bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature variance portends and indicates the extent of abrupt climate shifts
Authors: Ramadhin Christine , Yi Chuixiang , Hendrey George
Published: January 2021

Here, we show a discernable increase in temperature variance before a glacial termination by both the Ansari-Bradley test and the moving variance methods plus introduce the idea that there is a correlation between the peak variance and peak temperature increase. The behavior of temperature variance shows potential as a useful tool in analyzing time series data of Earth systems to assess the risk and extent of an upcoming abrupt climate transition.
IsoMiRmap: fast, deterministic and exhaustive mining of isomiRs from short RNA-seq datasets
Authors: Loher Phillipe , Karathanasis Nestoras , Londin Eric , F. Bray Paul , Pliatsika Venetia , Telonis Aristeidis G. , Rigoutsos Isidore
Published: January 2021

Motivation

MicroRNA (miRNA) precursor arms give rise to multiple isoforms simultaneously called ‘isomiRs.’ IsomiRs from the same arm typically differ by a few nucleotides at either their 5′ or 3′ termini or both. In humans, the identities and abundances of isomiRs depend on a person’s sex and genetic ancestry as well as on tissue type, tissue state and disease type/subtype. Moreover, nearly half of the time the most abundant isomiR differs from the miRNA sequence found in public databases. Accurate mining of isomiRs from deep sequencing data is thus important.

Results

We developed isoMiRmap, a fast, standalone, user-friendly mining tool that identifies and quantifies all isomiRs by directly processing short RNA-seq datasets. IsoMiRmap is a portable ‘plug-and-play’ tool, requires minimal setup, has modest computing and storage requirements, and can process an RNA-seq dataset with 50 million reads in just a few minutes on an average laptop. IsoMiRmap deterministically and exhaustively reports all isomiRs in a given deep sequencing dataset and quantifies them accurately (no double-counting). IsoMiRmap comprehensively reports all miRNA precursor locations from which an isomiR may be transcribed, tags as ‘ambiguous’ isomiRs whose sequences exist both inside and outside of the space of known miRNA sequences and reports the public identifiers of common single-nucleotide polymorphisms and documented somatic mutations that may be present in an isomiR. IsoMiRmap also identifies isomiRs with 3’ non-templated post-transcriptional additions. Compared to similar tools, isoMiRmap is the fastest, reports more bona fide isomiRs, and provides the most comprehensive information related to an isomiR’s transcriptional origin.

Availability and implementation

The codes for isoMiRmap are freely available at https://cm.jefferson.edu/isoMiRmap/ and https://github.com/TJU-CMC-Org/isoMiRmap/. IsomiR profiles for the datasets of the 1000 Genomes Project, spanning five population groups, and The Cancer Genome Atlas (TCGA), spanning 33 cancer studies, are also available at https://cm.jefferson.edu/isoMiRmap/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Two-hit mechanism of cardiac arrhythmias in diabetic hyperglycaemia: reduced repolarization reserve, neurohormonal stimulation, and heart failure exacerbate susceptibility
Authors: Hegyi Bence , Ko Christopher Y , Bossuyt Julie , Bers Donald M
Published: January 2021

Aims

Diabetic hyperglycaemia is associated with increased arrhythmia risk. We aimed to investigate whether hyperglycaemia alone can be accountable for arrhythmias or whether it requires the presence of additional pathological factors.

Methods and results

Action potentials (APs) and arrhythmogenic spontaneous diastolic activities were measured in isolated murine ventricular, rabbit atrial, and ventricular myocytes acutely exposed to high glucose. Acute hyperglycaemia increased the short-term variability (STV) of action potential duration (APD), enhanced delayed afterdepolarizations, and the inducibility of APD alternans during tachypacing in both murine and rabbit atrial and ventricular myocytes. Hyperglycaemia also prolonged APD in mice and rabbit atrial cells but not in rabbit ventricular myocytes. However, rabbit ventricular APD was more strongly depressed by block of late Na+ current (INaL) during hyperglycaemia, consistent with elevated INaL in hyperglycaemia. All the above proarrhythmic glucose effects were Ca2+-dependent and abolished by CaMKII inhibition. Importantly, when the repolarization reserve was reduced by pharmacological inhibition of K+ channels (either Ito, IKr, IKs, or IK1) or hypokalaemia, acute hyperglycaemia further prolonged APD and further increased STV and alternans in rabbit ventricular myocytes. Likewise, when rabbit ventricular myocytes were pretreated with isoproterenol or angiotensin II, hyperglycaemia significantly prolonged APD, increased STV and promoted alternans. Moreover, acute hyperglycaemia markedly prolonged APD and further enhanced STV in failing rabbit ventricular myocytes.

Conclusion

We conclude that even though hyperglycaemia alone can enhance cellular proarrhythmic mechanisms, a second hit which reduces the repolarization reserve or stimulates G protein-coupled receptor signalling greatly exacerbates cardiac arrhythmogenesis in diabetic hyperglycaemia.
A new player in the game: treatment with antagomiR-21a-5p significantly attenuates histological and echocardiographic effects of experimental autoimmune myocarditis
Authors: Mirna Moritz , Paar Vera , Topf Albert , Kraus Theo , Sotlar Karl , Aigner Achim , Ewe Alexander , Watzinger Simon , Podesser Bruno K , Hackl Matthias , Pistulli Rudin , Hoppe Uta C , Kiss Attila , Lichtenauer Michael
Published: January 2021

Aims 

Myocarditis is associated with formidable symptoms and increased risk of adverse outcomes. Current approaches mostly rely on symptomatic treatments, warranting novel concepts for clinical practice. The aim of this study was to investigate the microRNA (miRNA) expression profile of Balb/c mice with experimental autoimmune myocarditis (EAM), choose a representative miRNA to antagonize after review of available literature and test its effects on myocardial inflammation in vitro and in vivo.

Methods and results 

Phase 1: EAM was induced in 12 male Balb/c mice, 10 animals served as controls. After sacrifice, next-generation sequencing (NGS) of the miRNA expression profile was performed. Based on these results, H9C2 cells and human ventricular cardiac fibroblasts exposed to lipopolysaccharide (LPS) were treated with the selected candidate antagomiR-21a-5p. Phase 2: EAM was induced in 48 animals. Thereof, 24 animals were either treated with antagomiR-21a-5p or negative control oligonucleotide in a nanoparticle formulation. Transthoracic echocardiography (TTE) was performed on Days 0, 7, 14, and 21. Histopathological examination was performed after sacrifice. Phase 1: EAM resulted in a significant up-regulation of 27 miRNAs, including miR-21a-5p (log2FC: 2.23, adj. P = 0.0026). Transfection with antagomiR-21a-5p resulted in a significant reduction of TNFα, IL-6, and collagen I in vitro. Phase 2: Treatment with antagomiR-21a-5p, formulated in polymeric nanoparticles for systemic injection, significantly attenuated myocardial inflammation (P = 0.001) and fibrosis (P = 0.013), as well as myocardial ‘hypertrophy’ on TTE.

Conclusions 

Silencing of miR-21a-5p results in a significant reduction of the expression of pro-inflammatory cytokines in vitro, as well as a significant attenuation of inflammation, fibrosis and echocardiographic effects of EAM in vivo.
Kcnk3 dysfunction exaggerates the development of pulmonary hypertension induced by left ventricular pressure overload
Authors: Lambert Mélanie , Mendes-Ferreira Pedro , Ghigna Maria-Rosa , LeRibeuz Hélène , Adão Rui , Boet Angèle , Capuano Véronique , Rucker-Martin Catherine , Brás-Silva Carmen , Quarck Rozenn , Domergue Valérie , Vachiéry Jean-Luc , Humbert Marc , Perros Frédéric , Montani David , Antigny Fabrice
Published: January 2021

Aims

Pulmonary hypertension (PH) is a common complication of left heart disease (LHD, Group 2 PH) leading to right ventricular (RV) failure and death. Several loss-of-function (LOF) mutations in KCNK3 were identified in pulmonary arterial hypertension (PAH, Group 1 PH). Additionally, we found that KCNK3 dysfunction is a hallmark of PAH at pulmonary vascular and RV levels. However, the role of KCNK3 in the pathobiology of PH due to LHD is unknown.

Methods and results

We evaluated the role of KCNK3 on PH induced by ascending aortic constriction (AAC), in WT and Kcnk3-LOF-mutated rats, by echocardiography, RV catheterization, histology analyses, and molecular biology experiments. We found that Kcnk3-LOF-mutation had no consequence on the development of left ventricular (LV) compensated concentric hypertrophy in AAC, while left atrial emptying fraction was impaired in AAC-Kcnk3-mutated rats. AAC-animals (WT and Kcnk3-mutated rats) developed PH secondary to AAC and Kcnk3-mutated rats developed more severe PH than WT. AAC-Kcnk3-mutated rats developed RV and LV fibrosis in association with an increase of Col1a1 mRNA in right ventricle and left ventricle. AAC-Kcnk3-mutated rats developed severe pulmonary vascular (pulmonary artery as well as pulmonary veins) remodelling with intense peri-vascular and peri-bronchial inflammation, perivascular oedema, alveolar wall thickening, and exaggerated lung vascular cell proliferation compared to AAC-WT-rats. Finally, in lung, right ventricle, left ventricle, and left atrium of AAC-Kcnk3-mutated rats, we found a strong increased expression of Il-6 and periostin expression and a reduction of lung Ctnnd1 mRNA (coding for p120 catenin), contributing to the exaggerated pulmonary and heart remodelling and pulmonary vascular oedema in AAC-Kcnk3-mutated rats.

Conclusions

Our results indicate that Kcnk3-LOF is a key event in the pathobiology of PH due to AAC, suggesting that Kcnk3 channel dysfunction could play a potential key role in the development of PH due to LHD.
Silent brain infarcts and early cognitive outcomes after transcatheter aortic valve implantation: a systematic review and meta-analysis
Authors: Woldendorp Kei , Indja Ben , Bannon Paul G , Fanning Jonathon P , Plunkett Brian T , Grieve Stuart M
Published: January 2021

Background

Silent brain infarcts (SBIs) are frequently identified after transcatheter aortic valve implantation (TAVI), when patients are screened with diffusion-weighted magnetic resonance imaging (DW-MRI). Outside the cardiac literature, SBIs have been correlated with progressive cognitive dysfunction; however, their prognostic utility after TAVI remains uncertain. This study’s main goals were to explore (i) the incidence of and potential risk factors for SBI after TAVI; and (ii) the effect of SBI on early post-procedural cognitive dysfunction (PCD).

Methods and results

A systematic literature review was performed to identify all publications reporting SBI incidence, as detected by DW-MRI after TAVI. Silent brain infarct incidence, baseline characteristics, and the incidence of early PCD were evaluated via meta-analysis and meta-regression models. We identified 39 relevant studies encapsulating 2408 patients. Out of 2171 patients who underwent post-procedural DW-MRI, 1601 were found to have at least one new SBI (pooled effect size 0.76, 95% CI: 0.72–0.81). The incidence of reported stroke with focal neurological deficits was 3%. Meta-regression noted that diabetes, chronic renal disease, 3-Tesla MRI, and pre-dilation were associated with increased SBI risk. The prevalence of early PCD increased during follow-up, from 16% at 10.0 ± 6.3 days to 26% at 6.1 ± 1.7 months and meta-regression suggested an association between the mean number of new SBI and incidence of PCD. The use of cerebral embolic protection devices (CEPDs) appeared to decrease the volume of SBI, but not their overall incidence.

Conclusions

Silent brain infarcts are common after TAVI; and diabetes, kidney disease, and pre-dilation increase overall SBI risk. While higher numbers of new SBIs appear to adversely affect early neurocognitive outcomes, long-term follow-up studies remain necessary as TAVI expands to low-risk patient populations. The use of CEPD did not result in a significant decrease in the occurrence of SBI.
Cardiovascular preventive pharmacotherapy stratified by predicted cardiovascular risk: a national data linkage study
Authors: Mehta Suneela , Zhao Jinfeng , Poppe Katrina , Kerr Andrew J , Wells Sue , Exeter Dan J , Selak Vanessa , Grey Corina , Jackson Rod
Published: January 2021

Aims

Cardiovascular disease (CVD) risk management guided by predicted CVD risk is widely recommended internationally. This is the first study to examine CVD preventive pharmacotherapy in a whole-of-country primary prevention population, stratified by CVD risk.

Methods and results

Anonymized individual-level linkage of New Zealand administrative health and non-health data identified 2 250 201 individuals without atherosclerotic CVD, alive, and aged 30–74 years on 31 March 2013. We identified individuals with ≥1 dispensing by community pharmacies of blood pressure lowering (BPL) and/or lipid-lowering (LL) medications at baseline (1 October 2012–31 March 2013) and in 6-month periods between 1 April 2013 and 31 March 2016. Individuals were stratified using 5-year CVD risk equations specifically developed for application in administrative datasets. One-quarter of individuals had ≥5% 5-year risk (the current New Zealand guideline threshold for discussing preventive medications) and 5% met the ≥15% risk threshold for recommended dual therapy. By study end, dual therapy was dispensed to 2%, 18%, 34%, and 49% of individuals with <5%, 5–9%, 10–14%, and ≥15% 5-year risk, respectively. Among those dispensed baseline dual therapy, 83–89% across risk strata were still treated after 3 years. Dual therapy initiation during follow-up occurred among only 13% of high-risk individuals untreated at baseline. People without diabetes and those aged ≥65 years were more likely to remain untreated.

Conclusion

Cardiovascular disease primary preventive pharmacotherapy was strongly associated with predicted CVD risk and, once commenced, was generally continued. However, only half of high-risk individuals received recommended dual therapy and treatment initiation was modest. Individually linked administrative datasets can identify clinically relevant quality improvement opportunities for entire populations.
The role of exercise in the prevention of cancer therapy-related cardiac dysfunction in breast cancer patients undergoing chemotherapy: systematic review
Authors: Murray James , Bennett Hunter , Bezak Eva , Perry Rebecca
Published: January 2021

Aims

Breast cancer (BC) patients undergoing chemotherapy are at risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD; however, its effectiveness remains unclear. The aim of this systematic review was to establish the effect of exercise on global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) in BC patients undergoing chemotherapy, to determine if exercise can prevent the development of CTRCD.

Methods and results

Four databases (Medline, Scopus, eMbase, SPORTDiscus) were searched. Studies were eligible for inclusion if they measured GLS or LVEF prior to and following an exercise intervention of any length in BC patients undergoing chemotherapy and were published in English from 2000 onwards. Risk of bias was evaluated using the QUADAS-2 tool. Of the 398 studies screened, eight were eligible. Changes were similar in exercising (EX) and non-exercising (CON) groups for GLS (EX: pre: −19.6 ± 0.4, post: −20.1 ± 1.0, CON: pre: −20.0 ± 0.4, post: −20.1 ± 1) and LVEF (EX: pre: 58.5 ± 4.1%, post: 58.6 ± 2%, CON: pre: 56.6 ± 4.2%, post: 55.6 ± 4.6%). Exercise maintained or improved peak oxygen uptake (VO2peak) during chemotherapy, while declines were observed in non-exercising groups. The included studies were limited by methodological deficiencies.

Conclusion

The ability of exercise to prevent CTRCD is unclear. However, exercise positively impacts cardiorespiratory fitness in BC patients undergoing chemotherapy. Future research must address the methodological limitations of current research to understand the true effect of exercise in the prevention of CTRCD.
INTEGRATION EFFICIENCY IN DNA-INDUCED TRANSFORMATION OF PNEUMOCOCCUS. II. GENETIC STUDIES OF MUTANT INTEGRATING ALL THE MARKERS WITH A HIGH EFFICIENCY
Authors: Tiraby Gérard , Sicard Michel Armand
Published: January 2021

Transformation of the pneumococcus mutant 401 by DNA's bearing the standard reference marker and several other markers belonging to two unlinked loci has shown that differences in the integration efficiencies of these markers were considerably reduced in this strain compared to the wild-type strain Cl  3. The sensitivities of mutant 401 to ultraviolet light and to X-ray irradiation are the same as those of Cl  3. However, in 401 all the markers tested are more resistant to inactivation as shown by transformation of 401 and Cl  3 by ultraviolet-irradiated DNA. The increase in resistance is greater for low efficiency (LE) markers than for high efficiency (HE) markers.—The decreased discrimination between LE and HE markers in strain 401 is not due to a mechanism related to modification of markers in the transforming DNA by the recipient cells, nor are the proteins inducing competence of the cells responsible for the differences in the integration efficiencies of various markers.—Genetic studies of the fate of recombinants as well as the measure of the amount of DNA taken up have shown that all the markers are integrated in strain 401 by the same recombination process, that specific to high efficiency markers.
INHERITED BIOCHEMICAL VARIATION IN DROSOPHILA MELANOGASTER: NOISE OR SIGNAL? I. SINGLE-LOCUS ANALYSES
Authors: Sing Charles F , Brewer George J , Thirtle Barbara
Published: January 2021

A study was conducted using small effective population size as an experimental design to test selective neutrality of seven isozyme polymorphisms. Loci varied as to the degree to which the decay of heterozygosity over 21 generations was retarded. Selection for heterozygotes, overdominance, is implicated for at least four of seven loci. Of these ADH gave the largest heterozygote excess in the presence of inbreeding. An interaction between the small population size treatment and excess heterozygosity suggests that (1) the loci studied may be selectively neutral and linked to other loci which are under the influence of selection or (2) the selection coefficients for the loci studied are not independent of the background genotype. In either case four of the seven enzymes studied are signaling the operation of selection. The problem of distinguishing the effect of a single marker from that of a chromosome segment is emphasized. The identification of the genetic unit of selection is crucial to any interpretation of the meaning of enzyme polymorphisms.
ISOZYME GENOTYPE-ENVIRONMENT ASSOCIATIONS IN NATURAL POPULATIONS OF THE HARVESTER ANT, POGONOMYRMEX BADIUS
Authors: Tomaszewski Elizabeth K , Schaffer Henry E , Johnson F M
Published: January 2021

Harvester ants (P. badius) were collected from 49 localities in the southeastern U.S. Amylase and naphthylamidase activities were assayed by gel electrophoresis, and the frequencies of alleles controlling electrophoretic variation were calculated. Soil samples were analyzed and plotted against allelic frequencies. Climatographic and genetic data were analyzed by the method of principal components. Statistically significant correlations were found to occur between the patterns of genetic variation, and between the genetic and environmental patterns. These correlations are consistent with a selective basis for the maintenance of isozyme polymorphisms.
RECOMBINATION AT THE BAR LOCUS IN AN INVERTED ATTACHED-X SYSTEM IN DROSOPHILA MELANOGASTER
Authors: Gabay Susan J , Laughnan John R
Published: January 2021

Recombination at the Bar locus in Drosophila melanogaster was investigated in an inverted attached-X system which enhanced the frequency of homozygosis for the Bar region. Females among the progeny of homozygous B mothers were searched for changes of B to BB and to B+. Marker genes were followed and exceptional half-tetrads were analyzed in regard to two hypotheses: that of exchange between obliquely synapsed members of the duplication, which is associated with exchange of outside markers, and that of intrachromosomal exchange, which does not involve recombination of markers.—Recombinant exceptions of B+ /BB genotype, carrying the outside marker combinations predicted on the hypothesis of exchange between obliquely synapsed duplication members, were encountered repeatedly. It is established that B+ and BB strands are reciprocal products of the same event.—Twelve nonrecombinant exceptional strands were isolated; ten of these were B+ and two were BB. Only one of the nonrecombinant half-tetrads offered the opportunity to test the prediction of reciprocity of the intrachromosomal event. Analysis showed the exceptional female to be of the constitution BB/B, a type not expected on the hypothesis. While it could have arisen through some kind of copy error in the repair of a chromatid break, a valid test of the hypothesis of intrachromosomal exchange must rest on the isolation and analysis of more cases of the appropriate exceptional genotype.—In several cases Bar changes were found to be associated with aberrations; all but one of these involved spontaneous, cytologically identifiable deletions.
ASPARAGINE-REQUIRING TUMOR CELL LINES AND THEIR NON-REQUIRING VARIANTS: CYTOGENETICS, BIOCHEMISTRY AND POPULATION DYNAMICS
Authors: Colofiore Joseph , Morrow John , Patterson Manford K
Published: January 2021

Asparagine-requiring Jensen and Walker rat tumor cells and their asparagine-independent variants have been analyzed. The following results were obtained: (1) Both cell lines have very low levels of asparagine synthetase, and non-requiring revertants isolated from these lines have elevated levels of the enzyme. (2) No differences in chromosome number were detected between the parent Jensen line and five Jensen non-requiring revertants isolated from it. (3) Both Jensen and Walker cells undergo asparagineless death when deprived of this amino acid, although the Jensen cells do so at a more rapid rate. (4) Jensen requiring lines are at a selective advantage when grown in competition with non-requiring variants in complete medium, and their growth rate is more rapid when grown separately. The selective coefficients for the variant with respect to the asparagine-requiring parent ASN- line were 0.94 for the competition experiments and 0.83 for growth rate estimates. (5) A somatic cell hybrid between Chinese hamster cells (which require asparagine at low densities, and posses measurable synthetase activity) and the Walker line was found to be asparagine-independent, and it possessed enzyme levels equivalent to the hamster parent. The results of these investigations suggest a parallel with microbial auxotrophic mutants and can be understood in terms of alterations within nuclear structural genes.
DERIVATION OF TK- CLONES FROM REVERTANT TK+ MAMMALIAN CELLS
Authors: Roufa D J , Sadow B N , Caskey C T
Published: January 2021

In order to obtain a large collection of Chinese hamster cell clones defective in thymidine kinase (TK-), BrdUr selection experiments have been performed on wild-type and revertant TK+ cell lines. No clones (< 10-9) were obtained from the wild-type TK+ cell line by single-step selection. In contrast, revertant TK+ clones readily gave rise to stable TK- derivatives (1 - 2 × 10-4). Both wild-type and revertant TK+ clones spontaneously yielded 8-AGr colonies with the same frequency (1 - 5 × 10-6), suggesting that the differences between wild-type and revertant cell lines specifically affected selection of the TK- phenotype. The increased frequency of TK- clones reflects perhaps the number (ploidy) or character of the autosomal TK loci in TK+ revertants, or perhaps the mechanisms which regulate expression of the TK genes. Several mutagens, EMS, MNNG and UV, stimulated the TK+ revertants' frequency of TK- subclones only slightly (< 3-fold). Biochemical and genetic data indicated that the TK- clones derived from one revertant are phenotypically different. The phenotypes displayed by these cell lines are stable and do not depend upon the continued presence of the selective agent.
APPARENT SELECTION OF ENZYME ALLELES IN LABORATORY POPULATIONS OF DROSOPHILA
Authors: Powell Jeffrey R
Published: January 2021

Twelve laboratory populations of recently collected Drosophila willistoni were begun with different frequencies of alleles at three enzyme loci, six populations at 25° and six at 19°. Periodic sampling of the populations allowed monitoring of the frequency changes in allozymes over time.—At Lap-5 (a locus coding for leucine amino peptidase), three alleles converged to the same frequencies in all populations at both temperatures. The apparent equilibrium frequency of the major allele was about.75; this is different from the frequency (.57) found in the natural population from which the experimental populations were begun. Allele frequency changes at the esterase-5 locus (Est-5) were slower but consistent in all cages. It is difficult to determine if an equilibrium has been reached. However, the frequency of the rare allele in all cages is about the same as in wild populations, 5%. Alleles at both Lap-5 and Est-5 are non-randomly associated with inversions in the chromosomes onto which they map. Because of these associations, it is impossible to unambiguously attribute the change in allele frequencies to selection at the loci being observed.—After one year, no significant gene frequency changes were detected at Est-7, the third locus studied.
LOW GENE VARIATION IN DROSOPHILA BUSCKII
Authors: Prakash Satya
Published: January 2021

Study of allozyme variation in D. busckii at thirty loci gives the proportion of polymorphic loci =.166 and the proportion of loci heterozygous per individual =.044. D. busckii has a narrower seasonal and food niche than the other domestic species D. melanogaster which has more allozyme variation. It is suggested that the low gene variation in D. busckii might be due to adaptation of this species to a narrow niche.
CHROMOSOME MARKERS IN MUS MUSCULUS: STRAIN DIFFERENCES IN C-BANDING
Authors: Dev V G , Miller D A , Miller O J
Published: January 2021

The mitotic chromosomes of several inbred strains of mice and a series of F1 hybrids have been analyzed by quinacrine staining and further characterized by the centromeric heterochromatin banding (C-banding). Inbred strains had the same amount of C-banding material on homologous chromosomes but showed variation in the amount on different chromosomes. F1 hybrids showed characteristics of each parent and it appears that the amount of C-banding on each chromosome is a simple inherited polymorphism. In this study 12 different chromosomes could be distinguished by their C-banding, and these can be used as normal chromosome markers.
AN EXPERIMENTAL EVALUATION OF GENETIC CORRELATION
Authors: Rutledge J J , Eisen E J , Legates J E
Published: January 2021

Heritability and genetic correlations realized from both single-trait and antagonistic index selection were compared with paternal half-sib estimates. Primary attention was focused on the genetic correlation between six-week body weight and six-week tail length. Parameters realized from single-trait selection were in excellent agreement with paternal half-sib estimates. However, the realized genetic correlation between six-week body weight and six-week tail length obtained from index selection was significantly greater than the other estimates. Differential inbreeding levels and realized selection intensities were considered and rejected as being causative factors for these results. Linkage disequilibrium probably was not a factor either, as the base population had been randomly mated and randomly selected with a large effective population size for many generations. It was concluded that with antagonistic index selection, the pleiotropic effects of genes may be more powerful in retarding response in aggregate genotype than current theory would suggest. Replication of all selected and control lines allowed the use of between-line estimators of sampling variances of realized genetic parameters in the above comparisons. Generally, standard errors of realized genetic parameters were much smaller than corresponding paternal half-sib standard errors. Thus, selection was an efficient method of estimation.
NINETEEN PARACENTRIC CHROMOSOMAL INVERSIONS IN MICE
Authors: Roderick Thomas H , Hawes Norman L
Published: January 2021

Using mutagens on sperm and spermatids we have produced nineteen chromosomal inversions in mice. The levels of radiation and chemical mutagen we used induced inversions in about one per cent of the animals screened. Nine inversions have been transmitted through successive generations, and the particular frequency of first meiotic anaphase bridges manifested by each inversion remained constant. The cytological properties of first meiotic anaphases varied considerably among the inversions. Chromosomal locations of five inversions are known. Four of the five are fully viable in homozygous condition.
DETECTION AND IDENTIFICATION OF TRANSLOCATIONS BY INCREASED SPECIFIC NONDISJUNCTION IN ASPERGILLUS NIDULANS
Authors: Upshall Alan , Käfer Etta
Published: January 2021

A meiotic technique for visual detection of translocations has been applied to ten mitotically identified interchanges, and three new translocations were discovered using this method. Testcrosses between "standard" strains and potential translocation strains—e.g. strains with newly induced mutants or descendants from translocation crosses—are inspected for the frequency of abnormal-looking colonies. In all heterozygous translocation crosses "abnormals" are increased at least tenfold compared to the average control level of 0.15%. Most of these are disomics, and can be recognized by their characteristic phenotypes. Each translocation produces a few specific types, since nondisjunction is increased mainly in the linkage groups involved in the translocation (50–100-fold over control values). Therefore, translocations were not only detected but often tentatively assigned to linkage groups from the analysis of the disomic progeny in crosses. In addition, this technique allows reciprocal and nonreciprocal translocations to be distinguished, since only the latter produce one-third phenotypically abnormal duplication progeny. While results are clearcut in most cases, occasionally problems are encountered, e.g. when morphological mutants segregate in crosses, or when other genetic factors which increase or reduce the frequency of nondisjunction are present in certain strains.
DIVERGENT OPERONS AND THE GENETIC STRUCTURE OF THE MALTOSE B REGION IN ESCHERICHIA COLI K12
Authors: Hofnung Maurice
Published: January 2021

Complementation and polarity suppression data are interpreted in terms of the genetic structure of the maltose B region. It is proposed that this region comprises two divergent operons. One operon includes malK, a cistron involved in maltose permeation, and lamB the only known cistron specifically involved in λ receptor synthesis. The other operon includes malJ1 and malJ2 which are most probably two different cistrons, both involved in maltose permeation*. It is further assumed that expression of the two operons is controlled by malT, the positive regulatory gene of the maltose system, located in the malA region. The target(s) for the action of the malT product is (are) most likely to be located between malJ1 and malK. There is an indication that the two operons might overlap in the region of their promoters. The structure of such an overlap as well as the possible function of the products of the different cistrons in malB are briefly discussed.
THE SUPPRESSION OF GENE CONVERSION AND INTRAGENIC CROSSING OVER IN ASCOBOLUS IMMERSUS: EVIDENCE FOR MODIFIERS ACTING IN THE HETEROZYGOUS STATE
Authors: Girard J , Rossignol J L
Published: January 2021

Four distinct systems cv1, cv2, cv4 and cv6 behaving as monogenic factors have been found in the stock 28 of Ascobolus immersus. They each specifically suppress gene conversion in a spore pigmentation gene (respectively, b1, b2, b4 and b6). In the gene b2, where this phenomenon was studied in most detail, the effect of cv2 on the suppression of gene conversion is almost total; intragenic recombination is very strongly diminished and crossing over is also affected. In the genes b1, b2 and b4 the suppression of conversion is observed only when the corresponding modifier (cv1, cv2 and cv4) is in the heterozygous condition. It is likely that cv6 acts in the same way on b6. cv1 and b1 on one hand, cv2 and b2 on the other, are very closely linked; no recombination was observed between these modifiers and the corresponding spore pigmentation genes. The same genetic distance is observed between the linked genes b4 and b6 and between cv4 and cv6. This could indicate that these two modifiers are also closely linked to the corresponding genes. A possible effect of cv4 on intergenic recombination between b4 and b6 was shown: here again it acts by diminishing the frequency of recombination when cv4 is in the heterozygous state. The problem of the nature of the cv modifiers is discussed.
THE GENETIC STRUCTURE OF NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER. XI. GENETIC VARIABILITY IN A LOCAL POPULATION
Authors: Mukai Terumi , Yamaguchi Osamu
Published: January 2021

Six hundred and ninety-one second chromosomes were extracted from a Raleigh, North Carolina population, and the following experimental results were obtained: (1) Salivary gland chromosomes of all lines were observed and the number of inversion-carrying chromosomes was 130, among which 76 carried In(2R)NS, 36 carried In(2L)t, 4 carried In(2L)t and In(2R)NS, and 14 carried different kinds of rare inversions. (2) Viabilities of homozygotes and heterozygotes were examined. The frequency of lethal-carrying chromosomes was 275/691 (or 0.398):70/130 (or 0.538) in inversion-carrying chromosomes and 205/561 (or 0.365) in inversion-free chromosomes. The former is significantly higher than the latter. The average homozygote viability was 0.4342 including lethal lines and 0.7163 excluding those, the average heterozygote viability being 1.0000. The detrimental load to lethal load ratio (D:L ratio) was 0.334/0.501 = 0.67. The average viability of lethal heterozygotes was less than that of lethal-free heterozygotes, significantly in inversion-free individuals but not significantly so in inversion-carrying individuals. Inversion heterozygotes seem to have slightly better viability than the inversion-free heterozygotes on the average, but not significantly so. (3) The average degree of dominance of viability polygenes was estimated to be 0.293 ± 0.071 for all heterozygotes whose component chromosomes had better viabilities than 0.6 of the average heterozygote viability, 0.177 ± 0.077 for inversion-free heterozygotes and 0.489 ± 0.082 for inversion heterozygotes. (4) Mutation rates of viability polygenes and lethal genes were estimated on the basis of genetic loads and average degrees of dominance of lethal genes and viability polygenes. Estimates were very close to those obtained by direct estimation. (5) Possible overdominance and epistasis were detected, but the magnitude must be very small. (6) The effective size of the population was estimated to be much greater than 10,000 by using the allelism rate of lethal-carrying chromosomes (0.0040) and their frequency.—On the basis of these findings and the comparison with the predicted result (Mukai and Maruyama 1971), the mechanisms of the maintenance of genetic variability in the population are discussed.
SAMPLING VARIANCES OF HETEROZYGOSITY AND GENETIC DISTANCE
Authors: Nei Masatoshi , Roychoudhury A K
Published: January 2021

Mathematical formulae for the sampling variances of average heterozygosity and Nei's genetic distance are developed. These sampling variances are decomposed into their two components, i.e. the inter-locus and intra-locus variances. The relationship between the number of loci and the number of individuals per locus to be examined for estimating average heterozygosity and genetic distance is also discussed. The utility of the inter-locus variance of heterozygosity for studying the mechanism of maintenance of genetic variability in populations is indicated.
THE RELATIVE NUMBERS OF DIFFERENT GENES IN EXPONENTIAL MICROBIAL CULTURES
Authors: Painter P R
Published: January 2021

It is shown that the results of the marker frequency analysis of Sueoka and Yoshikawa (1965) can be derived as very good approximations from a model where the rigid assumptions of their analysis are relaxed to take into account statistical variations in the timing of cell events. It is further shown that the expression for the amount of DNA per cell can be approximated by an elementary exponential function of the growth rate, and this result facilitates genetic mapping by DNA hybridization techniques. An analysis of recent data on gene frequencies in Escherichia coli corroborates a model of symmetric, bidirectional chromosome replication with a replication time of approximately thirty minutes.
CHROMOSOMAL AND NONCHROMOSOMAL MUTATIONS AFFECTING THE "KILLER CHARACTER" OF SACCHAROMYCES CEREVISIAE
Authors: Wickner Reed B
Published: January 2021

The "killer character" of Saccharomyces cerevisiae is a nonchromosomal genetic element which imparts to cells carrying it (a) the ability to kill cells which lack it, by secreting the soluble macromolecular killer substance and (b) the ability to resist the killing effects of the killer substance.—Mutants have been isolated from S. cerevisiae carrying the "killer character". Mutants were found in two nuclear genes (mak1 and mak2) involved in maintenance of the genetic element of the killer character. Mutants in three other nuclear genes could maintain the cytoplasmic genetic element normally; two of these were able to express resistance to killing, but not the ability to kill (kex1 and kex2), while the third could express the killing function, but was sensitive to killing and is thus a "suicide" strain (rex1). These five nuclear genes were all distinct.—Several mutants were detected which showed non—mendelian segregation indicating mutation of the "cytoplasmic" genetic element. Some such mutants had normal resistance to killing but were either unable to kill at all or showed marked reduction in the ability to kill. Others had lost both killing ability and resistance. None were suppressive.—Two nonkilling mutants, both of which showed cytoplasmic inheritance, were mated. A large, but variable, proportion of diploid colonies, plated after several generations of growth, showed normal killing which has then stably inherited on further subcloning.
SELECTION FOR REDUCED CROSSING OVER IN DROSOPHILA MELANOGASTER
Authors: Abdullah Nasr F , Charlesworth Brian
Published: January 2021

Selection was practiced for reducing crossing over between the third chromosome genes Sb and H2 of Drosophila melanogaster, the method employed was to select the repulsion double heterozygotes Sb+/+H2 every generation. Two replicate selection lines were maintained. After 24 generations of selection, Line 1 showed no significant difference from the control, although the regression of recombination value on generation was significant. In generation 20, Line 2 had a significantly lower recombination value than the control, as well as having a highly significant regression coefficient. No chromosome rearrangements were involved in the response. It was concluded that there was substantial genic variability in the frequency of crossing over between Sb and H2 in the base population.
Tool recommender system in Galaxy using deep learning
Authors: Kumar Anup , Rasche Helena , Grüning Björn , Backofen Rolf
Published: January 2021

Background

Galaxy is a web-based and open-source scientific data-processing platform. Researchers compose pipelines in Galaxy to analyse scientific data. These pipelines, also known as workflows, can be complex and difficult to create from thousands of tools, especially for researchers new to Galaxy. To help researchers with creating workflows, a system is developed to recommend tools that can facilitate further data analysis.

Findings

A model is developed to recommend tools using a deep learning approach by analysing workflows composed by researchers on the European Galaxy server. The higher-order dependencies in workflows, represented as directed acyclic graphs, are learned by training a gated recurrent units neural network, a variant of a recurrent neural network. In the neural network training, the weights of tools used are derived from their usage frequencies over time and the sequences of tools are uniformly sampled from training data. Hyperparameters of the neural network are optimized using Bayesian optimization. Mean accuracy of 98% in recommending tools is achieved for the top-1 metric.

Conclusions

The model is accessed by a Galaxy API to provide researchers with recommended tools in an interactive manner using multiple user interface integrations on the European Galaxy server. High-quality and highly used tools are shown at the top of the recommendations. The scripts and data to create the recommendation system are available under MIT license at https://github.com/anuprulez/galaxy_tool_recommendation.
Reducing Stunting through Multisectoral Efforts in Sub-Saharan Africa
Authors: Skoufias Emmanuel , Vinha Katja , Sato Ryoko
Published: January 2021

This paper lays the groundwork for more effective multisectoral action on reducing stunting, by analysing and generating empirical evidence useful for informing the joint targeting of nutrition-sensitive interventions in the countries in Sub-Saharan Africa. Using information from 33 recent Demographic and Health Surveys, measures are constructed to capture a child’s access to food security, care practices, healthcare and water, sanitation and hygiene (WASH), in order to identify gaps in access among different socio-economic groups and relate access to these nutrition drivers with nutrition outcomes. Three main questions are addressed. (a) What is the extent to which children have inadequate access to the underlying determinants of nutrition? (b) What is the association between stunting and overlapping deprivations in adequate food and care practices, health and WASH services? (c) What are the sectors that have the greatest impact on stunting?
Factors Associated With Health-Related Quality of Life Among Cancer Survivors in the United States
Authors: Han Xuesong , Robinson L Ashley , Jensen Roxanne E , Smith Tenbroeck G , Yabroff K Robin
Published: January 2021

Background

With increasing prevalence of cancer survivors in the United States, health-related quality of life (HRQOL) has become a major priority. We describe HRQOL in a nationally representative sample of cancer survivors and examine associations with key sociodemographic, clinical, and lifestyle characteristics.

Methods

Cancer survivors, defined as individuals ever diagnosed with cancer (N = 877), were identified from the 2016 Medical Expenditure Panel Survey-Experiences with Cancer Survivorship Supplement, a nationally representative survey. Physical and mental health domains of HRQOL were measured by the Global Physical Health (GPH) and Global Mental Health (GMH) subscales of the Patient-Reported Outcomes Measurement Information System Global-10. Multivariable linear regression was used to examine associations of sociodemographic, clinical, and lifestyle factors with GPH and GMH scores. All statistical tests were 2-sided.

Results

Cancer survivors’ mean GPH (49.28, SD = 8.79) and mean GMH (51.67, SD = 8.38) were similar to general population means (50, SD = 10). Higher family income was associated with better GPH and GMH scores, whereas a greater number of comorbidities and lower physical activity were statistically significantly associated with worse GPH and GMH. Survivors last treated 5 years ago and longer had better GPH than those treated during the past year, and current smokers had worse GMH than nonsmokers (all β > 3 and all P < .001).

Conclusions

Cancer survivors in the United States have generally good HRQOL, with similar physical and mental health scores to the general US population. However, comorbidities, poor health behaviors, and recent treatment may be risk factors for worse HRQOL. Multimorbidity management and healthy behavior promotion may play a key role in maximizing HRQOL for cancer survivors.
Arbitral Jurisdictional Regulation in Investment Treaty Arbitration and Domestic Courts
Authors: Radović Relja
Published: January 2021

Arbitral tribunals in the field of investment treaty arbitration have generated rules governing their own jurisdiction. This article examines the effect of the controlling role of domestic courts on the development of arbitral jurisdictional regulation, tracking the treatment of arbitrator-made jurisdictional rules by domestic courts reviewing investment arbitral decisions. The article finds that domestic courts have not been resistant to but rather supportive of the proliferation of arbitrator-made jurisdictional rules. First, domestic courts have relied on such rules and treated their development as parts of interpretative exercises and as part of the arbitral judicial function. Second, domestic courts have engaged in discourses on the appropriateness of arbitrator-made jurisdictional rules in substance. This practice contradicts the expectation that domestic courts would contest arbitral jurisdictional regulation and shows the potential of domestic courts to contribute to the production of nuanced rules governing the jurisdiction of investment arbitral tribunals.
Intersection between Domestic Violence and International Parental Child Abduction: Protection of Abducting Mothers in Return Proceedings
Authors: Trimmings Katarina , Momoh Onyója
Published: January 2021

The focus of the article is on the intersection between domestic violence and parental child abduction, in particular, the interpretation of the Article 13(1)(b) ‘grave risk of harm’ defence in cases involving allegations of domestic violence by the abducting mother against the left-behind father, and on the protection of such abducting mothers in return proceedings. The content of the article is divided into two substantive parts. The first part explores the courts' approach to the grave risk of harm exception to return in circumstances where allegations of domestic violence have been raised. The second part of the article examines the courts' approach to protective measures, including undertakings, in child abduction cases involving allegations of domestic violence. The article engages extensively with the work of the Hague Conference on Private International Law and the EU in the area of international parental child abduction, as inter alia, it explores the problem of effectiveness of protective measures with reference to the 1996 Hague Convention on Jurisdiction, Applicable Law, Recognition, Enforcement and Co-operation in Respect of Parental Responsibility and Measures for the Protection of Children and the Regulation 606/2013 on mutual recognition of protection measures in civil matters.