bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromatin Insulator Elements Block the Silencing of a Target Gene by the Drosophila Polycomb Response Element (PRE) but Allow trans Interactions Between PREs on Different Chromosomes
Authors: Sigrist Christian J A , Pirrotta Vincenzo
Published: January 2021

Polycomb response elements (PREs) can establish a silenced state that affects the expression of genes over considerable distances. We have tested the ability of insulator or boundary elements to block the repression of the miniwhite gene by the Ubx PRE. The gypsy element and the scs element interposed between PRE and miniwhite gene protect it against silencing but the scs' is only weakly effective. When the PRE-miniwhite gene construct is insulated from flanking chromosomal sequences by gypsy elements at both ends, it can still establish efficient silencing in some lines but not others. We show that this can be caused by interactions in trans with PREs at other sites. PRE-containing transposons inserted at different sites or even on different chromosomes can interact, resulting in enhanced silencing. These trans interactions are not blocked by the gypsy insulator and reveal the importance of nonhomologous associations between different regions of the genome for both silencing and activation of genes. The similarity between the behavior of PREs and enhancers suggests a model for their long-distance action.
The Y-Chromosomal and Autosomal Male-Determining M Factors of Musca domestica Are Equivalent
Authors: Schmidt R , Hediger M , Roth S , Nöthiger R , Dubendorfer A
Published: January 2021

In Musca domestica, male sex is determined by a dominant factor, M, located either on the Y, the X or on an autosome. M prevents the activity of the female-determining gene F. In the absence of M, F becomes active and dictates female development. The various M factors may represent translocated copies of an ancestral Y-chromosomal M. Double mutants and germ line chimeras show that MY, MI, MII, MIII and MV perform equivalent functions. When brought into the female germ line, they predetermine male development of the offspring. This maternal effect is overruled by the dominant female-determining factor FD. MI and MII are weak M factors, as demonstrated by the presence of yolk proteins in MI/+ males and by the occurrence of some intersexes among the offspring that developed from transplanted MI/+ and MII/+ pole cells. The arrhenogenic mutation Ag has its focus in the female germ line and its temperature-sensitive period during oogenesis. We propose that MI and Ag represent allelic M factors that are affected in their expression. Analysis of mosaic gonads showed that in M. domsticu the sex of the germ line is determined by inductive signals from the surrounding soma. We present a model to account for the observed phenomena.
Clusters of Identical New Mutations Can Account for the “Overdispersed” Molecular Clock
Authors: Huai Haiying , Woodruff R C
Published: January 2021

Germ-cell mutations may occur during meiosis, giving rise to independent mutant gametes in a Poisson process, or before meiosis, giving rise to multiple copies of identical mutant gametes at a much higher probability than the Poisson expectation. We report that the occurrence of these early premeiotic clusters of new identical mutant alleles increases the variance-to-mean ratio of mutation rate (R(u) > 1). This leads to an expected variance-to-mean ratio (R(t)) of the molecular clock that is always greater than one and may cover the observed range of R(t) values. Hence, the molecular clock may not be overdispersed based on this new mutational model that includes clusters. To get a better estimation of R(u) and R(t), one needs measurements of the intrageneration variation of reproductive success (Ni/Ne(i)), population dynamics (k‒i), and the proportion of new mutations that occur in clusters (rc), especially those formed before germ-cell differentiation.
In Vivo Analysis of Saccharomyces cerevisiae COX2 mRNA 5′-Untranslated Leader Functions in Mitochondrial Translation Initiation and Translational Activation
Authors: Dunstan Heather M , Green-Willms Noelle S , Fox Thomas D
Published: January 2021

We have used mutational and revertant analysis to study the elements of the 54-nucleotide COX2 5′-untranslated leader involved in translation initiation in yeast mitochondria and in activation by the COX2 translational activator, Pet111p. We generated a collection of mutants with substitutions spanning the entire COX2 5′-UTL by in vitro mutagenesis followed by mitochondrial transformation and gene replacement. The phenotypes of these mutants delimit a 31-nucleotide segment, from −16 to −46, that contains several short sequence elements necessary for COX2 5′-UTL function in translation. The sequences from −16 to −47 were shown to be partially sufficient to promote translation in a foreign context. Analysis of revertants of both the series of linker-scanning alleles and two short deletion/insertion alleles has refined the positions of several possible functional elements of the COX2 5′-untranslated leader, including a putative RNA stem-loop structure that functionally interacts with Pet111p and an octanucleotide sequence present in all S. cerevisiae mitochondrial mRNA 5′-UTLs that is a potential rRNA binding site.
Specialized Rap1p/Gcr1p Transcriptional Activation Through Gcr1p DNA Contacts Requires Gcr2p, as Does Hyperphosphorylation of Gcr1p
Authors: Zeng Xiao , Deminoff Stephen J , Santangelo George M
Published: January 2021

The multifunctional regulatory factor Rap1p of Saccharomyces cerevisiae accomplishes one of its tasks, transcriptional activation, by complexing with Gcr1p. An unusual feature of this heteromeric complex is its apparent capacity to contact simultaneously two adjacent DNA elements (UASRPG and the CT box, bound specifically by Rap1p and Gcr1p, respectively). The complex can activate transcription through isolated UASRPG but not CT elements. In promoters that contain both DNA signals its activity is enhanced, provided the helical spacing between the two elements is appropriate; this suggests that at least transient DNA loop formation is involved. We show here that this CT box-dependent augmentation of Rap1p/Gcr1p activation requires the presence of a third protein Gcr2p; the Gcr2– growth defect appears to result from a genome-wide loss of the CT box effect. Interestingly, a hyperphosphorylated form of Gcr1p disappears in Δgcr2 cells but reappears if they harbor a doubly point-mutated GCR1 allele that bypasses the Gcr2– growth defect. Gcr2p therefore appears to induce a conformation change in Gcr1p and/or stimulate its hyperphosphorylation; one or both of these effects can be mimicked in the absence of GCR2 by mutation of GCR1. This improved view of Rap1p/Gcr1p/Gcr2p function reveals a new aspect of eukaryotic gene regulation: modification of an upstream activator, accompanied by at least transient DNA loop formation, mediates its improved capacity to activate transcription.
Mobile Element 297 in the Abd-B gene of Drosophila melanogaster, Not Delta 88, Is Responsible for the tuh-3 Mutation
Authors: Mack Judith A , Smith Ronald D , Kuhn David T
Published: January 2021

The tumorous-head-3 (tuh-3) mutation has been associated with the insertion of mobile element Delta 88 at +200 on the bithorax complex (BX-C) DNA map, 5′ of all Abdominal-B (Abd-B) transcripts. Different phenotypes of tuh-3 are regulated by the tumorous-head-1 (tuh-1) maternal effect locus. In the presence of the recessive tuh-1h maternal effect, tuh-3 offspring produce homeotic abdominal and genital tissue in the head. In the presence of the dominant tuh-1g maternal effect, tuh-3 offspring have normal heads but now show genital defects. One other mutant, I127B, produces flies with identical defects to that of tuh-3 in the presence of both maternal effects. Molecular analysis of I127B revealed the insertion of mobile element 297 in the Abd-B gene, ∼25 kb downstream of the Delta 88 insertion in tuh-3. No other abnormalities were detected. Reexamination of our tuh-3 strain revealed a 297 insertion in an identical region to that of I127B, in addition to the Delta 88 insertion. Recombinants of tuh-3, carrying 297 only, produced homeotic head defects and genital defects in the presence of the tuh-1h and tuh-1R maternal effects, respectively. Recombinants of tuh-3, carrying Delta 88 only, failed to produce any defects in the presence of either maternal effect. Based upon these results, we propose that it is the 297 insertion in the Abd-B gene, not Delta 88, that is responsible for the tuh-3 mutation.
Mismatch Repair by Efficient Nick-Directed, and Less Efficient Mismatch-Specific, Mechanisms in Homologous Recombination Intermediates in Chinese Hamster Ovary Cells
Authors: Miller Elizabeth M , Hough Heather L , Cho Jennifer W , Nickoloff Jac A
Published: January 2021

Repair of single-base mismatches formed in recombination intermediates in vivo was investigated in Chinese hamster ovary cells. Extrachromosomal recombination was stimulated by double-strand breaks (DSBs) introduced into regions of shared homology in pairs of plasmid substrates heteroallelic at 11 phenotypically silent mutations. Recombination was expected to occur primarily by single-strand annealing, yielding predicted heteroduplex DNA (hDNA) regions with three to nine mismatches. Product spectra were consistent with hDNA only occurring between DSBs. Nicks were predicted on opposite strands flanking hDNA at positions corresponding to original DSB sites. Most products had continuous marker patterns, and observed conversion gradients closely matched predicted gradients for repair initiated at nicks, consistent with an efficient nick-directed, excision-based mismatch repair system. Discontinuous patterns, seen in ∼10% of products, and deviations from predicted gradients provided evidence for less efficient mismatch-specific repair, including G-A → G-C specific repair that may reflect processing by a homologue of Escherichia coli MutY. Mismatch repair was >80% efficient, which is higher than seen previously with covalently closed, artificial hDNA substrates. Products were found in which all mismatches were repaired in a single tract initiated from one or the other nick. We also observed products resulting from two tracts of intermediate length initiated from two nicks.
Inheritance and Mapping of Compact (Cmpt), a New Mutation Causing Hypermuscularity in Mice
Authors: Varga László , Szabó Gyula , Darvasi Ariel , Müller Géza , Sass Miklós , Soller Morris
Published: January 2021

During selection for protein content in mice at the Technical University of Berlin, individuals showing high protein content and a compact exterior were noted. Animals showing this “Compact” phenotype were separated to form a new line. The present investigations were carried out on a Hungarian subpopulation of this line, selected for maximum expression of the Compact phenotype, and apparently at fixation for the relevant genes. Fertility and viability of the Compact subpopulation was normal. As compared to normal mice, carcass percentage values for male and female Compact mice were 9.4 and 6.8% greater, respectively; and the muscle:bone weight ratio in males was 1.61-fold greater. The Compact phenotype showed variable expressivity and was of intermediate dominance in males, but almost fully recessive in females. The hypothesis that a single gene is solely responsible for the Compact phenotype was rejected by maximum likelihood analysis. Linkage mapping using selective DNA pooling located a single locus (denoted Cmpt) strongly associated with the Compact phenotype on mouse chromosome 1. Fine mapping, using individual selective genotyping and haplotype analysis, located Cmpt to the region between D1Mit375 and D1Mit21, approximately one third of the way to D1Mit21.
Analysis of Recombination Sites Within the Maize waxy Locus
Authors: Okagaki Ron J , Weil Clifford F
Published: January 2021

Genetic fine structure analysis of the maize wx locus has determined that the ratio of genetic to physical distance within wx was one to two orders of magnitude higher than the average for the maize genome. Similar results have been found at other maize loci. In this study, we examined several mechanisms that could account for this pattern. First, crossovers in two other maize genes resolve preferentially at specific sites. By mapping exchanges between wx-B1 and wx-I relative to a polymorphic SstI site, we found no evidence for such a hotspot at wx. Second, deletion of promoter sequences from wx alleles had little effect on recombination frequencies, in contrast to results in yeast where promoter sequences are important for initiating recombination in some genes. Third, high levels of insertion polymorphism may suppress intergenic recombination. However, the presence of a 2-kb Ds element 470 bp upstream of the wx transcription start site did not further suppress recombination between Ds insertions in nearby wx sequences. Thus, none of these mechanisms is sufficient to explain the difference between intergenic and intragenic recombination rates at wx.
Evolutionary Dynamics of Sporophytic Self-Incompatibility Alleles in Plants
Authors: Schierup Mikkel H , Vekemans Xavier , Christiansen Freddy B
Published: January 2021

The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model of gametophytic self-incompatibility, but the selection intensity is stronger. With dominance, dominant alleles invade the population more easily than recessive alleles and have a lower frequency at equilibrium. In the SSIdom model, recessive alleles have both a higher allele frequency and higher expected life span. In the SSIdomcod model, however, loss due to drift occurs more easily for pollen-recessive than for pollen-dominant alleles, and therefore, dominant alleles have a higher expected life span than the more recessive alleles. The process of allelic turnover in the SSIdomcod and SSIdom models is closely approximated by a random walk on a dominance ladder. Implications of the results for experimental studies of sporophytic self-incompatibility in natural populations are discussed.
The Effect of Marker Heterozygosity on the Power to Detect Linkage Disequilibrium
Authors: Ott Jurg , Rabinowitz Daniel
Published: January 2021

The relationship between marker heterozygosity and the power to detect linkage disequilibrium is examined through the analysis of an example and through a simulation study. The analysis suggests that, despite the penalties for multiple testing incurred with multiple alleles, greater heterozygosity results in greater power. The results of the simulation study are in accord with those of the analysis.
Mcs4, a Two-Component System Response Regulator Homologue, Regulates the Schizosaccharomyces pombe Cell Cycle Control
Authors: Cottarel Guillaume
Published: January 2021

The Schizosaccharomyces pombe cdc2-3w weel-50 double mutant displays a temperature-sensitive lethal phenotype termed mitotic catastrophe. Six mitotic catastrophe suppressor (mcs1-6) genes were identified in a genetic screen designed to identify regulators of cdc2. Mutations in mcs1-6 suppress the cdc2-3w weel-50 temperature-sensitive growth defect. Here, the cloning of mcs4 is described. The mcs4 gene product displays significant sequence homology to members of the two-component system response regulator protein family. Strains carrying the mcs4 and cdc25 mutations display a synthetic osmotic lethal phenotype along with an inability to grow on minimal synthetic medium. These phenotypes are suppressed by a mutation in wee1. In addition, the wis1 gene, encoding a stress-activated mitogen-activated protein kinase kinase, was identified as a dosage suppressor in this screen. These findings link the two-component signal transduction system to stress response and cell cycle control in S. pombe.
Mitochondrial and Nuclear DNA Diversity in the Chocó and Chibcha Amerinds of Panamá
Authors: Kolman Connie J , Bermingham Eldredge
Published: January 2021

Mitochondrial and nuclear DNA diversities were determined for two Chocó-speaking Amerind populations, the Emberá and Wounan, sampled widely across their geographic range in eastern Panamá. These data were compared with mitochondrial and nuclear diversities determined here and previously for neighboring Chibcha-speaking Ngöbé and Kuna populations. Chocoan groups exhibited mitochondrial diversity levels typical for Amerind populations while Chibchan groups revealed reduced mitochondrial diversity. A slight reduction in autosomal levels of heterozygosity was determined for the Chibcha while X and Y variation appeared equivalent in all populations. Genetic distinctiveness of the two linguistic groups contradicts the anthropological theory that Paleoindians migrated repeatedly through the isthmian region and, instead, supports the idea of cultural adaptation by endogenous populations. Reduced genetic diversity in Chibchan populations has been proposed to represent a population bottleneck dating to Chibchan ethnogenesis. The relative sensitivities of haplotype pairwise difference distributions and Tajima's D to detect demographic events such as population bottlenecks are examined. Also, the potential impact of substitution rate heterogeneity, population subdivision, and genetic selection on pairwise difference distributions are discussed. Evidence is presented suggesting that a larger effective population size may obscure the historical signal obtained from nuclear genes while the single mitochondrial locus may provide a moderately strong signal.
The Dynamics of Gynodioecy in Plantago lanceolatu L. II. Mode of Action and Frequencies of Restorer Alleles
Authors: de Haan Anita A , Koelewijn Hans P , Hundscheid Maria P J , Van Damme Jos M M
Published: January 2021

Male fertility in Plantago lanceolata is controlled by the interaction of cytoplasmic and nuclear genes. Different cytoplasmic male sterility (CMS) types can be either male sterile or hermaphrodite, depending on the presence of nuclear restorer alleles. In three CMS types of P. lanceolata (CMSI, CMSIIa, and CMSIIb) the number of loci involved in male fertility restoration was determined. In each CMS type, male fertility was restored by multiple genes with either dominant or recessive action and capable either of restoring male fertility independently or in interaction with each other (epistasis). Restorer allele frequencies for CMSI, CMSIIa and CMSIIb were determined by crossing hermaphrodites with “standard” male steriles. Segregation of male steriles vs. non-male steriles was used to estimate overall restorer allele frequency. The frequency of restorer alleles was different for the CMS types: restorer alleles for CMSI were less frequent than for CMSIIa and CMSIIb. On the basis of the frequencies of male steriles and the CMS types an “expected” restorer allele frequency could be calculated. The correlation between estimated and expected restorer allele frequency was significant.
Identification of a New Class of Negartive Regulators Affecting Sporulation-Specific Gene Expression in Yeast
Authors: Benni Mei Li , Neigeborn Lenore
Published: January 2021

We characterized two yeast loci, MDS3 and PMD1, that negatively regulate sporulation. Initiation of sporulation is mediated by the meiotic activator IME1, which relies on MCK1 for maximal expression. We isolated the MDS3-1 allele (encoding a truncated form of Mds3p) as a suppressor that restores IME1 expression in mck1 mutants. mds3 null mutations confer similar suppression phenotypes as MDS3-1, indicating that Mds3p is a negative regulator of sporulation and the MDS3-1 allele confers a dominant-negative phenotype. PMD1 is predicted to encode a protein sharing significant similarity with Mds3p. mds3 pmd1 double mutants are better suppressors of mck1 than is either single mutant, indicating that Mds3p and Pmd1p function synergistically. Northern blot analysis revealed that suppression is due to increased IME1 transcript accumulation. The roles of Mds3p and Pmd1p are not restricted to the MCK1 pathway because mds3 pmd1 mutations also suppress IME1 expression defects associated with MCK1-independent sporulation mutants. Furthermore, mds3 pmdl mutants express significant levels of IME1 even in vegetative cells and this unscheduled expression results in premature sporulation. These phenotypes, and interactions with RAS2-Val19 suggest that unscheduled derepression of IME1 is probably due to a defect in recognition of nutritional status.
Marker-Assisted Introgression of Quantitative Trait Loci
Authors: Hospital Frédéric , Charcosset Alain
Published: January 2021

The use of molecular markers for the introgression of one or several superior QTL alleles into a recipient line is investigated using analytic and simulation results. The positions of the markers devoted to the control of the genotype at the QTLs in a “foreground selection” step are optimized given the confidence interval of the QTL position. Results demonstrate that using at least three markers per QTL allows a good control over several generations. Population sizes that should be recommended for various numbers of QTLs are calculated and are used to determine the limit in the number of QTLs that can be monitored simultaneously. If “background selection” devoted to accelerate the return to the recipient parent genotype outside the QTL regions is applied, the positions of the markers devoted to the control of the QTLs have to be reconsidered. When several QTLs are monitored simultaneously, background selection among the limited number of individuals resulting from the foreground selection step accelerates the increase in genomic similarity with the recipient parent, with only limited costs. Background selection is even more efficient in a pyramidal backcross program where QTLs are first monitored one by one.
Genetic Analysis of Mutations Affecting pckA Regulation in Rhizobium (Sinorhizobium) meliloti
Authors: Østerås Magne , O'Brien Shelley A P , Finan Turlough M
Published: January 2021

The enzyme phosphoenolpyruvate carboxykinase (Pck) catalyzes the first step in the gluconeogenic pathway in most organisms. We are examining the genetic regulation of the gene encoding Pck, pckA, in Rhizobium (now Sinorhizobium) meliloti. This bacterium forms N2-fixing root nodules on alfalfa, and the major energy sources supplied to the bacteria within these nodules are C4-dicarboxylic acids such as malate and succinate. R. meliloti cells growing in glucose minimal medium show very low pckA expression whereas addition of succinate to this medium results in a rapid induction of pckA transcription. We identified spontaneous mutations (rpk) that alter the regulation of pckA expression such that pckA is expressed in media containing the non-inducing carbon sources lactose and glucose. Genetic and phenotypic analysis allowed us to differentiate at least four rpk mutant classes that map to different locations on the R. meliloti chromosome. The wild-type locus corresponding to one of these rpk loci was cloned by complementation, and two Tn5 insertions within the insert DNA that no longer complemented the rpk mutation were identified. The nucleotide sequence of this region revealed that both Tn5 insertions lay within a gene encoding a protein homologous to the Ga1R/LacI family of transcriptional regulators that are involved in metabolism.
Characterization of the Roles of the Saccharomyces cerevisiae RAD54 Gene and a Homologue of RAD54, RDH54/TID1, in Mitosis and Meiosis
Authors: Shinohara Miki , Shita-Yamaguchi Emi , Buerstedde Jean-Marie , Shinagawa Hideo , Ogawa Hideyuki , Shinohara Akira
Published: January 2021

The RAD54 gene, which encodes a protein in the SW12/SNF2 family, plays an important role in recombination and DNA repair in Saccharomyces cerevisiae. The yeast genome project revealed a homologue of RAD54, RDH54/TID1. Properties of the rdh54/tid1 mutant and the rad54 rdh54/tid1 double mutant are shown for mitosis and meiosis. The rad54 mutant is sensitive to the alkylating agent, methyl methanesulfonate (MMS), and is defective in interchromosomal and intrachromosomal gene conversion. The rdh54/tid1 single mutant, on the other hand, does not show any significant deficiency in mitosis. However, the rad54 rdh54/tid1 mutant is more sensitive to MMS and more defective in interchromosomal gene conversion than is the rad54 mutant, but shows the same frequency of intrachromosomal gene conversion as the rad54 mutant. These results suggest that RDH54/TID1 is involved in a minor pathway of mitotic recombination in the absence of RAD54. In meiosis, both single mutants produce viable spores at slightly reduced frequency. However, only the rdh54/tid1 mutant, but not the rad54 mutant, shows significant defects in recombination: retardation of the repair of meiosis-specific double-strand breaks (DSBs) and delayed formation of physical recombinants. Furthermore, the rad54 rdh54/tid1 double mutant is completely defective in meiosis, accumulating DSBs with more recessed ends than the wild type and producing fewer physical recombinants than the wild type. These results suggest that one of the differences between the late stages of mitotic recombination and meiotic recombination might be specified by differential dependency on the Rad54 and Rdh54/Tid1 proteins.
A MADS-Box Homologue in Ustilago maydis Regulates the Expression of Pheromone-Inducible Genes but Is Nonessential
Authors: Krüger Julia , Aichinger Christian , Kahmann Regine , Bölker Michael
Published: January 2021

Mating and pathogenic development in the smut fungus Ustilago maydis are controlled by a pheromone/receptor system and two homeodomain proteins, bEp and bWp, which form heterodimers in nonallelic combinations. We describe the isolation of a gene, umc1, encoding a MADS-box protein, which displays significant similarity to the Saccharomyces cerevisiae MCM1 gene. umc1 complemented the viability defect of yeast mcm1 mutants. In U. maydis, urn1 deletion mutants were viable and pathogenic development was unaffected. Nevertheless, the basal expression levels of several pheromone-inducible genes were significantly reduced leading to an attenuated mating reaction. In contrast to S. cerevisiae, where Mcm1p plays a crucial role in the cell-type specific expression of a- and α-specific genes, the U. maydis umc1 gene appears to have only a modulatory effect on the expression of mating type-specific genes.
The congested-like tracheae Gene of Drosophila melanogaster Encodes a Member of the Mitochondrial Carrier Family Required for Gas-Filling of the Tracheal System and Expansion of the Wings After Eclosion
Authors: Hartenstein Kirsten , Sinha Pradip , Mishra Arati , Schenkel Heide , Török Istvan , Mechler Bernard M
Published: January 2021

A recessive semi-lethal mutation resulting from the insertion of a P-lacW transposon at the cytological position 23A on the polytene chromosomes of Drosophila melanogaster was found to affect the unfolding and expansion of the wings resulting in a loss of venation and a marked decrease in their size. Lethality was polyphasic with numerous animals dying during early larval development and displaying apparently collapsed tracheal trees. The gene was therefore designated as congested-like tracheae, or colt. The colt mutation resulted from the insertion of a P-lacW transposon within the coding region of a 1.4kb transcript. Wild-type function was restored by inducing a precise excision of the P-lacWtransposon, while a deletion of the colt locus, produced by imprecise excision of the P element, showed a phenotype similar to that of the original P insert. The colt gene consists of a single exon and encodes a protein of 306 amino acids made of three tandem repeats, each characterized by two predicted transmembrane segments and a loop domain. The COLT protein shares extensive homology with proteins in the mitochondrial carrier family and particularly with the DIF-1 protein of Caenwhabditis ekgans, which has been shown to be maternally required for embryonic tissue differentiation. Our analysis revealed that zygotic colt function is dispensable for normal embryonic morphogenesis but is required for gas-filling of the tracheal system at hatching time of the embryo and for normal epithelial morphogenesis of the wings.
Additive genetic variance and covariance between relatives in synthetic wheat crosses with variable parental ploidy levels
Authors: Puhl L E , Crossa J , Munilla S , Pérez-Rodríguez P , Cantet R J C
Published: January 2021

Cultivated bread wheat (Triticum aestivum L.) is an allohexaploid species resulting from the natural hybridization and chromosome doubling of allotetraploid durum wheat (T. turgidum) and a diploid goatgrass Aegilops tauschii Coss (Ae. tauschii). Synthetic hexaploid wheat (SHW) was developed through the interspecific hybridization of Ae. tauschii and T. turgidum, and then crossed to T. aestivum to produce synthetic hexaploid wheat derivatives (SHWDs). Owing to this founding variability, one may infer that the genetic variances of native wild populations vs improved wheat may vary due to their differential origin and evolutionary history. In this study, we partitioned the additive variance of SHW and SHWD with respect to their breed origin by fitting a hierarchical Bayesian model with heterogeneous covariance structure for breeding values to estimate variance components for each breed category, and segregation variance. Two data sets were used to test the proposed hierarchical Bayesian model, one from a multi-year multi-location field trial of SHWD and the other comprising the two species of SHW. For the SHWD, the Bayesian estimates of additive variances of grain yield from each breed category were similar for T. turgidum and Ae. tauschii, but smaller for T. aestivum. Segregation variances between Ae. tauschii—T. aestivum and T. turgidum—T. aestivum populations explained a sizable proportion of the phenotypic variance. Bayesian additive variance components and the Best Linear Unbiased Predictors (BLUPs) estimated by two well-known software programs were similar for multi-breed origin and for the sum of the breeding values by origin for both data sets. Our results support the suitability of models with heterogeneous additive genetic variances to predict breeding values in wheat crosses with variable ploidy levels.
Longitudinal Correlates of Loneliness and Psychological Distress During the Lockdown Situation due to COVID-19. Effects of Age and Self-Perceptions of Aging
Authors: Losada-Baltar Andrés , Martínez-Huertas José Ángel , Jiménez-Gonzalo Lucía , Pedroso-Chaparro María del Sequeros , Gallego-Alberto Laura , Fernandes-Pires José , Márquez-González María
Published: January 2021

Objectives

To longitudinally analyze the correlates of loneliness and psychological distress in people exposed to the coronavirus disease 2019 (COVID-19) lockdown, exploring the effects of age and self-perceptions of aging (SPA).

Methods

A longitudinal follow-up of 1,549 participants was carried out at four different time points during the lockdown in Spain. Questions about the risk of COVID-19, age, SPA, family and personal resources, loneliness, and psychological distress were measured.

Results

Changes in loneliness showed a linear longitudinal trajectory through time, but changes in psychological distress showed a U-shaped relationship with time. Age was a relevant predictor of differences in distress, with older people reporting less psychological distress. Change in both dependent variables was related to change in different predictors like family and personal variables and also to negative SPA.

Discussion

In a stressful situation such as the COVID-19 pandemic, older adults may be more resilient to adverse mental health outcomes by using more adaptive resources that strengthen their resilience. Support is provided for the importance of stereotyped views of the aging process that, independently of chronological age, may put people at risk of suffering adverse mental health outcomes such as loneliness and psychological distress in times of crisis.
Regulating the Regulators: Mechanisms of Substrate Selection of the O-GlcNAc Cycling Enzymes OGT and OGA
Authors: Stephen Hannah M , Adams Trevor M , Wells Lance
Published: January 2021

Thousands of nuclear and cytosolic proteins are modified with a single β-N-acetylglucosamine on serine and threonine residues in mammals, a modification termed O-GlcNAc. This modification is essential for normal development and plays important roles in virtually all intracellular processes. Additionally, O-GlcNAc is involved in many disease states, including cancer, diabetes, and X-linked intellectual disability. Given the myriad of functions of the O-GlcNAc modification, it is therefore somewhat surprising that O-GlcNAc cycling is mediated by only two enzymes: the O-GlcNAc transferase (OGT), which adds O-GlcNAc, and the O-GlcNAcase (OGA), which removes it. A significant outstanding question in the O-GlcNAc field is how do only two enzymes mediate such an abundant and dynamic modification. In this review, we explore the current understanding of mechanisms for substrate selection for the O-GlcNAc cycling enzymes. These mechanisms include direct substrate interaction with specific domains of OGT or OGA, selection of interactors via partner proteins, posttranslational modification of OGT or OGA, nutrient sensing, and localization alteration. Altogether, current research paints a picture of an exquisitely regulated and complex system by which OGT and OGA select substrates. We also make recommendations for future work, toward the goal of identifying interaction mechanisms for specific substrates that may be able to be exploited for various research and medical treatment goals.
Assessing the relationship between monoallelic PRKN mutations and Parkinson’s risk
Authors: Lubbe Steven J , Bustos Bernabe I , Hu Jing , Krainc Dimitri , Joseph Theresita , Hehir Jason , Tan Manuela , Zhang Weijia , Escott-Price Valentina , Williams Nigel M , Blauwendraat Cornelis , Singleton Andrew B , Morris Huw R ,   for International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: January 2021

Biallelic Parkin (PRKN) mutations cause autosomal recessive Parkinson’s disease (PD); however, the role of monoallelic PRKN mutations as a risk factor for PD remains unclear. We investigated the role of single heterozygous PRKN mutations in three large independent case-control cohorts totalling 10 858 PD cases and 8328 controls. Overall, after exclusion of biallelic carriers, single PRKN mutations were more common in PD than controls conferring a >1.5-fold increase in the risk of PD [P-value (P) = 0.035], with meta-analysis (19 574 PD cases and 468 488 controls) confirming increased risk [Odds ratio (OR) = 1.65, P = 3.69E-07]. Carriers were shown to have significantly younger ages at the onset compared with non-carriers (NeuroX: 56.4 vs. 61.4 years; exome: 38.5 vs. 43.1 years). Stratifying by mutation type, we provide preliminary evidence for a more pathogenic risk profile for single PRKN copy number variant (CNV) carriers compared with single nucleotide variant carriers. Studies that did not assess biallelic PRKN mutations or consist of predominantly early-onset cases may be biasing these estimates, and removal of these resulted in a loss of association (OR = 1.23, P = 0.614; n = 4). Importantly, when we looked for additional CNVs in 30% of PD cases with apparent monoallellic PRKN mutations, we found that 44% had biallelic mutations, suggesting that previous estimates may be influenced by cryptic biallelic mutation status. While this study supports the association of single PRKN mutations with PD, it highlights confounding effects; therefore, caution is needed when interpreting current risk estimates. Together, we demonstrate that comprehensive assessment of biallelic mutation status is essential when elucidating PD risk associated with monoallelic PRKN mutations.
Epigenome-wide change and variation in DNA methylation in childhood: trajectories from birth to late adolescence
Authors: Mulder Rosa H , Neumann Alexander , Cecil Charlotte A M , Walton Esther , Houtepen Lotte C , Simpkin Andrew J , Rijlaarsdam Jolien , Heijmans Bastiaan T , Gaunt Tom R , Felix Janine F , Jaddoe Vincent W V , Bakermans-Kranenburg Marian J , Tiemeier Henning , Relton Caroline L , van IJzendoorn Marinus H , Suderman Matthew
Published: January 2021

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.
APOL1 risk variants affect podocyte lipid homeostasis and energy production in focal segmental glomerulosclerosis
Authors: Ge Mengyuan , Molina Judith , Ducasa G Michelle , Mallela Shamroop K , Varona Santos Javier , Mitrofanova Alla , Kim Jin-Ju , Liu Xiaochen , Sloan Alexis , Mendez Armando J , Banerjee Santanu , Liu Shaoyi , Szeto Hazel H , Shin Myung K , Hoek Maarten , Kopp Jeffrey B , Fontanesi Flavia , Merscher Sandra , Fornoni Alessia
Published: January 2021

Lipotoxicity was recently reported in several forms of kidney disease, including focal segmental glomerulosclerosis (FSGS). Susceptibility to FSGS in African Americans is associated with the presence of genetic variants of the Apolipoprotein L1 gene (APOL1) named G1 and G2. If and how endogenous APOL1 may alter mitochondrial function by the modifying cellular lipid metabolism is unknown. Using transgenic mice expressing the APOL1 variants (G0, G1 or G2) under endogenous promoter, we show that APOL1 risk variant expression in transgenic mice does not impair kidney function at baseline. However, APOL1 G1 expression worsens proteinuria and kidney function in mice characterized by the podocyte inducible expression of nuclear factor of activated T-cells (NFAT), which we have found to cause FSGS. APOL1 G1 expression in this FSGS-model also results in increased triglyceride and cholesterol ester contents in kidney cortices, where lipid accumulation correlated with loss of renal function. In vitro, we show that the expression of endogenous APOL1 G1/G2 in human urinary podocytes is associated with increased cellular triglyceride content and is accompanied by mitochondrial dysfunction in the presence of compensatory oxidative phosphorylation (OXPHOS) complexes elevation. Our findings indicate that APOL1 risk variant expression increases the susceptibility to lipid-dependent podocyte injury, ultimately leading to mitochondrial dysfunction.
Territory as a Victim of Armed Conflict
Authors: Huneeus Alexandra , Rueda Sáiz Pablo
Published: January 2021

Colombia’s peace jurisdiction has formally accredited the territories of indigenous and Black communities as victims of the armed conflict. But what does it mean for a territory to be treated not as the stage on which a conflict unfolds, but as its victim? The concept of territory-as-victim seeks to give a legal expression to the notion that it is not just human lives that are upended by armed conflict, but also relations with non-humans, including ‘earth beings’ such as rivers and mountains, and the spiritual world. Further, it is a tool through which indigenous peoples and Black Colombians gain greater control over their land. Transitional justice scholars and practitioners are just beginning to consider what the push to recognize non-humans in law could mean for a field that has its origins in the human rights movement. This article contributes to the debate, showing how Colombia’s peace process is transforming territory from an object to a legal subject that suffers harm and is in need of repair.
Frequency-weighted ℌ2-pseudo-optimal model order reduction
Authors: Zulfiqar Umair , Sreeram Victor , Ilyas Ahmad Mian , Du Xin
Published: January 2021

The frequency-weighted model order reduction techniques are used to find a lower-order approximation of the high-order system that exhibits high-fidelity within the frequency region emphasized by the frequency weights. In this paper, we investigate the frequency-weighted $\mathcal{H}_2$-pseudo-optimal model order reduction problem wherein a subset of the optimality conditions for the local optimum is attempted to be satisfied. We propose two iteration-free algorithms, for the single-sided frequency-weighted case of $\mathcal{H}_2$-model reduction, where a subset of the optimality conditions is ensured by the reduced system. In addition, the reduced systems retain the stability property of the original system. We also present an iterative algorithm for the double-sided frequency-weighted case, which constructs a reduced-order model that tends to satisfy a subset of the first-order optimality conditions for the local optimum. The proposed algorithm is computationally efficient as compared to the existing algorithms. We validate the theory developed in this paper on three numerical examples.
Design and convergence analysis of numerical methods for stochastic evolution equations with Leray–Lions operator
Authors: Droniou Jérôme , Goldys Beniamin , Le Kim-Ngan
Published: January 2021

The gradient discretization method (GDM) is a generic framework, covering many classical methods (finite elements, finite volumes, discontinuous Galerkin, etc.), for designing and analysing numerical schemes for diffusion models. In this paper we study the GDM for a general stochastic evolution problem based on a Leray–Lions type operator. The problem contains the stochastic $p$-Laplace equation as a particular case. The convergence of the gradient scheme (GS) solutions is proved by using discrete functional analysis techniques, Skorohod theorem and the Kolmogorov test. In particular, we provide an independent proof of the existence of weak martingale solutions for the problem. In this way we lay foundations and provide techniques for proving convergence of the GS approximating stochastic partial differential equations.
The quaternionic Calabi Conjecture on abelian Hypercomplex Nilmanifolds Viewed as Tori Fibrations
Authors: Gentili Giovanni , Vezzoni Luigi
Published: January 2021

We study the quaternionic Calabi–Yau problem in HyperKähler manifolds with torsion geometry, introduced by Alesker and Verbitsky in [ 5], on eight-dimensional two-step nilmanifolds $M$ with an Abelian hypercomplex structure. We show that on these manifolds the quaternionic Monge–Ampère equation can always be solved for any data that are invariant under the action of a three-torus.
Nature and Dimensions of Systemic Hyperinflammation and its Attenuation by Convalescent Plasma in Severe COVID-19
Authors: Bandopadhyay Purbita , D’Rozario Ranit , Lahiri Abhishake , Sarif Jafar , Ray Yogiraj , Paul Shekhar Ranjan , Roy Rammohan , Maiti Rajshekhar , Chaudhuri Kausik , Bagchi Saugata , Maiti Ayan , Perwez Mohammed Masoom , Sarkar Biswanath Sharma , Roy Devlina , Chakraborty Rahul , Vasudevan Janani Srinivasa , Sharma Sachin , Biswas Durba , Maiti Chikam , Saha Bibhuti , Bhattacharya Prasun , Pandey Rajesh , Chatterjee Shilpak , Paul Sandip , Ganguly Dipyaman
Published: January 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation.

Methods

First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease. Then, in an ongoing randomized controlled trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics as a correlate for the level of hypoxia experienced by the patients.

Results

We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content.

Conclusions

Neutralizing antibodies, as well as reductions in circulating interleukin-6 and interferon-γ–inducible protein 10, contributed to marked rapid reductions in hypoxia in response to CPT.

Clinical Trial Registry of India

CTRI/2020/05/025209. http://www.ctri.nic.in/
Assessment of Attractant Lures and Monitoring Traps for Drosophila suzukii (Diptera: Drosophidae) Using Electrophysiology, Laboratory Choice Assays, and Field Trials
Authors: Little Catherine M , Dixon Peggy L , Moreau Debra L , Chapman Thomas W , Hillier N Kirk
Published: January 2021

Monitoring is critical to control efforts for Drosophila suzukii Matsumura, an invasive polyphagous fly that has the potential to cause significant losses in commercial soft fruit and berry production worldwide. We used an iterative process to identify trap colors, trap designs, and volatile mixtures to improve monitoring efforts in commercial blueberry, raspberry, and blackberry crops. Our results suggest that the selection of trap color and design and attractant lures should be customized to the crop in which they are deployed. In raspberries grown in high tunnel systems, DrosaLure paired with Drosal traps painted green and purple were highly specific to D. suzukii although actual capture counts were low. However, in field grown raspberries, BioLure and Multilure traps were most effective, but with significant nontarget bycatch. In blueberries, we had greatest success with a 5 µg:50 ng mixture of ethyl acetate–acetoin in a green/purple-colored jar-style trap with large (5 cm) mesh covered openings.