bluuebunny/crossref_metadata_2025 huggingface dataset:
A Recombinationally Repressed Region Between mat2 and mat3 Loci Shares Homology to Centromeric Repeats and Regulates Directionality of Mating-Type Switching in Fission Yeast
Authors: Grewal Shiv I S , Klar Amar J S
Published: January 2021

Cells of the fission yeast Schizosaccharomyces pombe switch mating type by replacing genetic information at the transcriptionally active mat1 locus with sequences copied from one of two closely linked silent loci, mat2-P or mat3-M. By a process referred to as directionality of switching, cells predominantly switch to the opposite mat1 allele; the mat1-P allele preferentially recombines with mat3, while mat1-M selects the mat2. In contrast to efficient recombination at mat1, recombination within the adjoining mat2-mat3 interval is undetectable. We defined the role of sequences between mat2 and mat3, designated the K-region, in directionality as well as recombinational suppression. Cloning and sequencing analysis revealed that a part of the K-region is homologous to repeat sequences present at centromeres, which also display transcriptional and recombinational suppression. Replacement of 7.5 kb of the K-region with the ura4  + gene affected directionality in a variegated manner. Analysis of the swi6-mod locus, which was previously shown to affect directionality, in KΔ::ura4  + strains suggested the existence of at least two overlapping directionality mechanisms. Our work furthers the model that directionality is regulated by cell-type-specific organization of the heterochromatin-like structure in the mating-type region and provides evidence that the K-region contributes to silencing of the mat2-mat3 interval.
Induction of Duplication Reversion in Human Fibroblasts, by Wild-Type and Mutated SV40 T Antigen, Covaries With the Ability to Induce Host DNA Synthesis
Authors: Shammas Masood A , Xia Shujuan J , Shmookler Reis Robert J
Published: January 2021

Intrachromosomal homologous recombination, manifest as reversion of a 14-kbp duplication in the hypoxanthine phosphoribosyl transferase (HPRT) gene, is elevated in human cells either stably transformed or transiently transfected by the SV40 (simian virus 40) large T antigen gene. Following introduction of wild-type SV40, or any of several T-antigen point mutations in a constant SV40 background, we observed a strong correlation between the stimulation of chromosomal recombination and induction of host-cell DNA synthesis. Moreover, inhibitors of DNA replication (aphidicolin and hydroxyurea) suppress SV40-induced homologous recombination to the extent that they suppress DNA synthesis. Stable integration of plasmids encoding T antigen also augments homologous recombination, which is suppressed by aphidicolin. We infer that the mechanism by which T antigen stimulates homologous recombination in human fibroblasts involves DNA replicative synthesis.
Phylogeographic Structure of White Oaks Throughout the European Continent
Authors: Dumolin-Lapègue S , Demesure B , Fineschi S , Le Come V , Petit R J
Published: January 2021

Patterns of chloroplast DNA (cpDNA) variation were studied in eight white oak species by sampling 345 populations throughout Europe. The detection of polymorphisms by restriction analysis of PCR-amplified cpDNA fragments allowed the identification of 23 haplotypes that were phylogenetically ordered. A systematic hybridization and introgression between the eight species studied is evident. The levels of subdivision for unordered (G  ST) and ordered (N  ST) alleles are very high and close (0.83 and 0.85). A new statistical approach to the quantitative study of phylogeography is presented, which relies on the coefficients of differentiation G  ST and N  ST and the Mantel's test. Based on pairwise comparisons between populations, the significance of the difference between both coefficients is evaluated at a global and a local scale. The mapped distribution of the haplotypes indicates the probable routes of postglacial recolonization followed by oak populations that had persisted in southern refugia, especially in the Iberian peninsula, Italy and the Balkans. Most cpDNA polymorphisms appear to be anterior to the befinnina of the last recolonization. A subset of the preexisting haplotypes have merely expanded north, while others were left behind in the south.
The Prpl
+ Gene Required for Pre-mRNA Splicing in Schizosaccharomyces pombe Encodes a Protein That Contains TPR Motifs and Is Similar to Prp6p of Budding Yeast
Authors: Urushiyama Seiichi , Tani Tokio , Ohshima Yasumi
Published: January 2021

The prp (pre-mRNA processing) mutants of the fission yeast Schizosaccharomyces pombe have a defect in pre-mRNA splicing and accumulate mRNA precursors at a restrictive temperature. One of the prp mutants, prp1-4, also has a defect in poly(A)+ RNA transport. The prp1  + gene encodes a protein of 906 amino acid residues that contains 19 repeats of 34 amino acids termed tetratrico peptide repeat (TPR) motifs, which were proposed to mediate protein-protein interactions. The amino acid sequence of Prplp shares 29.6% identity and 50.6% similarity with that of the PRP6 protein of Saccharomyces cerevisiae, which is a component of the U4/U6 snRNP required for spliceosome assembly. No functional complementation was observed between S. pombe prp1  + and S. cerevisiae PRP6. We examined synthetic lethality of prp1-4 with the other known prp mutations in S. pombe. The results suggest that Prp1p interacts either physically or functionally with Prp4p, Prp6p and Prp13p. Interestingly, the prp1  + gene was found to be identical with the zer1  + gene that functions in cell cycle control. These results suggest that Prp1p/Zer1p is either directly or indirectly involved in cell cycle progression and/or poly(A)+ RNA nuclear export, in addition to pre-mRNA splicing.
Mu Element-Generated Gene Conversions in Maize Attenuate the Dominant Knotted Phenotype
Authors: Mathern Julie , Hake Sarah
Published: January 2021

The knotted1 gene was first defined by dominant mutations that affect leaf morphology. The original allele, Kn1-O, results from a 17-kb tandem duplication. Mutator (Mu) insertions near the junction of the two repeats suppress the leaf phenotype to different degrees depending on the position of the insertion. The Mu insertions also increase the frequency of recombination at Kn1-O to create derivative alleles in which the Mu element and one copy of the repeat are lost. These derivatives are normal in appearance. Here we describe two derivatives that retained the tandem duplication but gained insertions of 1.7 and 3 kb in length in place of the Mu element. In each case, the inserted DNA is a sequence that normally flanks the distal repeat unit. Thus, each derivative consists of a tandem duplication in which the repeat unit has been extended at its distal end by the length of the new insertion. The 1.7-kb insertion dampens the phenotype, as did the original Mu insertion, whereas the 3-kb insertion completely suppresses the knotted phenotype. We propose that gene conversion, stimulated by the double-strand break of the Mu excision, gave rise to these derivatives.
The Cak1p Protein Kinase Is Required at G1/S and G2/M in the Budding Yeast Cell Cycle
Authors: Sutton Ann , Freiman Richard
Published: January 2021

The CAK1 gene encodes the major CDK-activating kinase (CAK) in budding yeast and is required for activation of Cdc28p for cell cycle progression from G2 to M phase. Here we describe the isolation of a mutant allele of CAK1 in a synthetic lethal screen with the Sit4 protein phosphatase. Analysis of several different cak1 mutants shows that although the G2 to M transition appears most sensitive to loss of Cak1p function, Cak1p is also required for activation of Cdc28p for progression from G1 into S phase. Further characterization of these mutants suggests that, unlike the CAK identified from higher eukaryotes, Cak1p of budding yeast may not play a role in general transcription. Finally, although Cak1 protein levels and in vitro protein kinase activity do not fluctuate during the cell cycle, at least a fraction of Cak1p associates with higher molecular weight proteins, which may be important for its in vivo function.
Genetic Evidence That Recognition of cosQ the Signal for Termination of Phage λ DNA Packaging, Depends on the Extent of Head Filling
Authors: Cue David , Feiss Michael
Published: January 2021

Packaging a phage λ chromosome involves cutting the chromosome from a concatemer and translocating the DNA into a prohead. The cutting site, cos, consists of three subsites: cosN, the nicking site; cosB, a site required for packaging initiation; and cosQ a site required for termination of packaging. cosB contains three binding sites (R sequences) for gpNul, the small subunit of terminase. Because cosQ has sequence identity to the R sequences, it has been proposed that cosQ is also recognized by gpNul. Suppressors of cosB mutations were unable to suppress a cosQ point mutation. Suppressors of a cosQ mutation (cosQ1) were isolated and found to be of three sorts, the first affecting a base pair in cosQ. The second type of cosQ suppression involved increasing the length of the phage chromosome to a length near to the maximum capacity of the head shell. A third class of suppressors were missense mutations in gene B, which encodes the portal protein of the virion. It is speculated that increasing DNA length and altering the portal protein may reduce the rate of translocation, thereby increasing the efficiency of recognition of the mutant cosQ. None of the cosQ suppressors was able to suppress cosB mutations. Because cosQ and cosB mutations are suppressed by very different types of suppressors, it is concluded that cosQ and the R sequences of cosB are recognized by different DNA-binding determinants.
Homology-Dependent Silencing of the SC3 Gene in Schizophyllum commune
Authors: Schuurs Theo A , Schaeffer Eveline A M , Wessels Joseph G H
Published: January 2021

After introduction of extra copies of the SC3 hydrophobin gene into a wild-type strain of Schizophyllum commune, gene silencing was observed acting on both endogenous and introduced SC3 genes in primary vegetative transformants. Nuclear run-on experiments indicated that silencing acted at the transcriptional level. Southern analysis revealed that cytosine methylation of genomic DNA occurred. Moreover, SC3 silencing was suppressed by exposure to 5-azacytidine during growth. After growth of SC3-suppressed colonies from homogenized mycelium or from colonies stored at 4°, SC3 transcription was restored. However, after prolonged growth SC3 silencing was again observed. Introduction of a promoterless SC3 fragment into wild type gave less SC3 silencing.
Drosophila Immunity: Analysis of Larval Hemocytes by P-Element-Mediated Enhancer Trap
Authors: Braun Anne , Lemaitre Bruno , Lanot René , Zachary Daniel , Meister Marie
Published: January 2021

Our aim was to identify new genes involved in the cellular aspects of defense mechanisms of Drosophila, as well as in melanotic tumor formation processes that are linked to blood cell disregulation. We have screened 1341 enhancer detector fly lines for expression of the lacZ reporter gene in larval hemocytes at the end of the third instar. We have selected 21 lines in which we observed a reproducible lacZ expression in blood cells. These lines were classified according to the subsets of hemocytes in which lacZ was expressed, and we identified five lines that can be used as lamellocyte markers. Three lines were selected for further analysis. The first exhibited strong lacZ expression in all lamellocytes. The second expressed lacZ in plasmatocytes and lamellocytes, and exhibited a melanotic tumor phenotype in larvae homozygous for the insertion. A third line showed a striking insertion-linked phenotype of melanized lymph glands (the hematopoietic organ), which resulted in the total absence of circulating hemocytes in the mutant larvae. We anticipate that this mutation, which we named domino, will prove a useful tool in the analysis of the role of hemocytes during the various aspects of immune response and melanotic tumor formation.
Homology Requirements for Targeting Heterologous Sequences During P-Induced Gap Repair in Drosophila melanogaster
1
Authors: Dray Tammy , Gloor Gregory B
Published: January 2021

The effect of homology on gene targeting was studied in the context of P-element-induced double-strand breaks at the white locus of Drosophila melanogaster. Double-strand breaks were made by excision of P-whd, a P-element insertion in the white gene. A nested set of repair templates was generated that contained the 8 kilobase (kb) yellow gene embedded within varying amounts of white gene sequence. Repair with unlimited homology was also analyzed. Flies were scored phenotypically for conversion of the yellow gene to the white locus. Targeting of the yellow gene was abolished when all of the 3′ homology was removed. Increases in template homology up to 51 base pairs (bp) did not significantly promote targeting. Maximum conversion was observed with a construct containing 493 bp of homology, without a significant increase in frequency when homology extended to the tips of the chromosome. These results demonstrate that the homology requirements for targeting a large heterologous insertion are quite different than those for a point mutation. Furthermore, heterologous insertions strongly affect the homology requirements for the conversion of distal point mutations. Several aberrant conversion tracts, which arose from templates that contained reduced homology, also were examined and characterized.
Statistical Tests of Neutrality of Mutations Against Population Growth, Hitchhiking and Background Selection
Authors: Fu Yun-Xin
Published: January 2021

The main purpose of this article is to present several new statistical tests of neutrality of mutations against a class of alternative models, under which DNA polymorphisms tend to exhibit excesses of rare alleles or young mutations. Another purpose is to study the powers of existing and newly developed tests and to examine the detailed pattern of polymorphisms under population growth, genetic hitchhiking and background selection. It is found that the polymorphic patterns in a DNA sample under logistic population growth and genetic hitchhiking are very similar and that one of the newly developed tests, FS, is considerably more powerful than existing tests for rejecting the hypothesis of neutrality of mutations. Background selection gives rise to quite different polymorphic patterns than does logistic population growth or genetic hitchhiking, although all of them show excesses of rare alleles or young mutations. We show that Fu and Li's tests are among the most powerful tests against background selection. Implications of these results are discussed.
Repression of Drosophila Photoreceptor Cell Fate Through Cooperative Action of Two Transcriptional Repressors Yan and Tramtrack
Authors: Lai Zhi-Chun , Fetchkot Michael , Li Ying
Published: January 2021

The Drosophila yan gene encodes an E twenty-six (ETS) domain nuclear protein with a transcription repressor activity that can be downregulated through phosphorylation by mitogen-activated protein kinase (MAPK). Before photoreceptor precursor cells commit to a particular cell fate, Yan is required to maintain them in an undifferentiated state. We report here identification of tramtrack (ttk) mutations that act as dominant enhancers of yan. We show that ttk synergistically interacts with yan to inhibit the R7 photoreceptor cell fate. Since ttk products are nuclear proteins with zinc-finger DNA-binding motifs, yan and ttk represent two nuclear regulators essential for the control of cellular competence for neural differentiation. Reduction of either yan or ttk activity suppresses eye phenotypes of the kinase suppressor of ras (ksr) gene mutation, which is consistent with the involvement of yan and ttk in the Ras/MAPK pathway.
Incipient Speciation by Sexual Isolation in Drosophila melanogaster: Extensive Genetic Divergence Without Reinforcement
Authors: Hollocher Hope , Ting Chau-Ti , Wu Mao-Lien , Wu Chug-I
Published: January 2021

The collection of Drosophila melanogaster from Zimbabwe and nearby regions (the Z-type) yield females who would not mate with the cosmopolitan D. melanogaster males (the M-type). To dissect the genetic basis of this sexual isolation, we constructed 16 whole-chromosome substitution lines between two standard Z- and M-lines. The results were as follows: (1) All substitution lines appear normal in viability and fertility in both sexes, indicating no strong postmating isolation. (2) The genes for the behaviors are mapped to all three major chromosomes with the same ranking and comparable magnitude of effects for both sexes: III > II ⪢ X ≥ 0 (III, II and X designate the effects of the three chromosomes). The results suggest less evolution on the X than on autosomes at loci of sexual behavior. (3) The genes for “Z-maleness” are many and somewhat redundant. Whole-chromosome effects for Z-maleness appear nearly additive and show little dominance. (4) In contrast, “Z-femaleness” has less redundancy as partial genotypes never exhibit full phenotypic effects. Epistatic interactions and incomplete dominance can sometimes be detected. (5) The extensive genetic divergence underlying sexual isolation has evolved in the absence of detectable reduction in hybrid fitnesses. Sexual selection has apparently been a driving force of multiple facets of speciation at the nascent stage without reinforcement.
A Modified Autonomous En Transposon in Maize (Zea mays L.) Elicits a Differential Response of Reporter Alleles
Authors: Peterson Peter A
Published: January 2021

Transposable elements in maize are composed of a defined molecular structure that includes coding sequences, determiners of functionality and ordered terminal motifs that provide binding sites for transposase proteins. Alterations in these components change the phenotypic expression of unstable genes with transposon inserts. The molecular basis for the altered timing and frequency of transposition as determined by the size and number of spots on kernels or stripes on leaves has generally been described for defective inserts in genes. Most differential patterns can be ascribed to alterations in the terminal motifs of the reporter allele structure that supplies a substrate (terminal inverted repeat motifs) for transposase activity. For autonomously functioning alleles, the explanations for changes in phenotype are not so clear. In this report, an En-related element identified as F-En is described that shares with En the recognition of a specific defective element c1(mr)888104 but differs from En in that this F-En element does not recognize the canonical c1(mr) elements that are recognized by En. Evidence is provided suggesting that F-En does not recognize other En/Spm-related defective elements, some of whose sequences are known. This modified En arose from a c1-m autonomously mutating En allele.
Annealing vs. Invasion in Phage λ Recombination
Authors: Stahl Mary M , Thomason Lynn , Poteete Anthony R , Tarkowski Trudee , Kuzminov Andrei , Stahl Franklin W
Published: January 2021

Genetic recombination catalyzed by λ's Red pathway was studied in rec  + and recA mutant bacteria by examining both intracellular λ DNA and mature progeny particles. Recombination of nonreplicating phage chromosomes was induced by double-strand breaks delivered at unique sites in vivo. In rec  + cells, cutting only one chromosome gave nearly maximal stimulation of recombination; the recombinants formed contained relatively short hybrid regions, suggesting strand invasion. In contrast, in recA mutant cells, cutting the two parental chromosomes at non-allelic sites was required for maximal stimulation; the recombinants formed tended to be hybrid over the entire region between the two cuts, implying strand annealing. We conclude that, in the absence of RecA and the presence of non-allelic DNA ends, the Red pathway of λ catalyzes recombination primarily by annealing.
Unraveling a Region-Specific Hyper-Recombination Phenomenon: Genetic Control and Modalities of Terminal Recombination in Escherichia coli
Authors: Corre Jacqueline , Cornet François , Patte Josette , Louarn Jean-Michel
Published: January 2021

The propensity of the terminus of the Escherichia coli chromosome for recombination has been further explored, using a test based on the selectable loss of a λ prophage inserted between repeated sequences from Tn10. Terminal recombination appears region-specific and unrelated to replication termination in a strain harboring a major chromosomal rearrangement. It requires RecBC(D) activity and must therefore occur between sister chromosomes, to conserve genomic integrity in spite of DNA degradation by RecBCD. Terminal recombination is maximal in the dif region and its intensity on either side of this recombination site depends on the orientation of the repeated sequences, probably because of the single χ site present in each repeat. Additional observations support the model that the crossover is initiated by single-strand invasion between sister chromosomes followed by RecBCD action as a consequence of DNA breakage due to the initial invasion event. Crossover location within repeats inserted at dif position supports the possibility that sister chromosomes are tightly paired in the centre of the terminal recombination zone. These data reinforce the model that postreplicative reconstruction of nucleoid organization creates a localized synapsis between the termini of sister chromosomes.
Exceptional Convergent Evolution in a Virus
Authors: Bull J J , Badgett M R , Wichman H A , Huelsenbeck J P , Hillis D M , Gulati A , Ho C , Molineux I J
Published: January 2021

Replicate lineages of the bacteriophage ϕX 174 adapted to growth at high temperature on either of two hosts exhibited high rates of identical, independent substitutions. Typically, a dozen or more substitutions accumulated in the 5.4-kilobase genome during propagation. Across the entire data set of nine lineages, 119 independent substitutions occurred at 68 nucleotide sites. Over half of these substitutions, accounting for one third of the sites, were identical with substitutions in other lineages. Some convergent substitutions were specific to the host used for phage propagation, but others occurred across both hosts. Continued adaptation of an evolved phage at high temperature, but on the other host, led to additional changes that included reversions of previous substitutions. Phylogenetic reconstruction using the complete genome sequence not only failed to recover the correct evolutionary history because of these convergent changes, but the true history was rejected as being a significantly inferior fit to the data. Replicate lineages subjected to similar environmental challenges showed similar rates of substitution and similar rates of fitness improvement across corresponding times of adaptation. Substitution rates and fitness improvements were higher during the initial period of adaptation than during a later period, except when the host was changed.
The Saccharomyces cerevisiae RAD30 Gene, a Homologue of Escherichia coli dinB and umuC, Is DNA Damage Inducible and Functions in a Novel Error-Free Postreplication Repair Mechanism
Authors: McDonald John P , Levine Arthur S , Woodgate Roger
Published: January 2021

Damage-inducible mutagenesis in prokaryotes is largely dependent upon the activity of the UmuD'C like proteins. Since many DNA repair processes are structurally and/or functionally conserved between prokaryotes and eukaryotes, we investigated the role of RAD30 a previously uncharacterized Saccharomyces cerevisiae DNA repair gene related to the Escherichia coli dinB, umuC and S. cerevisiae REV1 genes, in UV resistance and UV-induced mutagenesis. Similar to its prokaryotic homologues, RAD30 was found to be damage inducible. Like many S. cerevisiae genes involved in error-prone DNA repair, epistasis analysis clearly places RAD30 in the RAD6 group and rad30 mutants display moderate UV sensitivity reminiscent of rev mutants. However, unlike rev mutants, no defect in UV-induced reversion was seen in rad30 strains. While rad6 and rad18 are both epistatic to rad30, no epistasis was observed with rev1, rev3, rev7 or rad5, all of which are members of the RAD6 epistasis group. These findings suggest that RAD30 participates in a novel error-free repair pathway dependent on RAD6 and RADl8, but independent of REV1, REV3, REV7 and RAD5.
Allele-Specific Suppression by Formation of New Protein-Protein Interactions in Yeast
Authors: Sandrock Tanya M , O'Dell Johanna L , Adams Alison E M
Published: January 2021

Yeast fimbrin is encoded by the SAC6 gene, mutations of which suppress temperature-sensitive mutations in the actin gene (ACT1). To examine the mechanism of suppression, we have conducted a biochemical analysis of the interaction between various combinations of wild-type and mutant actin and Sac6 proteins. Previously, we showed that actin mutations that are suppressed by sac6 mutations encode proteins with a reduced affinity for wild-type Sac6p. In the present study, we have found that mutant Sac6 proteins bind more tightly to mutant actin than does wild-type SacGp, and thus compensate for weakened interactions caused by the mutant actin. Remarkably, we have also found that mutant Sac6 proteins bind more tightly to wild-type actin than does wild-type Sac6p. This result indicates that suppression does not occur through the restoration of the original contact site, but rather through the formation of a novel contact site. This finding argues against suppression occurring through a “lock-and-key” mechanism and suggests a mechanism involving more global increases in affinity between the two proteins. We propose that the most common kind of suppressors involving interacting proteins will likely occur through this less specific mechanism.
P-Element Insertion Alleles of Essential Genes on the Third Chromosome of Drosophila melanogaster Correlation of Physical and Cytogenetic Maps in Chromosomal Region 86E-87F
Authors: Deák Peter , Omar Mahmoud M , Saunders Robert D C , Pál Margit , Komonyi Orbán , Szidonya János , Maróy Péter , Zhang Yong , Ashburner Michael , Benos Panayiotis , Savakis Charalambos , Siden-Kiamos Inga , Louis Christos , Bolshakov Viacheslav N , Kafatos Fotis C , Madueno Encarnación , Modolell Juan , Glover David M
Published: January 2021

We have established a collection of 2460 lethal or semi-lethal mutant lines using a procedure thought to insert single P elements into vital genes on the third chromosome of Drosophila melanogaster. More than 1200 randomly selected lines were examined by in situ hybridization and 90% found to contain single insertions at sites that mark 89% of all lettered subdivisions of the Bridges' map. A set of chromosomal deficiencies that collectively uncover ~25% of the euchromatin of chromosome 3 reveal lethal mutations in 468 lines corresponding to 145 complementation groups. We undertook a detailed analysis of the cytogenetic interval 86E-87F and identified 87 P-element-induced mutations falling into 38 complementation groups, 16 of which correspond to previously known genes. Twenty-one of these 38 complementation groups have at least one allele that has a P-element insertion at a position consistent with the cytogenetics of the locus. We have rescued P elements and flanking chromosomal sequences from the 86E-87F region in 35 lines with either lethal or genetically silent P insertions, and used these as probes to identify cosmids and P1 clones from the Drosophila genome projects. This has tied together the physical and genetic maps and has linked 44 previously identified cosmid contigs into seven “super-contigs” that span the interval. STS data for sequences flanking one side of the P-element insertions in 49 lines has identified insertions in the αγ element at 87C, two known transposable elements, and the open reading frames of seven putative single copy genes. These correspond to five known genes in this interval, and two genes identified by the homology of their predicted products to known proteins from other organisms.
Haldane's Rule and X-chromosome Size in Drosophila
Authors: Turelli Michael , Begun David J
Published: January 2021

The “dominance theory” of Haldane's rule postulates that hybrids of the heterogametic sex are more likely to be inviable or sterile than the homogametic sex because some of the epistatic incompatibilities contributing to postzygotic isolation behave as X-linked partial recessives. When this is true, pairs of taxa with relatively large X chromosomes should require less divergence time, on average, to produce Haldane's rule than pairs with smaller Xs. Similarly, if the dominance theory is correct and if the X chromosome evolves at a similar rate to the autosomes, the size of the X should not influence the rate at which homogametic hybrids become inviable or sterile. We use Drosophila data to examine both of these predictions. As expected under the dominance theory, pairs of taxa with large X chromosomes (~40% of the nuclear genome) show Haldane's rule for sterility at significantly smaller genetic distances than pairs with smaller X chromosomes (~20% of the genome). As also predicted, the genetic distances between taxa that exhibit female inviability/sterility show no differences between “large X” vs. “small X” pairs. We present some simple mathematical models to relate these data to the dominance theory and alternative hypotheses involving faster evolution of the X vs. the autosomes and/or faster evolution of incompatibilities that produce male-specific vs. female-specific sterility. Although the data agree qualitatively with the predictions of the dominance theory, they depart significantly from the quantitative predictions of simple models of the dominance theory and the other hypotheses considered. These departures probably stem from the many simplifying assumptions needed to tractably model epistatic incompatibilities and to analyze heterogeneous data from many taxa.
The Autosomal Chorion Locus of the Medfly Ceratitis capitata. I. Conserved Synteny, Amplification and Tissue Specificity but Sequence Divergence and Altered Temporal Regulation
Authors: Vlachou Dina , Konsolalti Mary , Tolias Peter P , Kafatos Fotis C , Komitopoulou Katia
Published: January 2021

We report the isolation, full sequence characterization, amplification and expression properties of medfly chorion genes corresponding to the autosomal chorion locus of Drosophila. These genes are found adjacent to the paramyosin gene and are organized in the same order and tandem orientation as their Drosophila homologues, although they are spaced further apart. They show substantial sequence divergence from their Drosophila homologues, including novel peptide repeats and a new spacing of the tyrosines, which are known to be cross-linked in Dipteran chorion. The genes are amplified and expressed during oogenesis, as in Drosophila. Three of them are expressed in the same relative temporal order as in Drosophila but the fourth gene, the homologue of s15, shows a clear shift to an earlier expression period. This is the first known instance of changed temporal regulation in dipteran chorion genes.
The Sampling Distribution of Disease-Associated Alleles
Authors: Slatkin Montgomery , Rannala Bruce
Published: January 2021

A theory is developed that provides the sampling distribution of low frequency alleles at a single locus under the assumption that each allele is the result of a unique mutation. The numbers of copies of each allele is assumed to follow a linear birth-death process with sampling. If the population is of constant size, standard results from theory of birth-death processes show that the distribution of numbers of copies of each allele is logarithmic and that the joint distribution of numbers of copies of k alleles found in a sample of size n follows the Ewens sampling distribution. If the population from which the sample was obtained was increasing in size, if there are different selective classes of alleles, or if there are differences in penetrance among alleles, the Ewens distribution no longer applies. Likelihood functions for a given set of observations are obtained under different alternative hypotheses. These results are applied to published data from the BRCA1 locus (associated with early onset breast cancer) and the factor VIII locus (associated with hemophilia A) in humans. In both cases, the sampling distribution of alleles allows rejection of the null hypothesis, but relatively small deviations from the null model can account for the data. In particular, roughly the same population growth rate appears consistent with both data sets.
Nucleotide Sequence Evolution at the κ-Casein Locus: Evidence for Positive Selection Within the Family Bovidae
Authors: Ward Todd J , Honeycutt Rodney L , Derr James N
Published: January 2021

κ-Casein is a mammalian milk protein involved in a number of important physiological processes. In the gut, the ingested protein is split into an insoluble peptide (para κ-casein) and a soluble hydrophilic glycopeptide (caseinomacropeptide). Caseinomacropeptide is responsible for increased efficiency of digestion, prevention of neonate hypersensitivity to ingested proteins, and inhibition of gastric pathogens. Variation within this peptide has significant effects associated with important traits such as milk production. The nucleotide sequences for regions of κ-casein exon and intron four were determined for representatives of the artiodactyl family Bovidae. The pattern of nucleotide substitution in κ-casein sequences for distantly related bovid taxa demonstrates that positive selection has accelerated their divergence at the amino acid sequence level. This selection has differentially influenced the molecular evolution of the two Kcasein split peptides and is focused within a 34-codon region of caseinomacropeptide.
The Self-Regulation of Healthy Aging: Goal-Related Processes in Three Domains
Authors: Hennecke Marie , Brandstätter Veronika , Oettingen Gabriele
Published: January 2021

As people age, they experience typical age-graded challenges and opportunities, for example, their own retirement, changes in their social networks, or a decline in health condition. The extent to which people successfully process, respond to, and act on these challenges and opportunities is highly important for their health, at the core of which the WHO sees the possibility of “doing what one has reason to value.” In this article, we posit that individuals can play an active role in determining whether they can, in response to these age-graded influences, continue doing what they have reason to value, and that they can do so by deploying the self-regulatory processes of goal setting (including reengagement in new goals after disengaging from a previous goal), goal pursuit, and goal disengagement. We discuss the role of these self-regulatory processes in three important goal domains: work/retirement, interpersonal relationships, and health. Across these domains, we consider typical challenges and opportunities including the increased availability of daily time in old age, the long past that lies behind older adults, and their limited future time perspective. Finally, we derive open research questions that may be studied to better understand how the very old may self-regulate their response to age-graded influences.
Middle–Late Permian magnetostratigraphy and the onset of the Illawarra Reversals in the northeastern Parana Basin, South America
Authors: Aragão Marcela , Scardia Giancarlo
Published: January 2021

Recent compilations of the Illawarra Reversals show remarkable differences in the onset age (265 Ma versus 269 Ma) and the magnetic polarity pattern, hampering the establishment of a reference geomagnetic timescale for the Middle–Late Permian. The Parana Basin hosts a 7-km-thick, discontinuous sedimentary succession spanning the Palaeozoic to the Mesozoic, including the Gondwana 1 supersequence which extends from Late Carboniferous to the Triassic or Jurassic. We provide the magnetostratigraphy of the middle and upper Permian part of this sequence of a ca. 300-m-long core, pertaining to the Passa Dois Group and the Piramboia Formation. Sample demagnetization of NRM revealed two magnetic overprints ascribed to the Brunhes chron and to the emplacement of Parana Large Igneous Province in the Early Cretaceous, respectively. Stable, dual polarity characteristic components (ChRM) were isolated at temperatures higher than 450 °C and interpreted as a primary detrital magnetic remanence (DRM), acquired during or soon after sediment deposition. Available U-Pb dating on volcanic zircons from the literature provided independent chronologic constraints for our magnetostratigraphy. A total of 8 reverse polarity intervals were identified, the lowermost of which (up to 110 m thick) correlates to the Kiaman Superchron. The overlying Illawarra is dominated by a reverse polarity magnetization with thin (4–5 m thick) normal polarity intervals. This pattern agrees with the Illawarra sequence from the Karoo Basin and other proposed timescales for the Permian. The onset of the Illawarra reversals is interpolated to ca. 270 Ma, close to the age of 269 Ma from the Karoo Basin. Combined magnetostratigraphy and geochronology yielded sediment accumulation rates of ca. 8 m Myr–1 for the Passa Dois Group in the northeastern (marginal) sector of the Parana Basin, indicating that Serra Alta and Teresina Formations span 279–274 Ma and 274–254 Ma, respectively.
The interaction between mantle plumes and lithosphere and its surface expressions: 3-D numerical modelling
Authors: Wang Yongming , Li Mingming
Published: January 2021

The rise of mantle plumes to the base of the lithosphere leads to observable surface expressions, which provide important information about the deep mantle structure. However, the process of plume–lithosphere interaction and its surface expressions remain not well understood. In this study, we perform 3-D spherical numerical simulations to investigate the relationship between surface observables induced by plume–lithosphere interaction (including dynamic topography, geoid anomaly and melt production rate) and the physical properties of plume and lithosphere (including plume size, plume excess temperature, plume viscosity, and lithosphere viscosity and thickness). We find that the plume-induced surface expressions have strong spatial and temporal variations. Before reaching the base of the lithosphere, the rise of a plume head in the deep mantle causes positive and rapid increase of dynamic topography and geoid anomaly at the surface but no melt production. The subsequent impinging of a plume head at the base of the lithosphere leads to further increase of dynamic topography and geoid anomaly and causes rapid increase of melt production. After reaching maximum values, these plume-induced observables become relatively stable and are more affected by the plume conduit. In addition, whereas the geoid anomaly and dynamic topography decrease from regions above the plume centre to regions above the plume edge, the melt production always concentrates at the centre part of the plume. We also find that the surface expressions have different sensitivities to plume and lithosphere properties. The dynamic topography significantly increases with the plume size, plume excess temperature and plume viscosity. The geoid anomaly also increases with the size and excess temperature of the plume but is less sensitive to plume viscosity. Compared to the influence of plume properties, the dynamic topography and geoid anomaly are less affected by lithosphere viscosity and thickness. The melt production significantly increases with plume size, plume excess temperature and plume viscosity, but decreases with lithosphere viscosity and thickness.
Double-difference seismic attenuation tomography method and its application to The Geysers geothermal field, California
Authors: Guo Hao , Thurber Clifford
Published: January 2021

Knowledge of attenuation structure is important for understanding subsurface material properties. We have developed a double-difference seismic attenuation (DDQ) tomography method for high-resolution imaging of 3-D attenuation structure. Our method includes two main elements, the inversion of event-pair differential ${t^*}$ ($d{t^*}$) data and 3-D attenuation tomography with the $d{t^*}$ data. We developed a new spectral ratio method that jointly inverts spectral ratio data from pairs of events observed at a common set of stations to determine the $d{t^*}$ data. The spectral ratio method cancels out instrument and site response terms, resulting in more accurate $d{t^*}$ data compared to absolute ${t^*}$ from traditional methods using individual spectra. Synthetic tests show that the inversion of $d{t^*}$ data using our spectral ratio method is robust to the choice of source model and a moderate degree of noise. We modified an existing velocity tomography code so that it can invert $d{t^*}$ data for 3-D attenuation structure. We applied the new method to The Geyser geothermal field, California, which has vapour-dominated reservoirs and a long history of water injection. A new Qp model at The Geysers is determined using P-wave data of earthquakes in 2011, using our updated earthquake locations and Vp model. By taking advantage of more accurate $d{t^*}$ data and the cancellation of model uncertainties along the common paths outside of the source region, the DDQ tomography method achieves higher resolution, especially in the earthquake source regions, compared to the standard tomography method using ${t^*}$ data. This is validated by both the real and synthetic data tests. Our Qp and Vp models show consistent variations in a normal temperature reservoir that can be explained by variations in fracturing, permeability and fluid saturation and/or steam pressure. A prominent low-Qp and Vp zone associated with very active seismicity is imaged within a high temperature reservoir at depths below 2 km. This anomalous zone is likely partially saturated with injected fluids.
Residual Malaria Transmission in Select Countries of Asia-Pacific Region: Old Wine in a New Barrel
Authors: Hii Jeffrey , Hustedt John , Bangs Michael J
Published: January 2021

Background

Despite substantial reductions in malaria burden and improvement in case management, malaria remains a major public health challenge in the Asia-Pacific region. Residual malaria transmission (RMT) is the fraction of total transmission that persists after achievement of full operational coverage with effective insecticide-treated bed nets (ITNs)/long-lasting insecticidal nets (LLINs) and/or indoor residual spray interventions. There is a critical need to standardize and share best practices for entomological, anthropological, and product development investigative protocols to meet the challenges of RMT and elimination goals.

Methods

A systematic review was conducted to describe when and where RMT is occurring, while specifically targeting ownership and usage of ITN/LLINs, indoor residual spray application, insecticide susceptibility of vectors, and human and vector biting behavior, with a focus on nighttime activities.

Results

Sixty-six publications from 1995 to present met the inclusion criteria for closer review. Associations between local vector control coverage and use with behaviors of human and mosquito vectors varied by locality and circumstance. Consequently, the magnitude of RMT is insufficiently studied and analyzed with sparse estimates of individual exposure in communities, insufficient or incomplete observations of ITN/LLIN use, and the local human population movement into and from high-risk areas.

Conclusions

This review identified significant gaps or deficiencies that require urgent attention, namely, developing standardized procedures and methods to estimate risk exposure beyond the peridomestic setting, analytical approaches to measure key human-vector interactions, and seasonal location-specific agricultural or forest use calendars, and establishing the collection of longitudinal human and vector data close in time and location.
Uropathogenic Escherichia coli Virulence Factor α-Hemolysin Reduces Histone Acetylation to Inhibit Expression of Proinflammatory Cytokine Genes
Authors: Zhang Zhengguo , Wang Ming , Zhang Yu , Zhang Yiming , Bartkuhn Marek , Markmann Melanie , Hossain Hamid , Chakraborty Trinad , Hake Sandra B , Jia Zhankui , Meinhardt Andreas , Bhushan Sudhanshu
Published: January 2021

Urinary tract infections are common and costly diseases affecting millions of people. Uropathogenic Escherichia coli (UPEC) is a primary cause of these infections and has developed multiple strategies to avoid the host immune response. Here, we dissected the molecular mechanisms underpinning UPEC inhibition of inflammatory cytokine in vitro and in vivo. We found that UPEC infection simulates nuclear factor-κB activation but does not result in transcription of cytokine genes. Instead, UPEC-mediated suppression of the metabolic enzyme ATP citrate lyase results in decreased acetyl-CoA levels, leading to reduced H3K9 histone acetylation in the promotor region of CXCL8. These effects were dependent on the UPEC virulence factor α-hemolysin and were reversed by exogenous acetate. In a murine cystitis model, prior acetate supplementation rapidly resolved UPEC-elicited immune responses and improved tissue recovery. Thus, upon infection, UPEC rearranges host cell metabolism to induce chromatin remodeling processes that subvert expression of host innate immune response genes.
Reporting antimicrobial susceptibilities and resistance phenotypes inStaphylococcusspp.: a nationwide proficiency study
Authors: Fernández-Cuenca Felipe , López-Hernández Inmaculada , Cercenado Emilia , Conejo Carmen , Tormo Nuria , Gimeno Concha , Pascual Alvaro
Published: January 2021

Objectives

To evaluate the proficiency of microbiology laboratories in Spain in antimicrobial susceptibility testing (AST) of Staphylococcus spp.

Materials and methods

Eight Staphylococcus spp. with different resistance mechanisms were selected: six Staphylococcus aureus (CC-01/mecA, CC-02/mecC, CC-03/BORSA, CC-04/MLSBi, CC-06/blaZ and CC-07/linezolid resistant, cfr); one Staphylococcus epidermidis (CC-05/linezolid resistant, 23S rRNA mutation); and one Staphylococcus capitis (CC-08/daptomycin non-susceptible). Fifty-one laboratories were asked to report: (i) AST system used; (ii) antimicrobial MICs; (iii) breakpoints used (CLSI or EUCAST); and (iv) clinical category. Minor, major and very major errors (mEs, MEs and VMEs, respectively) were determined.

Results

The greatest MIC discrepancies found were: (i) by AST method: 19.4% (gradient diffusion); (ii) by antimicrobial agent: daptomycin (21.3%) and oxacillin (20.6%); and (iii) by isolate: CC-07/cfr (48.0%). The greatest error rates were: (i) by AST method: gradient diffusion (4.3% and 5.1% VMEs, using EUCAST and CLSI, respectively); (ii) by breakpoint: 3.8% EUCAST and 2.3% CLSI; (iii) by error type: mEs (0.8% EUCAST and 1.0% CLSI), MEs (1.8% EUCAST and 0.7% CLSI) and VMEs (1.2% EUCAST and 0.6% CLSI); (iii) by antimicrobial agent: VMEs (4.7% linezolid and 4.3% oxacillin using EUCAST); MEs (14.3% fosfomycin, 9.1% tobramycin and 5.7% gentamicin using EUCAST); and mEs (22.6% amikacin using EUCAST).

Conclusions

Clinical microbiology laboratories should improve their ability to determine the susceptibility of Staphylococcus spp. to some antimicrobial agents to avoid reporting false-susceptible or false-resistant results. The greatest discrepancies and errors were associated with gradient diffusion, EUCAST breakpoints and some antimicrobials (mEs for aminoglycosides; MEs for fosfomycin, aminoglycosides and oxacillin; and VMEs for linezolid and oxacillin).