bluuebunny/crossref_metadata_2025 huggingface dataset:
Theme and Variation Among Silencing Proteins in Saccharomyces cerevisiae and Kluyveromyces lactis
Authors: Åström Stefan U , Rine Jasper
Published: February 2021

The cryptic mating type loci in Saccharomyces cerevisiae act as reservoirs of mating type information used in mating type switching in homothallic yeast strains. The transcriptional silencing of these loci depends on the formation of a repressive chromatin structure that is reminiscent of heterochromatin. Silent information regulator (Sir) proteins 2–4 are absolutely required for silencing. To learn more about silencing, we investigated mating type and Sir proteins in the yeast Kluyveromyces lactis, which contains cryptic copies of the mating type genes. A functional homolog of SIR4 from K. lactis complements the silencing defect of sir4 null mutations in S. cerevisiae. K. lactis sir2 and sir4 mutant strains showed partial derepression of the silent α1 gene, establishing that the silencing role of these proteins is conserved. K. lactis sir2 mutants are more sensitive than the wild type to ethidium bromide, and K. lactis sir4 mutants are more resistant phenotypes that are not observed for the corresponding mutants of S. cerevisiae. Finally, the deletion of sir4 in the two yeasts leads to opposite effects on telomere length. Thus, Sir proteins from K. lactis have roles in both silencing and telomere length maintenance, reflecting conserved functional themes. The various phenotypes of sir mutants in K. lactis and S. cerevisiae, however, revealed unanticipated variation between their precise roles.
A Large Pheromone and Receptor Gene Complex Determines Multiple B Mating Type Specificities in Coprinus cinereus
Authors: O'Shea Suzanne F , Chaure Pushpalata T , Halsall John R , Olesnicky Natalie S , Leibbrandt Andreas , Connerton Ian F , Casselton Lorna A
Published: February 2021

Pheromone signaling plays an essential role in the mating and sexual development of mushroom fungi. Multiallelic genes encoding the peptide pheromones and their cognate 7-transmembrane helix (7-TM) receptors are sequestered in the B mating type locus. Here we describe the isolation of the B6 mating type locus of Coprinus cinereus. DNA sequencing and transformation analysis identified nine genes encoding three 7-TM receptors and six peptide pheromone precursors embedded within 17 kb of mating type-specific sequence. The arrangement of the nine genes suggests that there may be three functionally independent subfamilies of genes each comprising two pheromone genes and one receptor gene. None of the nine B6 genes showed detectable homology to corresponding B gene sequences in the genomic DNA from a B3 strain, and each of the B6 genes independently alter B mating specificity when introduced into a B3 host strain. However, only genes in two of the B6 groups were able to activate B-regulated development in a B42 host. Southern blot analysis showed that these genes failed to cross-hybridize to corresponding genes in the B42 host, whereas the three genes of the third subfamily, which could not activate development in the B42 host, did cross-hybridize. We conclude that cross-hybridization identifies the same alleles of a particular subfamily of genes in different B loci and that B6 and B42 share alleles of one subfamily. There are an estimated 79 B mating specificities: we suggest that it is the different allele combinations of gene subfamilies that generate these large numbers.
The Mitochondrial Genome of the Sea Anemone Metridium senile (Cnidaria): Introns, a Paucity of tRNA Genes, and a Near-Standard Genetic Code
Authors: Beagley C Timothy , Okimoto Ronald , Wolstenholme David R
Published: February 2021

The circular, 17,443 nucleotide-pair mitochondrial (mt) DNA molecule of the sea anemone, Metridium senile (class Anthozoa, phylum Cnidaria) is presented. This molecule contains genes for 13 energy pathway proteins and two ribosomal (r) RNAs but, relative to other metazoan mtDNAs, has two unique features: only two transfer RNAs (tRNAf-Met and tRNATrp) are encoded, and the cytochrome c oxidase subunit I (COI) and NADH dehydrogenase subunit 5 (ND5) genes each include a group I intron. The COI intron encodes a putative homing endonuclease, and the ND5 intron contains the molecule's ND1 and ND3 genes. Most of the unusual characteristics of other metazoan mtDNAs are not found in M. senile mtDNA: unorthodox translation initiation codons and partial translation termination codons are absent, the use of TGA to specify tryptophan is the only genetic code modification, and both encoded tRNAs have primary and secondary structures closely resembling those of standard tRNAs. Also, with regard to size and secondary structure potential, the mt-s-rRNA and mt-l-rRNA have the least deviation from Escherichia coli 16S and 23S rRNAs of all known metazoan mt-rRNAs. These observations indicate that most of the genetic variations previously reported in metazoan mtDNAs developed after Cnidaria diverged from the common ancestral line of all other Metazoa.
Mutant Alleles of Small Effect Are Primarily Responsible for the Loss of Fitness With Slow Inbreeding in Drosophila melanogaster
Authors: Latter B D H
Published: February 2021

Multilocus simulation is used to identify genetic models that can account for the observed rates of inbreeding and fitness decline in laboratory populations of Drosophila melanogaster. The experimental populations were maintained under crowded conditions for ~200 generations at a harmonic mean population size of Nh ~65–70. With a simulated population size of N = 50, and a mean selective disadvantage of homozygotes at individual loci ~1–2% or less, it is demonstrated that the mean effective population size over a 200-generation period may be considerably greater than N, with a ratio matching the experimental estimate of Ne/Nh ~1.4. The buildup of associative overdominance at electrophoretic marker loci is largely responsible for the stability of gene frequencies and the observed reduction in the rate of inbreeding, with apparent selection coefficients in favor of the heterozygote at neutral marker loci increasing rapidly over the first N generations of inbreeding to values ~5–10%. The observed decline in fitness under competitive conditions in populations of size ~50 in D. melanogaster therefore primarily results from mutant alleles with mean effects on fitness as homozygotes of sm ≤ 0.02. Models with deleterious recessive mutants at the background loci require that the mean selection coefficient against heterozygotes is at most hsm ~0.002, with a minimum mutation rate for a single Drosophila autosome 100 cM in length estimated to be in the range 0.05–0.25, assuming an exponential distribution of s. A typical chromosome would be expected to carry at least 100–200 such mutant alleles contributing to the decline in competitive fitness with slow inbreeding.
Genetic and Developmental Characterization of Dmca1D, a Calcium Channel α1 Subunit Gene in Drosophila melanogaster
Authors: Eberl Daniel F , Ren Dejian , Feng Guoping , Lorenz Lori J , Van Vactor David , Hall Linda M
Published: February 2021

To begin unraveling the functional significance of calcium channel diversity, we identified mutations in Dmca1D, a Drosophila calcium channel α1 subunit cDNA that we recently cloned. These mutations constitute the l(2)35Fa lethal locus, which we rename Dmca1D. A severe allele, Dmca1DX10, truncates the channel after the IV-S4 transmembrane domain. These mutants die as late embryos because they lack vigorous hatching movements. In the weaker allele, Dmca1DAR66, a cysteine in transmembrane domain I-S1 is changed to tyrosine. Dmca1DAR66 embryos hatch but pharate adults have difficulty eclosing. Those that do eclose have difficulty in fluid-filling of the wings. These studies show that this member of the calcium channel α1 subunit gene family plays a nonredundant, vital role in larvae and adults.
Genetic Variation and Causes of Genotype-Environment Interaction in the Body Size of Blue Tit (Parus caeruleus)
Authors: Merilä Juha , Fry James D
Published: February 2021

In several studies of natural populations of birds, the heritability of body size estimated by parent-offspring regression has been lower when offspring have developed in poor feeding regimens than when they developed in good feeding regimens. This has led to the suggestion that adaptation under poor regimens may be constrained by lack of genetic variation. We examined the influence of environmental conditions on expression of genetic variation in body size of nestling blue tits (Parus caeruleus) by raising full sibs in artificially reduced and enlarged broods, corresponding to good and poor feeding regimens, respectively. Individuals grown in the poor regimen attained smaller body size than their sibs grown in the good regimen. However, there was among-family variation in response to the treatments—i.e., genotype-environment interactions (GEIs). Partitioning the GEI variance into contributions attributable to (1) differences in the among-family genetic variance between the treatments and (2) imperfect correlation of genotypic values across treatments identified the latter as the main cause of the GEI. Parent-offspring regressions were not significantly different when offspring were reared in the good environment (h2 = 0.75) vs. when they were reared in the poor environment (h2 = 0.63). Thus, there was little evidence that genetic variance in body size was lower under the poor conditions than under the good conditions. These results do not support the view that the genetic potential for adaptation to poor feeding conditions is less than that for adaptation to good conditions, but they do suggest that different genotypes may be favored under the different conditions.
Fixation Indices in Subdivided Populations
Authors: Nagylaki Thomas
Published: February 2021

Without restricting the evolutionary forces that may be present, the theory of fixation indices, or F-statistics, in an arbitrarily subdivided population is developed systematically in terms of allelic and genotypic frequencies. The fixation indices for each homozygous genotype are expressed in terms of the fixation indices for the heterozygous genotypes. Therefore, together with the allelic frequencies, the latter suffice to describe population structure. Possible random fluctuations in the allelic frequencies (which may be caused, e.g., by finiteness of the subpopulations) are incorporated so that the fixation indices are parameters, rather than random variables, and these parameters are expressed in terms of ratios of evolutionary expectations of heterozygosities. The interpretation of some measures of population differentiation is also discussed. In particular, FST is an appropriate index of gene-frequency differentiation if and only if the genetic diversity is low.
The Mutation Rate and Cancer
Authors: Jackson Aimee L , Loeb Lawrence A
Published: February 2021

The stability of the human genome requires that mutations in the germ line be exceptionally rare events. While most mutations are neutral or have deleterious effects, a limited number of mutations are required for adaptation to environmental changes. Drake has provided evidence that DNA-based microbes have evolved a mechanism to yield a common spontaneous mutation rate of ~0.003 mutations per genome per replication (Drake 1991). In contrast, mutation rates of RNA viruses are much larger (Holland et al. 1982) and can approach the maximum tolerable deleterious mutation rate of one per genome (Eigen and Schuster 1977; Eigen 1993). Drake calculates that lytic RNA viruses display spontaneous mutation rates of approximately one per genome while most have mutation rates that are approximately 0.1 per genome (Drake 1993). This constancy of germline mutation rates among microbial species need not necessarily mean constancy of the somatic mutation rates. Furthermore, there need not be a constant rate for somatic mutations during development. In this review, we consider mutations in cancer, a pathology in which there appears to be an increase in the rate of somatic mutations throughout the genome. Moreover, within the eukaryotic genome, as in microbes, there are “hot-spots” that exhibit unusually high mutation frequencies. It seems conceivable to us that many tumors contain thousands of changes in DNA sequence. The major question is: how do these mutations arise, and how many are rate-limiting for tumor progression?
A New Look at Old Mutants of T4 DNA Polymerase
Authors: Nossal Nancy G
Published: February 2021

The DNA polymerase and nuclease activities of bacteriophage T4 DNA polymerase mutants are discussed in the context of the crystal structure of the closely related bacteriophage RB69 DNA polymerase.
Aspects of the Ultraviolet Photobiology of Some T-Even Bacteriophages
Authors: Smith Leslie A , Drake John W
Published: February 2021

Bacteriophage T4 DNA metabolism is largely insulated from that of its host, although some host functions assist in the repair of T4 DNA damage. Environmental factors sometimes affect survival and mutagenesis after ultraviolet (UV) irradiation of T4, and can affect mutagenesis in many organisms. We therefore tested the effect of certain environmental factors and host genetic defects upon spontaneous and UV-induced mutagenesis and survival in T4 and some related T-even phages. Plating at pH 9 enhances UV resistance in T4 by about 14% compared to pH 7. The host cAMP regulatory system affects host survival after UV irradiation but does not affect T4 survival. Thermal rescue, the increasing survival of irradiated T4 with increasing plating temperature, occurs also in phage T6, but only weakly in phages T2 and RB69; this temperature effect is not altered by supplementing infected cells with additional Holliday resolvase (gp49) early in infection. Phage RB69 turns out to have almost 50% greater UV resistance than T4, but has a genome of about the same size; RB69 is UV-mutable but does not produce r mutants, which are easily seen in T2, T4, and T6. Spontaneous mutagenesis in T4 shows no dependence on medium and little dependence on temperature overall, but mutation rates can increase and probably decrease with temperature at specific sites. UV mutagenesis is not affected by incubating irradiated particles under various conditions before plating, in contrast to phage S13.
Reversion of the Tyrosine Ochre Strain Escherichia coli WU3610 under Starvation Conditions Depends on a New Gene tas
Authors: Timms Andrew R , Bridges Bryn A
Published: February 2021

When 3 × 108 bacteria of the Escherichia coli tyrA14(oc) leu308(am) strain WU3610 are plated on glucose salts agar supplemented with leucine only, colonies of slow-growing Tyr+ suppressor mutants begin to appear after about a week and increase in numbers roughly linearly with time thereafter (stationary phase or starvation-associated mutation). From a library constructed from two of these mutants, a clone was obtained that suppressed the tyrosine requirement of WU3610 when present on a multicopy plasmid. The activity was identified to an open reading frame we call tas, the sequence for which has homology with a variety of known genes with aldo-keto reductase activity. The activity of tas complements the prephenate dehydrogenase dysfunction of tyrA14 (the chorismate mutase activity of tyrA possibly being still functional). A strain deleted for tas showed no spontaneous mutation under starvation conditions. Whereas neither tas+ nor tas bacteria showed any increase in viable or total count when plated under conditions of tyrosine starvation at 3 × 108 cells per plate, at lower density (~107 per plate) tas+ but not tas bacteria showed considerable residual growth. We suggest that the single copy of tas present in WU3610 allows cryptic cell or DNA turnover under conditions of tyrosine starvation and that this is an essential prerequisite for starvation-associated mutation in this system. The target gene for mutation is not tas, although an increase in the expression of this gene, for example, resulting from a suppressor mutation affecting supercoiling, could be responsible for the slow-growing Tyr+ phenotype.
Effects of A and B Wolbachia and Host Genotype on Interspecies Cytoplasmic Incompatibility in Nasonia
Authors: Bordenstein Seth R , Werren John H
Published: February 2021

Wolbachia endosymbionts cause postmating reproductive isolation between the sibling species Nasonia vitripennis and N. giraulti. Most Nasonia are doubly infected with a representative from each of the two major Wolbachia groups (A and B). This study investigates the role of single (A or B) and double (A and B) Wolbachia infections in interspecies cytoplasmic incompatibility (CI) and host genomic influences on the incompatibility phenotype. Results show that the single A Wolbachia harbored in N. vitripennis (wAv) is bidirectionally incompatible with the single A Wolbachia harbored in N. giraulti (wAg). Results also indirectly show that the N. vitripennis wBv is bidirectionally incompatible with the N. giraulti wBg. The findings support current phylogenetic evidence that suggests these single infections have independent origins and were acquired via horizontal transfer. The wAv Wolbachia expresses partial CI in the N. vitripennis nuclear background. However, following genomic replacement by introgression, wAv expresses complete CI in the N. giraulti background and remains bidirectionally incompatible with wAg. Results show that double infections can reinforce interspecies reproductive isolation through the addition of incompatibility types and indicate that the host genome can influence incompatibility levels. This study has implications for host-symbiont coevolution and the role of Wolbachia in speciation.
High Apparent Rate of Simultaneous Compensatory Base-Pair Substitutions in Ribosomal RNA
Authors: Tillier Elisabeth R M , Collins Richard A
Published: February 2021

We present a model for the evolution of paired bases in RNA sequences. The new model allows for the instantaneous rate of substitution of both members of a base pair in a compensatory substitution (e.g., A-U→G-C) and expands our previous work by allowing for unpaired bases or noncanonical pairs. We implemented the model with distance and maximum likelihood methods to estimate the rates of simultaneous substitution of both bases, αd, vs. rates of substitution of individual bases, αs in rRNA. In the rapidly evolving D2 expansion segments of Drosophila large subunit rRNA, we estimate a low ratio of αd/αs, indicating that most compensatory substitutions involve a G-U intermediate. In contrast, we find a surprisingly high ratio of αd/αs in the core small subunit rRNA, indicating that the evolution of the slowly evolving rRNA sequences is modeled much more accurately if simultaneous substitution of both members of a base pair is allowed to occur approximately as often as substitution of individual bases. Using simulations, we have ruled out several potential sources of error in the estimation of αd/αs. We conclude that in the core rRNA sequences compensatory substitutions can be fixed so rapidly as to appear to be instantaneous.
A Screen for Dynein Synthetic Lethals in Aspergillus nidulans Identifies Spindle Assembly Checkpoint Genes and Other Genes Involved in Mitosis
Authors: Efimov Vladimir P , Morris N Ronald
Published: February 2021

Cytoplasmic dynein is a ubiquitously expressed microtubule motor involved in vesicle transport, mitosis, nuclear migration, and spindle orientation. In the filamentous fungus Aspergillus nidulans, inactivation of cytoplasmic dynein, although not lethal, severely impairs nuclear migration. The role of dynein in mitosis and vesicle transport in this organism is unclear. To investigate the complete range of dynein function in A. nidulans, we searched for synthetic lethal mutations that significantly reduced growth in the absence of dynein but had little effect on their own. We isolated 19 sld (synthetic lethality without dynein) mutations in nine different genes. Mutations in two genes exacerbate the nuclear migration defect seen in the absence of dynein. Mutations in six other genes, including sldA and sldB, show a strong synthetic lethal interaction with a mutation in the mitotic kinesin bimC and, thus, are likely to play a role in mitosis. Mutations in sldA and sldB also confer hypersensitivity to the microtubule-destabilizing drug benomyl. sldA and sldB were cloned by complementation of their mutant phenotypes using an A. nidulans autonomously replicating vector. Sequencing revealed homology to the spindle assembly checkpoint genes BUB1 and BUB3 from Saccharomyces cerevisiae. Genetic interaction between dynein and spindle assembly checkpoint genes, as well as other mitotic genes, indicates that A. nidulans dynein plays a role in mitosis. We suggest a model for dynein motor action in A. nidulans that can explain dynein involvement in both mitosis and nuclear distribution.
Transcriptionally Active MuDR, the Regulatory Element of the Mutator Transposable Element Family of Zea mays, Is Present in Some Accessions of the Mexican land race Zapalote chico
Authors: de la Luz Gutiérrez-Nava María , Warren Christine A , León Patricia , Walbot Virginia
Published: February 2021

To date, mobile Mu transposons and their autonomous regulator MuDR have been found only in the two known Mutator lines of maize and their immediate descendants. To gain insight into the origin, organization, and regulation of Mutator elements, we surveyed exotic maize and related species for cross-hybridization to MuDR. Some accessions of the mexican land race Zapalote chico contain one to several copies of full-length, unmethylated, and transcriptionally active MuDR-like elements plus non-autonomous Mu elements. The sequenced 5.0-kb MuDR-Zc element is 94.6% identical to MuDR, with only 20 amino acid changes in the 93-kD predicted protein encoded by mudrA and ten amino acid changes in the 23-kD predicted protein of mudrB. The terminal inverted repeat (TIR) A of MuDR-Zc is identical to standard MuDR; TIRB is 11.2% divergent from TIRA. In Zapalote chico, mudrA transcripts are very rare, while mudrB transcripts are as abundant as in Mutator lines with a few copies of MuDR. Zapalote chico lines with MuDR-like elements can trans-activate reporter alleles in inactive Mutator backgrounds; they match the characteristic increased forward mutation frequency of standard Mutator lines, but only after outcrossing to another line. Zapalote chico accessions that lack MuDR-like elements and the single copy MuDR a1-mum2 line produce few mutations. New mutants recovered from Zapalote chico are somatically stable.
Circadian Expression of the Maize Catalase Cat3 Gene Is Highly Conserved Among Diverse Maize Genotypes With Structurally Different Promoters
Authors: Polidoros Alexios N , Scandalios John G
Published: February 2021

The Cat3 gene of maize exhibits a transcriptionally regulated circadian rhythm. In the present study we examined the following: (1) the extent of the circadian Cat3 expression between maize genotypes of diverse origin; (2) the functional significance of a Tourist transposable element located in the Cat3 promoter of the inbred line W64A, which harbors putative regulatory elements (GATA repeat, CCAAT boxes) shown to be involved in the light induction and circadian regulation of the Arabidopsis CAB2, as well as other plant genes; and (3) aspects of the physiological role of CAT-3 in maize metabolism. Results confirm that the circadian Cat3 expression is a general phenomenon in maize. Regulation of Cat3 gene expression is not dependent on the presence of the Tourist element in the promoter of the gene nor on the presence of motifs similar to those found significant in the circadian expression of the Arabidopsis CAB2 gene. Structural diversity was revealed in the Cat3 promoters of maize genotypes of diverse origins. However, highly conserved regions with putative regulatory motifs were identified. Relevance of the conserved regions to the circadian regulation of the gene is discussed. Possible physiological roles of CAT-3 are suggested.
IACUC and Veterinary Considerations for Review of ABSL3 and ABSL4 Research Protocols
Authors: Klages Curtis
Published: February 2021

With the recent upswing of infectious disease outbreaks (coronavirus, influenza, Ebola, etc), there is an ever-increasing need for biocontainment animal use protocols to better address the research of emerging diseases and to increase the health of both animals and humans. It is imperative that we as a research community ensure these protocols are conducted with the utmost scrutiny and regulatory compliance for the welfare of the animals as well as the health and safety concerns of the individual conducting these studies. Both the welfare of the animals and the health and safety of the research staff must be balanced with the integrity of the science being studied. Even prior to reviewing biocontainment protocols, the research stakeholders should have professional and collegial interactions across all levels of the proposed project. These stakeholders should include the attending veterinarian, the principal investigator, the sponsor, and any organic institutional health and safety assets (environmental health and safety, occupational health, biosafety personnel, medical personnel, facilities operations and maintenance, etc). At most institutions, these stakeholders are members of the Institutional Animal Care and Use Committee and may not possess the necessary tools to properly assess an Animal Biosafety Level 3 and 4 animal use protocol. It is the goal of this article to review some basic concepts of biocontainment, discuss critical communications and preapprovals, clinical observations, medical interventions and supportive care, scientific and study endpoints, euthanasia criteria, animal manipulations, documentation, training, emergency response and contingency plans, security, and decontamination and provide a scenario-based and informative thought-provoking process Institutional Animal Care and Use Committee members and veterinary staff may consider during Animal Biosafety Level 3 and 4 protocol review. These topics will enhance the ability of all stakeholders to balance the protection of the people with the integrity of the science and ultimately the welfare of the animal.
Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania
Authors: Mohamed Sagal , Mvungi Happiness C , Sariko Margaretha , Rao Prakruti , Mbelele Peter , Jongedijk Erwin M , van Winkel Claudia A J , Touw Daan J , Stroup Suzanne , Alffenaar Jan-Willem C , Mpagama Stellah , Heysell Scott K
Published: February 2021

Background

Early detection and correction of low fluoroquinolone exposure may improve treatment of MDR-TB.

Objectives

To explore a recently developed portable, battery-powered, UV spectrophotometer for measuring levofloxacin in saliva of people treated for MDR-TB.

Methods

Patients treated with levofloxacin as part of a regimen for MDR-TB in Northern Tanzania had serum and saliva collected concurrently at 1 and 4 h after 2 weeks of observed levofloxacin administration. Saliva levofloxacin concentrations were quantified in the field via spectrophotometry, while serum was analysed at a regional laboratory using HPLC. A Bayesian population pharmacokinetics model was used to estimate the area under the concentration–time curve (AUC0–24). Subtarget exposures of levofloxacin were defined by serum AUC0–24 <80 mg·h/L. The study was registered at Clinicaltrials.gov with clinical trial identifier NCT04124055.

Results

Among 45 patients, 11 (25.6%) were women and 16 (37.2%) were living with HIV. Median AUC0–24 in serum was 140 (IQR = 102.4–179.09) mg·h/L and median AUC0–24 in saliva was 97.10 (IQR = 74.80–121.10) mg·h/L. A positive linear correlation was observed with serum and saliva AUC0–24, and a receiver operating characteristic curve constructed to detect serum AUC0–24 below 80 mg·h/L demonstrated excellent prediction [AUC 0.80 (95% CI = 0.62–0.94)]. Utilizing a saliva AUC0–24 cut-off of 91.6 mg·h/L, the assay was 88.9% sensitive and 69.4% specific in detecting subtarget serum AUC0–24 values, including identifying eight of nine patients below target.

Conclusions

Portable UV spectrophotometry as a point-of-care screen for subtarget levofloxacin exposure was feasible. Use for triage to other investigation or personalized dosing strategy should be tested in a randomized study.
Wind loads on a solar PV panel with side plates
Authors: Chung K M , Chou C C , Chung C Y
Published: February 2021

This study determines the lift force on a tilted solar PV panel with/without side plates (upward and downward types). The tilt angles are 15° and 30° and the wind incidence is at an angle of 0–180° (in increments of 15°). Measurements of mean surface pressure are conducted in a closed-loop wind tunnel. The corner vortices are lessened with the presence of upward or downward side plates for the wind angle of incidence of 0°. The mean surface pressure on the lower surface with downward side plates is more positive (greater wind loads). With upward side plates, there is less suction on the upper surface near the windward corner for the wind angle of incidence from 15° to 60°, resulting in significantly reduced wind loads.
Made in Italy, tailored for Danes: Giuseppe Sarti and Italian Opera in Copenhagen
Authors: Jeanneret Christine
Published: February 2021

The institutionalization of a permanent Italian opera house in Copenhagen happened comparatively late for a European capital. The emergence of a new bourgeois audience, which for the first time shared loges with the aristocracy, created political and aesthetic turmoil linked to the politics of ‘Danishness’, Italophobia and anti-opera sentiment. This study focuses on Giuseppe Sarti, the first director of the opera in Copenhagen, and his strategies to adapt and translate opera for local audiences. The study examines connections between aesthetics, nationalism, and politics in Enlightenment Copenhagen. Bringing this perspective from the North into the study of opera in the age of reform allows us to understand not only the local context, but also the general processes by which Italian opera was adapted, produced, and consumed outside Italy—and the problems faced by the diaspora of Italian musicians to Europe’s Northern periphery.
An N-body approach to modelling debris and ejecta off small bodies: implementation and application
Authors: Larson Jennifer N , Sarid G
Published: February 2021

We introduce here our new approach to modelling particle cloud evolution off surface of small bodies (asteroids and comets), following the evolution of ejected particles requires dealing with various time and spatial scales, in an efficient, accurate, and modular way. In order to improve computational efficiency and accuracy of such calculations, we created an N-body modelling package as an extension to the increasingly popular orbital dynamics N-body integrator rebound. Our code is currently a stand-alone variant of the rebound code and is aimed at advancing a comprehensive understanding of individual particle trajectories, external forcing, and interactions, at the scale that is otherwise overlooked by other modelling approaches. The package we developed – rebound ejecta dynamics (red) – is a python-based implementation with no additional dependences. It incorporates several major mechanisms that affect the evolution of particles in low-gravity environments and enables a more straightforward simulation of combined effects. We include variable size and velocity distributions, solar radiation pressure, ellipsoidal gravitational potential, binary or triple asteroid systems, and particle–particle interactions. In this paper, we present a sample of the red package capabilities. These are applied to a small asteroid binary system (characterized following the Didymos/Dimorphos system, which is the target for NASA’s Double Asteroid Redirection Test mission).
Photometric studies of five eclipsing binaries: RS Ser, V0449 Per, MR Del, V593 Cen, and V1095 Her
Authors: Meng Gang , Zhang Li-yun , Han Xianming L , Long Liu , Misra Prabhakar , Lu Hong-Peng , Pi Qingfeng , Liu Qiong , Cheng Yao , Wang Shuai
Published: February 2021

RS Ser, V449 Per, MR Del, V593 Cen, and V1095 Her are short-period eclipsing binaries. We made photometric observations on 38 nights using four 1-m-class telescopes and plotted eight light curves. We determined the spectral type of V449 Per as K0(±2)V using low-resolution spectra from the Lijiang 2.4-m telescope. We found cyclic variation in the orbital periods for RS Ser and V1095 Her, and confirmed the cyclic variation of MR Del. The periods of the hypothetical third bodies are close to the duration of observation, and the detected cycles are questionable. For V593 Cen, we followed the previously published suggestion that it probably has a black hole with a minimum mass of 3.68 M⊙. We used the orbital period decreasing at a rate of 8.2(0.1) × 10−8 d yr–1 to explain it. There are two alternative interpretations, and hence the black hole candidate of V593 Cen remains questionable because the minimum points are concentrated in four clusters. The period of V449 Per increases continuously at a rate of 9.5 × 10−8 d yr–1, which can be attributed to mass transfer from the less massive component to the more massive component. For MR Del, we used a new light curve and the published radial velocity to revise its absolute parameters. Furthermore, we revised the photometric solution of V593 Cen and confirmed it as an early-type contact binary with a higher contact factor. We obtained preliminary photometric parameters for RS Ser, V1095 Her, and V449 Per.
Critical spin periods of sub-km-sized cohesive rubble-pile asteroids: dependences on material parameters
Authors: Hu Shoucun , Richardson Derek C , Zhang Yun , Ji Jianghui
Published: February 2021

In this work, we employ a soft-sphere discrete element method with a cohesion implementation to model the dynamical process of sub-km-sized cohesive rubble piles under continuous spin-up. The dependences of the critical spin periods Tc on several material parameters for oblate rubble piles with different diameters were explored. Our simulations show that the interparticle cohesive force can strengthen the bodies as expected, especially for the smaller ones. The simulated results of Tc were fitted with the continuum theory developed by Holsapple, through which we find the interparticle cohesion is proportional to the best-fitting bulk cohesion and the ratio shows no dependence on the density. In addition, we find Tc decreases as the density increases in the compressive regime, while the trend reverses when transitioning to the tensile regime. Besides, though a higher friction angle can strengthen the bodies, its influence on Tc is minimized near the separation between the two regimes. Our numerical findings are generally consistent with the continuum theory, except that the latter predicts that Tc should increase as the friction angle increases in the tensile regime, which is contrary to the numerical results. This remarkable difference reminds us to take caution when applying the continuum theory to critically spinning cohesive rubble piles in the tensile regime, especially when dealing with the effect of the friction angle. Finally, we emphasize that the separation between the regimes can be specified by a characteristic period, which is only a function of density for a given shape.
Newtonian fractional-dimension gravity and rotationally supported galaxies
Authors: Varieschi Gabriele U
Published: February 2021

We continue our analysis of Newtonian fractional-dimension gravity, an extension of the standard laws of Newtonian gravity to lower dimensional spaces, including those with fractional (i.e. non-integer) dimension. We apply our model to three rotationally supported galaxies: NGC 7814 (bulge-dominated spiral), NGC 6503 (disc-dominated spiral), and NGC 3741 (gas-dominated dwarf). As was done in the general cases of spherically symmetric and axially symmetric structures, which were studied in previous work on the subject, we examine a possible connection between our model and modified Newtonian dynamics, a leading alternative gravity model that explains the observed properties of these galaxies without requiring the dark matter hypothesis. In our model, the modified Newtonian dynamics acceleration constant $a_{0} \simeq 1.2 \times 10^{ -10}\,\mbox{m}\, \mbox{s}^{ -2}$ can be related to a natural scale length l0, namely $a_{0} \approx GM/l_{0}^{2}$ for a galaxy of mass M. Also, the empirical radial acceleration relation, connecting the observed radial acceleration gobs with the baryonic one gbar, can be explained in terms of a variable local dimension D. As an example of this methodology, we provide detailed rotation curve fits for the three galaxies mentioned above.
Luciferase-based reporter system for in vitro evaluation of elongation rate and processivity of ribosomes
Authors: Kisly Ivan , Kattel Carolin , Remme Jaanus , Tamm Tiina
Published: February 2021

The elongation step of translation is a key contributor to the abundance, folding and quality of proteins and to the stability of mRNA. However, control over translation elongation has not been thoroughly investigated. In this study, a Renilla–firefly luciferase fusion reporter system was further developed to investigate the in vitro elongation rate and processivity of ribosomes independent of the initiation and termination steps. The reporter mRNA was constructed to contain a single ORF encoding in-frame Renilla luciferase, a specific domain moiety and firefly luciferase. Such a reporter structure enables the quantitative and individual evaluation of the synthesis of a specific domain. As a proof of principle, the synthesis of three protein domains of different lengths and structures was analyzed. Using a cell-free translation assay, both the elongation rate and processivity of ribosomes were shown to vary depending on the domain synthesized. Additionally, a stalling sequence consisting of ten rare arginine codons notably reduced the elongation rate and the processivity of the ribosomes. All these results are consistent with the previously known dynamics of elongation in vivo. Overall, the methodology presented in this report provides a framework for studying aspects that contribute to the elongation step of translation.
Modeling multi-species RNA modification through multi-task curriculum learning
Authors: Xiong Yuanpeng , He Xuan , Zhao Dan , Tian Tingzhong , Hong Lixiang , Jiang Tao , Zeng Jianyang
Published: February 2021

N6-methyladenosine (m6A) is the most pervasive modification in eukaryotic mRNAs. Numerous biological processes are regulated by this critical post-transcriptional mark, such as gene expression, RNA stability, RNA structure and translation. Recently, various experimental techniques and computational methods have been developed to characterize the transcriptome-wide landscapes of m6A modification for understanding its underlying mechanisms and functions in mRNA regulation. However, the experimental techniques are generally costly and time-consuming, while the existing computational models are usually designed only for m6A site prediction in a single-species and have significant limitations in accuracy, interpretability and generalizability. Here, we propose a highly interpretable computational framework, called MASS, based on a multi-task curriculum learning strategy to capture m6A features across multiple species simultaneously. Extensive computational experiments demonstrate the superior performances of MASS when compared to the state-of-the-art prediction methods. Furthermore, the contextual sequence features of m6A captured by MASS can be explained by the known critical binding motifs of the related RNA-binding proteins, which also help elucidate the similarity and difference among m6A features across species. In addition, based on the predicted m6A profiles, we further delineate the relationships between m6A and various properties of gene regulation, including gene expression, RNA stability, translation, RNA structure and histone modification. In summary, MASS may serve as a useful tool for characterizing m6A modification and studying its regulatory code. The source code of MASS can be downloaded from https://github.com/mlcb-thu/MASS.
Personalizing heart failure management in chronic kidney disease patients
Authors: Banerjee Debasish , Wang Angela Yee-Moon
Published: February 2021

Chronic kidney disease (CKD) in heart failure (HF) patients is common, present in 49%, and is associated with a higher mortality hazard ratio [2.34 (95% confidence interval 2.20–2.50); P < 0.001] and multiple hospital admissions. The management of HF in CKD can be challenging due to drug-induced electrolyte and creatinine changes, resistance to diuretics and infections related to device therapy. Evidence for improvement in mortality and HF hospitalizations exists in HF with reduced ejection fraction (HFrEF) in Stage 3 CKD patients from randomized controlled trials of angiotensin-converting enzyme inhibitor (ACEi) and mineralocorticoid receptor antagonist therapy but not in dialysis patients, where higher doses can cause hyperkalaemia. Evidence of improvement in cardiovascular death and HF hospitalizations has emerged with the angiotensin receptor neprilysin inhibitor ivabradine and more recently with sodium–glucose cotransporter inhibitors in HFrEF patients with CKD Stages 1–3. However, these studies have excluded CKD Stages 4 and 5 patients. Evidence for β-blocker therapy exists in CKD Stages 1–3 and separately in haemodialysis patients. Cardiac resynchronization therapy reduces HF hospitalizations and mortality in patients with CKD Stages 1–3 but has not been shown to do so in CKD Stages 4 and 5 or dialysis patients. Internal cardioverter and defibrillator therapy in HFrEF patients has been shown to be beneficial in CKD 3 patients but not in dialysis patients, where it is associated with high rates of infection. For HFpEF patients with CKD, therapy is symptomatic, as there is no proven therapy for improvement in survival or hospitalizations. HF patients with end-stage kidney disease with fluid overload may benefit from peritoneal dialysis. A multidisciplinary, personalized approach has been associated with better care and improved patient satisfaction.
Therapeutic cancer vaccines for pediatric malignancies: advances, challenges, and emerging technologies
Authors: Olsen Hannah E , Lynn Geoffrey M , Valdes Pablo A , Cerecedo Lopez Christian D , Ishizuka Andrew S , Arnaout Omar , Bi W Linda , Peruzzi Pier Paolo , Chiocca E Antonio , Friedman Gregory K , Bernstock Joshua D
Published: February 2021

Though outcomes for pediatric cancer patients have significantly improved over the past several decades, too many children still experience poor outcomes and survivors suffer lifelong, debilitating late effects after conventional chemotherapy, radiation, and surgical treatment. Consequently, there has been a renewed focus on developing novel targeted therapies to improve survival outcomes. Cancer vaccines are a promising type of immunotherapy that leverage the immune system to mediate targeted, tumor-specific killing through recognition of tumor antigens, thereby minimizing off-target toxicity. As such, cancer vaccines are orthogonal to conventional cancer treatments and can therefore be used alone or in combination with other therapeutic modalities to maximize efficacy. To date, cancer vaccination has remained largely understudied in the pediatric population. In this review, we discuss the different types of tumor antigens and vaccine technologies (dendritic cells, peptides, nucleic acids, and viral vectors) evaluated in clinical trials, with a focus on those used in children. We conclude with perspectives on how advances in combination therapies, tumor antigen (eg, neoantigen) selection, and vaccine platform optimization can be translated into clinical practice to improve outcomes for children with cancer.
Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 1 newly diagnosed disease
Authors: Taslimi Shervin , Ye Vincent C , Zadeh Gelareh
Published: February 2021

Background

Glioblastoma (GB) is the most common malignant brain tumor with a dismal prognosis despite standard of care (SOC). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) beyond the SOC.

Methods

We included RCTs that investigated the addition of a new treatment to the SOC in patients with newly diagnosed GB. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) regarding OS and PFS were extracted from each paper. We utilized a frequentist network meta-analysis. We planned a subgroup analysis based on O6-methylguanine-DNA methyl-transferase (MGMT) status. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Results

Twenty-one studies were included representing a total of 7403 patients with GB. There was significant heterogeneity among studies impacting important factors such as timing of randomization and sample size. A confidence analysis on the network meta-analysis results revealed a score of low or very low for all treatment comparisons, across subgroups. Allowing for the heterogeneity within the study population, alkylating nitrosoureas (Lomustine and ACNU) and tumor-treating field improved both OS (HR = 0.53, 95% CI 0.33–0.84 and HR = 0.63 95% CI 0.42–0.94, respectively) and PFS (HR = 0.88, 95% CI 0.77–1.00 and HR = 0.63 95% CI 0.52–0.76, respectively).

Conclusions

Our analysis highlights the numerous studies performed on newly diagnosed GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity raises the need for better standardization in neuro-oncology studies.
Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 recurrent glioblastoma
Authors: Taslimi Shervin , Ye Vincent C , Wen Patrick Y , Zadeh Gelareh
Published: February 2021

Background

There exists no consensus standard of treatment for patients with recurrent glioblastoma (GB). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) to determine if any consensus treatment can be determined for recurrent GB.

Methods

We included all recurrent GB RCTs with at least 20 patients in each arm, and for whom patients underwent standard of care at the time of their GB initial diagnosis. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio (HR) and its 95% confidence interval (CI) of the comparison of study arms regarding OS and PFS were extracted from each paper. For comparative efficacy analysis, we utilized a frequentist network meta-analysis, an extension of the classic pair-wise meta-analysis. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Results

Fifteen studies were included representing 29 separate treatment arms and 2194 patients. In our network meta-analysis, combination treatment with tumor-treating field and Vascular endothelial growth factor (VEGF) inhibitor ranked first in improving OS (P = .80). Concomitant anti-VEGF and Lomustine treatment was superior to Lomustine alone for extending PFS (HR 0.57, 95% CI 0.41–0.79) and ranked first in improving PFS compared to other included treatments (P = .86).

Conclusions

Our analysis highlights the numerous studies performed on recurrent GB, with no proven consensus treatment that is superior to the current SOC. Intertrial heterogeneity precludes drawing strong conclusions, and confidence analysis was low to very low. Further confirmation by future trials is recommended for our exploratory results.