. For CgA, the glycosylation site carried either CS or HS, making it a so-called hybrid site. Additional HS sites were found on syndecan-1, syndecan-4, nerurexin-2, protein NDNF and testican-1. These results demonstrate that several prohormones, and other constituents of the insulin-secreting cells are PGs. Cell-targeted mapping of the GAG glycoproteome forms an important basis for better understanding of endocrine cellular physiology, and the novel CS and HS sites presented here provide important knowledge for future studies.
Forging liberal states: Palmerston’s foreign policy and the rise of a constitutional monarchy in Spain, 1833–7
Authors: Goizueta Alfaro Alfonso 
Published: April 2021

Abstract
British and Spanish historiography have consolidated the idea that Palmerston’s foreign policy toward Spain during the first Carlist War is representative of a ‘liberal phase’ in his career as foreign secretary. However, a close study of Palmerston’s private correspondence with his minister in Madrid, George Villiers, reveals that this compromise with liberalism actually masked a brute struggle with France for political ascendancy in Spain. Historiography considers realpolitik to appear only in his late career (c.1848–65), but this study of Palmerston’s approach to the Spanish Question reveals that it was the moving force of his foreign policy from the very beginning.
Investigation of association between smoke haze and under-five mortality in Malaysia, accounting for time lag, duration and intensity
Authors: Phung Vera Ling Hui , Ueda Kayo , Sahani Mazrura , Seposo Xerxes Tesoro , Wan Mahiyuddin Wan Rozita , Honda Akiko , Takano Hirohisa 
Published: April 2021

Abstract

Background
Studies on the association between smoke haze (hereafter ‘haze’) and adverse health effects have increased in recent years due to extreme weather conditions and the increased occurrence of vegetation fires. The possible adverse health effects on under-five children (U5Y) is especially worrying due to their vulnerable condition. Despite continuous repetition of serious haze occurrence in Southeast Asia, epidemiological studies in this region remained scarce. Furthermore, no study had examined the association accounting for three important aspects (time lag, duration and intensity) concurrently.

Objective
This study aimed to examine the association between haze and U5Y mortality in Malaysia, considering time lag, duration and intensity of exposure.

Methods
We performed a time-stratified case-crossover study using a generalized additive model to examine the U5Y mortality related to haze in 12 districts in Malaysia, spanning from 2014 to 2016. A ‘haze day’ was characterized by intensity [based on concentrations of particulate matter (PM)] and duration (continuity of haze occurrence, up to 3 days).

Results
We observed the highest but non-significant odds ratios (ORs) of U5Y mortality at lag 4 of Intensity-3. Lag patterns revealed the possibility of higher acuteness at prolonged and intensified haze. Stratifying the districts by the 95th-percentile of PM distribution, the ‘low’ category demonstrated marginal positive association at Intensity-2 Duration-3 [OR: 1.210 (95% confidence interval: 1.000, 1.464)].

Conclusions
We found a null association between haze and U5Y mortality. The different lag patterns of the association observed over different duration and intensity suggest consideration of these aspects in future studies.
A Flexible Approach to Terminological Definitions: Representing Thematic Variation
Authors: San Martín Antonio 
Published: April 2021

AbstractTo formulate definitions that meet user needs, terminologists and specialised lexicographers must know how to effectively select information. However, most definition writing guidelines are based on the specification of necessary and sufficient characteristics, which has serious drawbacks because it downplays the role of context (understood as any factor affecting how a term is interpreted) in specialised meaning construction. This paper focuses on thematic variation, an important type of contextual variation, and its representation in terminological definitions. To this end, this paper presents a corpus-based approach to writing definitions that takes into account thematic variation in the selection of information.
Growth Rates of Coxeter Groups and Perron Numbers
Authors: Kolpakov Alexander , Talambutsa Alexey 
Published: April 2021

AbstractWe define a large class of abstract Coxeter groups that we call $\infty $–spanned, and for which the word growth rate and the geodesic growth rate appear to be Perron numbers. This class contains a fair amount of Coxeter groups acting on hyperbolic spaces, thus corroborating a conjecture by Kellerhals and Perren. We also show that for this class the geodesic growth rate strictly dominates the word growth rate.
Museomics: Phylogenomics of the Moth Family Epicopeiidae (Lepidoptera) Using Target Enrichment
Authors: Call Elsa , Mayer Christoph , Twort Victoria , Dietz Lars , Wahlberg Niklas , Espeland Marianne 
Published: April 2021

AbstractBillions of specimens can be found in natural history museum collections around the world, holding potential molecular secrets to be unveiled. Among them are intriguing specimens of rare families of moths that, while represented in morphology-based works, are only beginning to be included in genomic studies: Pseudobistonidae, Sematuridae, and Epicopeiidae. These three families are part of the superfamily Geometroidea, which has recently been defined based on molecular data. Here we chose to focus on these three moth families to explore the suitability of a genome reduction method, target enrichment (TE), on museum specimens. Through this method, we investigated the phylogenetic relationships of these families of Lepidoptera, in particular the family Epicopeiidae. We successfully sequenced 25 samples, collected between 1892 and 2001. We use 378 nuclear genes to reconstruct a phylogenetic hypothesis from the maximum likelihood analysis of a total of 36 different species, including 19 available transcriptomes. The hypothesis that Sematuridae is the sister group of Epicopeiidae + Pseudobistonidae had strong support. This study thus adds to the growing body of work, demonstrating that museum specimens can successfully contribute to molecular phylogenetic studies.
Pharmacokinetic/pharmacodynamic investigation of raltegravir with or without lamivudine in the context of HIV-1 pre-exposure prophylaxis (PrEP)
Authors: Herrera Carolina , Lwanga Julianne , Lee Ming , Mantori Suna , Amara Alieu , Else Laura , Penchala Sujan Dilly , Egan Deirdre , Challenger Elizabeth , Dickinson Laura , Boffito Marta , Shattock Robin , Khoo Saye , Fox Julie 
Published: April 2021

Abstract

Background
To characterize their potential use in pre-exposure prophylaxis (PrEP) we compared the pharmacokinetics of raltegravir and lamivudine in genital tissue against ex vivo tissue infection with HIV-1.

Methods
Open-label trial of 36 HIV-negative females and males randomized to 7 days raltegravir 400 mg twice daily and 7 days raltegravir 400 mg+lamivudine 150 mg twice daily (after washout), or vice versa. Blood, saliva, rectal fluid, rectal tissue, vaginal fluid and vaginal tissue were sampled at baseline and on and off PrEP during a total of 12 days, for pharmacokinetics and antiviral activity via ex vivo HIV-1BaL challenge. Ex vivo infectivity was compared with baseline. The trial has been registered in https://clinicaltrials.gov/ with the identifier NCT03205566.

Results
Steady state for both drugs was reached by day 4. Dosing with raltegravir alone provided modest ex vivo HIV protection with higher drug levels in rectal tissue and vaginal tissue than in plasma on and off PrEP. Off PrEP, plasma and vaginal concentrations declined rapidly, while persisting in the rectum. On PrEP, the highest lamivudine concentrations were in the rectum, followed by vaginal tissue then plasma. Lamivudine washout was rapid in plasma, while persisting in the rectum and vagina. Raltegravir/lamivudine increased ex vivo protection on and off PrEP compared with raltegravir alone, reaching maximum protection at day 2 in rectal tissue and at day 8 in vaginal tissue.

Conclusions
Raltegravir 400 mg+lamivudine 150 mg showed high levels of ex vivo HIV protection, associated with high drug concentrations persisting after discontinuation in vaginal and rectal compartments, supporting further investigation of these agents for PrEP.
Activity of plazomicin against carbapenem-intermediate or -resistantEscherichia coliisolates from the United States and international sites in relation to clonal background, resistance genes, co-resistance, and region
Authors: Johnston Brian D , Thuras Paul , Porter Stephen B , Anacker Melissa , VonBank Brittany , Snippes Vagnone Paula , Witwer Medora , Castanheira Mariana , Johnson James R 
Published: April 2021

AbstractBackgroundEmerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), threatens therapeutic efficacy. Plazomicin (PLZ), a semisynthetic aminoglycoside approved by the FDA in 2018, overcomes the most common aminoglycoside resistance mechanisms and maintains activity against many carbapenem-intermediate or -resistant (CIR) E. coli strains.ObjectivesTo assess plazomicin susceptibility among CIR E. coli in relation to region and multiple bacterial characteristics.MethodsWe determined broth microdilution MICs for plazomicin and 11 comparators against 343 CIR clinical E. coli isolates, then compared susceptibility results by bacterial characteristics and region. The collection comprised 203 US isolates (2002–17) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003–17). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant β-lactamase-encoding genes.ResultsPlazomicin exhibited the highest percentage susceptible (89%) after tigecycline (99%). The percentage susceptible to plazomicin varied significantly by phylogroup (63%, group B1; versus &gt;93%, others) and ST131 subclone (92%, H30Rx; versus 87%–89%, H30R1 and non-H30), but not ST. It also varied by resistance genotype [higher with Klebsiella pneumoniae carbapenemase (KPC), lower with metallo-β-lactamases], global region [highest for Latin America (94%), lowest for Asia-West Pacific (69%)], and US region (80%, South, versus 96%–100%, others). Although reduced susceptibility to comparators often predicted reduced susceptibility to plazomicin, even among comparator-intermediate or -resistant isolates the plazomicin-susceptible fraction was ≥77%, except for amikacin (53%).ConclusionsThe likely utility of plazomicin against CIR E. coli is high overall, but varies with region and multiple bacterial characteristics.
Antibiotic exposure and the risk of hospital-acquired diarrhoea and Clostridioides difficile infection: a cohort study
Authors: Schechner Vered , Fallach Noga , Braun Tali , Temkin Elizabeth , Carmeli Yehuda 
Published: April 2021

Abstract

Background
Hospital-acquired diarrhoea (HAD) and Clostridioides difficile infection (CDI) may be triggered by antibiotic use.

Objectives
To determine the effect of specific antibiotic agents and duration of therapy on the risk of HAD and CDI.

Patients and methods
A single-centre retrospective cohort study was conducted between May 2012 and December 2014 in the internal medicine division. HAD was defined based on documentation of diarrhoea in the medical record or an uncancelled C. difficile test in the laboratory database. CDI was diagnosed using a two-step test (initial glutamate dehydrogenase and toxin A/B EIA, with PCR for discrepant results). Outcomes first occurred on hospital Day 4 or later. Treatment with antibiotics and days of therapy were modelled.

Results
In 29 063 hospitalizations there were 970 HAD events [incidence rate per 10 000 patient days (IR) = 38.5] and 105 CDI events (IR = 3.9). Any antibiotic treatment increased the risk of HAD [adjusted relative risk (aRR) 2.79; 95% CI 2.27–3.43] and CDI (aRR 5.31; 95% CI 2.23–12.69). Each day of β-lactam/β-lactamase inhibitors (βL/βLIs), carbapenems, IV glycopeptides and metronidazole increased the risk of HAD. Each day of βL/βLIs, third- and fourth-generation cephalosporins and carbapenems increased the risk of CDI by over 2%.

Conclusions
Preventing HAD and CDI should focus on reducing the overall use of antibiotics and shortening antibiotic exposure, rather than focusing on specific agents.