Structure and comparative analysis of the mitochondrial genomes of Liolaemus lizards with different modes of reproduction and ploidy levels

Liolaemus is the most specious genus of the Squamata lizards in South America, presenting exceptional evolutionary radiation and speciation patterns. This recent diversification complicates the formal taxonomic treatment and the phylogenetic analyses of this group, causing relationships among species to remain controversial. Here we used Next-Generation Sequencing to do a comparative analysis of the structure and organization of the complete mitochondrial genomes of three differently related species of Liolaemus and with different reproductive strategies and ploidy levels. The annotated mitochondrial genomes of ca. 17 kb are the first for the Liolaemidae family. Despite the high levels of sequence similarity among the three mitochondrial genomes over most of their lengths, the comparative analyses revealed variations at the stop codons of the protein coding genes and the structure of the tRNAs among species. The presence of a non-canonical dihydrouridine loop is a novelty for the pleurodonts iguanians. But the highest level of variability was observed in two repetitive sequences of the control region, which were responsible for most of the length heterogeneity of the mitochondrial genomes. These tandem repeats may be useful markers to analyze relationships of closely related species of Liolaemus and related genera and to conduct population and phylogenetic studies.Fil: Valdes, José Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Samoluk, Sergio Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Abdala, Cristian Simón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Baldo, Juan Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Seijo, José Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentin

High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS) that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes

High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS) that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes

Niveles de proteina C reactiva ultrasensible pre y post tratamiento periodontal ni quirurgico en pacientes con periodontitis cronica.

57 p.Introducción: La existencia de una relación entre las enfermedades cardiovasculares y la patologías orales ha sido de gran interés en los últimos años. Este interés, probablemente esté muy motivado por la alta prevalencia de ambas patologías, que las convierte, sin lugar a dudas, en uno de los principales problemas de salud pública a nivel mundial. Gracias al avance en la biología molecular se ha podido identificar diferentes moléculas en pacientes periodontales que producen diferentes alteraciones a distancia como lo es la Proteína C Reactiva. La PCR es un marcador altamente específico y preciso en la detección de procesos inflamatorios e infecciosos, produciéndose un aumento en los niveles plasmáticos de esta, además de ser de uso clínico corriente, a esta molécula proteica se le reconocen efectos proinflamatorios y esta catalogado como factor de riesgo cardiovascular por la Asociación Americana del Corazón. Esta claro en la literatura que la enfermedad periodontal(EP) puede ser la responsable de estos aumentos, lo que no esta claro es si la terapia periodontal no quirúrgica pueda reestablecer valores normales de PCR. Objetivos: (1)Determinar, mediante el Test Tina-quant® los niveles de HS-PCR (Proteína C Ultrasensible) pre y post terapia periodontal no quirúrgica, en pacientes con periodontitis crónica, en sus diferentes grados de severidad. (2)Establecer si existen diferencias en los niveles plasmáticos de PCR HS antes y después de una terapia periodontal no quirúrgica. Materiales y métodos: se estudiaron 6 pacientes con Periodontitis Crónica y sin patología sistémica (ECV) a los cuales se les realizó el tratamiento periodontal no quirúrgico correspondiente. Se les tomaron dos muestras de PCR una 7 días previo y otra 7 días posterior al tratamiento. Resultados: se encontraron diferencias pero no fueron estadísticamente significativas entre los niveles de PCR 7 días antes y 7 días después del tratamiento periodontal no quirúrgico. Discusión: Si separamos al grupo por severidad de la periodontitis, 2 de los 3 pacientes que tenían periodontitis crónica avanzada tanto antes como después del tratamiento, tendrían un alto riesgo cardiovascular según la asociación americana del corazón, en tanto el paciente restante tendría un moderado riesgo. Los pacientes con Periodontitis crónica moderada antes del tratamiento se dividían en un 33,3% para cada tipo de riesgo cardiovascular, mientras que para las muestras 7 días después de concluido el tratamiento, el 66,7% fue catalogado con un moderado riesgo cardiovascular y un 33,4% con un alto riesgo cardiovascular. Conclusiones: (1) En este estudio no existen diferencias significativas entre los niveles de PCR plasmáticos antes y después del tratamiento periodontal. (2) No existen diferencias estadísticamente significativas en los niveles de PCR previo al tratamiento periodontal en los diferentes grados de severidad de Periodontitis. 3)No existen diferencias estadísticamente significativas en los niveles de PCR posterior al tratamiento periodontal en los diferentes grados de severidad de Periodontitis

Extractos polifenólicos de las hojas de Ilex paraguariensis y Larrea divaricata y su potencial antioxidante y antiCOVID-19

Yerba mate (Ilex paraguariensis A.St. Hil) and jarilla (Larrea divaricata Cav.) leaves are commonly used as tea infusions in some Latin American countries. This study was conducted to evaluate the antioxidant activity (FRAP, ABTS, and DPPH) and the inhibitory potential of yerba mate and jarilla extracts on the 3CL protease (Mpro) from coronavirus SARS-COV-2 by a molecular docking approach. The main bioactive compounds present in the plant extracts were identified by HPLC-MS. According to the results, the extracts of yerba mate and jarilla showed high antioxidant activity in DPPH (> 91 %), ABTS (> 90 %), and FRAP (> 47 mg TE/g) assays. Additionally, the phenolic compounds present in yerba mate, quercetin-3-O-rutinoside (rutin) (-9.60 kcal/mol) and 3,4-dicaffeoylquinic acid (-8.20 kcal/mol) were more effective on Mpro than the antiviral drugs remdesivir and ribavirin. The compounds rutin and 3,4-dicaffeoylquinic acid have a high affinity and interaction with one of the catalytic residues Cys145 of Mpro. The glycosylation of phenolic compounds affects biological activities: positively anti-COVID-19 and negatively antioxidant. The results suggest that extracts of yerba mate and jarilla leaves could enhance the body's antioxidant defenses and can be used to improve health.Las hojas de yerba mate (Ilex paraguariensis A.St. Hil) y jarilla (Larrea divaricata Cav.) se usan comúnmente como infusión de té en algunos países de América Latina. Este estudio se realizó para evaluar la actividad antioxidante (FRAP, ABTS y DPPH) y el potencial inhibitorio de los extractos de yerba mate y jarilla sobre la proteasa 3CL (Mpro) de coronavirus SARS-COV-2 por enfoque de acoplamiento molecular. Los principales compuestos bioactivos presentes en los extractos de plantas fueron identificados por HPLC-MS. De acuerdo con los resultados, los extractos polifenólicos de yerba mate y jarilla presentaron alta actividad antioxidante en los ensayos DPPH (> 91 %), ABTS (> 90 %) y FRAP (> 47 mg TE/g). Además, los compuestos fenólicos presentes en la yerba mate, quercetina-3-O-rutinósido (rutina) (-9,60 kcal/mol) y ácido 3,4-dicafeoilquínico (-8,20 kcal/mol) han demostrado ser más efectivos (en Mpro) que los medicamentos antivirales remdesivir y ribavirin. Los compuestos rutina y ácido 3,4-dicafeoilquínico tienen alta afinidad e interacción con uno de los residuos catalíticos Cys145 de Mpro. Estos resultados sugieren que las hojas de yerba mate y jarilla podrían potenciar las defensas antioxidantes del organismo y podrían beneficiar la salud

Unravelling interspecific relationships among highland lizards: First phylogenetic hypothesis using total evidence of the Liolaemus montanus group (Iguania: Liolaemidae)

The South American lizard genus Liolaemus comprises > 260 species, of which > 60 are recognized as members of the Liolaemus montanus group, distributed throughout the Andes in central Peru, Bolivia, Chile and central Argentina. Despite its great morphological diversity and complex taxonomic history, a robust phylogenetic estimate is still lacking for this group. Here, we study the morphological and molecular diversity of the L. montanus group and present the most complete quantitative phylogenetic hypothesis for the group to date. Our phylogeny includes 103 terminal taxa, of which 91 are members of the L. montanus group (58 are assigned to available species and 33 are of uncertain taxonomic status). Our matrix includes 306 morphological and ecological characters and 3057 molecular characters. Morphological characters include 48 continuous and 258 discrete characters, of which 70% (216) are new to the literature. The molecular characters represent five mitochondrial markers. We performed three analyses: A morphology-only matrix, a molecular-only matrix and a matrix including both morphological and molecular characters (total evidence hypothesis). Our total evidence hypothesis recovered the L. montanus group as monophyletic and included ≥ 12 major clades, revealing an unexpectedly complex phylogeny.Fil: Abdala, Cristian Simón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Quinteros, Andres Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Semhan, Romina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Bulacios Arroyo, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Schulte, James. Belloit College; Estados UnidosFil: Paz, Marcos Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Ruiz Monachesi, Mario Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Laspiur, Julio Alejandro. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Aguilar Kirigin, Alvaro Juan. Colección Boliviana de Fauna; Bolivia. Universidad Mayor de San Andrés; BoliviaFil: Gutierrez Poblete, Ricardo. Universidad Nacional de San Agustín. Facultad de Ciencias Biológicas. Departamento Académico de Biología. Museo de Historia Natural; PerúFil: Valladares Faundez, Pablo. Universidad de Tarapaca.; ChileFil: Valdes, José Julian. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Botánica del Nordeste. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias. Instituto de Botánica del Nordeste; ArgentinaFil: Portelli, Sabrina Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Santa Cruz, Roy. Universidad Nacional de San Agustín. Facultad de Ciencias Biológicas. Departamento Académico de Biología. Museo de Historia Natural; PerúFil: Aparicio, James. Colección Boliviana de Fauna; Bolivia. Universidad Mayor de San Andrés; BoliviaFil: García, Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Langstroth, Robeert. Colección Boliviana de Fauna; Bolivia. Universidad Mayor de San Andrés; Bolivi

Transcriptional supercoiling boosts topoisomerase II-mediated knotting of intracellular DNA

Recent studies have revealed that the DNA cross-inversion mechanism of topoisomerase II (topo II) not only removes DNA supercoils and DNA replication intertwines, but also produces small amounts of DNA knots within the clusters of nucleosomes that conform to eukaryotic chromatin. Here, we examine how transcriptional supercoiling of intracellular DNA affects the occurrence of these knots. We show that although (-) supercoiling does not change the basal DNA knotting probability, (+) supercoiling of DNA generated in front of the transcribing complexes increases DNA knot formation over 25-fold. The increase of topo II-mediated DNA knotting occurs both upon accumulation of (+) supercoiling in topoisomerase-deficient cells and during normal transcriptional supercoiling of DNA in TOP1 TOP2 cells. We also show that the high knotting probability (Pkn 65 0.5) of (+) supercoiled DNA reflects a 5-fold volume compaction of the nucleosomal fibers in vivo. Our findings indicate that topo II-mediated DNA knotting could be inherent to transcriptional supercoiling of DNA and other chromatin condensation processes and establish, therefore, a new crucial role of topoisomerase II in resetting the knotting-unknotting homeostasis of DNA during chromatin dynamics

HIV and COVID-19: two pandemics with significant (but different) central nervous system complications

Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements