bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the HumanASPMGene, a Major Determinant of Brain Size
Authors: Zhang Jianzhi
Published: April 2021

The size of human brain tripled over a period of ∼2 million years (MY) that ended 0.2–0.4 MY ago. This evolutionary expansion is believed to be important to the emergence of human language and other high-order cognitive functions, yet its genetic basis remains unknown. An evolutionary analysis of genes controlling brain development may shed light on it. ASPM (abnormal spindle-like microcephaly associated) is one of such genes, as nonsense mutations lead to primary microcephaly, a human disease characterized by a 70% reduction in brain size. Here I provide evidence suggesting that human ASPM went through an episode of accelerated sequence evolution by positive Darwinian selection after the split of humans and chimpanzees but before the separation of modern non-Africans from Africans. Because positive selection acts on a gene only when the gene function is altered and the organismal fitness is increased, my results suggest that adaptive functional modifications occurred in human ASPM and that it may be a major genetic component underlying the evolution of the human brain.
Fission Yeast Mus81·Eme1 Holliday Junction Resolvase Is Required for Meiotic Crossing Over but Not for Gene Conversion
Authors: Smith Gerald R , Boddy Michael N , Shanahan Paul , Russell Paul
Published: April 2021

Most models of homologous recombination invoke cleavage of Holliday junctions to explain crossing over. The Mus81·Eme1 endonuclease from fission yeast and humans cleaves Holliday junctions and other branched DNA structures, leaving its physiological substrate uncertain. We report here that Schizosaccharomyces pombe mus81 mutants have normal or elevated frequencies of gene conversion but 20- to 100-fold reduced frequencies of crossing over. Thus, gene conversion and crossing over can be genetically separated, and Mus81 is required for crossing over, supporting the hypothesis that the fission yeast Mus81·Eme1 protein complex resolves Holliday junctions in meiotic cells.
Distinguishing the Hitchhiking and Background Selection Models
Authors: Innan Hideki , Stephan Wolfgang
Published: April 2021

A simple method to distinguish hitchhiking and background selection is proposed. It is based on the observation that these models make different predictions about the average level of nucleotide diversity in regions of low recombination. The method is applied to data from Drosophila melanogaster and two highly selfing tomato species.
Derivation of a Bayes Factor to Distinguish Between Linked or Pleiotropic Quantitative Trait Loci
Authors: Varona L , Gómez-Raya L , Rauw W M , Clop A , Ovilo C , Noguera J L
Published: April 2021

A simple procedure to calculate the Bayes factor between linked and pleiotropic QTL models is presented. The Bayes factor is calculated from the marginal prior and posterior densities of the locations of the QTL under a linkage and a pleiotropy model. The procedure is computed with a Gibbs sampler, and it can be easily applied to any model including the location of the QTL as a variable. The procedure was compared with a multivariate least-squares method. The proposed procedure showed better results in terms of power of detection of linkage when low information is available. As information increases, the performance of both procedures becomes similar. An example using data provided by an Iberian by Landrace pig intercross is presented. The results showed that three different QTL segregate in SSC6: a pleiotropic QTL affects myristic, palmitic, and eicosadienoic fatty acids; another pleiotropic QTL affects palmitoleic, stearic, and vaccenic fatty acids; and a third QTL affects the percentage of linoleic acid. In the example, the Bayes factor approach was more powerful than the multivariate least-squares approach.
Influence of Spatial and Temporal Heterogeneities on the Estimation of Demographic Parameters in a Continuous Population Using Individual Microsatellite Data
Authors: Leblois Raphael , Rousset François , Estoup Arnaud
Published: April 2021

Drift and migration disequilibrium are very common in animal and plant populations. Yet their impact on methods of estimation of demographic parameters was rarely evaluated especially in complex realistic population models. The effect of such disequilibria on the estimation of demographic parameters depends on the population model, the statistics, and the genetic markers used. Here we considered the estimation of the product Dσ2 from individual microsatellite data, where D is the density of adults and σ2 the average squared axial parent-offspring distance in a continuous population evolving under isolation by distance. A coalescence-based simulation algorithm was used to study the effect on Dσ2 estimation of temporal and spatial fluctuations of demographic parameters. Estimation of present-time Dσ2 values was found to be robust to temporal changes in dispersal, to density reduction, and to spatial expansions with constant density, even for relatively recent changes (i.e., a few tens of generations ago). By contrast, density increase in the recent past gave Dσ2 estimations biased largely toward past demographic parameters values. The method was also robust to spatial heterogeneity in density and estimated local demographic parameters when the density is homogenous around the sampling area (e.g., on a surface that equals four times the sampling area). Hence, in the limit of the situations studied in this article, and with the exception of the case of density increase, temporal and spatial fluctuations of demographic parameters appear to have a limited influence on the estimation of local and present-time demographic parameters with the method studied.
Homology Modeling and Mutational Analysis of Ho Endonuclease of Yeast
Authors: Bakhrat Anya , Jurica Melissa S , Stoddard Barry L , Raveh Dina
Published: April 2021

Ho endonuclease is a LAGLIDADG homing endonuclease that initiates mating-type interconversion in yeast. Ho is encoded by a free-standing gene but shows 50% primary sequence similarity to the intein (protein-intron encoded) PI-SceI. Ho is unique among LAGLIDADG endonucleases in having a 120-residue C-terminal putative zinc finger domain. The crystal structure of PI-SceI revealed a bipartite enzyme with a protein-splicing domain (Hint) and intervening endonuclease domain. We made a homology model for Ho on the basis of the PI-SceI structure and performed mutational analysis of putative critical residues, using a mating-type switch as a bioassay for activity and GFP-fusion proteins to detect nuclear localization. We found that residues of the N-terminal sequence of the Hint domain are important for Ho activity, in particular the DNA recognition region. C-terminal residues of the Hint domain are dispensable for Ho activity; however, the C-terminal putative zinc finger domain is essential. Mutational analysis indicated that residues in Ho that are conserved relative to catalytic, active-site residues in PI-SceI and other related homing endonucleases are essential for Ho activity. Our results indicate that in addition to the conserved catalytic residues, Hint domain residues and the zinc finger domain have evolved a critical role in Ho activity.
Genetic and Bioinformatic Analysis of 41C and the 2R Heterochromatin ofDrosophila melanogaster: A Window on the Heterochromatin-Euchromatin Junction
Authors: Myster Steven H , Wang Fei , Cavallo Robert , Christian Whitney , Bhotika Seema , Anderson Charles T , Peifer Mark
Published: April 2021

Genomic sequences provide powerful new tools in genetic analysis, making it possible to combine classical genetics with genomics to characterize the genes in a particular chromosome region. These approaches have been applied successfully to the euchromatin, but analysis of the heterochromatin has lagged somewhat behind. We describe a combined genetic and bioinformatics approach to the base of the right arm of the Drosophila melanogaster second chromosome, at the boundary between pericentric heterochromatin and euchromatin. We used resources provided by the genome project to derive a physical map of the region, examine gene density, and estimate the number of potential genes. We also carried out a large-scale genetic screen for lethal mutations in the region. We identified new alleles of the known essential genes and also identified mutations in 21 novel loci. Fourteen complementation groups map proximal to the assembled sequence. We used PCR to map the endpoints of several deficiencies and used the same set of deficiencies to order the essential genes, correlating the genetic and physical map. This allowed us to assign two of the complementation groups to particular “computed/curated genes” (CGs), one of which is Nipped-A, which our evidence suggests encodes Drosophila Tra1/TRRAP.
EXO1 Contributes to Telomere Maintenance in Both Telomerase-Proficient and Telomerase-Deficient Saccharomyces cerevisiae
Authors: Bertuch Alison A , Lundblad Victoria
Published: April 2021

Previous work in budding yeast has indicated that telomeres are protected, at least in part, from the action of Exo1, which degrades the C-rich strand of partially uncapped telomeres. To explore this further, we examined the consequences of Exo1-mediated activity in strains that lacked Ku, telomerase, or both. Loss of Exo1 partially rescued the telomere length defect in a yku80Δ strain, demonstrating that exonuclease action can directly contribute to telomere shortening. The rapid loss of inviability displayed by a yku80Δ est2Δ strain was also partially alleviated by an exo1Δ mutation, further supporting the proposal that Exo1 is one target of the activities that normally protect wild-type telomeres. Conversely, however, Exo1 activity was also capable of enhancing telomere function and consequently cell proliferation, by contributing to a telomerase-independent pathway for telomere maintenance. The recovery of recombination-dependent survivors that arose in a yku80Δ est2Δ strain was partially dependent on Exo1 activity. Furthermore, the types of recombination events that facilitate telomerase-independent survival were influenced by Exo1 activity, in both est2Δ and yku80Δ est2Δ strains. These data demonstrate that Exo1 can make either positive or negative contributions to telomere function and cell viability, depending on whether telomerase or recombination is utilized to maintain telomere function.
Construction of Transgenic Drosophila by Using the Site-Specific Integrase From Phage φC31
Authors: Groth Amy C , Fish Matthew , Nusse Roel , Calos Michele P
Published: April 2021

The φC31 integrase functions efficiently in vitro and in Escherichia coli, yeast, and mammalian cells, mediating unidirectional site-specific recombination between its attB and attP recognition sites. Here we show that this site-specific integration system also functions efficiently in Drosophila melanogaster in cultured cells and in embryos. Intramolecular recombination in S2 cells on transfected plasmid DNA carrying the attB and attP recognition sites occurred at a frequency of 47%. In addition, several endogenous pseudo attP sites were identified in the fly genome that were recognized by the integrase and used as substrates for integration in S2 cells. Two lines of Drosophila were created by integrating an attP site into the genome with a P element. φC31 integrase injected into embryos as mRNA functioned to promote integration of an attB-containing plasmid into the attP site, resulting in up to 55% of fertile adults producing transgenic offspring. A total of 100% of these progeny carried a precise integration event at the genomic attP site. These experiments demonstrate the potential for precise genetic engineering of the Drosophila genome with the φC31 integrase system and will likely benefit research in Drosophila and other insects.
Mitochondrial Cytochrome b DNA Variation in the High-Fecundity Atlantic Cod: Trans-Atlantic Clines and Shallow Gene Genealogy
Authors: Árnason Einar
Published: April 2021

An analysis of sequence variation of 250 bp of the mitochondrial cytochrome b gene of 1278 Atlantic cod Gadus morhua ranging from Newfoundland to the Baltic shows four high-frequency (>8%) haplotypes and a number of rare and singleton haplotypes. Variation is primarily synonymous mutations. Natural selection acting directly on these variants is either absent or very weak. Common haplotypes show regular trans-Atlantic clines in frequencies and each of them reaches its highest frequency in a particular country. A shallow multifurcating constellation gene genealogy implies young age and recent turnover of polymorphism. Haplotypes characterizing populations at opposite ends of the geographic distribution in Newfoundland and the Baltic are mutationally closest together. The haplotypes are young and have risen rapidly in frequency. Observed differentiation among countries is due primarily to clinal variation. Hypotheses of historical isolation and polymorphisms balanced by local selection and gene flow are unlikely. Instead the results are explained by demic selection of mitochondria carried by highly fit females winning reproductive sweepstakes. By inference the Atlantic cod, a very high-fecundity vertebrate, is characterized by a high variance of offspring number and strong natural selection that leads to very low effective to actual population sizes.
Dynamic Changes in the Distribution of a Satellite Homologous to Intergenic 26-18S rDNA Spacer in the Evolution of Nicotiana
Authors: Lim K Y , Skalicka K , Koukalova B , Volkov R A , Matyasek R , Hemleben V , Leitch A R , Kovarik A
Published: April 2021

An ∼135-bp sequence called the A1/A2 repeat was isolated from the transcribed region of the 26-18S rDNA intergenic spacer (IGS) of Nicotiana tomentosiformis. Fluorescence in situ hybridization (FISH) and Southern blot analysis revealed its occurrence as an independent satellite (termed an A1/A2 satellite) outside of rDNA loci in species of Nicotiana section Tomentosae. The chromosomal location, patterns of genomic dispersion, and copy numbers of its tandemly arranged units varied between the species. In more distantly related Nicotiana species the A1/A2 repeats were found only at the nucleolar organizer regions (NOR). There was a trend toward the elimination of the A1/A2 satellite in N. tabacum (tobacco), an allotetraploid with parents closely related to the diploids N. sylvestris and N. tomentosiformis. This process may have already commenced in an S3 generation of synthetic tobacco. Cytosine residues in the IGS were significantly hypomethylated compared with the A1/A2 satellite. There was no clear separation between the IGS and satellite fractions in sequence analysis of individual clones and we found no evidence for CG suppression. Taken together the data indicate a dynamic nature of the A1/A2 repeats in Nicotiana genomes, with evidence for recurrent integration, copy number expansions, and contractions.
Mapping Quantitative Trait Loci in F2 Incorporating Phenotypes of F3 Progeny
Authors: Zhang Yuan-Ming , Xu Shizhong
Published: April 2021

In plants and laboratory animals, QTL mapping is commonly performed using F2 or BC individuals derived from the cross of two inbred lines. Typical QTL mapping statistics assume that each F2 individual is genotyped for the markers and phenotyped for the trait. For plant traits with low heritability, it has been suggested to use the average phenotypic values of F3 progeny derived from selfing F2 plants in place of the F2 phenotype itself. All F3 progeny derived from the same F2 plant belong to the same F2:3 family, denoted by F2:3. If the size of each F2:3 family (the number of F3 progeny) is sufficiently large, the average value of the family will represent the genotypic value of the F2 plant, and thus the power of QTL mapping may be significantly increased. The strategy of using F2 marker genotypes and F3 average phenotypes for QTL mapping in plants is quite similar to the daughter design of QTL mapping in dairy cattle. We study the fundamental principle of the plant version of the daughter design and develop a new statistical method to map QTL under this F2:3 strategy. We also propose to combine both the F2 phenotypes and the F2:3 average phenotypes to further increase the power of QTL mapping. The statistical method developed in this study differs from published ones in that the new method fully takes advantage of the mixture distribution for F2:3 families of heterozygous F2 plants. Incorporation of this new information has significantly increased the statistical power of QTL detection relative to the classical F2 design, even if only a single F3 progeny is collected from each F2:3 family. The mixture model is developed on the basis of a single-QTL model and implemented via the EM algorithm. Substantial computer simulation was conducted to demonstrate the improved efficiency of the mixture model. Extension of the mixture model to multiple QTL analysis is developed using a Bayesian approach. The computer program performing the Bayesian analysis of the simulated data is available to users for real data analysis.
Inhibition of hyaluronan secretion by novel coumarin compounds and chitin synthesis inhibitors
Authors: Tsitrina Alexandra A , Krasylov Igor V , Maltsev Dmitry I , Andreichenko Irina N , Moskvina Viktoria S , Ivankov Dmitry N , Bulgakova Elena V , Nesterchuk Mikhail , Shashkovskaya Vera , Dashenkova Nataliya O , Khilya Vladimir P , Mikaelyan Arsen , Kotelevtsev Yuri
Published: April 2021

Elevated plasma levels of hyaluronic acid (HA) is a disease marker in liver pathology and other inflammatory disorders. Inhibition of HA synthesis with coumarin 4-methylumbelliferone (4MU) has a beneficial effect in animal models of fibrosis, inflammation, cancer and metabolic syndrome. 4MU is an active compound of approved choleretic drug hymecromone with low bioavailability and a broad spectrum of action. New, more specific and efficient inhibitors of hyaluronan synthases (HAS) are required. We have tested several newly synthesized coumarin compounds and commercial chitin synthesis inhibitors to inhibit HA production in cell culture assay. Coumarin derivative compound VII (10′-methyl-6′-phenyl-3′H-spiro[piperidine-4,2′-pyrano[3,2-g]chromene]-4′,8′-dione) demonstrated inhibition of HA secretion by NIH3T3 cells with the half-maximal inhibitory concentration (IC50) = 1.69 ± 0.75 μΜ superior to 4MU (IC50 = 8.68 ± 1.6 μΜ). Inhibitors of chitin synthesis, etoxazole, buprofezin, triflumuron, reduced HA deposition with IC50 of 4.21 ± 3.82 μΜ, 1.24 ± 0.87 μΜ and 1.48 ± 1.44 μΜ, respectively. Etoxazole reduced HA production and prevented collagen fibre formation in the CCl4 liver fibrosis model in mice similar to 4MU. Bioinformatics analysis revealed homology between chitin synthases and HAS enzymes, particularly in the pore-forming domain, containing the proposed site for etoxazole binding.
The Integrative Biology of Pigment Organelles, a Quantum Chemical Approach
Authors: Figon Florent , Casas Jérôme
Published: April 2021

Synopsis

Coloration is a complex phenotypic trait involving both physical and chemical processes at a multiscale level, from molecules to tissues. Pigments, whose main property is to absorb specific wavelengths of visible light, are usually deposited in specialized organelles or complex matrices comprising proteins, metals, ions, and redox compounds, among others. By modulating electronic properties and stability, interactions between pigments and these molecular actors can lead to color tuning. Furthermore, pigments are not only important for visual effects but also provide other critical functions, such as detoxification and antiradical activity. Hence, integrative studies of pigment organelles are required to understand how pigments interact with their cellular environment. In this review, we show how quantum chemistry, a computational method that models the molecular and optical properties of pigments, has provided key insights into the mechanisms by which pigment properties, from color to reactivity, are modulated by their organellar environment. These results allow us to rationalize and predict the way pigments behave in supramolecular complexes, up to the complete modeling of pigment organelles. We also discuss the main limitations of quantum chemistry, emphasizing the need for carrying experimental work with identical vigor. We finally suggest that taking into account the ecology of pigments (i.e., how they interact with these various other cellular components and at higher organizational levels) will lead to a greater understanding of how and why animals are vividly and variably colored, two fundamental questions in organismal biology.
Oral and Palmitate Paliperidone Long-Acting Injectable Formulations’ Use in Schizophrenia Spectrum Disorders: A Retrospective Cohort Study from the First Episode Psychosis Intervention Program (CRUPEP)
Authors: Segarra R , Recio-Barbero M , Sáenz-Herrero M , Mentxaka O , Cabezas-Garduño J , Eguíluz J I , Callado L F
Published: April 2021

Background

Long-acting injectable antipsychotics (LAIs) may be a suitable therapeutic option for those patients in earlier stages of psychosis to avoid relapses and disease progression. Despite that, there is a lack of evidence in the literature regarding the use of LAIs in this profile of patients.

Methods

This is a retrospective cohort analysis to assess the efficacy, tolerability, and pattern of use of palmitate paliperidone long-acting injectable (PPLAI) formulations (1- and 3-month doses) compared to oral paliperidone/risperidone in patients with a nonaffective first episode of psychosis (FEP) over 12 months of follow-up. Relevant sociodemographic and clinical information were assessed, as well as main clinical scales: Positive and Negative Syndrome Scale, Personal and Social Performance Scale, and Clinical Global Impression Scale Improvement and Severity measures.

Results

The study included 48 patients, 16 per arm, who were aged 20–50 years and had an FEP. Significant improvements were registered for all treatment groups. Despite that, patients receiving PPLAI 1- and 3-month formulations obtained greater improvements than those in the oral group in the main domains assessed (P < .001). We found no statistically significant differences in hospitalizations between groups. Side effects were presented in 24% of patients. A trend towards reducing antipsychotic doses was observed in 43.8% of patients to achieve the minimum effective dose and avoid the occurrence of side effects.

Conclusions

To our knowledge, this is the first study assessing the use of palmitate paliperidone long-acting formulations versus oral risperidone or paliperidone in FEP. Treatment with PPLAI formulations seems to be an effective therapeutic choice at earlier stages of the disease.
Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) Monoclonal Antibody VRC01LS in HIV-1–Exposed Newborn Infants
Authors: McFarland Elizabeth J , Cunningham Coleen K , Muresan Petronella , Capparelli Edmund V , Perlowski Charlotte , Morgan Patricia , Smith Betsy , Hazra Rohan , Purdue Lynette , Harding Paul A , Theron Gerhard , Mujuru Hilda , Agwu Allison , Purswani Murli , Rathore Mobeen H , Flach Britta , Taylor Alison , Lin Bob C , McDermott Adrian B , Mascola John R , Graham Barney S ,   International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1112 Team, Rossouw Magdel , Rossouw Lindie , Louw Jeanne , Vhembo Tichaona , Mhembere Tsungai Patience , Matibe Petronella , Mahmoudi Saniyyah , Maldonado Alexandrea , Maraqa Nizar , Baig Mahboobullah M , Rogo Tanya , Cavallo Martha , Collinson-Streng Aleisha , Anderson Thuy , Golden W Christopher , Persaud Deborah , Puga Ana M , Robinson Lisa-Gaye , Eysallenne Zulma , Leon Dayana , Paul Mary E , McMullen-Jackson Chivon , Buschur Shelley , Pontifes Mariam , Sung Joyce , Glenny Carrie , Dunn Jennifer , Navarro Kacey
Published: April 2021

Background

Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs).

Methods

An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1–exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort.

Results

Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37–41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1.

Conclusions

VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.
CD49d marks Th1 and Tfh-like antigen-specific CD4+ T cells during Plasmodium chabaudi infection
Authors: Jian Jiun-Yu , Inoue Shin-Ichi , Bayarsaikhan Ganchimeg , Miyakoda Mana , Kimura Daisuke , Kimura Kazumi , Nozaki Eriko , Sakurai Takuya , Fernandez-Ruiz Daniel , Heath William R , Yui Katsuyuki
Published: April 2021

Upon activation, specific CD4+ T cells up-regulate the expression of CD11a and CD49d, surrogate markers of pathogen-specific CD4+ T cells. However, using T-cell receptor transgenic mice specific for a Plasmodium antigen, termed PbT-II, we found that activated CD4+ T cells develop not only to CD11ahiCD49dhi cells, but also to CD11ahiCD49dlo cells during acute Plasmodium infection. CD49dhi PbT-II cells, localized in the red pulp of spleens, expressed transcription factor T-bet and produced IFN-γ, indicating that they were type 1 helper T (Th1)-type cells. In contrast, CD49dlo PbT-II cells resided in the white pulp/marginal zones and were a heterogeneous population, with approximately half of them expressing CXCR5 and a third expressing Bcl-6, a master regulator of follicular helper T (Tfh) cells. In adoptive transfer experiments, both CD49dhi and CD49dlo PbT-II cells differentiated into CD49dhi Th1-type cells after stimulation with antigen-pulsed dendritic cells, while CD49dhi and CD49dlo phenotypes were generally maintained in mice infected with Plasmodium chabaudi. These results suggest that CD49d is expressed on Th1-type Plasmodium-specific CD4+ T cells, which are localized in the red pulp of the spleen, and can be used as a marker of antigen-specific Th1 CD4+ T cells, rather than that of all pathogen-specific CD4+ T cells.
Initial Experience Combining Negative Pressure Wound Therapy With Autologous Skin Cell Suspension and Meshed Autografts
Authors: Carney Bonnie C , Johnson Laura S , Shupp Jeffrey W , Travis Taryn E
Published: April 2021

The success of autologous split-thickness skin grafts (STSGs) in the treatment of full-thickness burns is often dependent on the dressing used to secure it. Tie-over bolsters have been used traditionally; however, they can be uncomfortable for patients and preclude grafting large areas in one definitive operation. Negative pressure wound therapy (NPWT) is used as an alternative to bolster dressings and may afford additional wound healing benefits. In our center, NPWT has become the dressing of choice for securing STSGs. While the RECELL® system is being used in conjunction with STSGs, it is currently unknown whether autologous skin cell suspensions (ASCS) can be used with NPWT. This report is a retrospective chart review of nine patients treated in this manner. All wounds were almost completely re-epithelialized within 14 days, and their healing was as expected. Wound healing trajectories are shown. There were no significant complications in these patients. This dressing technique can be considered as an option when using ASCS and widely meshed STSG.
Efficacy and Nontarget Effects of Net Exclusion Enclosures on Apple Pest Management
Authors: Marshall A T , Beers E H
Published: April 2021

Management of direct apple pests, such as codling moth, continues to be problematic despite the widespread implementation of behavioral and chemical controls. Apple growers have increased their use of netting to protect fruit from environmental injury, with some structures enclosing the entire orchard. These enclosures represent a new pest management tactic through physical exclusion. We conducted a two-year trial to examine the effects of full exclusion netting on pests and natural enemies of apples. Insect densities and damage in trees under fully enclosed (net) cages were compared with conventionally (insecticide only) treated and untreated plots. Caged plots had 18.1- and 11.4-fold less codling moth damage than the check, and 4.9- and 4.2-fold less damage than the insecticide-only plots in 2016 and 2017, respectively. However, densities of woolly apple aphid and its parasitoid Aphelinus mali (Haldeman) (Hymenoptera: Aphelinidae) were significantly greater in the caged plots. Densities of earwigs, a typically flightless generalist predator, were not different among treatments, while adults of more mobile flying generalist predators, lacewings and syrphids, were significantly lower in cages compared with uncaged plots. These results demonstrate that although biological control may be partially disrupted, net enclosures have significant potential as a holistic apple management technique.
Quantifying the Contribution of Seed Blended Refugia in Field Corn to Helicoverpa zea (Lepidoptera: Noctuidae) Populations
Authors: Towles T B , Buntin G D , Catchot A L , Gore J , Cook D R , Caprio M A , Daves C
Published: April 2021

Helicoverpa zea (Boddie), a pest of cotton that also occurs in field corn, is commonly controlled through the use of foliar-applied insecticides or transgenic crops expressing Bacillus thuringiensis (Berliner) (Bt) genes. To minimize the risk of Bt resistance in pest populations, refuge systems have been implemented for sustainable agroecosystem management. Historically, structured refuge compliance among growers has been low, leading to the commercialization of seed blended refugia. To test the viability of seed blended refugia in southern U.S. field corn, field studies were conducted in Mississippi and Georgia during 2016, 2017, and 2018 growing seasons. To quantify adult H. zea emergence from structured (non-Bt corn) and seed blended refuge options, emergence traps were utilized. Kernel damage among seed blended refuge and structured refuge corn ears were recorded and compared. The timing of moth emergence was recorded. When compared to a structured refuge, H. zea adult moth emergence from seed blended refugia did not significantly differ. Kernel damage of non-Bt plants in the seed blended treatments was not significantly different than non-Bt plants in the structured refuge treatments. Moth emergence timing was not significantly delayed between the structured refuge and seed blended refuge treatments. Results of this study suggest that a seed blended refuge may provide an effective insecticide resistance management alternative for H. zea in areas where structured refuge compliance is low.
Impacts of Fire on Butterfly Genetic Diversity and Connectivity
Authors: Gates Daisy , Jackson Breeanne , Schoville Sean D
Published: April 2021

How do novel fire regimes and a long history of fire suppression influence species genetic diversity? Genetic diversity provides the raw materials for sustaining viable populations and for allowing adaptation to novel environmental challenges, and at present, few studies address the genetic responses of animals to fire management. Here we study the genetic responses of 2 butterfly species to a landscape gradient of fire timing and severity in Yosemite National Park using a large set of genome-wide single nucleotide polymorphisms (SNPs). Butterflies are important bio-indicators of invertebrate diversity and play important roles in both bottom–up and top–down ecosystem processes, and typically increase in abundance following wildfires, due to an increase in abundance of flowering plants. However, it is not clear how genetic diversity and genetic connectivity of butterflies respond to landscape change following fire, and whether fire management has positive or negative effects. We found evidence to suggest that fire increases genetic diversity and reduces isolation in 2 butterfly species, but that aspects of the fire regime (severity, extent, timing, and frequency) differ in importance depending on the ecology of the specific species. This research is the first study to address fire management impacts on genetic diversity in invertebrates, and the results will allow fire managers to predict that fire reintroduction in protected areas will generally benefit butterfly populations.
Transcriptome Analysis of Myzus persicae to UV-B Stress
Authors: Yang Chang-Li , Meng Jian-Yu , Yao Meng-Shuang , Zhang Chang-Yu
Published: April 2021

As an environmental stress factor, ultraviolet-B (UV-B) radiation directly affects the growth and development of Myzus persicae (Sulzer) (Homoptera: Aphididae). How M. persicae responds to UV-B stress and the molecular mechanisms underlying this adaptation remain unknown. Here, we analyzed transcriptome data for M. persicae following exposure to UV-B radiation for 30 min. We identified 758 significant differentially expressed genes (DEGs) following exposure to UV-B stress, including 423 upregulated and 335 downregulated genes. In addition, enrichment analysis using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases illustrated that these DEGs are associated with antioxidation and detoxification, metabolic and protein turnover, immune response, and stress signal transduction. Simultaneously, these DEGs are closely related to the adaptability to UV-B stress. Our research can raise awareness of the mechanisms of insect responses to UV-B stress.
The inhibitory effect of trimetazidine on detrusor contractility – a potential repositioning of trimetazidine for the treatment of overactive bladder
Authors: Engin Seckin , Kaya Yasar Yesim , Barut Elif Nur , Getboga Damla , Erac Yasemin , Sezen Sena F
Published: April 2021

Objectives

This study aimed to identify the effect of trimetazidine (TMZ), an antianginal drug, on detrusor smooth muscle (DSM) contractility and its possible mechanisms of action.

Methods

We performed in-vitro contractility studies on isolated mouse DSM strips and investigated the effect of TMZ on Ca2+ levels in fura-2-loaded A7r5 cells.

Key ﬁndings

TMZ (300 or 1000 µM) inhibited carbachol (CCh)- and KCl-induced contractions and produced a concentration-dependent (10–1000 µM) relaxation in KCl-precontracted DSM strips. TMZ-induced relaxation was markedly decreased by BaCl2, an inward-rectifying K+ channel blocker, but was not altered by preincubation with tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. TMZ (300 or 1000 µM) reduced both the CaCl2-induced contraction of depolarized DSM strips under Ca2+-free conditions and the CCh-induced contraction of DSM strips preincubated with nifedipine in Ca2+-containing Krebs solution. Furthermore, TMZ (1000 µM) significantly decreased the Ca2+ levels in fura-2-loaded A7r5 cells.

Conclusions

TMZ decreased DSM contractility and caused a concentration-dependent relaxation of the tissue possibly through its actions on Ca2+ transients and K+ channels. Our results provide preclinical evidence that TMZ would be a potential candidate to treat disorders related to the overactivity of the bladder.
Pathologic validation of an yttrium-90 trans-arterial radioembolization dosimetry: a case report
Authors: Baikovitz Jacqueline B , Thornton Lindsay , Garcia-Buitrago Monica T , Livingstone Alan S , Studenski Matthew T , Portelance Lorraine
Published: April 2021

Yttrium-90 (Y-90) trans-arterial radioembolization (TARE) is used in the management of unresectable hepatocellular carcinoma (HCC). During the last 5 years, dosimetry software has been developed to allow for a more rigorous approach of dose prescription in Y-90 TARE. We present here a case study of a 77-year-old woman diagnosed with HCC, who underwent a Y-90 TARE as a bridge procedure to liver resection. This clinical scenario represents a unique opportunity to illustrate the predictive value of dosimetric findings correlating dosimetry with pathological findings. In this case, Y-90 TARE dosimetry was predictive of treatment response in which the tumor received a mean dose of 156 Gy and demonstrated a complete pathologic response.
Minimally invasive approach in radio distal end fractures, three different types of incisions
Authors: Romero Prieto Fernando Xavier , Reyes García Carlos Raúl
Published: April 2021

Two techniques are described to treat distal radius fractures: conventional (Henry approach) and minimally invasive plate osteosynthesis. The latter technique has been described by different authors such as Imatani et al. and Zenke et al.

This was a descriptive retrospective study, analyzing 26 adult patients with unstable distal radius fracture, extra-articular type A or partially intra-articular type B according to AO. The approaches used were: (i) single longitudinal palmar incision; (ii) double T-incision (horizontal and vertical) and (iii) double position II.

Ages were between 21 and 78 years. Most affected hand was the right. Most common fracture was 23B2 (AO classification). In total, 84.6% of the patients did not present complications. According to the functional evaluation of the wrist by the Mayo Clinic, 31% showed excellent results, 42% showed good results, 27% showed fair results.

The techniques had satisfactory results for the osteosynthesis with more aesthetic and less invasive approach.
Phenotypic diploidization in plant functional traits uncovered by synthetic neopolyploids inDianthus broteri
Authors: Domínguez-Delgado Juan José , López-Jurado Javier , Mateos-Naranjo Enrique , Balao Francisco
Published: April 2021

Whole-genome duplication and post-polyploidization genome downsizing play key roles in the evolution of land plants; however, the impact of genomic diploidization on functional traits still remains poorly understood. Using Dianthus broteri as a model, we compared the ecophysiological behaviour of colchicine-induced neotetraploids (4xNeo) to diploids (2x) and naturally occurring tetraploids (4xNat). Leaf gas-exchange and chlorophyll fluorescence analyses were performed in order to asses to what extent post-polyploidization evolutionary processes have affected 4xNat. Genomic diploidization and phenotypic novelty were evident. Distinct patterns of variation revealed that post-polyploidization processes altered the phenotypic shifts directly mediated by genome doubling. The photosynthetic phenotype was affected in several ways but the main effect was phenotypic diploidization (i.e. 2x and 4xNat were closer to each other than to 4xNeo). Overall, our results show the potential benefits of considering experimentally synthetized versus naturally established polyploids when exploring the role of polyploidization in promoting functional divergence.
Rice transcription factor GAMYB modulates bHLH142 and is homeostatically regulated by TDR during anther tapetal and pollen development
Authors: Ko Swee-Suak , Li Min-Jeng , Ho Yi-Cheng , Yu Chun-Ping , Yang Ting-Ting , Lin Yi-Jyun , Hsing Hung-Chien , Chen Tien-Kuan , Jhong Chung-Min , Li Wen-Hsiung , Sun-Ben Ku Maurice
Published: April 2021

GIBBERELLIN MYB GENE (GAMYB), UNDEVELOPED TAPETUM1 (UDT1), TDR INTERACTING PROTEIN2 (TIP2/bHLH142), TAPETUM DEGENERATION RETARDATION (TDR), and ETERNAL TAPETUM 1/DELAYED TAPETUM DEGENERATION (EAT1/DTD) are important transcription factors that play a crucial role during pollen development in rice. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a ‘hub’ in these two pollen pathways. We show that GAMYB modulates bHLH142 expression through specific binding to the MYB motif of the bHLH142 promoter during the early stage of pollen development, while TDR acts as a transcriptional repressor of the GAMYB modulation of bHLH142 by binding to the E-box close to the MYB motif on the promoter. Altered expression of these transcription factors highlights that a tight, precise, and coordinated regulation among them is essential for normal pollen development. Most notably, we show that the regulatory pathways of GAMYB and UDT1 rely on bHLH142 in a direct and indirect manner, respectively, and function in different tissues with distinct biological roles during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.
A transcriptional hub integrating gibberellin–brassinosteroid signals to promote seed germination in Arabidopsis
Authors: Zhong Chunmei , Patra Barunava , Tang Yi , Li Xukun , Yuan Ling , Wang Xiaojing
Published: April 2021

Seed germination is regulated by multiple phytohormones, including gibberellins (GAs) and brassinosteroids (BRs); however, the molecular mechanism underlying GA and BR co-induced seed germination is not well elucidated. We demonstrated that BRs induce seed germination through promoting testa and endosperm rupture in Arabidopsis. BRs promote cell elongation, rather than cell division, at the hypocotyl–radicle transition region of the embryonic axis during endosperm rupture. Two key basic helix–loop–helix transcription factors in the BR signaling pathway, HBI1 and BEE2, are involved in the regulation of endosperm rupture. Expression of HBI1 and BEE2 was induced in response to BR and GA treatment. In addition, HBI1- or BEE2-overexpressing Arabidopsis plants are less sensitive to the BR biosynthesis inhibitor, brassinazole, and the GA biosynthesis inhibitor, paclobutrazol. HBI1 and BEE2 promote endosperm rupture and seed germination by directly regulating the GA-Stimulated Arabidopsis 6 (GASA6) gene. Expression of GASA6 was altered in Arabidopsis overexpressing HBI1, BEE2, or SRDX-repressor forms of the two transcription factors. In addition, HBI1 interacts with BEE2 to synergistically activate GASA6 expression. Our findings define a new role for GASA6 in GA and BR signaling and reveal a regulatory module that controls GA and BR co-induced seed germination in Arabidopsis.
Strategic calculations? Partisan differences in support for Puerto Rican migration to the mainland USA
Authors: Whitaker Beth Elise ,   and, Giersch Jason
Published: April 2021

Building on research about political determinants of migration attitudes, this study examines whether public opinion is influenced by the potential political participation of migrants themselves. We use the opportunity presented by the recent increase in the number of US citizens moving from Puerto Rico to the mainland to investigate how partisanship and political calculations shape attitudes toward their migration. Using data from an online survey experiment in early 2020, we find partisan differences in support for Puerto Rican migration. Democrats were significantly more likely than Republicans and independents to support Puerto Rican migration to the mainland in the aftermath of recent natural disasters, while Republicans were more likely to support Puerto Ricans returning home for the rebuilding process. The partisan divide was exacerbated when respondents were given additional information about the voting eligibility of Puerto Ricans and the possibility that their votes could help a Democratic presidential candidate win the state of Florida in the 2020 election. Specifically, Republicans who received this information were significantly less likely than all other respondents, including Republicans in the control group, to support Puerto Rican migration to the mainland USA. Findings on several related variables also show significant partisan differences, though treatment effects are less pronounced. Although further research is necessary to determine whether similar patterns hold in situations where migrants are not immediately eligible to vote or perceived as supporting one side, this study provides initial evidence that strategic partisan calculations can influence attitudes toward migration in a competitive political context.
Sarcoidosis Presenting as Dorsal Wrist Mass: A Case Report
Authors: Kim Gabriel , Banks Willie , Sadr Bahman , Paal Edina , Martin Jabari
Published: April 2021

Patients with sarcoidosis have an indolent course in which the disease is not detected unless seemingly benign symptoms appear. Such was the case in a 42-year-old man who was referred to the orthopedic service for evaluation of a slowly enlarging mass over the left wrist without prior history of trauma. In this article, we will review the symptoms and histopathology of sarcoidosis with a particular focus on orthopedic manifestations of the disease. We believe that clinicians should be aware of these associations so that patients can be diagnosed and treated accordingly.
Forward modelling of Kepler-band variability due to faculae and spots
Authors: Johnson Luke J , Norris Charlotte M , Unruh Yvonne C , Solanki Sami K , Krivova Natalie , Witzke Veronika , Shapiro Alexander I
Published: April 2021

Variability observed in photometric light curves of late-type stars (on time-scales longer than a day) is a dominant noise source in exoplanet surveys and results predominantly from surface manifestations of stellar magnetic activity, namely faculae and spots. The implementation of faculae in light-curve models is an open problem, with scaling typically based on spectra equivalent to hot stellar atmospheres or assuming a solar-derived facular contrast. We modelled rotational (single period) light curves of active G2, K0, M0, and M2 stars, with Sun-like surface distributions and realistic limb-dependent contrasts for faculae and spots. The sensitivity of light-curve variability to changes in model parameters such as stellar inclination, feature area coverage, spot temperature, facular region magnetic flux density, and active band latitudes is explored. For our light-curve modelling approach we used actress, a geometrically accurate model for stellar variability. actress generates two-sphere maps representing stellar surfaces and populates them with user-prescribed spot and facular region distributions. From this, light curves can be calculated at any inclination. Quiet star limb darkening and limb-dependent facular contrasts were derived from MURaM 3D magnetoconvection simulations using ATLAS9. 1D stellar atmosphere models were used for the spot contrasts. We applied actress in Monte Carlo simulations, calculating light-curve variability amplitudes in the Kepler band. We found that, for a given spectral type and stellar inclination, spot temperature and spot area coverage have the largest effect on variability of all simulation parameters. For a spot coverage of $1{{\ \rm per\ cent}}$, the typical variability of a solar-type star is around 2 parts per thousand. The presence of faculae clearly affects the mean brightness and light-curve shape, but has relatively little influence on the variability.