bluuebunny/crossref_metadata_2025 huggingface dataset:
PrInCE: an R/Bioconductor package for protein–protein interaction network inference from co-fractionation mass spectrometry data
Authors: Skinnider Michael A. , Cai Charley , Stacey R. Greg , Foster Leonard J.
Published: January 2021

We present PrInCE, an R/Bioconductor package that employs a machine-learning approach to infer protein–protein interaction networks from co-fractionation mass spectrometry (CF-MS) data. Previously distributed as a collection of Matlab scripts, our ground-up rewrite of this software package in an open-source language dramatically improves runtime and memory requirements. We describe several new features in the R implementation, including a test for the detection of co-eluting protein complexes and a method for differential network analysis. PrInCE is extensively documented and fully compatible with Bioconductor classes, ensuring it can fit seamlessly into existing proteomics workflows.

Availability and implementation

PrInCE is available from Bioconductor (https://www.bioconductor.org/packages/devel/bioc/html/PrInCE.html). Source code is freely available from GitHub under the MIT license (https://github.com/fosterlab/PrInCE). Support is provided via the GitHub issues tracker (https://github.com/fosterlab/PrInCE/issues).

Supplementary information

Supplementary data are available at Bioinformatics online.
Measurement of 45 cytokine, chemokine and growth factors in established cell culture supernatants and autologous serum from advanced melanoma patients
Authors: Montoyo-Pujol Yoel Genaro , Wang Xu , Bermúdez-Sánchez Sandra , Martin Aurelio , Almazan Francisco , López-Nevot Miguel Ángel
Published: January 2021

Melanoma is one of the most aggressive forms of human cancer and its incidence has significantly increased worldwide over the last decades. This neoplasia has been characterized by the release of a wide variety of soluble factors, which could stimulate tumor cell proliferation and survival in an autocrine and paracrine manner. Consequently, we sought to evaluate the pattern of soluble factors produced by pre-metastatic and metastatic melanoma established cultures, and to determine whether these factors can be detected in the autologous serum of malignant melanoma patients. Our results showed that both melanoma cultures had a common profile of 27 soluble factors mainly characterized by the high expression of VEGF-A, IL-6, MCP-1, IL-8, and SDF-1. In addition, when we compared supernatants, we observed significant differences in VEGF-A, BDNF, FGF-2, and NGF-β concentrations. As we found in melanoma cultures, serum samples also had their specific production pattern composed by 21 soluble factors. Surprisingly, PDGF-BB and EGF were only found in serum, whereas IL-2, IL-4, IL-8, IL31, FGF2, and GRO-α were only expressed in the supernatant. Significant differences in PDGF-BB, MIP-1β, HGF, PIGF-1, BDNF, EGF, Eotaxin, and IP-10 were also found after comparing autologous serum with healthy controls. According to this, no correlation was found between culture supernatants and autologous serum samples, which suggests that some factors may act locally, and others systemically. Nonetheless, after validation of our results in an independent cohort of patients, we concluded that PDGF-BB, VEGF-A, and IP-10 serum levels could be used to monitor different melanoma stages.
A New Application of PARAFAC Model to UPLC Dataset for the Quantitative Resolution of a Tri-Component Drug Mixture
Authors: Güzel Remziye , Ertekin Zehra Ceren , Dinç Erdal
Published: January 2021

In the presented work, a three-way analysis of ultra-performance liquid chromatography-photodiode array (UPLC-PDA) dataset was performed by parallel factor analysis (PARAFAC) for quantitatively resolving a ternary mixture containing paracetamol and methocarbamol with indapamide selected as an internal standard in their co-eluted chromatographic conditions. Paracetamol and methocarbamol were quantified in the working range between 3–24 and 5–50 μg/mL by applying PARAFAC decomposition to UPLC-PDA data array obtained under unresolved chromatographic peak conditions. To compare the experimental results provided by co-eluted UPLC-PARAFAC method, an ordinary UPLC method was developed ensuring proper separation of the peaks. The performance of both PARAFAC and ordinary UPLC methods were assessed by quantifying independent test samples, intra- and inter-day samples and spiked samples of pharmaceutical preparations. Then, both methods were applied for quantitative estimation of the related drugs in a commercial pharmaceutical preparation. In this study, PARAFAC method was proved to be a very powerful alternative for the quality control of pharmaceutical preparations containing paracetamol and methocarbamol even in their co-eluted chromatograms with high precision and accuracy in a short chromatographic runtime of 1.2 min.
Emergence and Transmission of Daptomycin and Vancomycin-Resistant Enterococci Between Patients and Hospital Rooms
Authors: El Haddad Lynn , Hanson Blake M , Arias Cesar A , Ghantoji Shashank S , Harb Cynthia P , Stibich Mark , Chemaly Roy F
Published: January 2021

Background

Vancomycin-resistant enterococci (VRE) are a major cause of morbidity and mortality in immunocompromised patients. Tracking the dissemination of VRE strains is crucial to understand the dynamics of emergence and spread of VRE in the hospital setting.

Methods

Whole genome sequencing (WGS) and phylogenetic analyses were performed to identify dominant VRE strains and potential transmission networks between 35 patients with VRE-positive rectal swabs and their rooms (main rooms and bathrooms) on the leukemia (LKM) and the hematopoietic cell transplant (HCT) floors. Sequence types (STs), drug resistance genes, and patients’ outcomes were also determined.

Results

A total of 89 VRE strains grouped into 10 different STs, of which newly described STs were isolated from both floors (ST736, ST494, ST772, and ST1516). We observed highly genetically related strains transmitted between rooms, floors, and time periods in an average period of 39 days (ranging from 3 to 90 days). Of 5 VRE bacteremia events, 3 strains were lacking the pili operon fms14–17–13 (ST203) and the remaining 2 were resistant to daptomycin (DAP; ST736, ST664). Of 10 patients harboring DAP-resistant strains, only 2 were exposed to DAP within 4 months before strain recovery.

Conclusions

Our comparisons of VRE strains derived from the environment and immunocompromised patients confirmed horizontal transfer of highly related genetic lineages of multidrug-resistant (particularly to DAP) VRE strains between HCT and LKM patients and their room environment. Implementing WGS can be useful in distinguishing VRE reservoirs where interventions can be targeted to prevent and control the spread of highly resistant organisms.
Outcomes after kidney transplantation, let’s focus on the patients’ perspectives
Authors: Wang Yiman , Snoep Jaapjan D , Hemmelder Marc H , van der Bogt Koen E A , Bos Willem Jan W , van der Boog Paul J M , Dekker Friedo W , de Vries Aiko P J , Meuleman Yvette
Published: January 2021

Graft function and patient survival are traditionally the most used parameters to assess the objective benefits of kidney transplantation. Monitoring graft function, along with therapeutic drug concentrations and transplant complications, comprises the essence of outpatient management in kidney transplant recipients (KTRs). However, the patient’s perspective is not always included in this process. Patients’ perspectives on their health after kidney transplantation, albeit subjective, are increasingly acknowledged as valuable healthcare outcomes and should be considered in order to provide patient-centred healthcare. Such outcomes are known as patient-reported outcomes (PROs; e.g. health-related quality of life and symptom burden) and are captured using PRO measures (PROMs). So far, PROMs have not been routinely used in clinical care for KTRs. In this review we will introduce PROMs and their potential application and value in the field of kidney transplantation, describe commonly used PROMs in KTRs and discuss structural PROMs implementation into kidney transplantation care.
Dietary Intake Pattern is Associated with Occurrence of Flares in IBD Patients
Authors: Peters Vera , Spooren Corinne E G M , Pierik Marie J , Weersma Rinse K , van Dullemen Hendrik M , Festen Eleonora A M , Visschedijk Marijn C , Masclee Adriaan A M , Hendrix Evelien M B , Almeida Rui Jorge , Perenboom Corine W M , Feskens Edith J M , Dijkstra Gerard , Campmans-Kuijpers Marjo J E , Jonkers Daisy M A E
Published: January 2021

Background

Diet is associated with the onset of inflammatory bowel disease [IBD]. Up to half of IBD patients believe that diet contributes to flares. However, studies on this topic are sparse and merely focus on specific nutrients, food items or food groups. We aimed to analyse the association between dietary patterns and flare occurrence in two geographically distinct Dutch cohorts.

Methods

In this longitudinal study, 724 IBD patients [Northern cohort: n = 486, Southern cohort: n = 238] were included and followed for 2 years. Habitual dietary intake was obtained via semi-quantitative food frequency questionnaires at baseline. Principal component analysis [PCA] was conducted on 22 food groups to identify dietary patterns. Flare occurrence was analysed in 427 patients in remission at baseline, using multivariable Cox proportional hazards.

Results

Compared to the Southern cohort, patients in the Northern cohort were younger at diagnosis, comprised more females, and had lower overall energy intakes [all p < 0.05]. PCA revealed three dietary patterns explaining 28.8% of the total variance. The most pronounced pattern [explaining 11.6%] was characterized by intake of grain products, oils, potatoes, processed meat, red meat, condiments and sauces, and sugar, cakes and confectionery. Of the 427 patients, 106 [24.8%] developed an exacerbation during follow-up. The above dietary pattern was associated with flare occurrence (hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.04–2.18, p = 0.029), as was female sex [HR: 1.63, 95% CI 1.04–2.55, p = 0.032].

Conclusions

A dietary pattern, which can be seen as a ‘traditional [Dutch]’ or “Western’ pattern was associated with flare occurrence. Confirmation in prospective studies is needed.
Real-world safety and efficacy of direct oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of 605 771 patients
Authors: Menichelli Danilo , Del Sole Francesco , Di Rocco Arianna , Farcomeni Alessio , Vestri Annarita , Violi Francesco , Pignatelli Pasquale , Lip Gregory Y H , Pastori Daniele
Published: January 2021

Aims

To analyse the safety and efficacy of direct oral anticoagulants (DOACs) in real-world studies including atrial fibrillation (AF) patients.

Methods and results

Systematic review and meta-analysis of observational studies including AF patients on DOACs. Primary endpoints: any, major, gastrointestinal (GI), intracranial haemorrhage (ICH), and haemorrhagic stroke (HS). Secondary endpoints: ischaemic stroke (IS), systemic embolism (SE), myocardial infarction (MI), and all-cause of death. A set of pair-wise meta-analyses using a random effect model and a random effect network meta-analysis under a Bayesian framework were performed. Prospero registration number: CRD42019137111. We included 21 studies with 605 771 AF patients. Apixaban was associated with lower major and GI bleeding compared with Rivaroxaban [hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.6–2.5] and Dabigatran (HR 1.6, 95% CI 1.3–2.1). The latter drug performed better than Rivaroxaban (HR 1.2, 95% CI 1.0–1.5). Dabigatran and Apixaban had a similar association with HS, but Apixaban performed better than Rivaroxaban (HR 1.8, 95% CI 1.1–3.0). Apixaban had a similar association with Rivaroxaban and Dabigatran for ICH, the latter drug performing better than Rivaroxaban (HR 1.3, 95% CI 1.0–1.7). Rankograms showed that Apixaban was likely to be the first-choice treatment in relation to any (65%) major (100%) and GI bleeding (100%) followed by Dabigatran (46%, 100%, 99%, respectively). Dabigatran and Apixaban had similar rank as first choice for ICH (44% and 55%) and HS (52% and 48%). DOACs showed similar association with IS/SE, MI, all-cause of death.

Conclusions

Analysis of real-world studies shows significant differences for safety among DOACs.
Treatment of infectious aortic disease with bovine pericardial tube grafts
Authors: Kreibich Maximilian , Siepe Matthias , Berger Tim , Pingpoh Clarence , Puiu Paul , Morlock Julia , Walter Tim , Kondov Stoyan , Beyersdorf Friedhelm , Rylski Bartosz , Czerny Martin
Published: January 2021

OBJECTIVES

Our aim was to evaluate the mid-term outcomes of bovine pericardial tube graft repair for infectious aortic disease in any aortic segment.

METHODS

Between May 2015 and July 2020, 45 patients were treated for infectious aortic disease of the native (n = 9) aorta or after (endo-)graft (n = 36) implantation with bovine pericardial tube grafts. Clinical, infectious details, outcomes and follow-up data were evaluated.

RESULTS

All aortic segments underwent pericardial tube graft or bifurcational replacement: the aortic root (n = 12, 27%), ascending aorta (n = 18, 40%), aortic arch (n = 7, 16%), descending aorta (n = 5, 11%), thoraco-abdominal aorta (n = 6, 13%) and abdominal aorta (n = 18, 40%) including the iliac arteries (n = 14, 31%). Organ fistulation (n = 15, 33%) was the most common underlying pathology. Seven patients (16%) expired in-hospital secondary to ongoing sepsis (n = 5, 11%), respiratory failure (n = 1, 2%) and unknown cause (n = 1, 2%). A fungal infection was predictive for in-hospital mortality (P = 0.026, odds ratio: 19.470). After a median follow-up of 11 [first quartile: 2, third quartile 26] months, 9 additional patients (20%) expired and 1 patient developed a postoperative spondylodiscitis at the level of the aortic tube graft. Hence, freedom from proven aortic graft re-infection was 98%.

CONCLUSIONS

Orthotopic aortic reconstruction using bovine pericardial tube grafts to treat infectious aortic disease is possible in any aortic segment. Organ fistulation is a frequently observed disease mechanism requiring concomitant treatment. Granted, the early attrition rate is substantial, but after the initial period, both survival and freedom from re-infection appear encouraging.
Five-year outcomes of patients supported with HeartMate 3: a single-centre experience
Authors: Schmitto Jan D , Mariani Silvia , Li Tong , Dogan Guenes , Hanke Jasmin S , Bara Christoph , Pya Yuriy , Zimpfer Daniel , Krabatsch Thomas , Garbade Jens , Rao Vivek , Morshuis Michiel , Beyersdorf Friedhelm , Marasco Silvana , Netuka Ivan , Bauersachs Johann , Haverich Axel
Published: January 2021

OBJECTIVES

The HeartMate 3 left ventricular assist device was first implanted in 2014 and received the Conformité Européenne mark in 2015. Since then, several trials demonstrated its high haemocompatibility associated with good survival and low adverse events rates. Herein, we report our institutional experience with patients supported with HeartMate 3 for 5 years.

METHODS

This prospective cohort study included patients receiving a HeartMate 3 implantation in 2014 as part of the HeartMate 3 Conformité Européenne Mark clinical trial. Patients had follow-up visits every 3 months while on left ventricular assist device support, and all patients completed the 5-year follow-up. The primary end point was survival at 5 years. Secondary end points included adverse events, health status and quality of life.

RESULTS

Eight patients (men: 75%) aged 59 years (min–max: 52–66 years) were enrolled. At 5 years, survival was 100%. Patients remained on support for a median time of 1825 days (min–max: 101–1825 days); 2 patients successfully received cardiac transplants. No right heart failure, haemolysis, pump thrombosis, pump malfunction or neurological events occurred in any patients. A driveline infection was observed in 6 patients (0.25 events/patient-year). Compared to baseline, a significant improvement in quality of life and in New York Heart Association functional class was noted after the implant and for the whole follow-up time. A slight decline in kidney function and in the 6-min walk test results occurred after 3 years.

CONCLUSIONS

This study reports the longest single-centre follow-up of the HeartMate 3, showing excellent haemocompatibility over time with high survival and low complication rates at 5 years.
Does family farming reduce rural unemployment?
Authors: Wuepper David , Wimmer Stefan , Sauer Johannes
Published: January 2021

This article investigates the causal relationship between family farming and rural labour markets. To this end, we combine farm accountancy data and public labour market statistics at the district level (NUTS-3) for the years 2008–2013. While cross-sectional regressions reveal a strong and robust negative correlation between the share of family farm labour and unemployment rate in a region, fixed-effects panel data regressions suggest this is not causal. Instead, we find evidence that cultural differences in work ethic spuriously connect family farming with unemployment. Thus, supporting family farming to fight rural unemployment is not an effective strategy in Germany.
Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials
Authors: Ibrahim Omar A , Belley-Côté Emilie P , Um Kevin J , Baranchuk Adrian , Benz Alexander P , Dalmia Shreyash , Wang Chang N , Alhazzani Waleed , Conen David , Devereaux P J , Whitlock Richard P , Healey Jeff S , McIntyre William F
Published: January 2021

Aims

Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain.

Methods

We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration.

Results

From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4–14.0], propafenone (70%, OR 4.6, CrI 2.9–7.3), and pilsicainide (59%, OR 10.0, CrI 1.8–69.0), but not amiodarone (28%, OR 1.0, CrI 0.4–2.8) were superior. Flecainide (OR 7.5, CrI 2.6–24.0) and propafenone (OR 4.5, CrI 1.6–13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3–1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2–41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19–3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092–1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1–4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs.

Conclusion

Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.
Antibiotic eluting envelopes: evidence, technology, and defining high-risk populations
Authors: Callahan Thomas D , Tarakji Khaldoun G , Wilkoff Bruce L
Published: January 2021

Cardiovascular implantable electronic devices (CIED) are effective and important components of modern cardiovascular care. Despite the dramatic improvements in the functionality and reliability of these devices, over time patients are at risk for developing several morbidities, the most feared of which are local and systemic infections. Despite significant financial investment and aggressive therapy with hospitalization, intravenous antibiotics, and transvenous lead extraction, the outcomes include a 1-year mortality rate as high as 25%. This risk of infection has increased over time, likely due to the increased complexity of the surgical interventions required to insert and replace these devices. The only way to reduce this morbidity and mortality is to prevent these infections, and other than preoperative antibiotics, there were little data supporting effective therapy until the WRAP-IT trial provided randomized data showing that pocket infections can be reduced by 60% at 12 months and major CIED infections reduced by 40% at 1 year with the use of the absorbable antibiotic eluting envelope in patient CIED procedures at high risk of infection. Not all CIED procedures are at high risk of infection and justify the use of the envelope, but cost-effectiveness data support the use of the antibiotic envelope particularly in patients with defibrillator replacements, revisions, and upgrades, such as to a resynchronization device and in patients with prior CIED infection, history of immunocompromise, two or more prior procedures, or a history of renal dysfunction.
Transcriptomic analysis of Sur7-mediated response ofBeauveria bassianato different nutritional conditions
Authors: Zhang Long-Bin , Qiu Ting-Ting , Huang Zhi-Hong , Ye Xiu-Yun , Guan Yi
Published: January 2021

Integrity of the cell wall is requisite for fungal growth and function. Sur7 governs cell wall composition, and affects conidial sporulation and germination in Beauveria bassiana, a filamentous entomopathogenic fungus. The role of Sur7 in fungal growth on various nutrients remains unclear. We have previously reported that Sur7 deletion results in the attenuation of B. bassiana growth on supplemented Sabouraud dextrose agar (SDAY) and minimal Czapek–Dox agar (CDA) compared to wild type (WT). Here, we used transcriptomic analysis to compare WT and Sur7 mutant (ΔSur7) responses to CDA and SDAY. Growth on CDA, compared with that on SDAY, affected the expression of more genes in the WT than in the mutant. Differentially expressed genes were enriched for transportation process terms in the ΔSur7 mutant and metabolic process terms in the WT. Different processes were repressed in the ΔSur7 (metabolic process) and WT (ribosome synthesis) cells. Despite the shared enrichment of nitrogen metabolism genes, differentially expressed genes were enriched in distinct saccharide-energy metabolism terms in each strain. We conclude that Sur7 ensures the growth of B. bassiana in a minimal medium by influencing the expression of genes involved in the consumption of sucrose via specific energy metabolism pathways.
Biotin, a universal and essential cofactor: synthesis, ligation and regulation
Authors: Sirithanakorn Chaiyos , Cronan John E
Published: January 2021

Biotin is a covalently attached enzyme cofactor required for intermediary metabolism in all three domains of life. Several important human pathogens (e.g. Mycobacterium tuberculosis) require biotin synthesis for pathogenesis. Humans lack a biotin synthetic pathway hence bacterial biotin synthesis is a prime target for new therapeutic agents. The biotin synthetic pathway is readily divided into early and late segments. Although pimelate, a 7-carbon α,ω-dicarboxylic acid that contributes 7 of the 10 biotin carbons atoms, was long known to be a biotin precursor, its biosynthetic pathway was a mystery until the Escherichia colipathway was discovered in 2010. Since then, diverse bacteria encode evolutionarily distinct enzymes that replace enzymes in the E. coli pathway. Two new bacterial pimelate synthesis pathways have been elucidated. In contrast to the early pathway, the late pathway, assembly of the fused rings of the cofactor, was long thought settled. However, a new enzyme that bypasses a canonical enzyme was recently discovered as well as homologs of another canonical enzyme that functions in synthesis of another protein-bound coenzyme, lipoic acid. Most bacteria tightly regulate transcription of the biotin synthetic genes in a biotin-responsive manner. The bifunctional biotin ligases which catalyze attachment of biotin to its cognate enzymes and repress biotin gene transcription are best understood regulatory system.
Estimation of Cry3Bb1 resistance allele frequency in field populations of western corn rootworm using a genetic marker
Authors: Willse Alan , Flagel Lex , Head Graham
Published: January 2021

Following the discovery of western corn rootworm (WCR; Diabrotica virgifera virgifera) populations resistant to the Bacillus thuringiensis (Bt) protein Cry3Bb1, resistance was genetically mapped to a single locus on WCR chromosome 8 and linked SNP markers were shown to correlate with the frequency of resistance among field-collected populations from the US Corn Belt. The purpose of this paper is to further investigate the relationship between one of these resistance-linked markers and the causal resistance locus. Using data from laboratory bioassays and field experiments, we show that one allele of the resistance-linked marker increased in frequency in response to selection, but was not perfectly linked to the causal resistance allele. By coupling the response to selection data with a genetic model of the linkage between the marker and the causal allele, we developed a model that allowed marker allele frequencies to be mapped to causal allele frequencies. We then used this model to estimate the resistance allele frequency distribution in the US Corn Belt based on collections from 40 populations. These estimates suggest that chromosome 8 Cry3Bb1 resistance allele frequency was generally low (<10%) for 65% of the landscape, though an estimated 13% of landscape has relatively high (>25%) resistance allele frequency.
The genetic analysis of distributive segregation in Drosophila melanogaster. I. Isolation and characterization of Aberrant X segregation (Axs), a mutation defective in chromosome partner choice.
Authors: Zitron A E , Hawley R S
Published: January 2021

We describe the isolation and characterization of Aberrant X segregation (Axs), a dominant female-specific meiotic mutation. Although Axs has little or no effect on the frequency or distribution of exchange, or on the disjunction of exchange bivalents, nonexchange X chromosomes undergo nondisjunction at high frequencies in Axs/+ and Axs/Axs females. This increased X chromosome nondisjunction is shown to be a consequence of an Axs-induced defect in distributive segregation. In Axs-bearing females, fourth chromosome nondisjunction is observed only in the presence of nonexchange X chromosomes and is argued to be the result of improper X and fourth chromosome associations within the distributive system. In XX females bearing a compound fourth chromosome, the frequency of nonhomologous disjunction of the X chromosomes from the compound fourth chromosome is shown to account for at least 80% of the total X nondisjunction observed. In addition, Axs diminishes or ablates the capacity of nonexchange X chromosomes to form trivalents in females bearing either a Y chromosome or a small free duplication for the X. Axs also impairs compound X from Y segregation. The effect of Axs on these segregations parallels the defects observed for homologous nonexchange X chromosome disjunction in Axs females. In addition to its dramatic effects on the X chromosome, Axs exerts a similar effect on the segregation of a major autosome. We conclude that Axs defines a locus required for proper homolog disjunction within the distributive system.
A new kind of informational suppression in the nematode Caenorhabditis elegans.
Authors: Hodgkin J , Papp A , Pulak R , Ambros V , Anderson P
Published: January 2021

Independent reversions of mutations affecting three different Caenorhabditis elegans genes have each yielded representatives of the same set of extragenic suppressors. Mutations at any one of six loci act as allele-specific recessive suppressors of certain allels of unc-54 (a myosin heavy chain gene), lin-29 (a heterochronic gene), and tra-2 (a sex determination gene). The same mutations also suppress certain alleles of another sex determination gene, tra-1, and of a morphogenetic gene, dpy-5. In addition to their suppression phenotype, the suppressor mutations cause abnormal morphogenesis of the male bursa and the hermaphrodite vulva. We name these genes smg-1 through smg-6 (suppressor with morphogenetic effect on genitalia), in order to distinguish them from mab (male abnormal) genes that can mutate to produce abnormal genitalia but which do not act as suppressors (smg-1 and smg-2 are new names for two previously described genes, mab-1 and mab-11). The patterns of suppression, and the interactions between the different smg genes, are described and discussed. In general, suppression is recessive and incomplete, and at least some of the suppressed mutations are hypomorphic in nature. A suppressible allele of unc-54 contains a deletion in the 3' noncoding region of the gene; the protein coding region of the gene is apparently unaffected. This suggests that the smg suppressors affect a process other than translation, for example mRNA processing, transport, or stability.
Genetic analysis of olfactory behavior in Drosophila: a new screen yields the ota mutants.
Authors: Woodard C , Huang T , Sun H , Helfand S L , Carlson J
Published: January 2021

A simple means of measuring Drosophila olfactory response is described, and the behavior which it measures is characterized. The assay was used to screen for X-linked mutants defective in olfactory function. Six ota mutants were isolated and characterized (ota = olfactory trap abnormal). Four of the mutants were found to be abnormal in another chemosensory behavior as well. Two of the mutant phenotypes extend to include another sensory system: they are defective in visual system physiology. All were normal, however, in a test of giant fiber system physiology. Two of the mutations are dominant, and the recessive mutations define two complementation groups. Mutations representing each complementation group, as well as one of the dominant mutations, were mapped. For the mutants with defective visual system physiology, the visual defects were shown to cosegregate with olfactory phenotypes.
The subtelomeric Y' repeat family in Saccharomyces cerevisiae: an experimental system for repeated sequence evolution.
Authors: Louis E J , Haber J E
Published: January 2021

The subtelomeric Y' repeated sequence families in two divergent strains of the yeast Saccharomyces cerevisiae have been characterized in terms of copy number, location and restriction site differences. The strain YP1 has 26 to 30 Y's that fall into two previously described, long (6.7 kb) and short (5.2 kb), size classes. These Y's reside at 19 of the 32 chromosome ends and are concentrated in the higher molecular weight chromosomes. Five ends contain tandem arrays, each of which has only one size class of Y's. There is restriction site homogeneity among the Y's of YP1 even between size classes. The Y's of strain Y55 contrast sharply with the Y's of YP1 in terms of copy number, location and sequence differences. There are 14 to 16 Y's, both long and short, most of which are found at different chromosome ends than those of YP1. None of these are tandemly arrayed. Four to six of the Y's appear degenerate in that they have homology with a telomere distal end Y' probe but no homology with sequences at the telomere proximal end. The majority of the Y55 Y's have the same restriction sites as in YP1. Despite the conservation of restriction sites among Y's, a great deal of restriction fragment length heterogeneity between the strains is observed. The characterized Y' repeated sequence families provide an experimental system in which repeated sequence interactions and subsequent evolution can be studied.
Increased selection response in larger populations. II. Selection for ethanol vapor resistance in Drosophila melanogaster at two population sizes.
Authors: Weber K E , Diggins L T
Published: January 2021

The effect of large population size on selection response was investigated using Drosophila melanogaster, with four "small" lines of 160 selected parents/generation compared to two "large" lines of 1,600 selected parents/generation. All lines were selected under similar conditions at a selection intensity of approximately 0.55 standard deviations, for 65 generations, for increased ethanol vapor resistance (measured in minutes required to become anesthetized). Two unselected control lines of 320 parents/generation were also maintained. A significant effect of population size was found. The final treatment means and standard errors were: 27.91 +/- 1.28 min (two "large" lines); 19.40 +/- 1.54 min (four "small" lines); and 4.98 +/- 0.35 min (two control lines). To estimate the mutation rate for the trait, two isogenic lines of about 400 selected parents were selected for 29 generations. The mean increase in additive genetic variance per generation was 0.0009 times the initial environmental variance of the outbred lines. This is comparable to other reported mutation rates. Mutation can explain part of the difference in evolved resistance between treatments, but it appears that even at rather large population sizes, a large difference in long-term response can be obtained in larger outbred lines, from more complete utilization of the initial genetic variation.
Isolation and characterization of PEP5, a gene essential for vacuolar biogenesis in Saccharomyces cerevisiae.
Authors: Woolford C A , Dixon C K , Manolson M F , Wright R , Jones E W
Published: January 2021

pep5 mutants of Saccharomyces cerevisiae accumulate inactive precursors to the vacuolar hydrolases. The PEP5 gene was isolated from a genomic DNA library by complementation of the pep5-8 mutation. Deletion analysis localized the complementing activity to a 3.3-kb DNA fragment. DNA sequence analysis of the PEP5 gene revealed an open reading frame of 1029 codons with a calculated molecular mass for the encoded protein of 117,403 D. Deletion/disruption of the PEP5 gene did not kill the cells. The resulting strains grow very slowly at 37 degrees. The disruption mutant showed greatly decreased activities of all vacuolar hydrolases examined, including PrA, PrB, CpY, and the repressible alkaline phosphatase. Apparently normal precursors forms of the proteases accumulated in pep5 mutants, as did novel forms of PrB antigen. Antibodies raised to a fusion protein that contained almost half of the PEP5 open reading frame allowed detection by immunoblot of a protein of relative molecular mass 107 kD in extracts prepared from wild-type cells. Cell fractionation showed the PEP5 gene product is enriched in the vacuolar fraction and appears to be a peripheral vacuolar membrane protein.
Molecular characterization of a catalase null allele at the Cat3 locus in maize.
Authors: Wadsworth G J , Scandalios J G
Published: January 2021

Previous analysis has identified line IDS28 of maize (Zea mays L.) as being homozygous for a Catalase-3 (Cat3) null allele. Catalase-3 (CAT-3) protein-specific antibodies could not detect CAT-3 in extracts of several tissues of IDS28, which in a typical maize line possess CAT-3. The absence of CAT-3 resulted in a significant decrease in total catalase activity in those tissues where CAT-3 is the predominant catalase isozyme. RNA blot analysis indicated that IDS28 does not accumulate Cat3 transcript in any tissues. Genomic DNA blots revealed significant structural alterations in the Cat3 gene in IDS28. The results suggest that the molecular basis for Cat3 null phenotype in IDS28 may be a deletion in the 5' end of the Cat3 gene.
DNA sequence evolution of the amylase multigene family in Drosophila pseudoobscura.
Authors: Brown C J , Aquadro C F , Anderson W W
Published: January 2021

The alpha-Amylase locus in Drosophila pseudoobscura is a multigene family of one, two or three copies on the third chromosome. The nucleotide sequences of the three Amylase genes from a single chromosome of D. pseudoobscura are presented. The three Amylase genes differ at about 0.5% of their nucleotides. Each gene has a putative intron of 71 (Amy1) or 81 (Amy2 and Amy3) bp. In contrast, Drosophila melanogaster Amylase genes do not have an intron. The functional Amy1 gene of D. pseudoobscura differs from the Amy-p1 gene of D. melanogaster at an estimated 13.3% of the 1482 nucleotides in the coding region. The estimated rate of synonymous substitutions is 0.398 +/- 0.043, and the estimated rate of nonsynonymous substitutions is 0.068 +/- 0.008. From the sequence data we infer that Amy2 and Amy3 are more closely related to each other than either is to Amy1. From the pattern of nucleotide substitutions we reason that there is selection against synonymous substitutions within the Amy1 sequence; that there is selection against nonsynonymous substitutions within the Amy2 sequence, or that Amy2 has recently undergone a gene conversion with Amy1; and that Amy3 is nonfunctional and subject to random genetic drift.
Major effects on teratogen-induced facial clefting in mice determined by a single genetic region.
Authors: Karolyi J , Erickson R P , Liu S , Killewald L
Published: January 2021

A major correlation has been found between the incidence of glucocorticoid-induced cleft palate and the chromosome 8 segment identified by N-acetyl transferase in mice. The resistant strain became fully susceptible while the susceptible strain became resistant when this chromosomal region, representing less than 0.7% of the genome, was transferred from one strain to the other by the construction of congenic strains. 6-Aminonicotinamide-induced cleft palate and phenytoin-induced cleft lip with or without cleft palate are also influenced by this genetic region but not as strongly. In both cases the susceptible strain became quite resistant to the teratogen-induced clefting when the N-acetyl transferase region of chromosome 8 was transferred. However, this chromosomal region does not make the resistant strain susceptible to these two teratogens.
Selection on wing allometry in Drosophila melanogaster.
Authors: Weber K E
Published: January 2021

Five bivariate distributions of wing dimensions of Drosophila melanogaster were measured, in flies 1) subjected to four defined environmental regimes during development, 2) taken directly from nature in seven U.S. states, 3) selected in ten populations for change in wing form, and 4) sampled from 21 long inbred wild-type lines. Environmental stresses during development altered both wing size and the ratios of wing dimensions, but regardless of treatment all wing dimensions fell near a common allometric baseline in each bivariate distribution. The wings of wild-caught flies from seven widely separated localities, and of their laboratory-reared offspring, also fell along the same baselines. However, when flies were selected divergently for lateral offset from these developmental baselines, response to selection was rapid in every case. The mean divergence in offset between oppositely selected lines was 14.68 SD of the base population offset, after only 15 generations of selection at 20%. Measurements of 21 isofemale lines, founded from wild-caught flies and maintained in small populations for at least 22 years, showed large reductions in phenotypic variance of offsets within lines, but a large increase in the variance among lines. The variance of means of isofemale lines within collection localities was ten times the variance of means among localities of newly established wild lines. These observations show that much additive genetic variance exists for individual dimensions within the wing, such that bivariate developmental patterns can be changed in any direction by selection or by drift. The relative invariance of the allometric baselines of wing morphology in nature is most easily explained as the result of continuous natural selection around a local optimum of functional design.
Studies on the rate and site-specificity of P element transposition.
Authors: Berg C A , Spradling A C
Published: January 2021

A single genetically marked P element can be efficiently mobilized to insertionally mutagenize the Drosophila genome. We have investigated how the structure of the starting element and its location along the X chromosome influenced the rate and location of mutations recovered. The structure of two P[rosy+] elements strongly affected mobilization by the autonomous "Jumpstarter-1" element. Their average transposition rates differed more than 12-fold, while their initial chromosomal location had a smaller effect. The lethal and sterile mutations induced by mobilizing a P[rosy+] element from position 1F were compared with those identified previously using a P[neoR] element at position 9C. With one possible exception, insertion hotspots for one element were frequently also targets of the other transposon. These experiments suggested that the genomic location of a P element does not usually influence its target sites on nonhomologous chromosomes. During the course of these experiments, Y-linked insertions expressing rosy+ were recovered, suggesting that marked P elements can sometimes insert and function at heterochromatic sites.
Quantitative genetics of postponed aging in Drosophila melanogaster. I. Analysis of outbred populations.
Authors: Hutchinson E W , Rose M R
Published: January 2021

Selection has been used to create replicated outbred stocks of Drosophila melanogaster with increased longevity, increased later fecundity, and increased levels of physiological performance at later ages. The present study analyzed the quantitative transmission patterns of such stocks, employing extensive replication in numbers of stocks, individuals, and assayed characters. The populations used derived from five lines with postponed aging and five control lines, all created in 1980 from the same founding base population. The following characters were studied: early 24-hr fecundity, early ovary weight, early female starvation resistance, early male starvation resistance, female longevity and male longevity. Numerous crosses were performed to test for non-Mendelian inheritance, average dominance, maternal effects, sex-linkage and between-line heterogeneity. There was only slight evidence for any of these phenomena arising reproducibly in the characters studied. These findings suggest the value of this set of stocks for studies of the physiological basis of postponed aging.
Second-site suppressors of a cold-sensitive prohead accessory protein of bacteriophage phi X174.
Authors: Fane B A , Hayashi M
Published: January 2021

This study describes the isolation of second-site suppressors which correct for the defects associated with cold-sensitive (cs) prohead accessory proteins of bacteriophage phi X174. Five phenotypically different suppressors were isolated. Three of these suppressors confer novel temperature-sensitive (ts) phenotypes. They were unable to complement a ts mutation in gene F which encodes the major coat protein of the phage. All five suppressor mutations confer nucleotide changes in the gene F DNA sequence. These changes define four amino acid sites in the gene F protein. Three suppressor mutations placed into an otherwise wild-type background display a cold resistant phenotype in liquid culture infections when compared to a wild-type phi X174 control.
Causes of sex ratio bias may account for unisexual sterility in hybrids: a new explanation of Haldane's rule and related phenomena.
Authors: Hurst L D , Pomiankowski A
Published: January 2021

Unisexual hybrid disruption can be accounted for by interactions between sex ratio distorters which have diverged in the species of the hybrid cross. One class of unisexual hybrid disruption is described by Haldane's rule, namely that the sex which is absent, inviable or sterile is the heterogametic sex. This effect is mainly due to incompatibility between X and Y chromosomes. We propose that this incompatibility is due to a mutual imbalance between meiotic drive genes, which are more likely to evolve on sex chromosomes than autosomes. The incidences of taxa with sex chromosome drive closely matches those where Haldane's rule applies: Aves, Mammalia, Lepidoptera and Diptera. We predict that Haldane's rule is not universal but is correct for taxa with sex chromosome meiotic drive. A second class of hybrid disruption affects the male of the species regardless of which sex is heterogametic. Typically the genes responsible for this form of disruption are cytoplasmic. These instances are accounted for by the release from suppression of cytoplasmic sex ratio distorters when in a novel nuclear cytotype. Due to the exclusively maternal transmission of cytoplasm, cytoplasmic sex ratio distorters cause only female-biased sex ratios. This asymmetry explains why hybrid disruption is limited to the male.
Associations between DNA sequence variation and variation in expression of the Adh gene in natural populations of Drosophila melanogaster.
Authors: Laurie C C , Bridgham J T , Choudhary M
Published: January 2021

A large part of the genetic variation in alcohol dehydrogenase (ADH) activity level in natural populations of Drosophila melanogaster is associated with segregation of an amino acid replacement polymorphism at nucleotide 1490, which generates a difference in electrophoretic mobility. Part of the allozymic difference in activity level is due to a catalytic efficiency difference, which is also caused by the amino acid replacement, and part is due to a difference in the concentration of ADH protein. A previous site-directed in vitro mutagenesis experiment clearly demonstrated that the amino acid replacement has no effect on the concentration of ADH protein, nor does a strongly associated silent polymorphism at nucleotide 1443. Here we analyze associations between polymorphisms within the Adh gene and variation in ADH protein level for a number of chromosomes derived from natural populations. A sequence length polymorphism within the first intron of the distal (adult) transcript, 1, is in strong linkage disequilibrium with the amino acid replacement. Among a sample of 46 isochromosomal lines analyzed, all but one of the 14 Fast lines have 1 and all but one of the 32 Slow lines lack 1. The exceptional Fast line has an unusually low level of ADH protein (typical of Slow lines) and the exceptional Slow line has an unusually high level (typical of Fast lines). These results suggest that the 1 polymorphism may be responsible for the average difference in ADH protein between the allozymic classes. A previous experiment localized the effect on ADH protein to a 2.3-kb restriction fragment. DNA sequences of this fragment from several alleles of each allozymic type indicate that no other polymorphisms within this region are as closely associated with the ADH protein level difference as the 1 polymorphism.