bluuebunny/crossref_metadata_2025 huggingface dataset:
THE TIMING OF Mu ACTIVITY IN MAIZE
Authors: Robertson Donald S
Published: April 2021

The timing of mutator activity of Mu in maize was tested in three ways: (1) by allelism tests of phenotypically similar male-transmitted mutants, (2) by studying the clustering of phenotypically similar mutants as demonstrated by ear maps and the subsequent allelism tests of these mutants, and (3) by the induction of somatic sectors in Mu plants heterozygous for plant and endosperm marker genes. Allelism tests of phenotypically similar mutants in out-crosses of Mu plants as males established that 18.8% were allelic and that premeiotic mutants are induced. This conclusion was supported by ear maps of Mu-bearing plants, which revealed sectors of seeds that produced plants bearing phenotypically similar allelic mutants. The smallness of these sectors indicated that the premeiotic activity of Mu that gave rise to them occurred very late. The lack of visible sectors in mature sporophytic, endosperm and aleurone tissue in plants carrying Mu supports the conclusion that the mutator activity of Mu does not occur throughout the ontogeny of the plant and seems to be restricted to a time shortly before and/or during meiosis.
CONDITIONALLY EXPRESSED MISSENSE MUTATIONS: THE BASIS FOR THE UNUSUAL PHENOTYPE OF AN APPARENT trpD NONSENSE MUTANT OF SALMONELLA TYPHIMURIUM
Authors: Tanemura Shigeji , Bauerle Ronald
Published: April 2021

Tryptophan auxotroph trp-28 is anomalous since preliminary mapping and suppression studies indicate the presence of a single amber nonsense mutation either late in trpE or early in trpD, but enzymological tests indicate the complete inactivation of both genes in this strain. Since the trpE and trpD genes are contiguous and encode the two subunits of a multifunctional enzyme complex, it was of interest to learn the mechanism of action of this apparent pleiotropic nonsense mutation. Our study has revealed that the phenotype of this strain derives not from a single mutation, but from the presence and interaction of multiple mutations. Besides the recognized amber mutation (designated trpD28), this strain carries two additional, conditionally expressed missense mutations (designated trpEl651 and trpD1652). The trpD28 amber codon maps in the promoter-proximal region 1 of trpD and eliminates the glutamine amidotransferase activity of the bifunctional trpD polypeptide. The trpD1652 mutation maps in the promoter-distal region 2 of trpD and severely reduces (but does not eliminate) the phosphoribosyl transferase activity of the trpD polypeptide. The trpE1651 mutation maps in the anterior part of trpE and causes a rapid loss of activity of the trpE polypeptide, but only when it exists as an uncomplexed subunit. The existence of the two missense mutations escaped prior notice in standard recombinational tests since the nature of each mutation is such that neither is detectable by the nutritional screens normally used in such tests unless an unsuppressed chainterminating mutation, such as trpD28, is also present.
GENETIC CHANGES WITH GENERATIONS OF ARTIFICIAL SELECTION
Authors: Silvela Luis
Published: April 2021

Using conditional probabilities and moment-generating matrices, I derived approximate algebraic equations that give expectations of gene frequency, population mean, gene frequency variance within lines, or heterozygosity, and gene frequency variance between lines, or drift, for repeated cycles of recurrent selection in populations of finite size. For genes of large effect, the responses to selection differ substantially from the classical expectations, and equations are derived that give quantitative estimates of asymmetry of response when selection is done in opposite directions. Particular cases of the derived formulae yield equations given by other authors. The error involved in the approximations is discussed in the APPENDIX.
BIOCHEMICAL DIFFERENCES BETWEEN PRODUCTS OF THE Adh LOCUS IN DROSOPHILA
Authors: McDonald John F , Anderson Steven M , Santos Mauro
Published: April 2021

An analysis of the molecular properties of the major alcohol dehydrogenase (E.C.1.1.1.1) allozyme variants found segregating in natural populations of D. melanogaster is presented. Our results indicate: (1) ADH-S enzyme has generally lower Michaelis-Menten constants than those of ADH-F; (2) ADH-S and ADH-F enzymes display opposite interactions for both co-factor and substrate; and (3) higher levels of ADH are associated with the Adh-fast genotype. The possible adaptive significance of these findings is discussed.
FRAMESHIFT SUPPRESSION IN SACCHAROMYCES CEREVISIAE. III. ISOLATION AND GENETIC PROPERTIES OF GROUP III SUPPRESSORS
Authors: Cummins Claudia M , Gaber Richard F , Culbertson Michael R , Mann Richard , Fink Gerald R
Published: April 2021

Suppressors of ICR-induced mutations that exhibit behavior similar to bacterial frameshift suppressors have been identified in the yeast Saccharomyces cerevisiae. The yeast suppressors have been divided into two groups. Previous evidence indicated that suppressors of one group (Group II: SUFI, SUF3, SUF4, SUF5 and SUF6) represent mutations in the structural genes for glycyl-tRNA's. Suppressors of the other group (Group III: SUF2 and SUF7) were less well characterized. Although they suppressed some ICR-revertible mutations, they failed to suppress Group II frameshift mutations. This communication provides a more thorough characterization of the Group III suppressors and describes the isolation and properties of four new suppressors in that group (SUF1, SUF9, SUF10 and suf11).—In our original study, Group III suppressors were isolated as revertants of the Group III mutations his4-712 and his4-713. All suppressors obtained as ICR-induced revertants of these mutations mapped at the SUF2 locus near the centromere of chromosome III. Suppressors mapping at other loci were obtained in this study by analyzing spontaneous and UV-induced revertants of the Group III mutations. SUF2 and SUF10 suppress both Group III his4 mutations, whereas SUF7, SUF8, SUF9 and suf11 suppress his4-713, but not his4-712. All of the suppressors except suf11 are dominant in diploids homozygous for his4-713. The suppressors fail to suppress representative UAA, UAG and UGA nonsense mutations.—SUP9 is linked to the centromere of chromosome VI, and SUF10 is linked to the centromere of chromosome XIV. A triploid mapping procedure was used to determine the chromosome locations of SUF7 and SUF8. Subsequent standard crosses revealed linkage of SUF7 to cdc5 on chromosome XIII and linkage of SUF8 to cdcl2 and pet3 on chromosome VIII.
THE GENETICS OF LEVAMISOLE RESISTANCE IN THE NEMATODE CAENORHABDITIS ELEGANS
Authors: Lewis James A , Wu C-H , Berg Howard , Levine Joseph H
Published: April 2021

We have characterized a small group of genes (13 loci) in the nematode Caenorhabditis elegans that, when mutated, confer resistance to the potent anthelmintic levamisole. Mutants at the 7 loci conferring the most extreme resistance generally possess almost identical visible and pharmacological phenotypes: uncoordinated motor behavior, most severe in early larval life, extreme resistance to cholinergic agonists and sensitivity to hypo-osmotic shock. Mutants with exceptional phenotypes suggest possible functions for several of the resistance loci. The most extreme mutants can readily be selected by their drug resistance (211 mutants, as many as 74 alleles of one gene). The more common resistance loci are likely to be unessential genes, while loci identified by only a few alleles may be essential genes or genes conferring resistance only when mutated in a special way. We propose that these mutants represent a favorable system for understanding how a small group of related genes function in a simple animal. The extreme drug resistance of these mutants makes them useful tools for the genetic manipulation of C. elegans. And, as the most resistant class of mutants might lack pharmacologically functional acetylcholine receptors (Lewis e t al. 1980), these mutants may also be of some neurobiological significance.
DEFECTIVE KERNEL MUTANTS OF MAIZE II. MORPHOLOGICAL AND EMBRYO CULTURE STUDIES
Authors: Sheridan William F , Neuffer M G
Published: April 2021

This report presents the initial results of our study of the immature kernel stage of 150 defective kernel maize mutants. They are single gene, recessive mutants that map throughout the gemme, defective in both endosperm and embryo development and, for the most part, lethal (Neuffer and Sheridan 1980). All can be distinguished on immature ears, and 85% of them reveal a mutant phenotype within 11 to 17 days post-pollination. Most have immature kernels that are smaller and lighter in color than their normal counterparts. Forty of the mutants suffer from their defects early in kernel development and are blocked in embryogenesis before their primordia differentiate, or, if primordia are formed, they are unable to germinate when cultured as immature embryos or tested at maturity; a few begin embryo degeneration prior to the time that mutant kernels became visually distinguishable. The others express the associated lesion later in kernel development and form at least one leaf primordium by the time kernels are distinguishable and will germinate when cultured or tested at maturity. In most cases, on a fresh weight basis, the mutants have embryos that are more severely defective than the endosperm; their embryos usually are no more than one-half to two-thirds the size, and lag behind by one or two developmental stages. in comparison with embryos in normal kernels from the same ear. One hundred and two mutants were examined by culturing embryos on basal and enriched media; 21 simply enlarged or completely failed to grow on any of the media tested; and 81 produced shoots and roots on at least one medium. Many grew equally well on basal and enriched media; 16 grew at a faster rate on basal medium and 23 displayed a superior growth on enriched medium. Among the latter group, 10 may be auxotrophs. One of these mutants and another mutant isolated by E. H. COE are proline-requiring mutants, allelic to pro-1. Considering their diversity of expression as evidenced by their differences in morphological appearance, degree of defectiveness and response to embryo culturing, we believe that they represent many different gene loci.
CYTOGENETICS OF FLOWER MODIFICATION OF A CYTOPLASMIC MALE-STERILE TOBACCO
Authors: Gerstel D U , Burns J A , Sand S A
Published: April 2021

Plants combining the cytoplasm of Nicotiana debneyi and the 48 chromosomes from N. tabacum are male sterile. Early backcross generations of the amphidiploid hybrid to male N. tabacum produced a great variety of plants from which a series of phenotypes with characteristic flower forms and transmission rates have been isolated. Type 1A possesses completely feminized stamens and deeply split corollas, breeds true when backcrossed to normal males and carries 48 N. tabacum chromosomes. Other phenotypes, 2C, 3E and 4H, range toward normal morphology of corollas and stamens. Like 1A, 2C forms no anther tissue and has 48 chromosomes. This type is transmitted to 36.3% of the backcross progeny, the remainder being of type 1A; presumably 2C carries a chromosome segment from N. debneyi that is responsible for the partial restoration of flower structure. In contrast, both 3E and 4H produce anthers and possess an extra chromosome. The extra chromosomes are transmitted to only 19.9% and 7.1% of the progeny, respectively. Significantly, the extra chromosomes found in the anther-forming types are nucleolus organizing and carry a satellite from N. debneyi. On the basis of these observations, we surmise that differentiation of anthers in plants with N. debneyi cytoplasm may depend on the presence of a nucleolus-organizing chromosome from that species. This chromosome is unstable; unaltered, it conditions a highly restored phenotype (4H), but when structurally modified, it may control different phenotypic expressions. Other examples of satellited restorer chromosomes had been reported for different cytoplasmically male-sterile combinations; therefore, the phenomenon may have more general significance.
DISTINCTIONS AMONG ALLELIC VARIANTS ASSOCIATED WITH CHROMOSOME 3 INVERSIONS IN DROSOPHILA PSEUDOOBSCURA AND DROSOPHILA PERSIMILIS
Authors: Norman R A , Prakash Satya
Published: April 2021

Efforts were made to discriminate new genetic variants among electrophoretic alleles that are associated with chromosome 3 inversions of Drosophila pseudoobscura and D. persimilis. Apparent genetic similarities for electrophoretic alleles between these two species and among the common inversions they carry were reexamined by altering gel concentration and buffer pH. At the amylase locus, the 1.09 electrophoretic allele could be further separated into two allelic classes that differentiated the WT and KL arrangements. Similarly, the 0.84 electrophoretic allele was divided into two allelic classes, one characteristic of the Santa Cruz phylad arrangements, TL and SC, and the other found in strains of the Standard phylad arrangements and CH. Uncommon amylase alleles proved to be different alleles in the two species. No new allelic variants, however, could be found among strains with the amylase 1.00 allele, the commonest allele in the Standard phylad of both species. No major new allelic variation was detected for acid phosphatase-3 and larval protein-10 that revealed any further differentiation among species or inversions. Variation at all three loci in strains of the Bogota population remained genetically similar to variation in strains of mainland D. pseudoobscura.
IMP1/imp1: A GENE INVOLVED IN THE NUCLEO-MITOCHONDRIAL CONTROL OF GALACTOSE FERMENTATION IN SACCHAROMYCES CEREVISIAE
Authors: Algeri A A , Bianchi L , Viola A M , Puglisi P P , Marmiroli N
Published: April 2021

In some strains of Saccharomyces cerevisiae, the induction of enzymes of the Leloir pathway, galactose fermentation and growth on galactose depend on mitochondrial function; mitochondrial dependence is elicited through the recessive allele imp1 of the nuclear gene IMP1. The genetic element IMP1 is not allelic to any of the known GAL genes; IMP1 strains can grow on and ferment galactose in respiratory-deficient (RD) condition or in the presence of the mitochondrial inhibitors ethidium bromide and erythromycin; whereas, imp1 strains can grow on and ferment galactose only in respiratory-sufficient (RS) condition. The imp1 elicited mitochondrial dependence apparently involves regulation of the synthesis of the galactose catabolizing enzymes and synthesis of the galactose specific permease. IMP1 is not the only genetic determinant that elicits an interaction of the mitochondrion and the expression of the Gal system; the GAL3 gene, whose role in galactose utilization is demonstrated by the long-term adaptation phenotype of gal3 RS mutants, gives rise to a noninducible phenotype in RD condition or in the presence of mitochondrial inhibitors.
SUPPRESSION AND FUNCTION OF X-LINKED LETHAL AND STERILE MUTATIONS IN CAENORHABDITIS ELEGANS
Authors: Meneely Philip M , Herman Robert K
Published: April 2021

We have expanded our collection of recessive lethal and sterile mutants in the region of the X chromosome balanced by mnDp1(X;V), about 15% of the X linkage map, to a total of 54 mutants. The mutations have been mapped with respect to 20 overlapping deficiencies and five X duplications, and they have been assigned to 24 genes by complementation testing. Nine mutants are hermaphrodite-sterile: one of these is a sperm-defect mutant, two have abnormal gonadogeneses and six, in five genes, are maternally influenced mutants, producing inviable zygote progeny. One of the gonadogenesis mutants and two of the maternally influenced mutants are male fertile. All but one of the maternally influenced mutants give cross progeny when mated with wild-type males. Forty-three mutants were tested for suppression by homozygous sup-5(e1464), which is believed to be specific for null alleles. Ten mutants that were judged by independent criteria not to be null mutants are not suppressed. Nine of the other 33 mutants, in nine genes, are suppressed, five in both heterozygous and homozygous suppressor stocks and four only in homozygous suppressor stocks.
AN ENDOMITOTIC EFFECT OF A CELL CYCLE MUTATION OF SACCHAROMYCES CEREVISIAE
Authors: Schild David , Ananthaswamy Honnavara N , Mortimer Robert K
Published: April 2021

A recessive temperature-sensitive mutation of Saccharomyces cerevisiae has been isolated and shown to cause an increase in ploidy in both haploids and diploids. Genetic analysis revealed that the strain carrying the mutation was an aa diploid, although MNNG mutagenesis had been done on an a haploid strain. When the mutant strain was crossed with an aa diploid and the resultant tetraploid sporulated, some of the meiotic progeny of this tetraploid were themselves tetraploid, as shown by both genetic analysis and DNA measurements, instead of diploid as expected of tetraploid meiosis. The ability of these tetraploids to continue to produce tetraploid meiotic progeny was followed for four generations. Homothallism was excluded as a cause of the increase in ploidy; visual pedigree analysis of spore clones to about the 32-cell stage failed to reveal any zygotes, and haploids that diploidized retained their mating type. An extra round of meiotic DNA synthesis was also considered and excluded. It was found that tetraploidization was independent of sporulation temperature, but was dependent on the temperature of germination and the growth of the spores. Increase in ploidy occurred when the spores were germinated and grown at 30°, but did not occur at 23°. Two cycles of sporulation and growth at 23° resulted in haploids, which were shown to diploidize within 24 hr when grown at 30°. Visual observation of the haploid cells incubated at 36° revealed a celldivisioncycle phenotype characteristic of mutations that affect nuclear division; complementation analysis demonstrated that the mutation, cdc31-2, is allelic to cdc31-1, a mutation isolated by HARTWEeLL et al.(1973) and characterized as causing a temperature-sensitive arrest during late nuclear division. The segregation of cdc31-2 in heterozygous diploids was 2:2 and characteristic of a noncentromere-linked gene.
BIOLOGICAL PARAMETERS AND THE SEGREGATION DISTORTION (SD) PHENOMENON IN DROSOPHILA MELANOGASTER
Authors: Trippa G , Cicchetti R , Loverre A , Micheli A
Published: April 2021

The relationship between some biological parameters (mortality, longevity, fertility, fecundity and sex rat:o) and segregation of second chromosomes in heterozygous and homozygous SD males has been analyzed. The results obtained in SD/SD+ heterozygous males show: (1) their reduced fertility with respect to that of control males, (2) an alteration in the sex ratio in the SD+ progeny only, and (3) inversely related sex-ratio and segregation distortion values. In SDi/SDi combinations: (1) surprisingly, fertility is intermediate between that of SD/SD+ heterozygous males and that of control males, (2) the segregation ratios of the second chromosomes are normal (0.50), and (3) the sex ratio= 0.50 in both classes of SD progeny. The relat'onship between mortality (and therefore longevity) and fertility of the different genotypes and fecundity per male indicates that the total productivity of heterozygous males is less than that so far claimed. Indeed, their productivity depznds not only on the mechanism of nonformation of the SD+ sperm, but also on their reduced longevity. The k = 0.50 and the high fecundity of SDi/SDj combinations indicate that in these males the SD phenomenon is partially suppressed, the SD chromosomes being insensitive to each other, thus implying that particular Rsp alleles are sensitive to given Sd alleles. The complementation pattern for male fertility of SD homozygous males again supports previous evidence that Sd factors from natural populations are, in effect, different Sd genes.
EXPERIMENTAL POPULATION GENETICS OF MEIOTIC DRIVE SYSTEMS. III. NEUTRALIZATION OF SEX-RATIO DISTORTION IN DROSOPHILA THROUGH SEX-CHROMOSOME ANEUPLOIDY
Authors: Lyttle Terrence W
Published: April 2021

Laboratory populations of Drosophila melanogaster were challenged by pseudo-Y drive, which mimics true Y-chromosome meiotic drive through the incorporation of Segregation Distorter (SD) in a T(Y;2) complex. This causes extreme sex-ratio distrotion and can ultimately lead to population extinction. Populations normally respond by the gradual accumulation of drive suppressors, and this reduction in strength of distortion allows the sex ratio to move closer to the optimal value of 1:1. One population monitored, however, was rapidly able to neutralize the effects of sex-ratio distortion by the accumulation of sex-chromosome aneuploids (XXY, XYY). This apparently occurs because XX-bearing eggs, produced in relatively high numbers (~4%) by XXY genotypes, become the main population source of females under strong Y-chromosome drive. Computer simulation for a discrete generation model incorporating random mating with differences in fitness and segregation permits several predictions that can be compared to the data. First, sex-chromosome aneuploids should rapidly attain equilibrium, while stabilizing the population at ~60% males. This sex ratio should be roughly independent of the strength of the meiotic drive. Moreover, conditions favoring the accumulation of drive suppressors (e.g., weak distortion, slow population extinction) are insufficient for maintaining aneuploidy, while conditions favoring aneuploidy (e.g., strong distortion, low production of females) lead to population extinction before drive suppressors can accumulate. Thus, the different mechanisms for neutralizing sex-ratio distortion are complementary. In addition, Y drive and sex-chromosome aneuploidy are potentially co-adaptive, since under some conditions neither will survive alone. Finally, these results suggest the possibility that genetic variants promoting sex-chromosome nondisjunction may have a selective advantage in natural populations faced with sex-ratio distortion.
EXPRESSION OF CYCLOHEXIMIDE RESISTANCE IN CARROT SOMATIC HYBRIDS AND THEIR SEGREGANTS
Authors: Lazar G B , Dudits D , Sung Z R
Published: April 2021

Cycloheximide resistance (CHr) was shown to be a function expressed in differentiated plant tissues, but not in unorganized callus tissues. A variant, WCH105, expressing CHr in the callus, as well as in regenerated plantlets, was isolated from a cell line derived from a wild carrot plant. The plantlets regenerated from WCH105 are green, but do not produce normal, dissected leaves. Protoplasts of WCH105 were fused with that of a cycloheximidesensitive (CHs) cell line derived from an albino, domesticated carrot. Hybrid selection was based on (1) irreversible growth inhibition of WCH105 protoplasts by iodacetamide, and (2) restoration of green plants producing dissected leaves.——Analysis of the CHr trait as an unselected marker in the callus cells of the somatic hybrids indicated that it behaved as a recessive. The combined recessive and resistant phenotype of this trait allowed the recovery of CHr segregants from CHs hybrids at a frequency of 10-4, 1000 times higher than the spontaneous frequency of CHr. The recovery of CHr somatic segregants confirmed the recessiveness of the CHr trait.
GENETIC VARIABILITY AND RATE OF GENE SUBSTITUTION IN A FINITE POPULATION UNDER MUTATION AND FLUCTUATING SELECTION
Authors: Takahata Naoyuki
Published: April 2021

By using a numerical method of solving stochastic difference equations, the level of genetic variability maintained in a finite population and the rate of gene substitution under several models of fluctuating selection intensities were studied. It is shown that mutation and random genetic drift both play an important role in determining genetic variability and the rate of gene substitution. Compared with the case of neutral mutations, the fluctuation of selection intensity caused by temporal and spatial heterogeneity of environments generally increases the rate of gene substitution, but the level of genetic variability may be increased or decreased, depending upon the model and the parameters used. Although such a type of selection per se can not be ruled out, when mutation is taken into account, it is difficult to explain both the observed amount of genetic variability and the rough constancy of evolutionary rate within a framework of fluctuating selection models.
GENETIC DIVERSITY AND TEMPORAL VARIATION IN THE E. COLI POPULATION OF A HUMAN HOST
Authors: Caugant Dominique A , Levin Bruce R , Selander Robert K
Published: April 2021

Electrophoretic techniques were employed to study variation in chromosomal genes encoding enzymes and in the distribution of cryptic plasmids in the E. coli population of a human host over an 11-month period. Thirteen of the 15 enzymes studied were polymorphic, and mean genetic diversity per locus was 0.39. Among 550 clones isolated from fecal samples, protein electrophoresis revealed 53 distinct electrophoretic types (ETs). Most ETs appeared on only one or a few days and were considered transients, but two (ET-12 and ET-13) were observed many times over extended periods and represented residents. Complete turnover in the transient ETs in the population occurred in periods of from two weeks to a month. ETs appearing in one month showed no particular genetic similarity to those of the previous month. — All but 4 of the 53 ETs carried one or more "cryptic" plasmids with molecular weights ranging from 1 to 80 megadaltons. With few exceptions, the plasmid composition of each ET was unique. In the course of the 11-month sampling period, there were changes in the plasmid profiles of the resident strains ET-12 and ET-13, and also in the profile of a recurrent strain, ET-2, which was isolated on four days. Modification of the plasmid profile of ET-12 involved the sequential addition of relatively high molecular weight bands. For ET-2 and ET-13, the changes in the plasmid profiles were radical, suggesting invasions of new cell types rather than merely the addition and deletion of plasmids. — The results of this study provide three lines of evidence that recombination plays a minor role in the generation of genetic diversity in the E. coli population of a single host. (1) Several pairs of loci were in strong linkage disequilibrium; compared to a randomly generated array of genotypes, the sample of ETs contained an excess of pairs differing at one or two loci and too many pairs with highly distinctive combinations of electromorphs. (2) In most cases where pairs of ETs differed at a single locus and, therefore, could reasonably have been generated by phage- or plasmid-mobilized gene transfer, the plasmid profiles of the pair members were radically different and/or the potentially transmitted alleles were not present in other ETs in the population. (3) Although ET-12 was abundant, being represented by 252 of the 550 clones sampled, the electrophoretic type most similar to ET-12 different from it at six loci, and ET-12 carried two unique alleles. We conclude that most of the genetic diversity observed in this human host is a consequence of successive invasions of E. coli genotypes.
EVOLUTIONARY RELATIONSHIPS AMONG FIVE SUBSPECIES OF MUS MUSCULUS BASED ON RESTRICTION ENZYME CLEAVAGE PATTERNS OF MITOCHONDRIAL DNA
Authors: Yonekawa Hiromichi , Moriwaki Kazuo , Gotoh Osamu , Hayashi Jun-Ichi , Watanabe Junko , Miyashita Nobumoto , Petras Michael L , Tagashira Yusaku
Published: April 2021

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

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

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

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

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

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

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

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

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

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

Background

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

Objective

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

Methods

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

Results

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

Conclusions

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

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

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

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

Background

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

Methods

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

Results

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

Conclusions

Raltegravir 400 mg+lamivudine 150 mg showed high levels of ex vivo HIV protection, associated with high drug concentrations persisting after discontinuation in vaginal and rectal compartments, supporting further investigation of these agents for PrEP.