bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing Effective Population Size and the McDonald-Kreitman Test
Authors: Eyre-Walker Adam 
Published: April 2021

Abstract
Artifactual evidence of adaptive amino acid substitution can be generated within a McDonald-Kreitman test if some amino acid mutations are slightly deleterious and there has been an increase in effective population size. Here I investigate the conditions under which this occurs. I show that fairly small increases in effective population size can generate artifactual evidence of positive selection if there is no selection upon synonymous codon use. This problem is exacerbated by the removal of low-frequency polymorphisms. However, selection on synonymous codon use restricts the conditions under which artifactual evidence of adaptive evolution is produced.
The Global Transcriptional Activator of Saccharomyces cerevisiae, Gcr1p, Mediates the Response to Glucose by Stimulating Protein Synthesis and CLN-Dependent Cell Cycle Progression
Authors: Willis Kristine A , Barbara Kellie E , Menon Balaraj B , Moffat Jason , Andrews Brenda , Santangelo George M 
Published: April 2021

Abstract
Growth of Saccharomyces cerevisiae requires coordination of cell cycle events (e.g., new cell wall deposition) with constitutive functions like energy generation and duplication of protein mass. The latter processes are stimulated by the phosphoprotein Gcr1p, a transcriptional activator that operates through two different Rap1p-mediated mechanisms to boost expression of glycolytic and ribosomal protein genes, respectively. Simultaneous disruption of both mechanisms results in a loss of glucose responsiveness and a dramatic drop in translation rate. Since a critical rate of protein synthesis (CRPS) is known to mediate passage through Start and determine cell size by modulating levels of Cln3p, we hypothesized that GCR1 regulates cell cycle progression by coordinating it with growth. We therefore constructed and analyzed gcr1Δ cln3Δ and gcr1Δ cln1Δ cln2Δ strains. Both strains are temperature and cold sensitive; interestingly, they exhibit different arrest phenotypes. The gcr1Δ cln3Δ strain becomes predominantly unbudded with 1N DNA content (G1 arrest), whereas gcr1Δ cln1Δ cln2Δ cells exhibit severe elongation and apparent M phase arrest. Further analysis demonstrated that the Rap1p/Gcr1p complex mediates rapid growth in glucose by stimulating both cellular metabolism and CLN transcription.
Suppressor Mutations Bypass the Requirement of fluG for Asexual Sporulation and Sterigmatocystin Production in Aspergillus nidulans
Authors: Seo Jeong-Ah , Guan Yajun , Yu Jae-Hyuk 
Published: April 2021

Abstract
Asexual sporulation (conidiation) in the filamentous fungus Aspergillus nidulans requires the early developmental activator fluG. Loss of fluG results in the blockage of both conidiation and production of the mycotoxin sterigmatocystin (ST). To investigate molecular mechanisms of fluG-dependent developmental activation, 40 suppressors of fluG (SFGs) that conidiate without fluG have been isolated and characterized. Genetic analyses showed that an individual suppression is caused by a single second-site mutation, and that all sfg mutations but one are recessive. Pairwise meiotic crosses grouped mutations to four loci, 31 of them to sfgA, 6 of them to sfgB, and 1 each to sfgC and sfgD, respectively. The only dominant mutation, sfgA38, also mapped to the sfgA locus, suggesting a dominant negative mutation. Thirteen sfgA and 1 sfgC mutants elaborated conidiophores in liquid submerged culture, indicating that loss of either of these gene functions not only bypasses fluG function but also results in hyperactive conidiation. While sfg mutants show varying levels of restored conidiation, all recovered the ability to produce ST at near wild-type levels. The fact that at least four loci are defined by recessive sfg mutations indicates that multiple genes negatively regulate conidiation downstream of fluG and that the activity of fluG is required to remove such repressive effects.
Quantitative Classification and Natural Clustering of Caenorhabditis elegans Behavioral Phenotypes
Authors: Geng Wei , Cosman Pamela , Baek Joong-Hwan , Berry Charles C , Schafer William R 
Published: April 2021

Abstract
Genetic analysis of nervous system function relies on the rigorous description of behavioral phenotypes. However, standard methods for classifying the behavioral patterns of mutant Caenorhabditis elegans rely on human observation and are therefore subjective and imprecise. Here we describe the application of machine learning to quantitatively define and classify the behavioral patterns of C. elegans nervous system mutants. We have used an automated tracking and image processing system to obtain measurements of a wide range of morphological and behavioral features from recordings of representative mutant types. Using principal component analysis, we represented the behavioral patterns of eight mutant types as data clouds distributed in multidimensional feature space. Cluster analysis using the k-means algorithm made it possible to quantitatively assess the relative similarities between different behavioral phenotypes and to identify natural phenotypic clusters among the data. Since the patterns of phenotypic similarity identified in this study closely paralleled the functional similarities of the mutant gene products, the complex phenotypic signatures obtained from these image data appeared to represent an effective diagnostic of the mutants' underlying molecular defects.
Recombination, Dominance and Selection on Amino Acid Polymorphism in the Drosophila Genome: Contrasting Patterns on the X and Fourth Chromosomes
Authors: Sheldahl Lea A , Weinreich Daniel M , Rand David M 
Published: April 2021

Abstract
Surveys of nucleotide polymorphism and divergence indicate that the average selection coefficient on Drosophila proteins is weakly positive. Similar surveys in mitochondrial genomes and in the selfing plant Arabidopsis show that weak negative selection has operated. These differences have been attributed to the low recombination environment of mtDNA and Arabidopsis that has hindered adaptive evolution through the interference effects of linkage. We test this hypothesis with new sequence surveys of proteins lying in low recombination regions of the Drosophila genome. We surveyed &gt;3800 bp across four proteins at the tip of the X chromosome and &gt;3600 bp across four proteins on the fourth chromosome in 24 strains of D. melanogaster and 5 strains of D. simulans. This design seeks to study the interaction of selection and linkage by comparing silent and replacement variation in semihaploid (X chromosome) and diploid (fourth chromosome) environments lying in regions of low recombination. While the data do indicate very low rates of exchange, all four gametic phases were observed both at the tip of the X and across the fourth chromosome. Silent variation is very low at the tip of the X (θS = 0.0015) and on the fourth chromosome (θS = 0.0002), but the tip of the X shows a greater proportional loss of variation than the fourth shows relative to normal-recombination regions. In contrast, replacement polymorphism at the tip of the X is not reduced (θR = 0.00065, very close to the X chromosome average). MK and HKA tests both indicate a significant excess of amino acid polymorphism at the tip of the X relative to the fourth. Selection is significantly negative at the tip of the X (Nes =-1.53) and nonsignificantly positive on the fourth (Nes ∼ 2.9), analogous to the difference between mtDNA (or Arabidopsis) and the Drosophila genome average. Our distal X data are distinct from regions of normal recombination where the X shows a deficiency of amino acid polymorphism relative to the autosomes, suggesting more efficient selection against recessive deleterious replacement mutations. We suggest that the excess amino acid polymorphism on the distal X relative to the fourth chromosome is due to (1) differences in the mutation rate for selected mutations on the distal X or (2) a greater relaxation of selection from stronger linkage-related interference effects on the distal X. This relaxation of selection is presumed to be greater in magnitude than the difference in efficiency of selection between X-linked vs. autosomal selection.
Mapping of Quantitative Trait Loci Controlling Adaptive Traits in Coastal Douglas Fir. III. Quantitative Trait Loci-by-Environment Interactions
Authors: Jermstad Kathleen D , Bassoni Daniel L , Jech Keith S , Ritchie Gary A , Wheeler Nicholas C , Neale David B 
Published: April 2021

Abstract
Quantitative trait loci (QTL) were mapped in the woody perennial Douglas fir (Pseudotsuga menziesii var. menziesii [Mirb.] Franco) for complex traits controlling the timing of growth initiation and growth cessation. QTL were estimated under controlled environmental conditions to identify QTL interactions with photoperiod, moisture stress, winter chilling, and spring temperatures. A three-generation mapping population of 460 cloned progeny was used for genetic mapping and phenotypic evaluations. An all-marker interval mapping method was used for scanning the genome for the presence of QTL and single-factor ANOVA was used for estimating QTL-by-environment interactions. A modest number of QTL were detected per trait, with individual QTL explaining up to 9.5% of the phenotypic variation. Two QTL-by-treatment interactions were found for growth initiation, whereas several QTL-by-treatment interactions were detected among growth cessation traits. This is the first report of QTL interactions with specific environmental signals in forest trees and will assist in the identification of candidate genes controlling these important adaptive traits in perennial plants.
A Consensus Linkage Map for Sugi (Cryptomeria japonica) From Two Pedigrees, Based on Microsatellites and Expressed Sequence Tags
Authors: Tani Naoki , Takahashi Tomokazu , Iwata Hiroyoshi , Mukai Yuzuru , Ujino-Ihara Tokuko , Matsumoto Asako , Yoshimura Kensuke , Yoshimaru Hiroshi , Murai Masafumi , Nagasaka Kazutoshi , Tsumura Yoshihiko 
Published: April 2021

Abstract
A consensus map for sugi (Cryptomeria japonica) was constructed by integrating linkage data from two unrelated third-generation pedigrees, one derived from a full-sib cross and the other by self-pollination of F1 individuals. The progeny segregation data of the first pedigree were derived from cleaved amplified polymorphic sequences, microsatellites, restriction fragment length polymorphisms, and single nucleotide polymorphisms. The data of the second pedigree were derived from cleaved amplified polymorphic sequences, isozyme markers, morphological traits, random amplified polymorphic DNA markers, and restriction fragment length polymorphisms. Linkage analyses were done for the first pedigree with JoinMap 3.0, using its parameter set for progeny derived by cross-pollination, and for the second pedigree with the parameter set for progeny derived from selfing of F1 individuals. The 11 chromosomes of C. japonica are represented in the consensus map. A total of 438 markers were assigned to 11 large linkage groups, 1 small linkage group, and 1 nonintegrated linkage group from the second pedigree; their total length was 1372.2 cM. On average, the consensus map showed 1 marker every 3.0 cM. PCR-based codominant DNA markers such as cleaved amplified polymorphic sequences and microsatellite markers were distributed in all linkage groups and occupied about half of mapped loci. These markers are very useful for integration of different linkage maps, QTL mapping, and comparative mapping for evolutional study, especially for species with a large genome size such as conifers.
Effect of Misoriented Sites on Neutrality Tests With Outgroup
Authors: Baudry Emmanuelle , Depaulis Frantz 
Published: April 2021

Abstract
Several neutrality tests use outgroups to infer the ancestral and derived states for polymorphism data. However, homoplasy can result in the incorrect inference of the derived variant. We show that empirically derived rates of misorientation strongly influence Fay and Wu's H-test, especially when the sample size is large.
Activity of Mitochondrially Synthesized Reporter Proteins Is Lower Than That of Imported Proteins and Is Increased by Lowering cAMP in Glucose-Grown Saccharomyces cerevisiae Cells
Authors: Demlow Christina M , Fox Thomas D 
Published: April 2021

Abstract
We selected for increased phenotypic expression of a synthetic cox2::arg8m-G66S reporter gene inserted into Saccharomyces cerevisiae mtDNA in place of COX2. Recessive mutations in ras2 and cyr1, as well as elevated dosage of PDE2, allowed cox2::arg8m-G66S to support Arg prototrophy. Each of these genetic alterations should decrease cellular cAMP levels. The resulting signal was transduced through redundant action of the three cAMP-dependent protein kinases, TPK1, TPK2, and TPK3. ras2 had little or no effect on the level of wild-type Arg8p encoded by cox2::ARG8m, but did increase Arg8p activity, as judged by growth phenotype. ras2 also caused increased fluorescence in cells carrying the synthetic cox3::GFPm reporter in mtDNA, but had little effect on the steady-state level of GFP polypeptide detected immunologically. Thus, decreased cAMP levels did not affect the synthesis of mitochondrially coded protein reporters in glucose-grown cells, but rather elevated activities in the matrix that promote efficient folding. Furthermore, we show that when Arg8p is synthesized in the cytoplasm and imported into mitochondria, it has greater activity than when it is synthesized in the matrix. Thus, mitochondrially synthesized proteins may not have the same access to matrix chaperones as cytoplasmically synthesized proteins emerging from the import apparatus.
Rights, proportionality, and process in EU counterterrorism lawmaking
Authors: de Londras Fiona , Tregidga Jasmin 
Published: April 2021

Abstract
Proportionality is a key principle of EU law. However, in spite of procedural requirements intended to ensure the full integration of proportionality as a design principle in EU law, the European Union continues to pass disproportionate counterterrorism laws. If proportionality is a fundamental constitutional principle of the European Union, and if lawmaking processes at EU level have been designed expressly with this in mind, then why do the EU’s counterterrorism laws consistently raise issues of disproportionate interference with rights? Taking as a case study the passage of the EU Directive on Combating Terrorism, this article argues that at least part of the answer lies in the curtailment and adjustment, in the counterterrorism field, of lawmaking processes that are designed to be participatory, evidence-based, and informed by proportionality.
Clinical Management of Gastrointestinal Disease in the Common Marmoset (Callithrix jacchus)
Authors: Fitz Casey , Goodroe Anna , Wierenga Lauren , Mejia Andres , Simmons Heather 
Published: April 2021

Abstract
Gastrointestinal disease is a frequently encountered problem among captive common marmoset (Callithrix jacchus) colonies. Management can be challenging due to the number of etiologies responsible for gastrointestinal disease in this species, limitations on diagnostic capabilities, and lack of effective treatments. Understanding commonly described GI diseases in the captive marmoset can provide insight on the impact these diseases have on research studies and aid in the development of appropriate management strategies. A review of commonly encountered GI disease processes as well as routinely implicated causes of GI disease in the common marmoset are provided. Current strategies in clinical management of GI disease in the common marmoset, including approaches to colony health, diagnostic testing, and commonly employed treatments are discussed.
Molecular and Binding Characteristics of OBP5 ofBradysia odoriphaga(Diptera: Sciaridae)
Authors: Yuting Yang , Dengke Hua , Caihua Shi , Wen Xie , Youjun Zhang 
Published: April 2021

AbstractOdorant-binding proteins (OBPs) capture and transport semiochemicals to olfactory receptors (OR) and function in the ﬁrst step in insect olfaction. In the present study, we cloned a full-length cDNA sequence of BodoOBP5 from the insect pest Bradysia odoriphaga (Diptera: Sciaridae). Real-time PCR (qRT-PCR) analysis revealed that BodoOBP5 was expressed at higher levels in female adults than in other developmental stages. In the different tissues, BodoOBP5 was highly expressed in the female antennae, whereas low levels were expressed in the head and the male antennae, expression was negligible in other tissues. The recombinant protein of BodoOBP5 was successfully expressed with a bacterial system. Competitive binding assays with nine host plant volatiles and a putative sex pheromone revealed that purified BodoOBP5 strongly bound to two sulfur compounds (methyl allyl disulfide and diallyl disulfide); the corresponding dissolution constants (Ki) were 10.38 and 9.23 μM, respectively. Molecular docking indicated that Leu99, Leu103, Ala143, Tyr107, Phe142, and Trp144 in the hydrophobic cavity of BodoOBP5 are the key residues mediating the interaction of BodoOBP5 with methyl allyl disulfide and diallyl disulfide. RNAi-based Y-tube olfactometer assay indicated that there is no significant difference in methyl allyl disulfide and diallyl disulfide. The results of this study increase our understanding of the binding of BodoOBP5 with plant volatiles, facilitating the development of novel ways to control B. odoriphaga.
Evaluation of the Preanalytical Interference of Hemoglobin, Bilirubin, or Lipids in Therapeutic Drug Monitoring Assays on Beckman Coulter AU Analyzers
Authors: Li Jieli , Rietschlin Jacqua , Miller Irene , Weber Charlene , Scheidegger Matt , Barringer Stephanie , Kerlin Rae , Williams JoAnna 
Published: April 2021

Abstract

Objective
The aim of this study was to evaluate the influence of hemolysis, icterus, and lipemia (HIL) interferences on 8 therapeutic drug monitoring (TDM) assays.

Methods
Amikacin, carbamazepine, digoxin, lidocaine, lithium, methotrexate, phenobarbital, and theophylline were spiked in specimen pools at the clinical decision cutoff values. The interferents were spiked in vitro in specimen pools. All analytes were tested on Beckman Coulter AU analyzers.

Results
Hemolysis interference was detected in quantitative microsphere system (QMS) amikacin at 55.59 μg/mL at a concentration of 500 mg/dL hemoglobin. Icterus interference was detected in enzyme multiplied immunoassay technique amikacin at 43.62 μg/mL and in QMS amikacin at 55.59 μg/mL, at a concentration of 20 mg/dL bilirubin.

Conclusion
Although the reference range value is recommended for clinical significance bias assessment for HIL interferences on most chemistry assays, an important investigation of the HIL interferences on TDM assays is to establish interferent thresholds at the clinical critical cutoff values.
COVID-19 and the Mental Health of Canadian Armed Forces Veterans: A Cross-Sectional Survey
Authors: Mahar Alyson L , Rindlisbacher Christina R , Edgelow Megan , Siddhpuria Shailee , Hallet Julie , Rochon Paula A , Cramm Heidi 
Published: April 2021

ABSTRACT

Background
There are no data on the impact of COVID-19 and associated public health measures, including sheltering at home, travel restrictions, and changes in health care provision, on the mental health of older veterans. This information is necessary for government and philanthropic agencies to tailor mental health supports, services, and resources for veterans in the peri- and post-pandemic periods. The objective of this study was to compare mental health symptoms between Canadian Armed Forces (CAFs) veterans and the general Canadian older adult population in the early months of the COVID-19 pandemic.

Materials and Methods
This was a secondary analysis of a cross-sectional study of older adults in the national Canadian COVID-19 Coping Study. Individuals aged 55 years and older were eligible. A convenience sample of older adults was recruited through a web-based survey administered between May 01, 2020 and June 30, 2020. Canadian Armed Force military service history status (yes/no) was ascertained. The eight-item Center for Epidemiological Studies Depression Scale, the five-item Beck Anxiety Inventory, and the three-item Loneliness Scale were used to measure mental health symptoms. Multivariable logistic regression compared the odds of screening positive for depression, anxiety, and loneliness between veterans and non-veterans.

Results
Of 1,541 respondents who answered the final question (87% survey completeness rate), 210 were veterans. Forty percent of veterans met criteria for at least one of the mental health diagnoses compared to 46% of non-veterans (P = .12). The odds of reporting elevated symptoms of depression, anxiety, and loneliness were similar for veteran and non-veteran respondents after adjusting for confounders.

Conclusion
Veterans’ report of mental health symptoms was similar to the general population Spring 2020 of the COVID-19 pandemic. Although veterans’ military training may better prepare them to adapt in the face of a pandemic, additional research is needed to understand the longitudinal impacts on physical and mental health.
Comparative Genome Analyses Highlight Transposon-Mediated Genome Expansion and the Evolutionary Architecture of 3D Genomic Folding in Cotton
Authors: Wang Maojun , Li Jianying , Wang Pengcheng , Liu Fang , Liu Zhenping , Zhao Guannan , Xu Zhongping , Pei Liuling , Grover Corrinne E , Wendel Jonathan F , Wang Kunbo , Zhang Xianlong 
Published: April 2021

Abstract
Transposable element (TE) amplification has been recognized as a driving force mediating genome size expansion and evolution, but the consequences for shaping 3D genomic architecture remains largely unknown in plants. Here, we report reference-grade genome assemblies for three species of cotton ranging 3-fold in genome size, namely Gossypium rotundifolium (K2), G. arboreum (A2), and G. raimondii (D5), using Oxford Nanopore Technologies. Comparative genome analyses document the details of lineage-specific TE amplification contributing to the large genome size differences (K2, 2.44 Gb; A2, 1.62 Gb; D5, 750.19 Mb) and indicate relatively conserved gene content and synteny relationships among genomes. We found that approximately 17% of syntenic genes exhibit chromatin status change between active (“A”) and inactive (“B”) compartments, and TE amplification was associated with the increase of the proportion of A compartment in gene regions (∼7,000 genes) in K2 and A2 relative to D5. Only 42% of topologically associating domain (TAD) boundaries were conserved among the three genomes. Our data implicate recent amplification of TEs following the formation of lineage-specific TAD boundaries. This study sheds light on the role of transposon-mediated genome expansion in the evolution of higher-order chromatin structure in plants.