bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mutation Rate and Cancer
Authors: Jackson Aimee L , Loeb Lawrence A 
Published: February 2021

Abstract
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?
Aspects of the Ultraviolet Photobiology of Some T-Even Bacteriophages
Authors: Smith Leslie A , Drake John W 
Published: February 2021

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractThe 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

Abstract
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

AbstractBackgroundEarly detection and correction of low fluoroquinolone exposure may improve treatment of MDR-TB.ObjectivesTo explore a recently developed portable, battery-powered, UV spectrophotometer for measuring levofloxacin in saliva of people treated for MDR-TB.MethodsPatients 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 &lt;80 mg·h/L. The study was registered at Clinicaltrials.gov with clinical trial identifier NCT04124055.ResultsAmong 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.ConclusionsPortable 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

AbstractThis 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

Abstract
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

ABSTRACT
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

ABSTRACT
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.