bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Sas2, an Acetyltransferase Homologue of Saccharomyces cerevisiae, in Silencing and ORC Function
Authors: Ehrenhofer-Murray Ann E , Rivier David H , Rine Jasper 
Published: January 2021

Silencing at the cryptic mating-type loci HML and HMR of Saccharomyces cerevisiae requires regulatory sites called silencers. Mutations in the Rap1 and Abf1 binding sites of the HMR-E silencer (HMR a-e**) cause the silencer to be nonfunctional, and hence, cause derepression of HMR. Here, we have isolated and characterized mutations in SAS2 as second-site suppressors of the silencing defect of HMR a-e**. Silencing conferred by the removal of SAS2 (sas2Δ) depended upon the integrity of the ARS consensus sequence of the HMR-E silencer, thus arguing for an involvement of the origin recognition complex (ORC). Restoration of silencing by sas2Δ required ORC2 and ORC5, but not SIR1 or RAP1. Furthermore, sas2Δ suppressed the·temperature sensitivity, but not the silencing defect of orc2-1 and orc5-1. Moreover, sas2Δ had opposing effects on silencing of HML and HMR. The putative Sas2 protein bears similarities to known protein acetyltransferases. Several models for the role of Sas2 in silencing are discussed.
Linkage Groups of Protein-Coding Genes in Western Palearctic Water Frogs Reveal Extensive Evolutionary Conservation
Authors: Hotz Hansjürg , Uzzell Thomas , Berger Leszek 
Published: January 2021

Abstract
Among progeny of a hybrid (Rana shqiperica × R. lessonae) × R lessonae, 14 of 22 loci form four linkage groups (LGs): (1) mitochondrial aspartate aminotransferase, carbonate dehydratase-2, esterase 4, peptidase D; (2) mannosephosphate isomerase, lactate dehydrogenase-B, sex, hexokinase-1, peptidase B; (3) albumin, fructose-biphosphatase-1, guanine deaminase; (4) mitochondrial superoxide dismutase, cytosolic malic enzyme, xanthine oxidase. Fructose-biphosphate aldolase-2 and cytosolic aspartate aminotransferase possibly form a fifth LG. Mitochondrial aconitate hydratase, α-glucosidase, glyceraldehyde-3+hosphate dehydrogenase, phosphogluconate dehydrogenase, and phosphoglucomutase-2 are unlinked to other loci. All testable linkages (among eight loci of LGs 1, 2, 3, and 4) are shared with eastern Palearctic water frogs. Including published data, 44 protein loci can be assigned to 10 of the 13 chromosomes in Holarctic Rana. Of testable pairs among 18 protein loci, agreement between Palearctic and Nearctic Rana is complete (125 unlinked, 14 linked pairs among 14 loci of five syntenies), and Holarctic Rana and Xenopus laevis are highly concordant (125 shared nonlinkages, 13 shared linkages, three differences). Several Rana syntenies occur in mammals and fish. Many syntenies apparently have persisted for 60–140 × 106 years (frogs), some even for 350–400 × 106 years (mammals and teleosts).
Probing Novel Elements for Protein Splicing in the Yeast Vmal Protozyme: A Study of Replacement Mutagenesis and Intragenic Suppression
Authors: Nogami Satoru , Satow Yoshinori , Ohya Yoshikazu , Anraku Yasuhiro 
Published: January 2021

Abstract
Protein splicing is a compelling chemical reaction in which two proteins are produced posttranslationally from a single precursor polypeptide by excision of the internal protein segment and ligation of the flanking regions. This unique autocatalytic reaction was first discovered in the yeast Vmalp protozyme where the 50-kD site-specific endonuclease (VDE) is excised from the 120-kD precursor containing the N- and C-terminal regions of the catalytic subunit of the vacuolar H+-ATPase. In this work, we randomized the conserved valine triplet residues three amino acids upstream of the C-terminal splicing junction in the Vmal protozyme and found that these site-specific random mutations interfere with normal protein splicing to different extents. Intragenic suppressor analysis has revealed that this particular hydrophobic triplet preceding the C-terminal splicing junction genetically interacts with three hydrophobic residues preceding the N-terminal splicing junction. This is the first evidence showing that the N-terminal portion of the V-ATPase subunit is involved in protein splicing. Our genetic evidence is consistent with a structural model that correctly aligns two parallel β-strands ascribed to the triplets. This model delineates spatial interactions between the two conserved regions both residing upstream of the splicing junctions.
The Sex-Ratio Trait in Drosophila simulans: Genetic Analysis of Distortion and Suppression
Authors: Cazemajor Michel , Landré Claudie , Montchamp-Moreau Catherine 
Published: January 2021

The sex-ratio trait described in several Drosophila species is a type of naturally occurring X-linked meiotic drive that causes males bearing a sex-ratio X chromosome to produce progenies with a large excess of females. We have previously reported the occurrence of sex-ratio X chromosomes in Drosophila simulans. In this species, because of the co-occurrence of drive suppressors, the natural populations and the derived laboratory strains show an equal sex-ratio even when sex-ratio X chromosomes are present at a high frequency. The presence of sex-ratio X chromosomes is established via crosses with a standard strain that is devoid of drive suppressors. In this article, we show first that the sex-ratio trait in D. simulans results from the action of several X-linked loci. Second we describe drive suppressors on each major autosome as well as on the Y chromosome. The Y-linked factors suppress the drive partially whereas the autosomal suppression can be complete.
Evolutionary Divergence of the Genetic Architecture Underlying Photoperiodism in the Pitcher-Plant Mosquito, Wyeomyia smithii
Authors: Lair Kevin P , Bradshaw William E , Holzapfel Christina M 
Published: January 2021

Abstract
We determine the contribution of composite additive, dominance, and epistatic effects to the genetic divergence of photoperiodic response along latitudinal, altitudinal, and longitudinal gradients in the pitcher-plant mosquito, Wyeomyia smithii. Joint scaling tests of crosses between populations showed wide-spread epistasis as well as additive and dominance differences among populations. There were differences due to epistasis between an alpine population in North Carolina and populations in Florida, lowland North Carolina, and Maine. Longitudinal displacement resulted in differences due to epistasis between Florida and Alabama populations separated by 300 km but not between Maine and Wisconsin populations separated by 2000 km. Genetic differences between New Jersey and Ontario did not involve either dominance or epistasis and we estimated the minimum number of effective factors contributing to a difference in mean critical photoperiod of 5 SD between them as nE = 5. We propose that the genetic similarity of populations within a broad northern region is due to their more recent origin since recession of the Laurentide Ice Sheet and that the unique genetic architecture of each population is the result of both mutation and repeated migration-founder-flush episodes during the dispersal of W. smithii in North America. Our results suggest that differences in composite additive and dominance effects arise early in the genetic divergence of populations while differences due to epistasis accumulate after more prolonged isolation.
Germinal Excisions of the Maize Transposon Activator Do Not Stimulate Meiotic Recombination or Homology-Dependent Repair at the bz Locus
Authors: Dooner Hugo K , Martínez-Férez Isabel M 
Published: January 2021

Abstract
Double-strand breaks have been implicated both in the initiation of meiotic recombination in yeast and as intermediates in the transposition process of nonreplicative transposons. Some transposons of this class, notably P of Drosophila and Tc1 of Caenorhabditis elegans, promote a form of homology-dependent premeiotic gene conversion upon excision. In this work, we have looked for evidence of an interaction between Ac transposition and meiotic recombination at the bz locus in maize. We find that the frequency of meiotic recombination between homologues is not enhanced by the presence of Ac in one of the bz heteroalleles and, conversely, that the presence of a homologous sequence in either trans (homologous chromosome) or cis (tandem duplication) does not promote conversion of the Ac insertion site. However, a tandem duplication of the bz locus may be destabilized by the insertion of Ac. We discuss possible reasons for the lack of interaction between Ac excision and homologous meiotic recombination in maize.
Pharmacokinetics and target attainment of intravenous posaconazole in critically ill patients during extracorporeal membrane oxygenation
Authors: Van Daele Ruth , Brüggemann Roger J , Dreesen Erwin , Depuydt Pieter , Rijnders Bart , Cotton Frédéric , Fage David , Gijsen Matthias , Van Zwam Kenny , Debaveye Yves , Wauters Joost , Spriet Isabel 
Published: January 2021

Abstract

Background
Posaconazole is an antifungal drug used for prophylaxis and treatment of invasive fungal infections. Severe influenza has been identified as a risk factor for invasive pulmonary aspergillosis in critically ill patients. In this population, extracorporeal membrane oxygenation (ECMO) is used as rescue therapy, although little is known about the pharmacokinetics (PK) of posaconazole during ECMO.

Objectives
To determine the PK and target attainment of six patients treated with IV posaconazole under ECMO and to develop a population PK model that can be used to simulate the PTA.

Methods
Critically ill patients treated with posaconazole and ECMO were included in this study. Plasma samples were collected at several timepoints within one dosing interval on two occasions: an early (Day 2–3) and a late (Day 4–7) sampling day. Daily trough concentrations were measured.

Results
The median (IQR) AUC0–24, CL and Vd were 34.3 (28.3–37.7) mg·h/L, 8.7 (8.0–10.6) L/h and 389 (314–740) L, if calculated with non-compartmental analysis based on the observed concentrations. All measured trough concentrations were ≥0.7 mg/L and 11/16 were ≥1 mg/L, which are the haematological thresholds for prophylaxis and treatment of invasive aspergillosis, respectively. The targeted PTA (&gt;90%) was attained for prophylaxis but not for treatment.

Conclusions
ECMO does not appear to influence posaconazole exposure compared with haematology patients. However, some trough levels were below the lower limit for treatment. An a priori dose adjustment does not appear to be necessary but drug monitoring is recommended.
Molecular characteristics and in vitro effects of antimicrobial combinations on planktonic and biofilm forms of Elizabethkingia anophelis
Authors: Tang Hung-Jen , Lin Yi-Tsung , Chen Chi-Chung , Chen Chih-Wei , Lu Ying-Chen , Ko Wen-Chien , Chen Hung-Jui , Su Bo-An , Chang Ping-Chin , Chuang Yin-Ching , Lai Chih-Cheng 
Published: January 2021

Abstract

Objectives
To investigate the in vitro activity of antibiotics against clinical Elizabethkingia anophelis isolates and to find a suitable antibiotic combination with synergistic effects to combat antibiotic-resistant E. anophelis and its associated biofilm.

Methods
E. anophelis isolates were identified by 16S rRNA sequencing; 30 strains with different pulsotypes were identified and the MIC, antibiotic resistance mechanism, antibiotic combination activity and killing effects of antimicrobial agents on biofilms of these strains were determined.

Results
All E. anophelis isolates were susceptible to minocycline and cefoperazone/sulbactam (1:1). More than 90% of clinical isolates were susceptible to cefoperazone/sulbactam (1:0.5), piperacillin/tazobactam and rifampicin. Some novel mutations, such as gyrA G81D, parE D585N and parC P134T, that have never been reported before, were identified. The synergistic effect was most prominent for the combination of minocycline and rifampicin, with 93.3% of their FIC index values ≤0.5, and no antagonism was observed using the chequerboard method. This synergistic effect between minocycline and rifampicin was also observed using time–killing methods for clinical E. anophelis isolates at both normal inoculum and high inoculum. Twenty-nine isolates tested positive for biofilm formation. Minocycline remained active against biofilm-embedded and biofilm-released planktonic E. anophelis cells; however, the enhanced effect of minocycline by adding rifampicin was only observed at 24 h (not at 72 and 120 h).

Conclusions
Although E. anophelis was resistant to many antibiotics and could exhibit biofilm formation, minocycline showed potent in vitro activity against this pathogen and its associated biofilm.
Clinical outcomes of temocillin use for invasive Enterobacterales infections: a single-centre retrospective analysis
Authors: Heard Katie L , Killington Kieran , Mughal Nabeela , Moore Luke S P , Hughes Stephen 
Published: January 2021

Abstract

Background
With increasing frequency of resistant Gram-negative bacteria, temocillin has potential utility in reducing carbapenem use. The 2020 EUCAST guideline changes temocillin breakpoints and reclassifies isolates with an MIC of 0.001–16 mg/L as ‘susceptible, increased exposure’ necessitating 6 g/day rather than the previous 4 g/day, associated with significant cost implications.

Objectives
We explore the clinical utility and treatment failure rate of temocillin at 4 g/day dosing.

Methods
All adult inpatient electronic prescriptions of temocillin (3 days or greater) from March 2016 to October 2019 were retrieved using a clinical decision support system (ICNET®). Treatment success was defined as survival, no switch to broad-spectrum agent for the same indication and no subsequent recrudescence of infection, occurring within 30 days.

Results
Temocillin was used in 205 eligible patient-episodes, median age 79 years (IQR : 71–87 years), 42.4% female. Median temocillin course length was 5.9 days (IQR : 4.6–7.8 days). Indications for use: urinary tract infection (UTI) (n = 141), pneumonia (n = 53), other (n = 11). In total, 144 (70.2%) patients had targeted treatment; 74 (36.1%) against Escherichia coli, 70 (34.4%) other Enterobacterales. A total of 130 (63%) patients received 4 g/day; the remaining patients had reduced renal function with dosing in accordance with guidance. Overall temocillin treatment success was 79.5%; highest when used to treat UTI 85.8% (versus 67.9% in respiratory infections, P = 0.008). Empirical treatment demonstrated 82.0% (50/61) success [versus 78.5% (113/144) among targeted treatment, P = 0. 71].

Conclusions
Temocillin at 4 g/day is an effective and safe alternative in treating patients with Gram-negative infections, but should be considered in the context of patient age and comorbidities. Increased dosing or alternate strategies may be indicated when the infection is not of a urinary source.
Healthcare Process Modeling to Phenotype Clinician Behaviors for Exploiting the Signal Gain of Clinical Expertise (HPM-ExpertSignals): Development and evaluation of a conceptual framework
Authors: Rossetti Sarah Collins , Knaplund Chris , Albers Dave , Dykes Patricia C , Kang Min Jeoung , Korach Tom Z , Zhou Li , Schnock Kumiko , Garcia Jose , Schwartz Jessica , Fu Li-Heng , Klann Jeffrey G , Lowenthal Graham , Cato Kenrick 
Published: January 2021

AbstractObjectiveThere are signals of clinicians’ expert and knowledge-driven behaviors within clinical information systems (CIS) that can be exploited to support clinical prediction. Describe development of the Healthcare Process Modeling Framework to Phenotype Clinician Behaviors for Exploiting the Signal Gain of Clinical Expertise (HPM-ExpertSignals).Materials and MethodsWe employed an iterative framework development approach that combined data-driven modeling and simulation testing to define and refine a process for phenotyping clinician behaviors. Our framework was developed and evaluated based on the Communicating Narrative Concerns Entered by Registered Nurses (CONCERN) predictive model to detect and leverage signals of clinician expertise for prediction of patient trajectories.ResultsSeven themes—identified during development and simulation testing of the CONCERN model—informed framework development. The HPM-ExpertSignals conceptual framework includes a 3-step modeling technique: (1) identify patterns of clinical behaviors from user interaction with CIS; (2) interpret patterns as proxies of an individual’s decisions, knowledge, and expertise; and (3) use patterns in predictive models for associations with outcomes. The CONCERN model differentiated at risk patients earlier than other early warning scores, lending confidence to the HPM-ExpertSignals framework.DiscussionThe HPM-ExpertSignals framework moves beyond transactional data analytics to model clinical knowledge, decision making, and CIS interactions, which can support predictive modeling with a focus on the rapid and frequent patient surveillance cycle.ConclusionsWe propose this framework as an approach to embed clinicians’ knowledge-driven behaviors in predictions and inferences to facilitate capture of healthcare processes that are activated independently, and sometimes well before, physiological changes are apparent.
Cost-Effectiveness of Smoking Cessation Interventions in the Lung Cancer Screening Setting: A Simulation Study
Authors: Cadham Christopher J , Cao Pianpian , Jayasekera Jinani , Taylor Kathryn L , Levy David T , Jeon Jihyoun , Elkin Elena B , Foley Kristie L , Joseph Anne , Kong Chung Yin , Minnix Jennifer A , Rigotti Nancy A , Toll Benjamin A , Zeliadt Steven B , Meza Rafael , Mandelblatt Jeanne ,   the CISNET-SCALE Collaboration, Cadham Christopher J , Cao Pianpian , Jayasekera Jinani , Taylor Kathryn L , Levy David T , Jeon Jihyoun , Meza Rafael , Mandelblatt Jeanne 
Published: January 2021

Abstract

Background
Guidelines recommend offering cessation interventions to smokers eligible for lung cancer screening, but there is little data comparing specific cessation approaches in this setting. We compared the benefits and costs of different smoking cessation interventions to help screening programs select specific cessation approaches.

Methods
We conducted a societal-perspective cost-effectiveness analysis using a Cancer Intervention and Surveillance Modeling Network model simulating individuals born in 1960 over their lifetimes. Model inputs were derived from Medicare, national cancer registries, published studies, and micro-costing of cessation interventions. We modeled annual lung cancer screening following 2014 US Preventive Services Task Force guidelines plus cessation interventions offered to current smokers at first screen, including pharmacotherapy only or pharmacotherapy with electronic and/or web-based, telephone, individual, or group counseling. Outcomes included lung cancer cases and deaths, life-years saved, quality-adjusted life-years (QALYs) saved, costs, and incremental cost-effectiveness ratios.

Results
Compared with screening alone, all cessation interventions decreased cases of and deaths from lung cancer. Compared incrementally, efficient cessation strategies included pharmacotherapy with either web-based cessation ($555 per QALY), telephone counseling ($7562 per QALY), or individual counseling ($35 531 per QALY). Cessation interventions continued to have costs per QALY well below accepted willingness to pay thresholds even with the lowest intervention effects and was more cost-effective in cohorts with higher smoking prevalence.

Conclusion
All smoking cessation interventions delivered with lung cancer screening are likely to provide benefits at reasonable costs. Because the differences between approaches were small, the choice of intervention should be guided by practical concerns such as staff training and availability.
In nomen omen: the effect of flower distance on female reproductive success of the lax-flowered orchidAnacamptis laxiflora(Orchidaceae)
Authors: Scopece Giovanni , Criscuolo Nicola , Cozzolino Salvatore 
Published: January 2021

AbstractAimsIn multiflowered species, the architecture of inflorescences is of primary importance in shaping plant attractiveness. The aim of this study was to disentangle the role of inflorescence traits in plant female reproductive success and pollination patterns along the inflorescence in the lax-flowered orchid Anacamptis laxiflora, a terrestrial species exploiting a deceptive pollination strategy. We also evaluated whether the relationship between inflorescence traits and female reproductive success was modified by the height of surrounding vegetation and/or by population density.MethodsWe delimited experimental plots in a natural population of A. laxiflora. We tallied the individuals within each plot and categorized low-density plots and high-density plots; then, in part of the plots we manually removed surrounding grass thus producing an equal number of plots with high grass and low grass. Within these plots, we recorded inflorescence traits and female reproductive success (i.e. the number of fruit and their position along the inflorescence). We analyzed these data using generalized linear mixed-effects models (GLMMs) and calculated selection gradients.Important FindingsWe found that all the investigated inflorescence traits influenced female reproductive success. In particular, our GLMMs showed that ‘average flower distance’ was the best predictor for shaping reproductive success patterns. We detected significant positive selection on the investigated inflorescence traits, but these selective trends were strictly linked to both the height of the surrounding vegetation and the population density, suggesting a significant influence of local environmental context in shaping selective patterns. Female reproductive success was not linked to the position of flowers along the inflorescence, suggesting that pollinators visit flowers randomly along the inflorescence without a detectable preference for a specific part. This study highlights the importance of inflorescence traits in shaping female reproductive success of multiflowered deceptive orchids, and confirms a primary role for the environmental context in modifying pollinator-mediated selection patterns.
Sleep and Psychological Difficulties in Italian School-Age Children During COVID-19 Lockdown
Authors: Cellini Nicola , Di Giorgio Elisa , Mioni Giovanna , Di Riso Daniela 
Published: January 2021

Abstract

Objective
On March 10, 2020, the Italian Government ordered a national lockdown to limit the viral transmission of coronavirus disease 2019 infections. This study investigated how these restrictive measures have impacted sleep quality, timing, and psychological difficulties in school-age children and their mothers during the lockdown.

Methods
In an online survey, 299 mothers reported their sleep habits, experience of time, and psychological difficulties as well as those of their children (6–10 years old) during and, retrospectively, before the lockdown.

Results
During the lockdown, children showed a marked delay in sleep timing—that is, later bedtime and rise time—and a mild worsening in sleep quality. They were less prone to respect daily routines or to keep track of the passage of time. They showed increased emotional, conduct, and hyperactive symptoms, and the increase in these psychological difficulties was predicted by the change in sleep quality, boredom, and mothers’ psychological difficulties. In addition, mothers showed a delayed sleep timing and worsening of sleep quality during the lockdown, in varying degrees depending on their working conditions. Mothers who kept working regularly outside their homes during lockdown reported more regular sleep patterns, whereas mothers who stopped working showed more emotional symptoms and relevant changes in their perception of time.

Conclusions
Overall, given the evidence of the adverse behavioral and psychological impact of home confinement and social restrictions, effective measures needed to be in place to mitigate long-term effects on children and their mothers, especially those who have had to stop working during lockdown.