Long-term exhaustion of the inbreeding load in Drosophila melanogaster

Inbreeding depression, the decline in fitness of inbred individuals, is a ubiquitous phenomenon of great relevance in evolutionary biology and in the fields of animal and plant breeding and conservation. Inbreeding depression is due to the expression of recessive deleterious alleles that are concealed in heterozygous state in noninbred individuals, the so-called inbreeding load. Genetic purging reduces inbreeding depression by removing these alleles when expressed in homozygosis due to inbreeding. It is generally thought that fast inbreeding (such as that generated by full-sib mating lines) removes only highly deleterious recessive alleles, while slow inbreeding can also remove mildly deleterious ones. However, a question remains regarding which proportion of the inbreeding load can be removed by purging under slow inbreeding in moderately large populations. We report results of two long-term slow inbreeding Drosophila experiments (125–234 generations), each using a large population and a number of derived lines with effective sizes about 1000 and 50, respectively. The inbreeding load was virtually exhausted after more than one hundred generations in large populations and between a few tens and over one hundred generations in the lines. This result is not expected from genetic drift alone, and is in agreement with the theoretical purging predictions. Computer simulations suggest that these results are consistent with a model of relatively few deleterious mutations of large homozygous effects and partially recessive gene actionAgencia Estatal de Investigación (AEI) | Ref. PGC2018-095810-B-I00Agencia Estatal de Investigación (AEI) | Ref. PID2020-114426GB-C21Xunta de Galicia | Ref. ED431C 2020-0

Caracterización de huertos urbanos y periurbanos de Xalapa de Enríquez, Veracruz

La necesidad de adquirir alimentos de forma adecuada y sana ha llevado a buscar y fortalecer alternativas para su producción; en las ciudades se practica la agricultura urbana y periurbana (AUyP) y Xalapa, Veracruz, México, es un ejemplo de ello. Desde el año 2013 se autogestiono la Red de Agricultura Urbana y Periurbana de Xalapa (RAUPX), en la cual se centró el objetivo de la presente investigación, que consistió en caracterizar los huertos de la RAUPX, en función de las variables: tamaño de huerto, diversidad (índice de Shannon), presencia de artropofauna y prácticas de manejo fitosanitarias; con el fin de diagnosticar y aportar propuestas para mejorar el manejo integrado de plagas. Los resultados incluyen datos generales productor-huerto tales como rango de edad, nivel de estudios, superficie, familias botánicas representativas, presencia de artropofauna en relación con las especies cultivadas y manejo de prácticas fitosanitarias de acuerdo con su complejidad. Las prácticas fitosanitarias que realizan los productores son de forma correctiva en vez de preventiva y están moderadamente relacionadas con la presencia de plagas

Synaptotagmins at the endoplasmic reticulum-plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress

Endoplasmic Reticulum-Plasma Membrane contact sites (ER-PM CS) play fundamental roles in all eukaryotic cells. Arabidopsis mutants lacking the ER-PM protein tether synaptotagmin1 (SYT1) exhibit decreased plasma membrane (PM) integrity under multiple abiotic stresses such as freezing, high salt, osmotic stress and mechanical damage. Here, we show that, together with SYT1, the stress-induced SYT3 is an ER-PM tether that also functions in maintaining PM integrity. The ER-PM CS localization of SYT1 and SYT3 is dependent on PM phosphatidylinositol-4-phosphate and is regulated by abiotic stress. Lipidomic analysis revealed that cold stress increased the accumulation of diacylglycerol at the PM in a syt1/3 double mutant relative to WT while the levels of most glycerolipid species remain unchanged. Additionally, SYT1-GFP preferentially binds diacylglycerol in vivo with little affinity for polar glycerolipids. Our work uncovers a SYT-dependent mechanism of stress adaptation counteracting the detrimental accumulation of diacylglycerol at the PM produced during episodes of abiotic stress

Markers of endothelial damage in patients with chronic kidney disease on hemodialysis

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.Support for this work was provided by Plan Nacional de IDi Proyectos de Investigación en Salud of Instituto de Salud Carlos III (ISCIII)–Subdirección General de Evaluación, Fondos de desarrollo regional (FEDER; PI11/01536, PI12/01489, PI14/00806, PI15/01785); Junta de Andalucía grants (P010-CTS-6337, P11-CTS-7352); and Fundación Nefrológica. P. Buendía, A. Carmona, and C. Luna-Ruiz are fellows from Consejería de Innovacion, Ciencia y Empresa, Junta de Andalucía

A Randomized Comparison of Drug-Eluting Balloon Versus Everolimus-Eluting Stent in Patients With Bare-Metal Stent–In-Stent Restenosis The RIBS V Clinical Trial (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-eluting Balloon vs. Everolimus-eluting Stent)

ObjectivesThis study sought to compare the efficacy of drug-eluting balloons (DEB) with that of everolimus-eluting stents (EES) in patients with bare-metal stents (BMS) in-stent restenosis (ISR).BackgroundTreatment of patients with ISR remains a challenge.MethodsThis was a prospective, multicenter, randomized trial comparing DEB with EES in patients with bare-metal stents (BMS) in-stent restenosis (ISR). The primary endpoint was the minimal lumen diameter at 9 months' follow-up.ResultsA total of 189 patients with BMS-ISR from 25 Spanish sites were included (95 were allocated to DEB and 94 to EES). Procedural success was achieved in all patients. At late angiography (median 249 days; 92% of eligible patients), patients in the EES arm had a significantly larger minimal lumen diameter (2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm, p < 0.001; absolute mean difference: 0.35 mm; 95% confidence interval [CI]: 0.16 to 0.53) and a lower percent of diameter stenosis (13 ± 17% vs. 25 ± 20%, p < 0.001). However, late loss (0.04 ± 0.5 mm vs. 0.14 ± 0.5 mm, p = 0.14) and binary restenosis rate (4.7% vs. 9.5%, p = 0.22) were very low and similar in both groups. Clinical follow-up (median 365 days) was obtained in all (100%) patients. Occurrences of the combined clinical outcome measure (cardiac death, myocardial infarction, and target vessel revascularization; 6% vs. 8%; hazard ratio [HR]: 0.76; 95% CI: 0.26 to 2.18, p = 0.6) and the need for target vessel revascularization (2% vs. 6%; HR: 0.32: 95% CI: 0.07 to 1.59, p = 0.17) were similar in the 2 groups.ConclusionsIn patients with BMS-ISR, both DEB and EES provided excellent clinical results with a very low rate of clinical and angiographic recurrences. However, compared with DEB, EES provide superior late angiographic findings. (Restenosis Intra-stent of Bare Metal Stents: Paclitaxel-eluting Balloon vs. Everolimus-eluting Stent [RIBS V]; NCT01239953

Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations With Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study

Background: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS. Methods: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization. Results: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was & GE;6 mm(2) in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45). Conclusions: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events

Rationale and design of the Concordance study between FFR and iFR for the assessment of lesions in the left main coronary artery. The ILITRO-EPIC-07 Trial

Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR 0.80/iFR 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm(2). The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients

Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster

Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we report the results of two independent inbreeding experiments carried out with two different populations of Drosophila melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but also among segregating alleles in natural populationsWe acknowledge the support by Uvigo Marine Research Centre funded by the “Excellence in Research (INUGA)” Programme from the Regional Council of Culture, Education and Universities, with co-funding from the European Union through the ERDF Operational Programme Galicia 2014-2020. This work was funded by Agencia Estatal de Investigación (AEI) (CGL2016-75904-C2-1-P), Xunta de Galicia (ED431C 2016-037) and Fondos Feder: “Unha maneira de facer Europa.” SD was founded by a predoctoral (FPI) grant from Ministerio de Economía y Competitividad, SpainS

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America : the ESTAMPA screening study protocol

Q1Q1Introduction Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. Methods and analysis Women aged 30–64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT01881659Revista Internacional - Indexad