bluuebunny/crossref_metadata_2025 huggingface dataset:
Sum1, a Highly Conserved WD-Repeat Protein, Suppresses S-M Checkpoint Mutants and Inhibits the Osmotic Stress Cell Cycle Response in Fission Yeast
Authors: Humphrey Timothy , Enoch Tamar
Published: February 2021

The S-M checkpoint ensures that entry into mitosis is dependent on completion of DNA replication. In the fission yeast Schizosaccharomyces pombe, the S-M checkpoint mutant cdc2-3w is thought to be defective in receiving the checkpoint signal. To isolate genes that function in the checkpoint pathway, we screened an S. pombe cDNA library for genes that, when overexpressed, could suppress the checkpoint defect of cdc2-3w. Using this approach, we have identified a novel gene, sum1+ (suppressor of uncontrolled mitosis). sum1+ encodes a highly conserved WD-transducin repeat protein with striking sequence similarity to the human transforming growth factor (TGF)-β-receptor interacting protein TRIP-1 and to the translation initiation factor 3 subunit eIF3-p39, encoded by the TIF34 gene in Saccharomyces cerevisiae. S. pombe sum1+ is an essential gene, required for normal cell growth and division. In addition to restoring checkpoint control, overexpression of sum1+ inhibits the normal cell cycle response to osmotic stress. Furthermore, we demonstrate that inactivation of the stress-activated MAP kinase pathway, required for cell cycle stress response, restores the S-M checkpoint in cdc2-3w cells. These results suggest that Sum1 interacts with the stress-activated MAP kinase pathway and raise the possibility that environmental conditions may influence the checkpoint response in fission yeast.
Functions of the High Mobility Group Protein, Abf2p, in Mitochondrial DNA Segregation, Recombination and Copy Number in Saccharomyces cerevisiae
Authors: Zelenaya-Troitskaya Olga , Newman Scott M , Okamoto Koji , Perlman Philip S , Butow Ronald A
Published: February 2021

Previous studies have established that the mitochondrial high mobility group (HMG) protein, Abf2p, of Saccharomyces cerevisiae influences the stability of wild-type (ρ+) mitochondrial DNA (mtDNA) and plays an important role in mtDNA organization. Here we report new functions for Abf2p in mtDNA transactions. We find that in homozygous Δabf2 crosses, the pattern of sorting of mtDNA and mitochondrial matrix protein is altered, and mtDNA recombination is suppressed relative to homozygous ABF2 crosses. Although Abf 2p is known to be required for the maintenance of mtDNA in ρ+ cells growing on rich dextrose medium, we find that it is not required for the maintenance of mtDNA in ρ− cells grown on the same medium. The content of both ρ+ and ρ− mtDNAs is increased in cells by 50–150% by moderate (two- to threefold) increases in the ABF2 copy number, suggesting that Abf2p plays a role in mtDNA copy control. Overproduction of Abf 2p by ≥10-fold from an ABF2 gene placed under control of the GAL1 promoter, however, leads to a rapid loss of ρ+ mtDNA and a quantitative conversion of ρ+ cells to petites within two to four generations after a shift of the culture from glucose to galactose medium. Overexpression of Abf2p in ρ− cells also leads to a loss of mtDNA, but at a slower rate than was observed for ρ+ cells. The mtDNA instability phenotype is related to the DNA-binding properties of Abf 2p because a mutant Abf 2p that contains mutations in residues of both HMG box domains known to affect DNA binding in vitro, and that binds poorly to mtDNA in vivo, complements Δabf2 cells only weakly and greatly lessens the effect of overproduction on mtDNA instability. In vivo binding was assessed by colocalization to mtDNA of fusions between mutant or wild-type Abf 2p and green fluorescent protein. These findings are discussed in the context of a model relating mtDNA copy number control and stability to mtDNA recombination.
The fluffy Gene of Neurospora crassa Encodes a Gal4p-Type C6 Zinc Cluster Protein Required for Conidial Development
Authors: Bailey Lori A , Ebbole Daniel J
Published: February 2021

Neurospora crassa fluffy (fl) mutants are unable to produce macroconidia. We cloned the fl gene to determine its role in regulating conidiation. A cosmid clone containing fl was identified by complementation. The sequence of fl revealed that it encodes a Gal4p-type C6 zinc cluster protein with greatest similarity to the N. crassa NIT4 protein that regulates genes required for nitrate utilization. Analysis of several fl mutant alleles demonstrated that null mutants are blocked in the budding phase of development required to produce conidiophores. fl mRNA is transiently induced just prior to the developmental commitment to budding growth. This timing of fl expression is consistent with a role for FL protein in activation of the previously characterized conidiation-specific (con) genes, con-6 and con-10. These data suggest that FL acts as a developmentally regulated transcription factor required for conidiophore morphogenesis.
High-Efficiency Transformation of Chlamydomonas reinhardtii by Electroporation
Authors: Shimogawara Kosuke , Fujiwara Shoko , Grossman Arthur , Usuda Hideaki
Published: February 2021

We have established a high-efficiency method for transforming the unicellular, green alga Chlamydomonas reinhardtii by electroporation. Electroporation of strains CC3395 and CC425, cell wall-less mutants devoid of argininosuccinate lyase (encoded by ARG7), in the presence of the plasmid pJD67 (which contains ARG7) was used to optimize conditions for the introduction of exogenous DNA. The conditions that were varied included osmolarity, temperature, concentration of exogenous DNA, voltage and capacitance. Following optimization, the maximum transformation frequency obtained was 2 × 105 transformants per μg of DNA; this frequency is two orders of magnitude higher than obtained with the current standard method using glass beads to introduce exogenous DNA. The electroporation procedure described in this article is of general utility, and makes it feasible to isolate genes by direct complementation of Chlamydomonas reinhardtii mutants.
Mapping of Drosophila Mutations Using Site-Specific Male Recombination
Authors: Chen Bin , Chu Tehyen , Harms Emily , Gergen J Peter , Strickland Sidney
Published: February 2021

Although recombination does not usually occur in the male Drosophila germline, site-specific recombination can be induced at the ends of P elements. This finding suggested that male recombination could be used to map Drosophila mutations. In this article, we describe the general method and its application to the mapping of two EMS-induced female-sterile mutations, grauzone and cortex. Within two months, the grauzone gene was mapped relative to seven different P-element insertion sites, and cortex was mapped relative to 23 different P-elements. The results allowed us to map grauzone to a region of about 50 kb, and cortex distal to the chromosomal region 33E. These experiments demonstrate that P-element-induced site-specific male recombination is an efficient and general method to map Drosophila autosomal mutations.
Molecular and Behavioral Analysis of Four period Mutants in Drosophila melanogaster Encompassing Extreme Short, Novel Long, and Unorthodox Arrhythmic Types
Authors: Hamblen Melanie J , White Neal E , Emery Philip T J , Kaiser Kim , Hall Jeffrey C
Published: February 2021

Of the mutationally defined rhythm genes in Drosophila melanogaster, period (per) has been studied the most. We have molecularly characterized three older per mutants—perT, perClk, and per04—along with a novel long-period one (perSLIH). Each mutant is the result of a single nucleotide change. perT, perClk, and perSLIH are accounted for by amino acid substitutions; per04 is altered at a splice site acceptor and causes aberrant splicing. perSLIH exhibits a long period of 27 hr in constant darkness and entrains to light/dark (L/D) cycles with a later-than-normal evening peak of locomotion. perSLIH males are more rhythmic than females. perSLIH's clock runs faster at higher temperatures and slower at lower ones, exhibiting a temperature-compensation defect opposite to that of perLong. The per-encoded protein (PER) in the perT mutant cycles in L/D with an earlier-than-normal peak; this peak in perSLIH is later than normal, and there was a slight difference in the PER timecourse of males vs. females. PER in per04 was undetectable. Two of these mutations, perSLIH and perClk, lie within regions of PER that have not been studied previously and may define important functional domains of this clock protein.
Spectra of Spontaneous Frameshift Mutations at the hisD3052 Allele of Salmonella typhimurium in Four DNA Repair Backgrounds
Authors: DeMarini David M , Shelton Melissa L , Abu-Shakra Amal , Szakmary Akos , Levine Jessie G
Published: February 2021

To characterize the hisD3052 −1 frameshift allele of Salmonella typhimurium, we analyzed ~6000 spontaneous revertants (rev) for a 2-base deletion hotspot within the sequence (CG)4, and we sequenced ~500 nonhotspot rev. The reversion target is a minimum of 76 bases (nucleotides 843–918) that code for amino acids within a nonconserved region of the histidinol dehydrogenase protein. Only 0.4–3.9% were true rev. Of the following classes, 182 unique second-site mutations were identified: hotspot, complex frameshifts requiring ΔuvrB + pKM101 (TA98-specific) or not (concerted), 1-base insertions, duplications, and nonhotspot deletions. The percentages of hotspot mutations were 13.8% in TA1978 (wild type), 24.5% in UTH8413 (pKM101), 31.6% in TA1538 (ΔuvrB), and 41.0% in TA98 (ΔuvrB, pKM101). The ΔuvrB allele decreased by three times the mutant frequency (MF, rev/108 survivors) of duplications and increased by about two times the MF of deletions. Separately, the ΔuvrB allele or pKM101 plasmid increased by two to three times the MF of hotspot mutations; combined, they increased this MF by five times. The percentage of 1-base insertions was not influenced by either ΔuvrB or pKM101. Hotspot deletions and TA98-specific complex frameshifts are inducible by some mutagens; concerted complex frameshifts and 1-base insertions are not; and there is little evidence for mutagen-induced duplications and nonhotspot deletions. Except for the base substitutions in TA98-specific complex frameshifts, all spontaneous mutations of the hisD3052 allele are likely templated. The mechanisms may involve (1) the potential of direct and inverted repeats to undergo slippage and misalignment and to form quasi-palindromes and (2) the interaction of these sequences with DNA replication and repair proteins.
Genetic Polymorphism and Natural Selection in the Malaria Parasite Plasmodium falciparum
Authors: Escalante Ananias A , Lal Altaf A , Ayala Francisco J
Published: February 2021

We have studied the genetic polymorphism at 10 Plasmodium falciparum loci that are considered potential targets for specific antimalarial vaccines. The polymorphism is unevenly distributed among the loci; loci encoding proteins expressed on the surface of the sporozoite or the merozoite (AMA-1, CSP, LSA-1, MSP-1, MSP-2, and MSP-3) are more polymorphic than those expressed during the sexual stages or inside the parasite (EBA-175, Pfs25, PF48/45, and RAP-1). Comparison of synonymous and nonsynonymous substitutions indicates that natural selection may account for the polymorphism observed at seven of the 10 loci studied. This inference depends on the assumption that synonymous substitutions are neutral, which we test by analyzing codon bias and G+C content in a set of 92 gene loci. We find evidence for an overall trend towards increasing A+T richness, but no evidence for mutation bias. Although the neutrality of synonymous substitutions is not definitely established, this trend towards an A+T rich genome cannot explain the accumulation of substitutions at least in the case of four genes (AMA-1, CSP, LSA-1, and PF48/45) because the G↔C transversions are more frequent than expected. Moreover, the Tajima test manifests positive natural selection for the MSP-1 and, less strongly, MSP-3 polymorphisms; the McDonald-Kreitman test manifests natural selection at LSA-1 and PF48/45. We conclude that there is definite evidence for positive natural selection in the genes encoding AMA-1, CSP, LSA-1, MSP-1, and Pfs48/45. For four other loci, EBA-175, MSP-2, MSP-3, and RAP-1, the evidence is limited. No evidence for natural selection is found for Pfs25.
Genes Expressed in the Ring Gland, the Major Endocrine Organ of Drosophila melanogaster
Authors: Harvie Peter D , Filippova Maria , Bryant Peter J
Published: February 2021

We have used an enhancer-trap approach to begin characterizing the function of the Drosophila endocrine system during larval development. Five hundred and ten different lethal PZ element insertions were screened to identify those in which a reporter gene within the P element showed strong expression in part or all of the ring gland, the major site of production and release of developmental hormones, and which had a mutant phenotype consistent with an endocrine defect. Nine strong candidate genes were identified in this screen, and eight of these are expressed in the lateral cells of the ring gland that produce ecdysteroid molting hormone (EC). We have confirmed that the genes detected by these enhancer traps are expressed in patterns similar to those detected by the reporter gene. Two of the genes encode proteins, protein kinase A and calmodulin, that have previously been implicated in the signaling pathway leading to EC synthesis and release in other insects. A third gene product, the translational elongation factor EF-1α F1, could play a role in the translational regulation of EC production. The screen also identified the genes couch potato and tramtrack, previously known from their roles in peripheral nervous system development, as being expressed in the ring gland. One enhancer trap revealed expression of the gene encoding the C subunit of vacuolar ATPase (V-ATPase) in the medial cells of the ring gland, which produce the juvenile hormone that controls progression through developmental stages. This could reveal a function of V-ATPase in the response of this part of the ring gland to adenotropic neuropeptides. However, the gene identified by this enhancer trap is ubiquitously expressed, suggesting that the enhancer trap is detecting only a subset of its control elements. The results show that the enhancer trap approach can be a productive way of exploring tissue-specific genetic functions in Drosophila.
Mapping the Genome of a Model Protochordate. I. A Low Resolution Genetic Map Encompassing the Fusion/Histocompatibility (Fu/HC) Locus of Botryllus schlosseri
Authors: De Tomaso Anthony W , Saito Yasunori , Ishizuka Katharine J , Palmeri Karla J , Weissman Irving L
Published: February 2021

The colonial protochordate, Botryllus schlosseri, undergoes a genetically defined, natural transplantation reaction when the edges of two growing colonies interact. Peripheral blood vessels of each colony touch and will either fuse together to form a common vasculature between the colonies, or reject each other in an active blood-based inflammatory process in which the interacting vessels are cut off and the two colonies no longer interact. Previous studies have demonstrated that allorecognition in Botryllus is principally controlled by a single Mendelian locus named the fusion/histocompatibility (Fu/HC) locus, with multiple codominantly expressed alleles. However, identification and cloning of this locus has been difficult. We are taking a genomic approach in isolating this locus by creating a detailed genetic linkage map of the 725 Mbp Botryllus genome using DNA polymorphisms (primarily identified as AFLPs) as molecular genetic markers. DNA polymorphisms are identified in inbred laboratory strains of Fu/HC defined Botryllus, and their segregation and linkage is analyzed in a series of defined crosses. Using bulk segregant analysis, we have focused our mapping efforts on the Fu/HC region of the genome, and have generated an initial map which delineates the Fu/HC locus to a 5.5 cM region.
Maximum Likelihood Estimation of Population Growth Rates Based on the Coalescent
Authors: Kuhner Mary K , Yamato Jon , Felsenstein Joseph
Published: February 2021

We describe a method for co-estimating 4Neμ (four times the product of effective population size and neutral mutation rate) and population growth rate from sequence samples using Metropolis-Hastings sampling. Population growth (or decline) is assumed to be exponential. The estimates of growth rate are biased upwards, especially when 4Neμ is low; there is also a slight upwards bias in the estimate of 4Neμ itself due to correlation between the parameters. This bias cannot be attributed solely to Metropolis-Hastings sampling but appears to be an inherent property of the estimator and is expected to appear in any approach which estimates growth rate from genealogy structure. Sampling additional unlinked loci is much more effective in reducing the bias than increasing the number or length of sequences from the same locus.
Testing for Epistasis Between Deleterious Mutations
Authors: West S A , Peters A D , Barton N H
Published: February 2021

Determining the way in which deleterious mutations interact in their effects on fitness is crucial to numerous areas in population genetics and evolutionary biology. For example, if each additional mutation leads to a greater decrease in log fitness than the last (synergistic epistasis), then the evolution of sex and recombination may be favored to facilitate the elimination of deleterious mutations. However, there is a severe shortage of relevant data. Three relatively simple experimental methods to test for epistasis between deleterious mutations in haploid species have recently been proposed. These methods involve crossing individuals and examining the mean and/or skew in log fitness of the offspring and parents. The main aim of this paper is to formalize these methods, and determine the most effective way in which tests for epistasis could be carried out. We show that only one of these methods is likely to give useful results: crossing individuals that have very different numbers of deleterious mutations, and comparing the mean log fitness of the parents with that of their offspring. We also reconsider experimental data collected on Chlamydomonas moewussi using two of the three methods. Finally, we suggest how the test could be applied to diploid species.
Proposed Genetic Nomenclature Rules for Tetrahymena thermophila, Paramecium primaurelia and Paramecium tetraurelia
Authors:   The Seventh International Meeting on Ciliate Molecular Biology Genetics Nomenclature Committee, Allen Sally Lyman , Altschuler Marsha I , Bruns Peter J , Cohen Jean , Doerder F Paul , Gaertig Jacek , Gorovsky Martin , Orias Eduardo , Turkewitz Aaron
Published: February 2021

The genetics of the ciliated protozoa Tetrahymena thermophila and certain species of Paramecium (P. primaurelia and P. tetraurelia) have reached a level of maturity such that rules for genetic nomenclature for micronuclear and macronuclear genetics need to be clarified for workers in the field as well as for other geneticists. After a short introduction, the rules follow.
Single-Strand DNA-Specific Exonucleases in Escherichia coli: Roles in Repair and Mutation Avoidance
Authors: Viswanathan Mohan , Lovett Susan T
Published: February 2021

Mutations in the genes encoding single-strand DNA-specific exonucleases (ssExos) of Escherichia coli were examined for effects on mutation avoidance, UV repair, and conjugational recombination. Our results indicate complex and partially redundant roles for ssExos in these processes. Although biochemical experiments have implicated RecJ exonuclease, Exonuclease I (ExoI), and Exonuclease VII (ExoVII) in the methyl-directed mismatch repair pathway, the RecJ− ExoI− ExoVII− mutant did not exhibit a mutator phenotype in several assays for base substitution mutations. If these exonucleases do participate in mismatch excision, other exonucleases in E. coli can compensate for their loss. Frameshift mutations, however, were stimulated in the RecJ− ExoI− ExoVII− mutant. For acridine-induced frameshifts, this mutator effect was due to a synergistic effect of ExoI− and ExoVII− mutations, implicating both ExoI and ExoVII in avoidance of frameshift mutations. Although no single exonuclease mutant was especially sensitive to UV irradiation, the RecJ− ExoVII− double mutant was extremely sensitive. The addition of an ExoI− mutation augmented this sensitivity, suggesting that all three exonucleases play partially redundant roles in DNA repair. The ability to inherit genetic markers by conjugation was reduced modestly in the ExoI− RecJ− mutant, implying that the function of either ExoI or RecJ exonucleases enhances RecBCD-dependent homologous recombination.
Prevalence of Memory-Related Diagnoses Among U.S. Older Adults With Early Symptoms of Cognitive Impairment
Authors: Qian Yuting , Chen Xi , Tang Diwen , Kelley Amy S , Li Jing
Published: February 2021

Background

Early diagnosis of cognitive impairment may confer important advantages. Yet the prevalence of memory-related diagnoses among older adults with early symptoms of cognitive impairment is unknown.

Methods

A retrospective, longitudinal cohort design using 2000–2014 Health and Retirement Survey–Medicare linked data. We leveraged within-individual variation to examine the relationship between incident cognitive impairment and receipt of diagnosis among 1225 individuals aged 66 or older. Receipt of a memory-related diagnosis was determined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Incident cognitive impairment was defined as the first assessment wherein the participant’s modified Telephone Interview for Cognitive Status score was less than 12.

Results

The unadjusted prevalence of memory-related diagnosis at cognitive impairment was 12.0%. Incident cognitive impairment was associated with a 7.3% (95% confidence interval [CI], 5.6% to 9.0%; p < .001) higher adjusted probability of any memory-related diagnosis overall, yielding 9.8% adjusted prevalence of diagnosis. The increase in likelihood of diagnosis associated with cognitive decline was significantly higher among non-Hispanic Whites than non-Hispanic Blacks (8.2% vs −0.7%), and among those with at least a college degree than those with a high school diploma or less (17.4% vs 6.8% vs 1.6%). Those who were younger, had below-median wealth, or without a partner had lower probability of diagnosis than their counterparts.

Conclusions

We found overall low prevalence of early diagnosis, or high rate of underdiagnosis, among older adults showing symptoms of cognitive impairment, especially among non-Whites and socioeconomically disadvantaged subgroups. Our findings call for targeted interventions to improve the rate of early diagnosis, especially among vulnerable populations.
The Effect of Frailty on Walking Recovery After Hip Fracture: A Secondary Analysis of the Community Ambulation Project
Authors: Mangione Kathleen K , Craik Rebecca L , Kenny Anne , Memaj Arteid , Miller Melissa F , Chen Menki , Weingart Molly , Orwig Denise , Magaziner Jay
Published: February 2021

Background

The impact of frailty on walking recovery after hip fracture has not been reported. We describe the prevalence of frailty approximately 3 months after hip fracture, and identify the impact of baseline frailty on ambulation recovery.

Methods

Data from the Community Ambulation Project, that examined the effects of 2 multicomponent home exercise programs on 6-minute walk test in participants post hip fracture, were used to reconstruct the 5-item frailty phenotype. We detailed the prevalence of frailty by subgroup and assessed the comparability between frailty groups for the categorical variable of achieving 300 m in 6-minute walk test (community ambulation threshold), and the continuous variable of total distance in 6-minute walk test before and after 16 weeks of intervention.

Results

Of the 210 participants, 9% were nonfrail, 59% were prefrail, and 32% were frail. The odds of a nonfrail participant achieving the 300-m threshold were 14.4 (95% CI: 2.4–87.6) times the odds of a frail participant, while a prefrail participant’s odds were 6.1 (95% CI: 1.3–28.4) times after controlling for treatment group and baseline walking distance. The nonfrail participants had an increase of 92.1 m from baseline to 16 weeks, the prefrail had a 50.8 m increase, and the frail group had the smallest increase of 36.6 m (p < .001 for all).

Conclusions

Prefrailty and frailty were highly prevalent in this sample of community-dwelling survivors of a recent hip fracture. Gains in walking distance and attaining a level of community ambulation were affected significantly by the level of baseline frailty.
Covert balancing: Great Powers, secondary states and US balancing strategies against China
Authors: Meijer Hugo , Simón Luis
Published: February 2021

Throughout history, Great Powers have devised balancing strategies aimed at checking the ambitions of rival Great Powers. To do that, they have sought to enter and mobilize alliances and security partnerships with secondary states. Yet, the influence of secondary states on the balancing strategies of Great Powers remains largely under-estimated in the International Relations literature. Contrary to conventional wisdom, we posit that secondary state preferences play a key enabling or constraining role in shaping the balancing choices of Great Powers. We focus specifically on how the adoption of hedging strategies on the part of secondary states affects the balancing strategies of established Great Powers. We argue that when secondary states adopt a hedging strategy established Great Powers are incentivized to engage in what we call ‘covert balancing’. Covert balancing occurs when an established Great Power conceals its security cooperation with a secondary state beneath a cover that is seemingly unrelated to balancing a rising Great Power, thus working around the secondary state's hedging strategy while at the same time helping to generate a latent capacity to balance. We probe our argument by examining US balancing strategy against China in the Asia–Pacific.
Overexpression of Cancer-Associated Stem Cell Gene OLFM4 in the Colonic Epithelium of Patients With Primary Sclerosing Cholangitis
Authors: Neyazi Mastura , Bharadwaj Sraddha S , Bullers Samuel , Varenyiova Zofia ,   Oxford IBD Cohort Study Investigators, Travis Simon , Arancibia-Cárcamo Carolina V , Powrie Fiona , Geremia Alessandra
Published: February 2021

Background

To examine immune-epithelial interactions and their impact on epithelial transformation in primary sclerosing cholangitis–associated ulcerative colitis (PSC-UC) using patient-derived colonic epithelial organoid cultures (EpOCs).

Methods

The EpOCs were originated from colonic biopsies from patients with PSC-UC (n = 12), patients with UC (n = 14), and control patients (n = 10) and stimulated with cytokines previously associated with intestinal inflammation (interferon (IFN) γ and interleukin (IL)-22). Markers of cytokine downstream pathways, stemness, and pluripotency were analyzed by real-time quantitative polymerase chain reaction and immunofluorescence. The OLFM4 expression in situ was assessed by RNAscope and immunohistochemistry.

Results

A distinct expression of stem cell–associated genes was observed in EpOCs derived from patients with PSC-UC, with lower expression of the classical stem-cell marker LGR5 and overexpression of OLFM4, previously associated with pluripotency and early stages of neoplastic transformation in the gastrointestinal and biliary tracts. High levels of OLFM4 were also found ex vivo in colonic biopsies from patients with PSC-UC. In addition, IFNγ stimulation resulted in the downregulation of LGR5 in EpOCs, whereas higher expression of OLFM4 was observed after IL-22 stimulation. Interestingly, expression of the IL-22 receptor, IL22RA1, was induced by IFNγ, suggesting that a complex interplay between these cytokines may contribute to carcinogenesis in PSC-UC.

Conclusions

Higher expression of OLFM4, a cancer stemness gene induced by IL-22, is present in PSC-UC, suggesting that IL-22 responses may result in alterations of the intestinal stem-cell niche in these patients.
Survival after left ventricular assist device implantation correlates with a novel device-based measure of heart rate variability: the heart rate score
Authors: Czermak Thomas , Seitelberger Valentina , Hagl Christian , Samson-Himmelstjerna Patrick-Nicolas , Groß Sven , Sadoni Sebastian , Heyn Oliver , Kellnar Antonia , Hartrampf Bonnie , Lemmermöhle Eric , Klier Ina , Rehms Raphael , Hoffmann Sabine , Estner Heidi L , Fichtner Stephanie , Lackermair Korbinian
Published: February 2021

OBJECTIVES

The heart rate score (HRS) serves as a device-based measure of impaired heart rate variability and is an independent predictor of death in patients with heart failure and a cardiac implantable electrical device. However, no data are available for predicting death from the HRS in patients with end stage heart failure and a left ventricular assist device.

METHODS

From November 2011 to July 2018, a total of 56 patients with a pre-existing cardiac implantable electrical device underwent left ventricular assist device implantation at our 2 study sites. The ventricular HRS was calculated retrospectively during the first cardiac implantable electrical device follow-up examination following the index hospitalization. Survival during follow-up was correlated with initial HRS.

RESULTS

During the follow-up period, 46.4% of the patients (n = 26) died. The median follow-up period was 33.2 months. The median HRS after the index hospitalization was 41.1 ± 21.8%. More patients with an HRS >65% died compared to patients with an HRS <30% (76.9% vs 14.4%; P = 0.007).

CONCLUSIONS

In our multicentre experience, survival of patients after an left ventricular assist device implant correlates with the HRS. After confirmation of our findings in a larger cohort, the effect of rate-responsive pacing will be within the scope of further investigation.
Balloon-expanding transcatheter aortic valve implantation for degenerated Mitroflow bioprostheses: clinical and echocardiographic long-term outcomes
Authors: Mosquera Victor X , Bouzas-Mosquera Alberto , Vilela-González Yago , Velasco Carlos , Salgado-Fernández Jorge , Calviño-Santos Ramón , Vázquez-González Nicolás , Vázquez-Rodríguez José M , Herrera-Noreña José M
Published: February 2021

OBJECTIVES

This study aims to analyse the risks associated with valve-in-valve procedures for treating structural valve deterioration in Mitroflow bioprostheses, as well as to determine the impact of the original Mitroflow size on the patients’ long-term outcomes.

METHODS

Between January 2012 and September 2019, 21 patients (61.9% males; mean age 82.4 ± 5.4 years) were treated for Mitroflow deterioration with valve-in-valve procedures (12 transapical and 9 transfemoral).

RESULTS

Mean EuroSCORE I and EuroSCORE II were 28.2% ± 13.6% and 10.5% ± 6.1%, respectively. Six patients presented an indexed aortic root diameter <14 mm/m2 and 7 patients a diameter of sinus of Valsalva <30 mm. Implanted transcatheter valve sizes were 20 mm in 6 cases, 23 mm in 14 cases and 26 mm in 1 patient. A Valve Academic Research Consortium-2 complication occurred in 23.8% of cases, including 3 coronary occlusions. In-hospital mortality was 9.5%. The 20 mm transcatheter valves presented significantly higher postoperative peak and mean aortic gradients than other sizes (54.1 ± 11.3 mmHg vs 29.9 ± 9.6 mmHg, P = 0.003; and 29.3 ± 7.7 mmHg vs 17.4 ± 5.9 mmHg, P = 0.015, respectively). There were 12 cases of patient–prosthesis mismatch (57.1%) and 3 cases (14.3%) of severe patient–prosthesis mismatch. Cumulative survival was 85.7% ± 7.6% at 1 year, 74.3% ± 10% at 2 years and 37.1% ± 14.1% at 5 years.

CONCLUSIONS

Valve-in-valve procedures with balloon-expandable transcatheter valves associate a high risk of coronary occlusion in patients with indexed aortic root diameter <14 mm/m2 and low coronary ostia <12 mm. Valve-in valve procedures with 20 mm balloon-expandable transcatheter valves in ≤21 mm Mitroflow bioprosthesis leave significant residual transvalvular gradients that might obscure patients’ long-term outcomes.
Global epidemiology and socio-economic development correlates of the reproductive ratio of COVID-19
Authors: Breitling Lutz P
Published: February 2021

Background

The most commonly cited argument for imposing or lifting various restrictions in the context of the coronavirus disease 2019 (COVID-19) pandemic is an assumed impact on the reproductive ratio of the pathogen. It has furthermore been suggested that less-developed countries are particularly affected by this pandemic. Empirical evidence for this is lacking.

Methods

Based on a dataset covering 170 countries, patterns of empirical 7-d reproductive ratios during the first months of the COVID-19 pandemic were analysed. Time trends and associations with socio-economic development indicators, such as gross domestic product per capita, physicians per population, extreme poverty prevalence and maternal mortality ratio, were analysed in mixed linear regression models using log-transformed reproductive ratios as the dependent variable.

Results

Reproductive ratios during the early phase of a pandemic exhibited high fluctuations and overall strong declines. Stable estimates were observed only several weeks into the pandemic, with a median reproductive ratio of 0.96 (interquartile range 0.72–1.34) 6 weeks into the analysis period. Unfavourable socio-economic indicators showed consistent associations with higher reproductive ratios, which were elevated by a factor of 1.29 (95% confidence interval 1.15 to 1.46), for example, in the countries in the highest compared with the lowest tertile of extreme poverty prevalence.

Conclusions

The COVID-19 pandemic has allowed for the first time description of the global patterns of reproductive ratios of a novel pathogen during pandemic spread. The present study reports the first quantitative empirical evidence that COVID-19 net transmissibility remains less controlled in socio-economically disadvantaged countries, even months into the pandemic. This needs to be addressed by the global scientific community as well as international politics.
Wide Diurnal Temperature Amplitude and High Population Density Can Positively Affect the Life History of Sitobion avenae (Hemiptera: Aphididae)
Authors: Xing Kun , Sun Dongbao , Zhang Jianzhen , Zhao Fei
Published: February 2021

Diurnal temperature amplitude is known to have a large influence on insect life history. Population density affects intraspecific competition and many other aspects of insect life history. However, there is limited information on the interactive effects of these factors on insects. Here, we tested the interactive effects of three diurnal temperature amplitudes (22 ± 0°C, 22 ± 6°C, and 22 ± 12°C) and three population densities on the development, survival, longevity, and fecundity of the English grain aphid Sitobion avenae (Fabricius) (Homoptera: Aphididae). At a constant temperature, increasing population density reduced the growth and survival of early-instar nymphs, increased longevity, and reduced fecundity. At a low population density, increasing temperature amplitude inhibited nymph development. However, even at a high temperature amplitude, nymph survival rate was higher than expected, and reproduction was possible because the recovery of the lower night-temperatures eliminated thermal stress. Increasing the population density reduced, and even reversed, the negative effects of the wide temperature amplitude. This may reflect synergistic interactions between population density and wide temperature amplitude as these stressors each incur energetic costs. These findings emphasize the importance of temperature amplitude and population density for improving prediction accuracy and damage assessment during pest control modeling.
The Superworm, Zophobas morio (Coleoptera:Tenebrionidae): A ‘Sleeping Giant’ in Nutrient Sources
Authors: Rumbos C I , Athanassiou C G
Published: February 2021

The aim of this review is to compile up-to-date information on the superworm, Zophobas morio (F.), regarding its biology and ecology, but also its further potential for use as a nutrient source for food and feed. We illustrate certain basic characteristics of the morphology and bio-ecology of this species, which is marginally considered as a ‘pest’ in durable amylaceous commodities. More recent data show that Z. morio can be a valuable nutrient and antimicrobial source that could be utilized further in insect-based feed and food production. The inclusion of this species in aquafeed has provided promising results in a wide range of feeding trials, both in terms of fish development and health. Additional data illustrate its potential for use in poultry, indicating that this species provides comparable results with those of other insect species that are used in feed. Moreover, Z. morio can be a viable waste management agent. This review aims to summarize the available data and underline data gaps for future research, toward the potential of the utilization of Z. morio for human food and animal feed. Based on the data presented, Z. morio appears to be a well-promising insect-based protein source, which potential still remains to be unfold.
Effects of silver nanoparticles–polysaccharide on bleomycin-induced pulmonary fibrosis in rats
Authors: Hassan Amal I , Samir Amer , Youssef Hanan F , Mohamed Sahar S , Asker Mohsen S , Mahmoud Manal G
Published: February 2021

Objectives

The first goal of this study was to synthesize the silver nanoparticles Alcaligenes xylosoxidans exopolysaccharide (Ag-AXEPS). The second objective was to analyse the role of Ag-AXEPS nanoparticles (NPS) in treating bleomycin (BLM)-induced lung fibrosis.

Methods

Intratracheal bleomycin (2.5 U/kg) was administered to prompt pulmonary fibrosis in rats, and pulmonary fibrosis was treated with Ag-AXEPS nanoparticles (100 ppm/twice a week for four weeks).

Key ﬁndings

Ag-AXEPS nanoparticles significantly decreased the diversity of pulmonary inflammatory agents in rats with BLM-induced fibrosis. Reduced levels of respiratory tumor necrosis factor-alpha, monocyte chemotactic protein-1, matrix metalloproteinases (MMP-2 and MMP-9) were observed on treatment with synthesized Ag-AXEPS. Similarly, the treatment decreased IL-12, mRNA levels of BAX and plasma fibrosis markers like N-terminal procollagen III propeptide and transforming growth factor-β1. On the other hand, the treatment increased mRNA BCL2 and total antioxidant capacity. It also lowered the level of fibrosis, as was shown by a quantified pathologic study of hematoxylin–eosin-stained lung parts. The treatment, however, ensured that lung collagen was restored, as assessed by Masson’s trichrome stain, and that overall survival was increased and enhanced.

Conclusions

Our work showed that nanoparticles could be obtained at 37°C and may be a possible pulmonary fibrosis therapeutic agent.
Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups
Authors: Mjøen Geir , Maggiore Umberto , Kessaris Nicos , Kimenai Diederik , Watschinger Bruno , Mariat Cristophe , Sever Mehmet Sukru , Crespo Marta , Peruzzi Licia , Spasovski Goce , Sørensen Søren Schwartz , Heemann Uwe , Pascual Julio , Viklicky Ondrej , Courtney Aisling E , Hadaya Karine , Wagner Laszlo , Nistor Ionut , Hadjianastassiou Vassilis , Durlik Magdalena , Helanterä Ilkka , Oberbauer Rainer , Oniscu Gabriel , Hilbrands Luuk , Abramowicz Daniel
Published: February 2021

Background

Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation.

Methods

All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks.

Results

The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes.

Conclusions

The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.
Dietary recommendations for women with gestational diabetes mellitus: a systematic review of clinical practice guidelines
Authors: Mustafa Sara T , Hofer Olivia J , Harding Jane E , Wall Clare R , Crowther Caroline A
Published: February 2021

Context

Dietary advice is the cornerstone of care for women with gestational diabetes mellitus (GDM) to improve maternal and infant health.

Objectives

This study aimed to compare dietary recommendations made in clinical practice guidelines (CPGs) for the management of GDM, evaluate their evidence base, identify research gaps, and assess CPG quality. The PRISMA guidelines were used.

Data Sources

Six databases were searched for CPGs, published between 2000 and 2019, that included dietary advice for the management of GDM.

Data Extraction

Two reviewers independently assessed CPG quality (using the AGREE II tool) with respect to dietary recommendations (their strength, evidence base, and research gaps).

Data Analysis

Of the 31 CPGs, 68% were assessed as low quality, mainly due to lack of editorial independence. Dietary advice was recommended as the first-line treatment by all CPGs, although the dietary recommendations themselves varied and sometimes were contradictory. Most dietary recommendations were strongly made (70%), but they were often based on very low-quality (54%), or low-quality (15%) evidence. Research gaps were identified for all diet-related recommendations.

Conclusion

High-quality research is needed to improve the evidence base and address the research gaps identified.

Systematic Review Registration

PROSPERO registration no. CRD42019147848.
Comparison of Transradial vs Transfemoral Access in Neurovascular Fellowship Training: Overcoming the Learning Curve
Authors: Al Saiegh Fadi , Sweid Ahmad , Chalouhi Nohra , Philipp Lucas , Mouchtouris Nikolaos , Khanna Omaditya , Avery Michael B , Schmidt Richard F , Ghosh Ritam , Hafazalla Karim , Weinberg Joshua H , Starke Robert M , Gooch M Reid , Tjoumakaris Stavropoula , Rosenwasser Robert H , Jabbour Pascal
Published: February 2021

BACKGROUND

The transradial access (TRA) is rapidly gaining popularity for neuroendovascular procedures as there is strong evidence for its benefits compared to the traditional transfemoral access (TFA). However, the transition to TRA bears some challenges including optimization of the interventional suite set-up and workflow as well as its impact on fellowship training.

OBJECTIVE

To compare the learning curves of TFA and TRA for diagnostic cerebral angiograms in neuroendovascular fellowship training.

METHODS

We prospectively collected diagnostic angiogram procedural data on the performance of 2 neuroendovascular fellows with no prior endovascular experience who trained at our institution from July 2018 until June 2019. Metrics for operator proficiency were minutes of fluoroscopy time, procedure time, and volume of contrast used.

RESULTS

A total of 293 diagnostic angiograms were included in the analysis. Of those, 57.7% were TRA and 42.3% were TFA. The median contrast dose was 60 cc, and the median radiation dose was 14 000 μGy. The overall complication rate was 1.4% consisting of 2 groin hematomas, 1 wrist hematoma, and 1 access-site infection using TFA. The crossover rate to TFA was 2.1%. Proficiency was achieved after 60 femoral and 95 radial cases based on fluoroscopy time, 52 femoral and 77 radial cases based on procedure time, and 53 femoral and 64 radial cases based on contrast volume.

CONCLUSION

Our study demonstrates that the use of TRA can be safely incorporated into neuroendovascular training without causing an increase in complications or significantly prolonging procedure time or contrast use.
The Role of Narrative Cues in Shaping ADT
Authors: Tamborini Ron , Grizzard Matthew , Hahn Lindsay , Kryston Kevin , Ulusoy Ezgi
Published: February 2021

In the current chapter, we provide additional specificity to Zillmann’s dispositional model of emotional reactivity to dramatic happenings. By integrating research on altruistic intuitions and egoistic intuitions we advance understandings of the mechanisms that underlie disposition formation processes (i.e., how viewers come to like/dislike narrative characters) and story outcome evaluation processes (i.e., whether viewers like/dislike a narrative’s resolution). We first explain how research on the disposition formation process has been advanced by applying an a priori categorization scheme of altruistic intuitions adapted from moral psychology. This scheme provides a definition of good/bad behavior as behavior that upholds/violates altruistic intuitions. We describe how audiences evaluate those upholding/violating behaviors to form liking/disliking toward narrative characters and highlight how narrative cues can amplify the effect of certain altruistic intuitions in this process. After discussion of disposition formation, we describe how an a priori categorization scheme of egoistic intuitions might similarly advance understanding of the story outcome evaluation process. We provide a more explicit definition of positive and negative story outcomes based on the satisfaction/thwarting of a character’s egoistic intuitions. Several important processes are described in better detail with such a definition, and we outline empirical investigations that could help advance disposition research considerably. We extend this discussion to examine the separate roles of altruistic and egoistic intuition satisfaction in determining audience response to more complex narratives involving conflict between two or more intuitions. The chapter concludes by discussing the potential advantages of integrating altruistic and egoistic intuitions into Zillmann’s dispositional model.
Who Stays and Who Goes: Understanding the Immigration Vote in the 2015 UK General Election
Authors: Maynard Julia
Published: February 2021

How do voters choose between a mainstream party and a populist radical right party (PRRP)? Existing research says that PRRP voters share specific attitudinal characteristics, but many mainstream party voters also have these attitudes. Drawing on spatial theories of party competition, voters make their decision to vote for a mainstream party or a PRRP based on their perceived placement of the mainstream party on immigration. Looking at the case of the 2015 United Kingdom (UK) General Election with the British Election Study Panel Survey, I analyse voters that think immigration is the most important issue facing the UK. These are the voters that prioritise the same issue as UK Independence Party (UKIP). The findings show that those who perceive the Conservative Party will reduce immigration are less likely to vote UKIP than those who perceive the Conservative Party will not reduce immigration. This relationship holds even when the respondent is highly Eurosceptic and anti-immigration.