bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of Gene Duplication and Functional Evolution During the Diversification of the AGAMOUS Subfamily of MADS Box Genes in Angiosperms
Authors: Kramer Elena M , Jaramillo M Alejandra , Di Stilio Verónica S 
Published: April 2021

Abstract
Members of the AGAMOUS (AG) subfamily of MIKC-type MADS-box genes appear to control the development of reproductive organs in both gymnosperms and angiosperms. To understand the evolution of this subfamily in the flowering plants, we have identified 26 new AG -like genes from 15 diverse angiosperm species. Phylogenetic analyses of these genes within a large data set of AG-like sequences show that ancient gene duplications were critical in shaping the evolution of the subfamily. Before the radiation of extant angiosperms, one event produced the ovule-specific D lineage and the well-characterized C lineage, whose members typically promote stamen and carpel identity as well as floral meristem determinacy. Subsequent duplications in the C lineage resulted in independent instances of paralog subfunctionalization and maintained functional redundancy. Most notably, the functional homologs AG from Arabidopsis and PLENA (PLE) from Antirrhinum are shown to be representatives of separate paralogous lineages rather than simple genetic orthologs. The multiple subfunctionalization events that have occurred in this subfamily highlight the potential for gene duplication to lead to dissociation among genetic modules, thereby allowing an increase in morphological diversity.
Identification of Edc3p as an Enhancer of mRNA Decapping inSaccharomyces cerevisiae
Authors: Kshirsagar Meenakshi , Parker Roy 
Published: April 2021

AbstractThe major pathway of mRNA decay in yeast initiates with deadenylation, followed by mRNA decapping and 5′-3′ exonuclease digestion. An in silico approach was used to identify new proteins involved in the mRNA decay pathway. One such protein, Edc3p, was identified as a conserved protein of unknown function having extensive two-hybrid interactions with several proteins involved in mRNA decapping and 5′-3′ degradation including Dcp1p, Dcp2p, Dhh1p, Lsm1p, and the 5′-3′ exonuclease, Xrn1p. We show that Edc3p can stimulate mRNA decapping of both unstable and stable mRNAs in yeast when the decapping enzyme is compromised by temperature-sensitive alleles of either the DCP1 or the DCP2 genes. In these cases, deletion of EDC3 caused a synergistic mRNA-decapping defect at the permissive temperatures. The edc3Δ had no effect when combined with the lsm1Δ, dhh1Δ, or pat1Δ mutations, which appear to affect an early step in the decapping pathway. This suggests that Edc3p specifically affects the function of the decapping enzyme per se. Consistent with a functional role in decapping, GFP-tagged Edc3p localizes to cytoplasmic foci involved in mRNA decapping referred to as P-bodies. These results identify Edc3p as a new protein involved in the decapping reaction.
Mec1 and Rad53 Inhibit Formation of Single-Stranded DNA at Telomeres of Saccharomyces cerevisiae cdc13-1 Mutants
Authors: Jia Xindan , Weinert Ted , Lydall David 
Published: April 2021

Abstract
Here we examine the roles of budding-yeast checkpoint proteins in regulating degradation of dsDNA to ssDNA at unprotected telomeres (in Cdc13 telomere-binding protein defective strains). We find that Rad17, Mec3, as well as Rad24, members of the putative checkpoint clamp loader (Rad24) and sliding clamp (Rad17, Mec3) complexes, are important for promoting degradation of dsDNA in and near telomere repeats. We find that Mec1, Rad53, as well as Rad9, have the opposite role: they inhibit degradation. Downstream checkpoint kinases Chk1 and Dun1 play no detectable role in either promoting degradation or inhibiting it. These data suggest, first, that the checkpoint sliding clamp regulates and/or recruits some nucleases for degradation, and, second, that Mec1 activates Rad9 to activate Rad53 to inhibit degradation. Further analysis shows that Rad9 inhibits ssDNA generation by both Mec1/Rad53-dependent and -independent pathways. Exo1 appears to be targeted by the Mec1/Rad53-dependent pathway. Finally, analysis of double mutants suggests a minor role for Mec1 in promoting Rad24-dependent degradation of dsDNA. Thus, checkpoint proteins orchestrate carefully ssDNA production at unprotected telomeres.
Molecular and Comparative Genetics of Mental Retardation
Authors: Inlow Jennifer K , Restifo Linda L 
Published: April 2021

Abstract
Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of &gt;1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the ∼700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR.
Enhancers and Suppressors of Testicular Cancer Susceptibility in Single- and Double-Mutant Mice
Authors: Lam Man-Yee Josephine , Youngren Kirsten K , Nadeau Joseph H 
Published: April 2021

Abstract
Susceptibility to spontaneous testicular germ cell tumors (TGCTs), a common cancer affecting young men, shows unusual genetic complexity. Despite remarkable progress in the genetics analysis of susceptibility to many cancers, TGCT susceptibility genes have not yet been identified. Various mutations that are inherited as Mendelian traits in laboratory mice affect susceptibility to spontaneous TGCTs on the 129/Sv inbred genetic background. We compared the frequency of spontaneous TGCTs in single- and double-mutant mice to identify combinations that show evidence of enhancer or suppressor effects. The lower-than-expected TGCT frequencies in mice with partial deficiencies of TRP53 and MGF-SLJ and in 129.MOLF-Chr19 (M19) consomic mice that were heterozygous for the Ay mutation suggest that either these genes complement each other to restore normal functionality in TGCT stem cells or together these genes activate mechanisms that suppress incipient TGCTs. By contrast, the higher-than-expected TGCT frequencies in Mgf Sl-J-M19 compound heterozygous mice suggest that these mutations exacerbate each other’s effects. Together, these results provide clues to the genetic and molecular basis for susceptibility to TGCTs in mice and perhaps in humans.
PIF- and Pong-Like Transposable Elements: Distribution, Evolution and Relationship With Tourist-Like Miniature Inverted-Repeat Transposable Elements
Authors: Zhang Xiaoyu , Jiang Ning , Feschotte Cédric , Wessler Susan R 
Published: April 2021

Abstract
Miniature inverted-repeat transposable elements (MITEs) are short, nonautonomous DNA elements that are widespread and abundant in plant genomes. Most of the hundreds of thousands of MITEs identified to date have been divided into two major groups on the basis of shared structural and sequence characteristics: Tourist-like and Stowaway-like. Since MITEs have no coding capacity, they must rely on transposases encoded by other elements. Two active transposons, the maize P Instability Factor (PIF) and the rice Pong element, have recently been implicated as sources of transposase for Tourist-like MITEs. Here we report that PIF- and Pong-like elements are widespread, diverse, and abundant in eukaryotes with hundreds of element-associated transposases found in a variety of plant, animal, and fungal genomes. The availability of virtually the entire rice genome sequence facilitated the identification of all the PIF/Pong-like elements in this organism and permitted a comprehensive analysis of their relationship with Tourist-like MITEs. Taken together, our results indicate that PIF and Pong are founding members of a large eukaryotic transposon superfamily and that members of this superfamily are responsible for the origin and amplification of Tourist-like MITEs.
Recombination and Migration of Cryphonectria hypovirus 1 as Inferred From Gene Genealogies and the Coalescent
Authors: Carbone Ignazio , Liu Yir-Chung , Hillman Bradley I , Milgroom Michael G 
Published: April 2021

Abstract
Genealogy-based methods were used to estimate migration of the fungal virus Cryphonectria hypovirus 1 between vegetative compatibility types of the host fungus, Cryphonectria parasitica, as a means of estimating horizontal transmission within two host populations. Vegetative incompatibility is a self/non-self recognition system that inhibits virus transmission under laboratory conditions but its effect on transmission in nature has not been clearly demonstrated. Recombination within and among different loci in the virus genome restricted the genealogical analyses to haplotypes with common mutation and recombinational histories. The existence of recombination necessitated that we also use genealogical approaches that can take advantage of both the mutation and recombinational histories of the sample. Virus migration between populations was significantly restricted. In contrast, estimates of migration between vegetative compatibility types were relatively high within populations despite previous evidence that transmission in the laboratory was restricted. The discordance between laboratory estimates and migration estimates from natural populations highlights the challenges in estimating pathogen transmission rates. Genealogical analyses inferred migration patterns throughout the entire coalescent history of one viral region in natural populations and not just recent patterns of migration or laboratory transmission. This application of genealogical analyses provides markedly stronger inferences on overall transmission rates than laboratory estimates do.
RuvAB and RecG Are Not Essential for the Recovery of DNA Synthesis Following UV-Induced DNA Damage in Escherichia coli
Authors: Donaldson Janet R , Courcelle Charmain T , Courcelle Justin 
Published: April 2021

Abstract
Ultraviolet light induces DNA lesions that block the progression of the replication machinery. Several models speculate that the resumption of replication following disruption by UV-induced DNA damage requires regression of the nascent DNA or migration of the replication machinery away from the blocking lesion to allow repair or bypass of the lesion to occur. Both RuvAB and RecG catalyze branch migration of three- and four-stranded DNA junctions in vitro and are proposed to catalyze fork regression in vivo. To examine this possibility, we characterized the recovery of DNA synthesis in ruvAB and recG mutants. We found that in the absence of either RecG or RuvAB, arrested replication forks are maintained and DNA synthesis is resumed with kinetics that are similar to those in wild-type cells. The data presented here indicate that RecG- or RuvAB-catalyzed fork regression is not essential for DNA synthesis to resume following arrest by UV-induced DNA damage in vivo.
The Putative RNA Helicase Dbp6p Functionally Interacts With Rpl3p, Nop8p and the Novel trans-acting Factor Rsa3p During Biogenesis of 60S Ribosomal Subunits in Saccharomyces cerevisiae
Authors: de la Cruz Jesús , Lacombe Thierry , Deloche Olivier , Linder Patrick , Kressler Dieter 
Published: April 2021

Abstract
Ribosome biogenesis requires at least 18 putative ATP-dependent RNA helicases in Saccharomyces cerevisiae. To explore the functional environment of one of these putative RNA helicases, Dbp6p, we have performed a synthetic lethal screen with dbp6 alleles. We have previously characterized the nonessential Rsa1p, whose null allele is synthetically lethal with dbp6 alleles. Here, we report on the characterization of the four remaining synthetic lethal mutants, which reveals that Dbp6p also functionally interacts with Rpl3p, Nop8p, and the so-far-uncharacterized Rsa3p (ribosome assembly 3). The nonessential Rsa3p is a predominantly nucleolar protein required for optimal biogenesis of 60S ribosomal subunits. Both Dbp6p and Rsa3p are associated with complexes that most likely correspond to early pre-60S ribosomal particles. Moreover, Rsa3p is co-immunoprecipitated with protA-tagged Dbp6p under low salt conditions. In addition, we have established a synthetic interaction network among factors involved in different aspects of 60S-ribosomal-subunit biogenesis. This extensive genetic analysis reveals that the rsa3 null mutant displays some specificity by being synthetically lethal with dbp6 alleles and by showing some synthetic enhancement with the nop8-101 and the rsa1 null allele.
The fluffy Gene of Neurospora crassa Is Necessary and Sufficient to Induce Conidiophore Development
Authors: Bailey-Shrode Lori , Ebbole Daniel J 
Published: April 2021

Abstract
The fl (fluffy) gene of Neurospora crassa encodes a binuclear zinc cluster protein that regulates the production of asexual spores called macroconidia. Two other genes, acon-2 and acon-3, play major roles in controlling development. fl is induced specifically in differentiating tissue during conidiation and acon-2 plays a role in this induction. We examined the function of fl by manipulating its level of expression in wild-type and developmental mutant strains. Increasing expression of fl from a heterologous promoter in a wild-type genetic background is sufficient to induce conidiophore development. Elevated expression of fl leads to induction of development of the acon-2 mutant in nitrogen-starved cultures, but does not bypass the conidiation defect of the acon-3 mutant. These findings indicate that fl acts downstream of acon-2 and upstream of acon-3 in regulating gene expression during development. The eas, con-6, and con-10 genes are induced at different times during development. Morphological changes induced by artificially elevated fl expression in the absence of environmental cues were correlated with increased expression of eas, but not con-6 or con-10. Thus, although inappropriate expression of fl in vegetative hyphae is sufficient to induce conidial morphogenesis, complete reconstitution of development leading to the formation of mature conidia may require environmental signals to regulate fl activity and/or appropriate induction of fl expression in the developing conidiophore.
Mating Within the Meiotic Tetrad and the Maintenance of Genomic Heterozygosity
Authors: Hood Michael E , Antonovics Janis 
Published: April 2021

Abstract
Mating among the products of a single meiosis (automixis or meiotic parthenogenesis) is found in diverse groups of plant, animal, and fungal taxa. Restoration of the diploid stage is often strictly controlled and brings together products separated at the first meiotic division. Despite apparent similarities to diploid selfing, the theoretical prediction is that heterozygosity should be maintained on all chromosomes when it is linked to the centromeres and thus also segregates at the first meiotic division. Using the fungus Microbotryum, we directly test this prediction by linear tetrad analysis. The patterns of meiotic segregation for chromosome size variation (electrophoretic karyotypes) and PCR products (AFLP procedures) were determined for Microbotryum lineages native to North America and Europe. Our data reveal a surprisingly dynamic genome that is rich in heterozygosity and where size-dimorphic autosomes are common. The genetic variation agrees with the prediction of centromere-linked heterozygosity. This was observed to the greatest extent in the lineage of Microbotryum native to North America where there was consistent first-division segregation and independent assortment of multiple linkage groups. The data also show properties that distinguish the fungal sex chromosomes from the autosomes in both lineages of Microbotryum. We describe a scenario where the mating system of automixis with first-division restitution is the result of feedback mechanisms to control exposure of genetic load.
Molecular and Functional Analysis of scalloped Recessive Lethal Alleles in Drosophila melanogaster
Authors: Srivastava Ajay , Simmonds Andrew J , Garg Ankush , Fossheim Leif , Campbell Shelagh D , Bell John B 
Published: April 2021

Abstract
The Drosophila melanogaster scalloped (sd) gene is a homolog of the human TEF-1 gene and is a member of the TEA/ATTS domain-containing family of transcription factors. In Drosophila, sd is involved in wing development as well as neural development. Herein, data are presented from a molecular analysis of five recessive lethal sd alleles. Only one of these alleles complements a viable allele associated with an sd mutant wing phenotype, suggesting that functions important for wing development are compromised by the noncomplementing alleles. Two of the wing noncomplementing alleles have mutations that help to define a VG-binding domain for the SD protein in vivo, and another noncomplementing allele has a lesion within the TEA DNA-binding domain. The VG-binding domain overlaps with a domain important for viability of the fly, since two of the sd lethal lesions are located there. The fifth lethal affects a yet undefined motif lying just outside the VG-binding domain in the C-terminal direction that affects both wing phenotype and viability. This is the first example linking mutations affecting specific amino acids in the SD protein with phenotypic consequences for the organism.
Integration and Modularity of Quantitative Trait Locus Effects on Geometric Shape in the Mouse Mandible
Authors: Klingenberg Christian Peter , Leamy Larry J , Cheverud James M 
Published: April 2021

AbstractThe mouse mandible has long served as a model system for complex morphological structures. Here we use new methodology based on geometric morphometrics to test the hypothesis that the mandible consists of two main modules, the alveolar region and the ascending ramus, and that this modularity is reflected in the effects of quantitative trait loci (QTL). The shape of each mandible was analyzed by the positions of 16 morphological landmarks and these data were analyzed using Procrustes analysis. Interval mapping in the F2 generation from intercrosses of the LG/J and SM/J strains revealed 33 QTL affecting mandible shape. The QTL effects corresponded to a variety of shape changes, but ordination or a parametric bootstrap test of clustering did not reveal any distinct groups of QTL that would affect primarily one module or the other. The correlations of landmark positions between the two modules tended to be lower than the correlations between arbitrary subsets of landmarks, indicating that the modules were relatively independent of each other and confirming the hypothesized location of the boundary between them. While these results are in agreement with the hypothesis of modularity, they also underscore that modularity is a question of the relative degrees to which QTL contribute to different traits, rather than a question of discrete sets of QTL contributing to discrete sets of traits.
Midterm results of stand-alone thoracoscopic epicardial ablation with box lesion for atrial fibrillation
Authors: Yu Chunyu , Li Haojie , Zhang Heng , Zheng Zhe 
Published: April 2021

Abstract OBJECTIVESThe short-term results of video-assisted thoracoscopic surgical ablation (VTSA) with box lesion have been highly variable, and the actual efficacy requires clarification through longer follow-ups. We aimed to report which patients might benefit more from VTSA with box lesion by longer follow-up.METHODSFrom September 2010 to November 2016, patients with atrial fibrillation (AF) who underwent VTSA with box lesion were screened. All enrolled patients visited the outpatient clinic and underwent 24-h Holter monitoring at 3, 6 and 12 months after surgery and annually thereafter.RESULTSA total of 91 consecutive patients [age, 58.0 (interquartile interval from 52.0 to 62.0) years; male, 71.4%] with paroxysmal (67%) or persistent/long-standing persistent (33%) AF were enrolled. After a median follow-up of 48 months (interquartile interval from 36 to 60 months), freedom from atrial tachyarrhythmias without antiarrhythmic drugs (AADs) was 76.5%, 66.0% and 66.0% for paroxysmal AF and 58.6%, 47.8% and 34.2% for persistent/long-standing persistent AF at 12, 36 and 60 months, respectively (P = 0.017). The preoperative left atrial diameter &gt;40 mm (hazard ratio: 2.837, 95% confidence interval: 1.408–5.716; P = 0.004) and age &gt;50 years (hazard ratio: 2.927, 95% confidence interval: 1.359–6.305; P = 0.006) were associated with recurrences of atrial tachyarrhythmias. In patients with paroxysmal AF and left atrial diameter ≤40 mm (n = 43), freedom from atrial tachyarrhythmias without AADs was 81.4%, 74.3% and 74.3% at 12, 36 and 60 months, respectively.CONCLUSIONSIn patients with paroxysmal AF and left atrial diameter ≤40 mm, 5-year freedom from atrial tachyarrhythmias without AADs was 74.3%, which was better than that in patients with left atrial diameter &gt;40 mm. A larger sample size and improved study design are needed to confirm our conclusions.
Basophils, a neglected minority in the immune system, have come into the limelight at last
Authors: Karasuyama Hajime , Shibata Sho , Yoshikawa Soichiro , Miyake Kensuke 
Published: April 2021

Abstract
Basophils, the rarest granulocytes, were identified by Paul Ehrlich more than 140 years ago, much earlier than the discovery of T and B cells. Unfortunately, basophils were often mixed up with tissue-resident mast cells because of some phenotypic similarities between them and considered erroneously as minor relatives or blood-circulating precursors of mast cells. Moreover, basophil research was hindered by the rarity of basophils and the paucity of useful analytical tools, and therefore basophils had often been neglected in immunological studies. A series of studies using newly developed tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have clearly defined previously unrecognized roles of basophils, that are distinct from those played by tissue-resident mast cells. In this mini-review, we highlight recent advances in our understanding of basophil functions, particularly focusing on their roles in the regulation of innate and acquired immunity, allergic reactions, autoimmunity and protective immunity against parasitic infections, mainly based on animal studies. Further studies on human basophils would facilitate the development of new strategies for the treatment of basophil-associated disorders.
Improving Information from Manipulable Data
Authors: Frankel Alex , Kartik Navin 
Published: April 2021

AbstractData-based decision making must account for the manipulation of data by agents who are aware of how decisions are being made and want to affect their allocations. We study a framework in which, due to such manipulation, data become less informative when decisions depend more strongly on data. We formalize why and how a decision maker should commit to underutilizing data. Doing so attenuates information loss and thereby improves allocation accuracy.