bluuebunny/crossref_metadata_2025 huggingface dataset:
Distributing bipartite quantum systems under timing constraints
Authors: Dolev Kfir , May Alex , Wan Kianna
Published: February 2021

In many quantum information processing protocols, entangled states shared among parties are an important resource. In this article, we study how bipartite states may be distributed in the context of a quantum network limited by timing constraints. We explore various tasks that plausibly arise in this context, and characterize the achievability of several of these in settings where only one-way communication is allowed. We provide partial results in the case where two-way communication is allowed. This builds on earlier work on summoning single and bipartite systems.
A control sub-areas division method based on improved FN algorithm
Authors: Li Enqun , Dong Baotian , Li Pengcheng , Chu Rusi
Published: February 2021

.In order to implement signal control more effectively and improve the operating efficiency of urban traffic systems, this paper proposes a control sub-area division method based on an improved FN division algorithm. Comprehensively consider the intersection spacing, link flow, traffic dispersion, signal cycle, link traffic state and other factors, respectively calculate the correlation degrees of link flow, the intersection signal cycle,the link traffic state of adjacent intersections.Then its introduce the intersection correlation degree to improve the FN algorithm to divide the regional road network traffic district. Finally, the paper select the regional traffic data of Beijing’s road network to verify the model. The result shows that the sub-area division based on improved FN algorithm is more reasonable and effective.
Experimental Study on Scour Model of Wujiagang Bridge Pier
Authors: Li Zhijing , Shan Miner , Huang Jiancheng , Zhou Yinjun
Published: February 2021

Local scouring of bridge piers is one of the main causes of structural damage and even water damage. In this study, an experimental study on scour model of Wujiagang bridge pier is carried out, the results show that the scope and depth of the pier scouring pit are closely related to the flow and water depth at the pier location, the maximum scouring depth and the scope of the scouring pit increase with the increase of unit-width discharge.
Discussion on operation safety and countermeasures of Highway tunnel Traffic Engineering Facilities
Authors: Pang Rong , Yuan Yuan , Guo Xinglong , Zhou Lijian , Su Yufeng , Jiang Mingxing , Li Xiang
Published: February 2021

In order to further improve the condition of road tunnel traffic engineering facilities, and thus improve the safety of tunnel operations. The paper analyzes the inspection results of traffic engineering facilities in dozens of tunnels in China, and summarizes the common operational safety risks of traffic engineering facilities. Then puts forward corresponding risk prevention and control measures, which is helpful to improve the status of tunnel traffic engineering facilities. It has certain guiding significance for the safety management of road tunnel operation.
Adsorption performance of reactive red 2BF onto magnetic Zn0.3Cu0.7Fe2O4 nanoparticles
Authors: Liu Min , Wang Zhou
Published: February 2021

The facile solution combustion and gel calcination process was applied to prepare magnetic Zn0.3Cu0.7Fe2O4 nanoparticles, and the characterization of the product was analyzed by SEM, TEM, XRD, and VSM techniques. The magnetic Zn0.3Cu0.7Fe2O4 nanoparticles prepared with absolute alcohol volume of 15 ml at 600 °C were expressed with the average particle size of approximately 60 nm and the saturation magnetization of 39.2 emu g−1. Where after, Zn0.3Cu0.7Fe2O4 nanoparticles were applied to remove reactive red 2BF (RR-2BF), and at room temperature, the adsorbance of RR-2BF onto them was examined. The results demonstrated that pseudo-second-order kinetics could well express the adsorption process, and Temkin isotherm conformed to experimental data. The adsorption capacity of the sample could reach 130 mg g−1, which was greatly affected by pH. The acidic environment was conducive to adsorption while the alkaline environment was conducive to desorption. Moreover, the material had excellent cycling performance.
Assessing heart disease using a novel magnetocardiography device
Authors: Beadle R , McDonnell D , Ghasemi-Roudsari S , Unitt L , Parker S J , Varcoe B T H
Published: February 2021

The aim of this paper is to present the use of a portable, unshielded magnetocardiograph (MCG) and identify key characteristics of MCG scans that could be used in future studies to identify parameters that are sensitive to cardiac pathology. We recruited 50 patients with confirmed myocardial infarction (MI) within the past 12 weeks and 46 volunteers with no history of cardiac disease. A set of 38 parameters were extracted from MCG features including both signals from the sensor array and from magnetic images obtained from the device and principal component analysis was used to concentrate the information contained in these parameters into uncorrelated predictors. Linear fits of these parameters were then used to examine the ability of MCG to distinguish between sub-groups of patients. In the first instance, the primary aim of this study was to ensure that MCG has a basic ability to separate a highly polarised patient group (young controls from post infarction patients) and to identify parameters that could be used in future studies to build a formal diagnostic tool kit. Parameters that parameterised left ventricular ejection fraction (LVEF) were identified and an example is presented to show differential low and high ejection fractions.
Restored Macrophage Function Ameliorates Disease Pathophysiology in a Mouse Model for IL10 Receptor-deficient Very Early Onset Inflammatory Bowel Disease
Authors: Ackermann Mania , Mucci Adele , McCabe Amanda , Frei Sandy , Wright Kayla , Snapper Scott B , Lachmann Nico , Williams David A , Brendel Christian
Published: February 2021

Background and Aims

Mutations in IL10 or the IL10 receptor lead to very early onset [VEO] inflammatory bowel disease [IBD], a life-threatening disease which is often unresponsive to conventional medication. Recent studies have demonstrated that defective IL-10 receptor signalling in innate immune cells is a key driver of severe intestinal inflammation in VEO-IBD. Specifically, IL10 unresponsiveness of macrophages, which govern the tight balance between pro- and anti-inflammatory responses in the intestinal system, plays a central role in the events leading to excessive inflammatory responses and the development of IBD.

Methods and Results

We here evaluated haematopoietic stem cell gene therapy in a VEO-IBD mouse model and demonstrated that the therapeutic response closely correlates with gene correction of the IL10 signalling pathway in intestinal macrophages. This finding prompted us to evaluate the therapeutic efficacy of macrophage transplantation in the Il10rb-/- VEO-IBD mouse model. A 6-week regimen employing a combination of depletion of endogenous hyperinflammatory macrophages followed by intraperitoneal administration of wild-type [WT] macrophages significantly reduced colitis symptoms.

Conclusions

In summary, we show that the correction of the IL10 receptor defect in macrophages, either by genetic therapy or transfer of WT macrophages to the peritoneum, can ameliorate disease-related symptoms and potentially represent novel treatment approaches for VEO-IBD patients.
A novel non-invasive and echocardiography-derived method for quantification of right ventricular pressure–volume loops
Authors: Richter Manuel J , Yogeswaran Athiththan , Husain-Syed Faeq , Vadász István , Rako Zvonimir , Mohajerani Emad , Ghofrani Hossein A , Naeije Robert , Seeger Werner , Herberg Ulrike , Rieth Andreas , Tedford Ryan J , Grimminger Friedrich , Gall Henning , Tello Khodr
Published: February 2021

Aims

We sought to assess the feasibility of constructing right ventricular (RV) pressure–volume (PV) loops solely by echocardiography.

Methods and results

We performed RV conductance and pressure wire (PW) catheterization with simultaneous echocardiography in 35 patients with pulmonary hypertension. To generate echocardiographic PV loops, a reference RV pressure curve was constructed using pooled PW data from the first 20 patients (initial cohort). Individual pressure curves were then generated by adjusting the reference curve according to RV isovolumic and ejection phase duration and estimated RV systolic pressure. The pressure curves were synchronized with echocardiographic volume curves. We validated the reference curve in the remaining 15 patients (validation cohort). Methods were compared with correlation and Bland–Altman analysis. In the initial cohort, echocardiographic and conductance-derived PV loop parameters were significantly correlated {rho = 0.8053 [end-systolic elastance (Ees)], 0.8261 [Ees/arterial elastance (Ea)], and 0.697 (stroke work); all P < 0.001}, with low bias [−0.016 mmHg/mL (Ees), 0.1225 (Ees/Ea), and −39.0 mmHg mL (stroke work)] and acceptable limits of agreement. Echocardiographic and PW-derived Ees were also tightly correlated, with low bias (−0.009 mmHg/mL) and small limits of agreement. Echocardiographic and conductance-derived Ees, Ees/Ea, and stroke work were also tightly correlated in the validation cohort (rho = 0.9014, 0.9812, and 0.9491, respectively; all P < 0.001), with low bias (0.0173 mmHg/mL, 0.0153, and 255.1 mmHg mL, respectively) and acceptable limits.

Conclusion

The novel echocardiographic method is an acceptable alternative to invasively measured PV loops to assess contractility, RV-arterial coupling, and RV myocardial work. Further validation is warranted.
Conserved Subfamilies of the Drosophila HeT-A Telomere-Specific Retrotransposon
Authors: Danilevskaya Olga N , Lowenhaupt Ky , Pardue Mary Lou
Published: February 2021

HeT-A, a major component of Drosophila telomeres, is the first retrotransposon proposed to have a vital cellular function. Unlike most retrotransposons, more than half of its genome is noncoding. The 3′ end contains >2.5 kb of noncoding sequence. Copies of HeT-A differ by insertions or deletions and multiple nucleotide changes, which initially led us to conclude that HeT-A noncoding sequences are very fluid. However, we can now report, on the basis of new sequences and further analyses, that most of these differences are due to the existence of a small number of conserved sequence subfamilies, not to extensive sequence change during each transposition event. The high level of sequence conservation within subfamilies suggests that they arise from a small number of replicatively active elements. All HeT-A subfamilies show preservation of two intriguing features. First, segments of extremely A-rich sequence form a distinctive pattern within the 3′ noncoding region. Second, there is a strong strand bias of nucleotide composition: The DNA strand running 5′ to 3′ toward the middle of the chromosome is unusually rich in adenine and unusually poor in guanine. Although not faced with the constraints of coding sequences, the HeT-A 3′ noncoding sequence appears to be under other evolutionary constraints, possibly reflecting its roles in the telomeres.
Su(Ste) Diverged Tandem Repeats in a Y Chromosome of Drosophila melanogaster Are Transcribed and Variously Processed
Authors: Kalmykova Alla I , Dobritsa Anna A , Gvozdev Vladimir A
Published: February 2021

We report the organization and transcription of diverged tandemly repeated Y-linked Su(Ste) genes that are considered as suppressors of testis-expressed X-linked-repeated Stellate genes that encode a protein sharing extensive homology with β-subunit of casein kinase 2. Clustering of restriction variants is confirmed. Size variants of Su(Ste) repeats appeared to be nonhomogeneously distributed among the P1 phage clones. Different ways of Su(Ste) RNA processing because of the appearance of new splice sites and polyadenylation signals were detected. The high extent of homology between Stellate and Su(Ste) repeats suggested a possibility of Stellate suppression by antisense transcription of Su(Ste) elements. The detection of only “sense” Su(Ste) cDNAs in testis cDNA library allows us to reject this proposal. The genomic and cDNA clones are shown to be equally diverged. This indicates widespread rather than restricted transcription capacity of these repeats.
A Genetically Marked I Element in Drosophila melanogaster Can Be Mobilized When ORF2 Is Provided in trans
Authors: Busseau Isabelle , Malinsky Sophie , Balakireva Maria , Chaboissier Marie-Christine , Teninges Danielle , Bucheton Alain
Published: February 2021

I factors in Drosophila melanogaster are non-LTR retrotransposons similar to mammalian LINEs. They transpose at very high frequencies in the germ line of SF females resulting from crosses between reactive females, devoid of active I factors, and inducer males, containing active I factors. The vermilion marked IviP2 element was designed to allow easy phenotypical screening for retrotransposition events. It is deleted in ORF2 and therefore cannot produce reverse transcriptase. IviP2 can be mobilized at very low frequencies by actively transposing I factors in the germ line of SF females. This paper shows that IviP2 can be mobilized more efficiently in the germ line of strongly reactive females in the absence of active I factors, when it is trans-complemented by the product of ORF2 synthesized from the hsp70 heat-shock promoter. This represents a promising step toward the use of marked I elements to study retrotransposition and as tools for mutagenesis.
Genetic Mapping of Quantitative Trait Loci Affecting Susceptibility to Marek's Disease Virus Induced Tumors in F2 Intercross Chickens
Authors: Vallejo Roger L , Bacon Larry D , Liu Hsiao-Ching , Witter Richard L , Groenen Martien A M , Hillel Jossi , Cheng Hans H
Published: February 2021

Marek's disease (MD) is a lymphoproliferative disease caused by the MD virus (MDV), which costs the poultry industry nearly $1 billion annually. To identify quantitative trait loci (QTL) affecting MD susceptibility, the inbred lines 63 (MD resistant) and 72 (MD susceptible) were mated to create more than 300 F2 chickens. The F2 chickens were challenged with MDV (JM strain, moderately virulent) at 1 wk of age and assessed for MD susceptibility. The QTL analysis was divided into three stages. In stage 1, 65 DNA markers selected from the chicken genetic maps were typed on the 40 most MD-susceptible and the 40 most MD-resistant F2 chickens, and 21 markers residing near suggestive QTL were revealed by analysis of variance (ANOVA). In stage 2, the suggestive markers plus available flanking markers were typed on 272 F2 chickens, and three suggestive QTL were identified by ANOVA. In stage 3, using the interval mapping program Map Manager and permutation tests, two significant and two suggestive MD QTL were identified on four chromosomal subregions. Three to five loci collected explained between 11 and 23% of the phenotypic MD variation, or 32–68% of the genetic variance. This study constitutes the first report in the domestic chicken on the mapping of non-major histocompatibility complex QTL affecting MD susceptibility.
Genetic Analysis of Chromosomal Rearrangements in the cyclops Region of the Zebrafish Genome
Authors: Talbot William S , Egan Elizabeth S , Gates Michael A , Walker Charline , Ullmann Bonnie , Neuhauss Stephan C F , Kimmel Charles B , Postlethwait John H
Published: February 2021

Genetic screens in zebrafish have provided mutations in hundreds of genes with essential functions in the developing embryo. To investigate the possible uses of chromosomal rearrangements in the analysis of these mutations, we genetically characterized three gamma-ray induced alleles of cyclops (cyc), a gene required for development of midline structures. We show that cyc maps near one end of Linkage Group 12 (LG 12) and that this region is involved in a reciprocal translocation with LG 2 in one gamma-ray induced mutation, cyc b213. The translocated segments together cover approximately 5% of the genetic map, and we show that this rearrangement is useful for mapping cloned genes that reside in the affected chromosomal regions. The other two alleles, cycb16 and cycb229, have deletions in the distal region of LG 12. Interestingly, both of these mutations suppress recombination between genetic markers in LG 12, including markers at a distance from the deletion. This observation raises the possibility that these deletions affect a site required for meiotic recombination on the LG 12 chromosome. The cycb16 and cycb229 mutations may be useful for balancing other lethal mutations located in the distal region of LG 12. These results show that chromosomal rearrangements can provide useful resources for mapping and genetic analyses in zebrafish.
Pth1/Vam3p Is the Syntaxin Homolog at the Vacuolar Membrane of Saccharomyces cerevisae Required for the Delivery of Vacuolar Hydrolases
Authors: Srivastava Amit , Jones Elizabeth W
Published: February 2021

The PEP12 homolog Pth1p (Pep twelve homolog 1) is predicted to be similar in size to Pep12p, the endosomal syntaxin homolog that mediates docking of Golgi-derived transport vesicles and, like other members of the syntaxin family, is predicted to be a cytoplasmically oriented, integral membrane protein with a C-terminal transmembrane domain. Kinetic analyses indicate that Δpth1/vam3 mutants fail to process the soluble vacuolar hydrolase precursors and that PrA, PrB and most of CpY accumulate within the cell in their Golgi-modified P2 precursor forms. This is in contrast to a pep12 mutant in which P2CpY is secreted from the cell. Furthermore, pep12 is epistatic to pth1/vam3 with respect to the CpY secretion phenotype. Alkaline phosphatase, a vacuolar membrane hydrolase, accumulates in its precursor form in the Δpth1/vam3 mutant. Maturation of pro-aminopeptidase I, a hydrolase precursor delivered directly to the vacuole from the cytoplasm, is also blocked in the Δpth1/vam3 mutant. Subcellular fractionation localizes Pth1/Vam3p to vacuolar membranes. Based on these data, we propose that Pth1/Vam3p is the vacuolar syntaxin/t-SNARE homolog that participates in docking of transport vesicles at the vacuolar membrane and that the function of Pth1/Vam3p impinges on at least three routes of protein delivery to the yeast vacuole.
Regulation of Septum Formation in Aspergillus nidulans by a DNA Damage Checkpoint Pathway
Authors: Harris Steven D , Kraus Peter R
Published: February 2021

In Aspergillus nidulans, germinating conidia undergo multiple rounds of nuclear division before the formation of the first septum. Previous characterization of temperature-sensitive sepB and sepJ mutations showed that although they block septation, they also cause moderate defects in chromosomal DNA metabolism. Results presented here demonstrate that a variety of other perturbations of chromosomal DNA metabolism also delay septum formation, suggesting that this is a general cellular response to the presence of sublethal DNA damage. Genetic evidence is provided that suggests that high levels of cyclin-dependent kinase (cdk) activity are required for septation in A. nidulans. Consistent with this notion, the inhibition of septum formation triggered by defects in chromosomal DNA metabolism depends upon Tyr-15 phosphorylation of the mitotic cdk p34nimX. Moreover, this response also requires elements of the DNA damage checkpoint pathway. A model is proposed that suggests that the DNA damage checkpoint response represents one of multiple sensory inputs that modulates p34nimX activity to control the timing of septum formation.
Heterogeneity of Microsatellite Mutations Within and Between Loci, and Implications for Human Demographic Histories
Authors: Di Rienzo Anna , Donnelly Peter , Toomajian Chris , Sisk Bronwyn , Hill Adrian , Petzl-Erler Maria Luiza , Haines G Ken , Barch David H
Published: February 2021

Microsatellites have been widely used to reconstruct human evolution. However, the efficient use of these markers relies on information regarding the process producing the observed variation. Here, we present a novel approach to the locus-by-locus characterization of this process. By analyzing somatic mutations in cancer patients, we estimated the distributions of mutation size for each of 20 loci. The same loci were then typed in three ethnically diverse population samples. The generalized stepwise mutation model was used to test the predicted relationship between population and mutation parameters under two demographic scenarios: constant population size and rapid expansion. The agreement between the observed and expected relationship between population and mutation parameters, even when the latter are estimated in cancer patients, confirms that somatic mutations may be useful for investigating the process underlying population variation. Estimated distributions of mutation size differ substantially amongst loci, and mutations of more than one repeat unit are common. A new statistic, the normalized population variance, is introduced for multilocus estimation of demographic parameters, and for testing demographic scenarios. The observed population variation is not consistent with a constant population size. Time estimates of the putative population expansion are in agreement with those obtained by other methods.
The Involvement of Cellular Recombination and Repair Genes in RNA-Mediated Recombination in Saccharomyces cerevisiae
Authors: Derr Leslie K
Published: February 2021

We previously demonstrated that a reverse transcript of a cellular reporter gene (his3-AI) can serve as the donor for gene conversion of a chromosomal his3-ΔMscI target sequence, and that this process requires the yeast recombination gene RAD52. In this study, we examine the involvement of other recombination and repair genes in RNA-mediated recombination, and gain insight into the nature of the recombination intermediate. We find that mutation of the mitotic RecA homologs RAD51, RAD55, and RAD57 increases the rate of RNA-mediated recombination relative to the wild type, and that these gene functions are not required for RNA-mediated gene conversion. Interestingly, RAD1 is required for RNA-mediated gene conversion of chromosomal his3-ΔMscI sequences, suggesting that the cDNA intermediate has a region of nonhomology that must be removed during recombination with target sequences. The observation that both RAD1 and RAD52 are required for RNA-mediated gene conversion of chromosomal but not plasmid sequences indicates a clear difference between these two pathways of homologous RNA-mediated recombination.
Genetic Analysis of Yeast RPA1 Reveals Its Multiple Functions in DNA Metabolism
Authors: Umezu Keiko , Sugawara Neal , Chen Clark , Haber James E , Kolodner Richard D
Published: February 2021

Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 104 to 105 times increased sensitivity to these agents. Some of the UV- and MMS-sensitive mutants were killed by an HO-induced double-strand break at MAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages.
A Species Barrier Between Bacteriophages T2 and T4: Exclusion, Join-Copy and Join-Cut-Copy Recombination and Mutagenesis in the dCTPase Genes
Authors: Gary Todd P , Colowick Nancy E , Mosig Gisela
Published: February 2021

Bacteriophage T2 alleles are excluded in crosses between T2 and T4 because of genetic isolation between these two virus species. The severity of exclusion varies in different genes, with gene 56, encoding an essential dCT(D)Pase/dUT(D)Pase of these phages, being most strongly affected. To investigate reasons for such strong exclusion, we have (1) sequenced the T2 gene 56 and an adjacent region, (2) compared the sequence with the corresponding T4 DNA, (3) constructed chimeric phages in which T2 and T4 sequences of this region are recombined, and (4) tested complementation, recombination, and exclusion with gene 56 cloned in a plasmid and in the chimeric phages in Escherichia coli CR63, in which growth of wild-type T2 is not restricted by T4. Our results argue against a role of the dCTPase protein in this exclusion and implicate instead DNA sequence differences as major contributors to the apparent species barrier. This sequence divergence exhibits a remarkable pattern: a major heterologous sequence counter-clockwise from gene 56 (and downstream of the gene 56 transcripts) replaces in T2 DNA the T4 gene 69. Gene 56 base sequences bordering this substituted region are significantly different, whereas sequences of the dam genes, adjacent in the clockwise direction, are similar in T2 and in T4. The gene 56 sequence differences can best be explained by multiple compensating frameshifts and base substitutions, which result in T2 and T4 dCTPases whose amino acid sequences and functions remain similar. Based on these findings we propose a model for the evolution of multiple sequence differences concomitant with the substitution of an adjacent gene by foreign DNA: invasion by the single-stranded segments of foreign DNA, nucleated from a short DNA sequence that was complementary by chance, has triggered recombination-dependent replication by “join-copy” and “join-cut-copy” pathways that are known to operate in the T-even phages and are implicated in other organisms as well. This invasion, accompanied by heteroduplex formation between partially similar sequences, and perhaps subsequent partial heteroduplex repair, simultaneously substituted T4 gene 69 for foreign sequences and scrambled the sequence of the dCTPase gene 56. We suggest that similar mechanisms can mobilize DNA segments for horizontal transfer without necessarily requiring transposase or site-specific recombination functions.
Cdc1 Is Required for Growth and Mn2+ Regulation in Saccharomyces cerevisiae
Authors: Paidhungat Madan , Garrett Stephen
Published: February 2021

Cdc1 function was initially implicated in bud formation and nuclear division because cdc1(Ts) cells arrested with a small bud, duplicated DNA, and undivided nucleus. Our studies show that Cdc1 is necessary for cell growth at several stages of the cell cycle, as well as in pheromone-treated cells. Thus, Cdc1 depletion might affect bud formation and nuclear division, as well as other cellular processes, by blocking a process involved in general cell growth. Cells depleted of intracellular Mn2+ also exhibit a cdc1-like phenotype and recent results suggested Cdc1 might be a Mn2+-dependent protein. We show that all of the conditional cdc1(Ts) alleles tested cause cells to become sensitive to Mn2+ depletion. In addition, Cdc1 overproduction alleviates the chelator sensitivity of several Mn2+ homeostasis mutants. These findings are compatible with a model in which Cdc1 regulates intracellular, and in particular cytosolic, Mn2+ levels which, in turn, are necessary for cell growth.
Cdc1 and the Vacuole Coordinately Regulate Mn2+ Homeostasis in the Yeast Saccharomyces cerevisiae
Authors: Paidhungat Madan , Garrett Stephen
Published: February 2021

The yeast CDC1 gene encodes an essential protein that has been implicated in the regulation of cytosolic [Mn2+]. To identify factors that impinge upon Cdc1 or the Cdc1-dependent process, we isolated secondsite suppressors of the conditional cdc1-1(Ts) growth defect. Recessive suppressors define 15 COS (CdcOne Suppressor) genes. Seven of the fifteen COS genes are required for biogenesis of the vacuole, an organelle known to sequester intracellular Mn2+. An eighth gene, COS16, encodes a vacuolar membrane protein that seems to be involved in Mn2+ homeostasis. These results suggest mutations that block vacuolar Mn2+ sequestration compensate for defects in Cdc1 function. Interestingly, Cdc1 is dispensable in a cos16Δ deletion strain, and a cdc1Δ cos16Δ double mutant exhibits robust growth on medium supplemented with Mn2+. Thus, the single, essential function of Cdc1 is to regulate intracellular, probably cytosolic, Mn2+.
A Proline-Rich Region in the Zeste Protein Essential for Transvection and white Repression by Zeste1
Authors: Rosen Christina , Dorsett Dale , Jack Joseph
Published: February 2021

The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. We characterized two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, we suggest that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the maintenance complexes.
Molecular Genetic Dissection of Mouse Unconventional Myosin-VA: Head Region Mutations
Authors: Huang Jian-Dong , Cope M Jamie T V , Mermall Valerie , Strobel Marjorie C , Kendrick-Jones John , Russell Liane B , Mooseker Mark S , Copeland Neal G , Jenkins Nancy A
Published: February 2021

The mouse dilute (d) locus encodes unconventional myosin-VA (MyoVA). Mice carrying null alleles of dilute have a lightened coat color and die from a neurological disorder resembling ataxia and opisthotonus within three weeks of birth. Immunological and ultrastructural studies suggest that MyoVA is involved in the transport of melanosomes in melanocytes and smooth endoplasmic reticulum in cerebellar Purkinje cells. In studies described here, we have used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles that vary in their effects on coat color and the nervous system. Seven of these mutations mapped to the MyoVA motor domain and are reported here. Crystallographic modeling and mutant expression studies were used to predict how these mutations might affect motor domain function and to attempt to correlate these effects with the mutant phenotype.
Genetic Diversity at a Single Locus Under Viability Selection and Facultative Apomixis: Equilibrium Structure and Deviations from Hardy-Weinberg Frequencies
Authors: Overath R Deborah , Asmussen Marjorie A
Published: February 2021

We extensively analyze the maintenance of genetic variation and deviations from Hardy-Weinberg frequencies at a diallelic locus under mixed mating with apomixis and constant viability selection. Analytical proofs show that: (1) at most one polymorphic equilibrium exists, (2) polymorphism requires overdominant or underdominant selection, and (3) a simple, modified overdominance condition is sufficient to maintain genetic variation. In numerical analyses, only overdominant polymorphic equilibria are stable, and these are stable whenever they exist, which happens for ~78% of random fitness and mating parameters. The potential for maintaining both alleles increases with increasing apomixis or outcrossing and decreasing selfing. Simulations also indicate that equilibrium levels of heterozygosity will often be statistically indistinguishable from Hardy-Weinberg frequencies and that adults, not seeds, should usually be censused to maximize detecting deviations. Furthermore, although both censuses more often have an excess rather than a deficit of heterozygotes, analytical sign analyses of the fixation indices prove that, overall, adults are more likely to have an excess and seeds a deficit at equilibrium.
white+ Transgene Insertions Presenting a Dorsal/Ventral Pattern Define a Single Cluster of Homeobox Genes That Is Silenced by the Polycomb-group Proteins in Drosophila melanogaster
Authors: Netter Sophie , Fauvarque Marie-Odile , del Corral Ruth Diez , Dura Jean-Maurice , Coen Dario
Published: February 2021

We used the white gene as an enhancer trap and reporter of chromatin structure. We collected white+ transgene insertions presenting a peculiar pigmentation pattern in the eye: white expression is restricted to the dorsal half of the eye, with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and heritable, indicating that phenotypic expression of the white reporter reflects positional information in the developing eye. Localization of these transgenes led us to identify a unique genomic region encompassing 140 kb in 69D1–3 subject to this D/V effect. This region contains at least three closely related homeobox-containing genes that are constituents of the iroquois complex (IRO-C). IRO-C genes are coordinately regulated and implicated in similar developmental processes. Expression of these genes in the eye is regulated by the products of the Polycomb -group (Pc-G) and trithorax-group (trx-G) genes but is not modified by classical modifiers of position-effect variegation. Our results, together with the report of a Pc -G binding site in 69D, suggest that we have identified a novel cluster of target genes for the Pc-G and trx-G products. We thus propose that ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin structure in a manner similar to that of the homeotic gene complexes, perhaps by local compaction of the region into a heterochromatin-like structure involving the Pc-G products.
Assessing the Impact of Secondary Structure and Solvent Accessibility on Protein Evolution
Authors: Goldman Nick , Thorne Jeffrey L , Jones David T
Published: February 2021

Empirically derived models of amino acid replacement are employed to study the association between various physical features of proteins and evolution. The strengths of these associations are statistically evaluated by applying the models of protein evolution to 11 diverse sets of protein sequences. Parametric bootstrap tests indicate that the solvent accessibility status of a site has a particularly strong association with the process of amino acid replacement that it experiences. Significant association between secondary structure environment and the amino acid replacement process is also observed. Careful description of the length distribution of secondary structure elements and of the organization of secondary structure and solvent accessibility along a protein did not always significantly improve the fit of the evolutionary models to the data sets that were analyzed. As indicated by the strength of the association of both solvent accessibility and secondary structure with amino acid replacement, the process of protein evolution—both above and below the species level—will not be well understood until the physical constraints that affect protein evolution are identified and characterized.
Effort Mobilization and Healthy Aging
Authors: Hess Thomas M , Freund Alexandra M , Tobler Philippe N
Published: February 2021

Healthy aging is in part dependent upon people’s willingness and ability to mobilize the effort necessary to support behaviors that promote health and well-being. People may have the best information relating to health along with the best intentions to stay healthy (e.g., health-related goals), but positive outcomes will ultimately be dependent upon them actually investing the necessary effort toward using this information to achieve their goals. In addition, the influences on effort mobilization may vary as a function of physical, psychological, and social changes experienced by the individual across the life span. Building on the overall theme of this special issue, we explore the relationships between motivation, effort mobilization, and healthy aging. We begin by characterizing the relationship between motivation and effort, and identify the factors that influence effort mobilization. We then consider the factors associated specifically with aging that may influence effort mobilization (e.g., changes in cardiovascular and neural mechanisms) and, ultimately, the health and well-being of older adults. Finally, distinguishing between those influential factors that are modifiable versus intractable, we identify ways to structure situations and beliefs to optimize mobilization in support of healthy aging.
Improvement of Gut Diversity and Composition After Direct-Acting Antivirals in Hepatitis C Virus–Infected Patients With or Without Human Immunodeficiency Virus Coinfection
Authors: Chuaypen Natthaya , Jinato Thananya , Avihingsanon Anchalee , Chirapongsathorn Sakkarin , Cheevadhanarak Supapon , Nookaew Intawat , Tanaka Yasuhito , Tangkijvanich Pisit
Published: February 2021

Background

The influence of direct-acting antivirals (DAAs) on the composition of gut microbiota in hepatitis C virus (HCV)–infected patients with or without human immunodeficiency virus (HIV) is unclear.

Methods

We enrolled 62 patients with HCV monoinfection and 24 patients with HCV/HIV coinfection receiving elbasvir-grazoprevir from a clinical trial. Fecal specimens collected before treatment and 12 weeks after treatment were analyzed using amplicon-based 16S ribosomal RNA sequencing.

Results

Sustained virological response rates in the monoinfection and coinfection groups were similar (98.4% vs 95.8%). Pretreatment bacterial communities in the patient groups were less diverse and distinct from those of healthy controls. Compared with HCV-monoinfected patients, HCV/HIV-coinfected individuals showed comparable microbial alpha diversity but decreased Firmicutes-Bacteroidetes ratios. The improvement of microbial dysbiosis was observed in responders achieving sustained virological response across fibrosis stages but was not found in nonresponders. Responders with a low degree of fibrosis exhibited a recovery in alpha diversity to levels comparable to those in healthy controls. Reciprocal alterations of increased beneficial bacteria and reduced pathogenic bacteria were also observed in responders.

Conclusions

This study indicates a short-term effect of direct-acting antivirals in restoration of microbial dysbiosis. The favorable changes in gut microbiota profiles after viral eradication might contribute toward the reduction of HCV-related complications among infected individuals.
Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 in Adults During the First and Second Wave of Coronavirus Disease 2019 Pandemic in Houston, Texas: The Potential of the Superspreader
Authors: Avadhanula Vasanthi , Nicholson Erin G , Ferlic-Stark Laura , Piedra Felipe-Andres , Blunck Brittani N , Fragoso Sonia , Bond Nanette L , Santarcangelo Patricia L , Ye Xunyan , McBride Trevor J , Aideyan Letisha O , Patel Kirtida D , Maurer Lauren , Angelo Laura S , Piedra Pedro A
Published: February 2021

Background

During the coronavirus disease 2019 pandemic, a minority of index cases are associated with a majority of secondary cases suggesting that superspreaders could drive the pandemic. We identified a phenotype in individuals with extremely high viral load who could act as superspreaders.

Methods

Data were analyzed from individuals tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 18 March through 15 August 2020. Outcomes were compared using contingency table and quantile regression to test the equality of medians between the pandemic waves and by viral load groups.

Results

Of the 11 564 samples tested, 1319 (11.4%) were positive for SARS-CoV-2. An increase in weekly median viral load occurred in the second wave of the SARS-CoV2 pandemic. This population was more likely to be women, outpatients, and symptomatic and to have an extremely high or high viral load. In patients with multiple reverse-transcription polymerase chain reaction–positive test results, the durations of viral shedding were comparable between individuals with asymptomatic/mild and mild/moderate illness severity.

Conclusions

We detected a small group of individuals with extremely high SARS-CoV-2 viral loads and mild illness. We believe that these individuals’ characteristics could be consistent with the superspreader phenomenon and that greater awareness of the social dynamics of these individuals is needed to understand the spread of SARS-CoV-2.
Bacterial Vaginosis and Behavioral Factors Associated With Incident Pelvic Inflammatory Disease in the Longitudinal Study of Vaginal Flora
Authors: Turpin Rodman , Tuddenham Susan , He Xin , Klebanoff Mark A , Ghanem Khalil G , Brotman Rebecca M
Published: February 2021

Background

Pelvic inflammatory disease (PID) leads to long-term reproductive consequences for cisgender women. Bacterial vaginosis (BV) and behavioral factors may play a role in PID pathogenesis. We assessed associations between BV, behavioral factors, and incident PID.

Methods

We analyzed participants (N = 2956) enrolled in the National Institutes of Health Longitudinal Study of Vaginal Flora, a cohort of nonpregnant cisgender women followed quarterly for 12 months. PID was defined by at least 1 of the following: cervical motion tenderness, uterine tenderness, or adnexal tenderness (160 cases). We tested associations between BV (measured using Nugent and Amsel criteria) and PID at the subsequent visit. Sociodemographic factors, sexual behaviors, and Chlamydia trachomatis (CT), untreated at baseline and concurrent with BV, were covariates in Cox proportional hazards models. Adjusting for the few Neisseria gonorrhoeae and Trichomonas vaginalis cases did not alter results.

Results

In multivariable modeling, Nugent-BV (adjusted hazard ratio [aHR], 1.53 [95% confidence interval {CI}, 1.05–2.21]), symptomatic Amsel-BV (aHR, 2.15 [95% CI, 1.23–3.75]), and vaginal douching (aHR, 1.47 [95% CI, 1.03–2.09]) were associated with incident PID.

Conclusions

BV was associated with incident PID in a large prospective cohort, controlling for behavioral factors and sexually transmitted infections (STIs). Larger studies on how BV, STIs, behaviors, and host responses interactively affect PID risk are needed.
Field Evidence of Mosquito Population Regulation by a Gregarine Parasite
Authors: Soghigian John , Livdahl Todd
Published: February 2021

Although parasites are by definition costly to their host, demonstrating that a parasite is regulating its host abundance in the field can be difficult. Here we present an example of a gregarine parasite, Ascogregarina taiwanensis Lien and Levine (Apicomplexa: Lecudinidae), regulating its mosquito host, Aedes albopictus Skuse (Diptera: Culicidae), in Bermuda. We sampled larvae from container habitats over 2 yr, assessed parasite prevalence, and estimated host abundance from egg counts obtained in neighboring ovitraps. We regressed change in average egg count from 1 yr to the next on parasite prevalence and found a significant negative effect of parasite prevalence. We found no evidence of host density affecting parasite prevalence. Our results demonstrate that even for a parasite with moderate virulence, host regulation can occur in the field.
Duodenal diverticulum at the site of the major papilla may be a risk factor for biliary stent migration
Authors: Morosin Tia , De Robles M Shella , Still Andrew
Published: February 2021

Stent migration is a well-documented complication following biliary stent insertion. The majority of cases demonstrate passage through the bowel without incident; however, migration may also result in complications, including bowel obstruction or perforation requiring urgent intervention. Risk factors for stent migration comprise of disease pathology as well as stent characteristics including dimension, material and number. Although duodenal diverticulae has been noted as a risk factor for duodenal perforation or obstruction post stent migration, it has yet to be implicated as a contributor to migration itself. Here, we present an unusual case of ileal obstruction secondary to biliary stent impaction, in which the presence of a duodenal diverticulum may be considered a viable risk factor for stent migration.
Potential transceptor AtNRT1.13 modulates shoot architecture and flowering time in a nitrate-dependent manner
Authors: Chen Hui-Yu , Lin Shan-Hua , Cheng Ling-Hsin , Wu Jeng-Jong , Lin Yi-Chen , Tsay Yi-Fang
Published: February 2021

Compared with root development regulated by external nutrients, less is known about how internal nutrients are monitored to control plasticity of shoot development. In this study, we characterize an Arabidopsis thaliana transceptor, NRT1.13 (NPF4.4), of the NRT1/PTR/NPF family. Different from most NRT1 transporters, NRT1.13 does not have the conserved proline residue between transmembrane domains 10 and 11; an essential residue for nitrate transport activity in CHL1/NRT1.1/NPF6.3. As expected, when expressed in oocytes, NRT1.13 showed no nitrate transport activity. However, when Ser 487 at the corresponding position was converted back to proline, NRT1.13 S487P regained nitrate uptake activity, suggesting that wild-type NRT1.13 cannot transport nitrate but can bind it. Subcellular localization and β-glucuronidase reporter analyses indicated that NRT1.13 is a plasma membrane protein expressed at the parenchyma cells next to xylem in the petioles and the stem nodes. When plants were grown with a normal concentration of nitrate, nrt1.13 showed no severe growth phenotype. However, when grown under low-nitrate conditions, nrt1.13 showed delayed flowering, increased node number, retarded branch outgrowth, and reduced lateral nitrate allocation to nodes. Our results suggest that NRT1.13 is required for low-nitrate acclimation and that internal nitrate is monitored near the xylem by NRT1.13 to regulate shoot architecture and flowering time.