bluuebunny/crossref_metadata_2025_split huggingface dataset:
SWITCHES: Searchable Web Interface for Topologies of CHEmical Switches
Authors: HarshaRani G V , Moza S , Ramakrishnan N , Bhalla U S 
Published: January 2021

Abstract

Summary
Bistable biochemical switches are key motifs in cellular state decisions and long-term storage of cellular ‘memory’. There are a few known biological switches that have been well characterized, however, these examples are insufficient for systematic surveys of properties of these important systems. Here we present a resource of all possible bistable biochemical reaction networks with up to six reactions between three molecules, and three reactions between four molecules. Over 35 000 reaction topologies were constructed by identifying unique combinations of reactions between a fixed number of molecules. Then, these topologies were populated with rates within a biologically realistic range. The Searchable Web Interface for Topologies of CHEmical Switches (SWITCHES, https://switches.ncbs.res.in) provides a bistability and parameter analysis of over seven million models from this systematic survey of chemical reaction space. This database will be useful for theoreticians interested in analyzing stability in chemical systems and also experimentalists for creating robust synthetic biological switches.

Availability and implementation
Freely available on the web at https://switches.ncbs.res.in. Website implemented in PHP, MariaDB, Graphviz and Apache, with all major browsers supported.
Ten Years of Population-Level Genomic Escherichia coli and Klebsiella pneumoniae Serotype Surveillance Informs Vaccine Development for Invasive Infections
Authors: Lipworth Samuel , Vihta Karina-Doris , Chau Kevin K , Kavanagh James , Davies Timothy , George Sophie , Barker Leanne , Vaughan Ali , Andersson Monique , Jeffery Katie , Oakley Sarah , Morgan Marcus , Peto Timothy E A , Crook Derrick W , Walker A Sarah , Stoesser Nicole 
Published: January 2021

Abstract

Background
The incidence of bloodstream infections (BSIs) caused by Escherichia coli and Klebsiella pneumoniae is increasing, with substantial associated morbidity, mortality, and antimicrobial resistance. Unbiased serotyping studies to guide vaccine target selection are limited.

Methods
We conducted unselected, population-level genomic surveillance of bloodstream E. coli and Klebsiella pneumoniae isolates from 2008 to 2018 in Oxfordshire, United Kingdom. We supplemented this with an analysis of publicly available global sequencing data (n = 3678).

Results
We sequenced 3478 E. coli isolates (3278 passed quality control) and 556 K. pneumoniae isolates (535 [K-antigen] and 549 [O-antigen] passed quality control). The 4 most common E. coli O-antigens (O1/O2/O6/O25) were identified in 1499/3278 isolates; the incidence of these O-types increased over time (incidence rate ratio per year [IRRy] = 1.14, 95% confidence interval [CI]: 1.11–1.16). These O-types accounted for 616/1434 multidrug-resistant (MDR) and 173/256 extended-spectrum beta-lactamase (ESBL)-resistant isolates in Oxfordshire but only 19/90 carbapenem-resistant isolates across all studies. For Klebsiella pneumoniae, the most common O-antigens (O2v2/O1v1/O3b/O1v2) accounted for 410/549 isolates; the incidence of BSIs caused by these also increased annually (IRRy = 1.09; 95% CI: 1.05–1.12). These O-types accounted for 122/148 MDR and 106/123 ESBL isolates in Oxfordshire and 557/734 carbapenem-resistant isolates across all studies. Conversely we observed substantial capsular antigen diversity. Analysis of 3678 isolates from global studies demonstrated the generalizability of these findings. For E. coli, based on serotyping, the ExPEC4V and ExPEC10V vaccines under investigation would cover 46% and 72% of Oxfordshire isolates respectively, and 47% and 71% of MDR isolates.

Conclusions
O-antigen targeted vaccines may be useful in reducing the morbidity, mortality, and antimicrobial resistance associated with E. coli and K. pneumoniae BSIs.
Camilo Barcia Trelles on the Meaning of the Monroe Doctrine and the Legacy of Vitoria in the Americas
Authors: Scarfi Juan Pablo 
Published: January 2021

Abstract
This article explores three important dimensions of the work and trajectory of Camilo Barcia Trelles: his understanding of the Monroe Doctrine; his vision and contribution to the debates in Latin America and the United States over intervention and the codification of American international law; and how his own understanding of the intellectual legacy of Francisco de Vitoria shaped his views and approaches to these topics. The article argues that Barcia Trelles provided a Spanish Americanist version of international law in the Americas, according to which, following the Spanish conquest of America and Vitoria’s important contribution to international law, a irreversible division began to emerge between the two Americas, that is, the Latin American and US traditions of international law, especially since the US Declaration of Independence, the collapse of the Spanish Monarchy and the independence of the Spanish American republics.
DCT4—A New Member of the Dicarboxylate Transporter Family in C4 Grasses
Authors: Weissmann Sarit , Huang Pu , Wiechert Madeline A , Furuyama Koki , Brutnell Thomas P , Taniguchi Mitsutaka , Schnable James C , Mockler Todd C 
Published: January 2021

AbstractMalate transport shuttles atmospheric carbon into the Calvin–Benson cycle during NADP-ME C4 photosynthesis. Previous characterizations of several plant dicarboxylate transporters (DCT) showed that they efficiently exchange malate across membranes. Here, we identify and characterize a previously unknown member of the DCT family, DCT4, in Sorghum bicolor. We show that SbDCT4 exchanges malate across membranes and its expression pattern is consistent with a role in malate transport during C4 photosynthesis. SbDCT4 is not syntenic to the characterized photosynthetic gene ZmDCT2, and an ortholog is not detectable in the maize reference genome. We found that the expression patterns of DCT family genes in the leaves of Zea mays, and S. bicolor varied by cell type. Our results suggest that subfunctionalization, of members of the DCT family, for the transport of malate into the bundle sheath plastids, occurred during the process of independent recurrent evolution of C4 photosynthesis in grasses of the PACMAD clade. We also show that this subfunctionalization is lineage independent. Our results challenge the dogma that key C4 genes must be orthologues of one another among C4 species, and shed new light on the evolution of C4 photosynthesis.
EXCEPTIONALLY HIGH LEVELS OF RESTRICTION SITE POLYMORPHISM IN DNA NEAR THE MAIZE Adh1 GENE
Authors: Johns Mitrick A , Strommer Judith N , Freeling Michael 
Published: January 2021

ABSTRACT
Restriction maps have been prepared for the chromosomal region near seven biochemically and genetically distinct maize alcohol dehydrogenase-1 (Adh1) alleles using a small cDNA probe for Adh1. Five restriction sites spanning about 4 kb in and near the Adh1 transcription unit appear identical in all seven alleles. Outside this conserved region, variation in restriction site position is the rule. Six of the seven alleles are distinguishable, and the alleles appear to fall into four groups. The DNA flanking the 1S-type alleles seems to share no restriction site homology with the DNA near the 1F-type alleles. Several hypotheses are put forward to explain how such high levels of polymorphism could have arisen in a species that has been domesticated for only about 10,000 years.
CHARACTERIZATION OF THE OPERATOR SITES OF THE exu REGULON IN ESCHERICHIA COLI K-12 BY OPERATOR-CONSTITUTIVE MUTATIONS AND REPRESSOR TITRATION
Authors: Mata-Gilsinger Mireille , Ritzenthaler Paul , Blanco Carlos 
Published: January 2021

ABSTRACT
In Escherichia coli, the exu regulon of the hexuronate system involves the three exuT, uxaCA and uxaB operons and is under the negative control of the exuR regulatory gene product. The technique developed by Casadaban, Chou and Cohen was employed to construct two plasmids containing operon fusions in which the lactose genes were fused to the uxaCA and exuT operons. These fusions were transferred into the chromosome by a reciprocal recombination event, and the resulting strains were used for isolation of mutants defective in repression. Two types of operator-constitutive mutants were obtained: one specific for the uxaCA operon expression and the other affecting the exuT gene expression. This genetic evidence confirms that these two operons which are divergently transcribed each possess their own operator site.—The derepressed expression of the two exuT-lac and uxaCA-lac operons and the uxaB gene was also examined upon introduction of plasmids bearing various operators of the exu regulon. The results of testing exuR repressor titration by multiple copies of the exu operators allowed us to show a gradation in the affinity degrees for the three exu operators: uxaBo has the strongest affinity for the exuR repressor and uxaCo the weakest, although that of exuTo seems to be just slightly greater. This gradation may play a role in the control of the exu regulon expression.
ISOLATION AND CHARACTERIZATION OF SEX-LINKED FEMALE-STERILE MUTANTS IN DROSOPHILA MELANOGASTER WITH SPECIAL ATTENTION TO EGGSHELL MUTANTS
Authors: Komitopoulou Katia , Gans Madeleine , Margaritis Lukas H , Kafatos Fotis C , Masson Michele 
Published: January 2021

ABSTRACT
To study genes that function mainly or exclusively during oogenesis, we have isolated and analyzed female-sterile mutations, with special emphasis on those that affect eggshell formation. Following treatment that induced 61 to 66% lethals, 8.1% of the 1071 X chromosomes tested carried recessive female sterility mutations (87 isolates), and 8.0% carried partial female-sterile mutations (86 isolates), respectively. In addition, three dominant female steriles were recovered. Some of the mutants had very low fecundity, and others laid morphologically normal eggs that failed to develop. A third category included 29 mutants that laid eggs with morphological abnormalities: 26 were female steriles, two were partial female steriles and one was fertile. Mutants of this third category were characterized in some detail and compared with 40 previously isolated mutants that laid similarly abnormal eggs. Approximately 28—31 complementation groups with morphological abnormalities were detected, some of which were large allelic series (11, 9, 7, 6 and 5 alleles). Twenty-four groups were mapped genetically or cytogenetically, and 21 were partially characterized by ultrastructural and biochemical procedures. Of the latter, one group showed clear deficiency of yolk proteins, and nine showed prominent ultrastructural defects in the chorion (at least eight accompanied by deficiencies in characterized chorion proteins). At least six groups with clear-cut effects were found at loci not previously identified with known chorion structural genes.
GENETIC COADAPTATION IN THE CHROMOSOMAL POLYMORPHISM OF DROSOPHILA SUBOBSCURA. I. SEASONAL CHANGES OF GAMETIC DISEQUILIBRIUM IN A NATURAL POPULATION
Authors: Fontdevila A , Zapata C , Alvarez G , Sanchez L , Méndez J , Enriquez I 
Published: January 2021

ABSTRACT
Seasonal changes in gene arrangement and allozyme frequencies have been investigated in Drosophila subobscura for several years. Some arrangements (Ost and O 3+4+7) show seasonal variation, which suggests that chromosomal polymorphism is flexible in this species. Seasonal changes in allozyme frequencies for Lap and Pept-1 loci, both located within the same inversions of chromosome O, are significant only inside the Ost arrangement, but not inside O 3+4 arrangement. This arrangement-dependent response of allozyme generates variation in arrangement-allozyme disequilibrium. The historical hypothesis on the maintenance of disequilibria cannot explain these seasonal changes, and some kind of natural selection must be invoked. Association between Lap and Pept-1 is also seasonal inside Ost but not inside O 3+4. We propose that Ost probably consists of a finite array of supergenes that are differentially favored in each season by natural selection. The present evidence on this supergene selection and other genetic, biogeographic and phylogenetic data points to O 3+4 as the most primitive gene order among the present arrangements
LINKAGE DISEQUILIBRIUM, SELECTION AND RECOMBINATION AT THREE LOCI
Authors: Hastings Alan 
Published: January 2021

ABSTRACT
Limits to the relationship among linkage disequilibrium, selection and recombination at equilibrium in three-locus, two-allele, deterministic, discrete generation models are determined using linear programming techniques. These results show that the commonly used measures of linkage disequilibrium are not appropriate for a multilocus setting. Additionally, interactions among three loci are important in reducing the strength of selection necessary to maintain a given level of disequilibrium, relative to a two-locus model.
CHROMOSOME-DESIGNATED MUTATION SELECTION IN TETRAHYMENA THERMOPHILA
Authors: Altschuler M I , Bruns P J 
Published: January 2021

ABSTRACT
Two protocols are presented that allow the selection of mutations mapping to micronuclear chromosome 5 in Tetrahymena thermophilia. One protocol involves crossing mutagenized diploid cells directly to a strain nullisomic for chromosome 5 and screening the monosomic progeny for a mutant phenotype. The second protocol first takes the mutagenized diploid cells through round I of genomic exclusion to create useful and reusable mutant heterokaryons, which are then assayed for the presence of mutations on chromosome 5 by crossing to the nullisomic 5 strain. Of 14 putative chromosome 5 mutations obtained by these two methods, seven are shown by genetic analysis to be recessive mutations on chromosome 5; one mapped elsewhere in the genome; six were infertile or failed to yield progeny in some of the diagnostic crosses and, thus, their genetic nature could not be determined with certainty.
SEMIDOMINANCE OF rad18-2 FOR SEVERAL PHENOTYPIC CHARACTERS IN SACCHAROMYCES CEREVISIAE
Authors: Mayer Vernon W , Goin Carol J 
Published: January 2021

ABSTRACT
Inbred diploid yeast strains heterozygous or homozygous for the rad18-2 allele and carrying markers for detection of mitotic recombination were constructed. The homozygous rad18-2/rad18-2 strain was highly sensitive to killing by UV light, showed greatly elevated frequencies of spontaneous and induced mitotic recombination and was more sensitive to trimethoprim than the wild-type diploid. The heterozygous strain RAD18/rad18-2 was intermediate in its response for these same phenotypic characters. These findings are discussed in the light of other studies in which incomplete dominance of genes involved in some aspect of DNA repair has been reported.
THE EFFECT OF INBREEDING ON COMPETITIVE MALE-MATING ABILITY IN DROSOPHILA MELANOGASTER
Authors: Sharp Paul M 
Published: January 2021

ABSTRACT
The effect of full-sib inbreeding on competitive male-mating ability (CI♂) in Drosophila melanogaster was investigated in two experiments. In the first, five inbred lines (with reserves) were assessed up to 18 generations. Linear inbreeding depression, of 5.9% per 10% increase in homozygosity, was observed. In a second experiment, 21 inbred lines were tested after three generations of full-sib mating (without reserves), and the decline with inbreeding was more severe, the male competitive index (CI♂) decreasing by 10.7% per 10% increase in F. The difference between these results is attributed to natural selection acting on variation within the inbred lines in extent of homozygosity, which can arise because of the peculiarly strong influence of linkage in Drosophila. Furthermore, differentiation between the lines may have reflected this variation rather than the various effects of different alleles fixed.—These results imply that the genetic variation in male-mating ability is largely due to dominance (no epistasis was detected) and are consonant with the proposition that intermale sexual selection is a very important component of fitness in D. melanogaster. There was no evidence of a positive correlation between male body size and competitive mating ability.
THE NATURE OF NUCLEOTIDE SEQUENCE DIVERGENCE BETWEEN BARLEY AND MAIZE CHLOROPLAST DNA
Authors: Zurawski Gerard , Clegg Michael T , Brown Anthony H D 
Published: January 2021

ABSTRACT
Analysis of a 2175-base pair (bp) SmaI-HindIII fragment of barley chloroplast DNA revealed that rbcL (the gene for the large subunit of ribulose 1,5-bisphosphate carboxylase) and atpB (the gene for the β subunit of ATPase) are transcribed divergently and are separated by an untranscribed region of 155-166 bp. The rbcL mRNA has a 320-residue untranslated leader region, whereas the atpB mRNA has a 296- to 309-residue leader region. The sequence of these regions, together with the initial 113 bp of the atpB-coding region and the initial 1279 bp of the rbcL-coding region, is compared with the analogous maize chloroplast DNA sequences. Two classes of nucleotide differences are present, substitutions and insertions/deletions. Nucleotide substitutions show a 1.9-fold bias toward transitions in the rbcL-coding region and a 1.5-fold bias toward transitions in the noncoding region. The level of nucleotide substitutions between the barley and maize sequences is about 0.065/bp. Seventy-one percent of the substitutions in the rbcL-coding region are at the third codon position, and 95% of these are synonymous changes. Insertion/deletion events, which are confined to the noncoding regions, are not randomly distributed in these regions and are often associated with short repeated sequences. The extent of change for the noncoding regions (about 0.093 events/bp) is less than the extent of change at the third codon positions in the rbcL-coding region (about 0.135 events/bp), including insertion/delection events. Limited sequence analysis of the analogous DNA from a wild line (Hordeum spontaneum) and a primitive Iranian barley (H. vulgare) suggested a low rate of chloroplast DNA evolution. Compared to spinach chloroplast DNA, the barley rbcL-atpB untranslated region is extremely diverged, with only the putative rbcL promoters and ribosome-binding site being extensively conserved.
TWO-STEP RESISTANCE BY ESCHERICHIA COLI B TO BACTERIOPHAGE T2
Authors: Lenski Richard E 
Published: January 2021

ABSTRACT
Numerous authors have noted the difficulty in obtaining mutants of E. coli B that are resistant to bacteriophage T2 using standard procedures of plating large numbers of cells in the presence of excess phage. Yet, T2-resistant mutants appear in continuous culture at rates inconsistent with this difficulty. This paradoxical result derives from the fact that resistance to T2 usually arises as a consequence of two nonindependent mutations. Mutant bacteria resistant to phage T4 are very common and increase rapidly in continuous culture with phage T2 owing to an approximate halving of the rate at which T2 adsorbs to and kills these partially resistant mutants. The rate at which these partially resistant mutants then give rise to fully resistant mutants is approximately two orders of magnitude higher than the rate obtained by direct selection. These results are consistent with biochemical evidence that T2 adsorption to E. coli B involves both the bacterial lipopolysaccharide (to which phage T4 adsorbs) and a bacterial surface protein. However, this genetic evidence suggests that T2 can adsorb to either receptor type alone, whereas the biochemical evidence suggests that T2 requires a complex of the two receptors for adsorption to E. coli B. These results also indicate that the effects of genetic background can influence not only the selective advantage associated with particular mutations but also the rate at which certain selectively defined characteristics arise via mutation.
SELECTION WITH GENE-CYTOPLASM INTERACTIONS. I. MAINTENANCE OF CYTOPLASM POLYMORPHISMS
Authors: Gregorius H R , Ross M D 
Published: January 2021

ABSTRACT
General conditions for the protectedness of gene-cytoplasm polymorphisms are considered for a biallelic model with two cytoplasm types and under the assumption that nuclear polymorphisms cannot be maintained in the presence of only one cytoplasm type. Analytical results involving male fertilities, female fertilities, viabilities and selfing rates are obtained, and numerical results show spiral and cyclic behavior of population trajectories. It is shown that a maternally inherited cytoplasmic polymorphism cannot be maintained in the absence of a nuclear polymorphism, and that a gene-cytoplasm polymorphism can only be maintained if the population shows sexual asymmetry, i.e., if the ratio of male to female fertility varies among genotypes. Thus, the classical viability selection model does not allow gene-cytoplasm polymorphisms.
RELATIONSHIPS BETWEEN A HYPER-REC MUTATION (rem1) AND OTHER RECOMBINATION AND REPAIR GENES IN YEAST
Authors: Malone Robert E , Hoekstra Merl F 
Published: January 2021

ABSTRACT
Mutations in the REM1 gene of Saccharomyces cerevisiae confer a semidominant hyper-recombination and hypermutable phenotype upon mitotic cells (Golin and Esposito 1977). These effects have not been observed in meiosis. We have examined the interactions of rem1 mutations with rad6-1, rad50-1, rad52-1 or spo11-1 mutations in order to understand the basis of the rem1 hyper-rec phenotype. The rad mutations have pleiotropic phenotypes; spo11 is only defective in sporulation and meiosis. The RAD6, RAD50 and SPO11 genes are not required for spontaneous mitotic recombination; mutations in the RAD52 gene cause a general spontaneous mitotic Rec- phenotype. Mutations in RAD50, RAD52 or SPO11 eliminate meiotic recombination, and mutations in RAD6 prevent spore formation. Evidence for the involvement of RAD6 in meiotic recombination is less clear. Mutations in all three RAD genes confer sensitivity to X rays; the RAD6 gene is also required for UV damage repair. To test whether any of these functions might be involved in the hyper-rec phenotype conferred by rem1 mutations, double mutants were constructed. Double mutants of rem1 spo11 were viable and demonstrated rem1 levels of mitotic recombination, suggesting that the normal meiotic recombination system is not involved in producing the rem1 phenotype. The rem1 rad6 double mutant was also viable and had rem1 levels of mitotic recombination. Neither rem1 rad50 nor rem1 rad52 double mutants were viable. This suggests that rem1 causes its hyper-rec phenotype because it creates lesions in the DNA that are repaired using a recombination-repair system involving RAD50 and RAD52.
OMNIPOTENT SUPPRESSORS EFFECTIVE IN Ψ+ STRAINS OF SACCHAROMYCES CEREVISIAE: RECESSIVENESS AND DOMINANCE
Authors: Ono Bun-Ichiro , Moriga Nozomi , Ishihara Kiyomi , Ishiguro Junpei , Ishino Yumiko , Shinoda Sumio 
Published: January 2021

ABSTRACT
We have characterized recessive and dominant omnipotent suppressor mutations obtained by conversion of the leu2-1 UAA mutation and the met8-UAG mutation in a ψ+ strain of Saccharomyces cerevisiae. The suppressors that act recessively upon these markers fell into two complementation groups; the sup47 and sup36 suppressors show linkage to the tyr1 locus and the aro1 locus, respectively. Of the suppressors acting dominantly upon both markers, those linked to the tyr1 locus are alleles of the SUP46 ribosomal mutation. The sup47 suppressors differ from the SUP46 suppressors not only in their suppressor activities in heterozygous diploids but also in their map positions relative to the tyr1 locus and their effects on the S11 ribosomal protein. The remaining dominant suppressors are not alleles of sup36 as judged by linkage analysis. The recessive suppressors and the dominant suppressors also differ in their effects on cell growth.