Calcisponges have a ParaHox gene and dynamic expression of dispersed NK homeobox genes

This study was funded by the Sars Centre core budget to M. Adamska. Sequencing was performed at the Norwegian High Throughput Sequencing Centre funded by the Norwegian Research Council. O.M.R. and D.E.K.F. acknowledge support from the BBSRC and the School of Biology, University of St Andrews.Sponges are simple animals with few cell types, but their genomes paradoxically contain a wide variety of developmental transcription factors1,2,3,4, including homeobox genes belonging to the Antennapedia (ANTP) class5,6, which in bilaterians encompass Hox, ParaHox and NK genes. In the genome of the demosponge Amphimedon queenslandica, no Hox or ParaHox genes are present, but NK genes are linked in a tight cluster similar to the NK clusters of bilaterians5. It has been proposed that Hox and ParaHox genes originated from NK cluster genes after divergence of sponges from the lineage leading to cnidarians and bilaterians5,7. On the other hand, synteny analysis lends support to the notion that the absence of Hox and ParaHox genes in Amphimedon is a result of secondary loss (the ghost locus hypothesis)8. Here we analysed complete suites of ANTP-class homeoboxes in two calcareous sponges, Sycon ciliatum and Leucosolenia complicata. Our phylogenetic analyses demonstrate that these calcisponges possess orthologues of bilaterian NK genes (Hex, Hmx and Msx), a varying number of additional NK genes and one ParaHox gene, Cdx. Despite the generation of scaffolds spanning multiple genes, we find no evidence of clustering of Sycon NK genes. All Sycon ANTP-class genes are developmentally expressed, with patterns suggesting their involvement in cell type specification in embryos and adults, metamorphosis and body plan patterning. These results demonstrate that ParaHox genes predate the origin of sponges, thus confirming the ghost locus hypothesis8, and highlight the need to analyse the genomes of multiple sponge lineages to obtain a complete picture of the ancestral composition of the first animal genome.PostprintPeer reviewe

Depression and microvascular complications predict poor goal achievement among Colombian patients with type 2 diabetes

Aims: Many patients with type 2 diabetes (DM2) in Latin American countries remain insufficiently controlled. We aimed to identify factors associated with persistent poor metabolic control in Colombian patients with DM2. Methods: Retrospective one-year follow-up cohort study of adult patients with DM2. The primary outcome was persistent poor metabolic control (PPMC): HbA1c level >8% in all measurements during follow-up. Secondary outcomes were intermittent poor metabolic control (IPMC) and good control (GC: simultaneous achievement of HbA1c, blood pressure and LDL cholesterol goals). Multiple demographic, clinical and laboratory variables were predictors in multivariable logistical models. Results: Of 399 patients included, 50 had the primary endpoint during follow-up. Older age was negatively associated with PPMC (OR 0.40, 95%CI 0.17-0.92 for extreme quartiles), even after multivariate adjustment. Depression and the presence of multiple microvascular complications were strongly associated with the secondary endpoint IPMC (multivariate OR respectively 4.2, 95%CI 1.08-16.4 for depression; 5.61, 95%CI 1.03-30.6 for microvascular complications). Being unemployed was associated with significantly less odds of achieving GC (multivariate OR 0.19, 95%CI 0.04-0.95). Conclusions: Age, depression, the presence of microvascular complications and employment status were associated with the success or failure of diabetes management. These factors were better correlates of therapeutic success than the pharmacological agent employed

COVID-19 y fisiopatología de la diabetes

La COVID-19, causada por la infección con el coronavirus SARS-CoV-2, es la pandemia actual sobre la que conocemos poco desde el punto de vista biológico y patológico, y cuyo pronóstico es ensombrecido por la presencia concomitante de diabetes mellitus (DM). Motivados por esto, realizamos una búsqueda bibliográfica para analizar la información disponible acerca de la fisiopatología de esta enfermedad en personas con DM. Encontramos que las personas con DM presentan alteraciones en la quimiotaxis de neutrófilos, la producción de citocinas proinflamatorias, la fagocitosis y la activación de linfocitos T, que en conjunto disminuyen la capacidad de respuesta contra cualquier patógeno, incluido el SARS-CoV-2. A ello se suma que los productos avanzados de glicosilación alteran la afinidad y la capacidad opsonizante de los anticuerpos. En cuanto al grupo de virus con tropismo por vías respiratorias, la hiperglucemia favorece su proliferación a nivel tisular. El virus SARS-CoV-2 entra a las células gracias a la proteína S (Spike), que se utiliza como receptor de la enzima convertidora de angiotensina tipo 2 (ECA-2), una glucoproteína transmembrana que se expresa no solo en el epitelio respiratorio, sino también en el miocardio y los islotes pancreáticos. La hiperglucemia aumenta la expresión de ECA-2 en la membrana celular, lo que potencializa el riesgo de infección en el caso en que la célula entre en contacto con el virus. Además, las células de personas con DM expresan niveles aumentados de la proteasa furina, que cliva la proteína S y permite el ingreso del virus a las células. Esto facilita la diseminación de la infección y el cuadro más grave que se observa en la clínica. Existe también evidencia de expresión aumentada de ECA-2 en personas con diabetes mellitus que reciben tratamiento con inhibidores de la enzima convertidora de la angiotensina o antagonistas del receptor tipo 1 de angiotensina II. Así, en el paciente con DM, se conjugan una mayor predisposición al contagio con una inmunidad humoral y celular desregulada en una combinación destructiva que desemboca en una COVID-19 más grave y letal

Low-Density Lipoproteins Containing Apolipoprotein C-III and the Risk of Coronary Heart Disease

BACKGROUND: Low-density lipoprotein (LDL) that contains apolipoprotein (apo) C-III makes up only 10% to 20% of plasma LDL but has a markedly altered metabolism and proatherogenic effects on vascular cells. METHODS AND RESULTS: We examined the association between plasma LDL with apoC-III and coronary heart disease in 320 women and 419 men initially free of cardiovascular disease who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow-up and matched controls who remained free of coronary heart disease. Concentrations of LDL with apoC-III (measured as apoB in this fraction) were associated with risk of coronary heart disease in multivariable analysis that included the ratio of total cholesterol to high-density lipoprotein cholesterol, LDL cholesterol, apoB, triglycerides, or high-density lipoprotein cholesterol and other risk factors. In all models, the relative risks for the top versus bottom quintile of LDL with apoC-III were greater than those for LDL without apoC-III. When included in the same multivariable-adjusted model, the risk associated with LDL with apoC-III (relative risk for top versus bottom quintile, 2.38; 95% confidence interval, 1.54-3.68; P for trend <0.001) was significantly greater than that associated with LDL without apoC-III (relative risk for top versus bottom quintile, 1.25; 95% confidence interval, 0.76-2.05; P for trend=0.97; P for interaction <0.001). This divergence in association with coronary heart disease persisted even after adjustment for plasma triglycerides. CONCLUSIONS: The risk of coronary heart disease contributed by LDL appeared to result to a large extent from LDL that contains apoC-III

Recent advances in understanding the roles of whole genome duplications in evolution

Ancient whole-genome duplications (WGDs)—paleopolyploidy events—are key to solving Darwin’s ‘abominable mystery’ of how flowering plants evolved and radiated into a rich variety of species. The vertebrates also emerged from their invertebrate ancestors via two WGDs, and genomes of diverse gymnosperm trees, unicellular eukaryotes, invertebrates, fishes, amphibians and even a rodent carry evidence of lineage-specific WGDs. Modern polyploidy is common in eukaryotes, and it can be induced, enabling mechanisms and short-term cost-benefit assessments of polyploidy to be studied experimentally. However, the ancient WGDs can be reconstructed only by comparative genomics: these studies are difficult because the DNA duplicates have been through tens or hundreds of millions of years of gene losses, mutations, and chromosomal rearrangements that culminate in resolution of the polyploid genomes back into diploid ones (rediploidisation). Intriguing asymmetries in patterns of post-WGD gene loss and retention between duplicated sets of chromosomes have been discovered recently, and elaborations of signal transduction systems are lasting legacies from several WGDs. The data imply that simpler signalling pathways in the pre-WGD ancestors were converted via WGDs into multi-stranded parallelised networks. Genetic and biochemical studies in plants, yeasts and vertebrates suggest a paradigm in which different combinations of sister paralogues in the post-WGD regulatory networks are co-regulated under different conditions. In principle, such networks can respond to a wide array of environmental, sensory and hormonal stimuli and integrate them to generate phenotypic variety in cell types and behaviours. Patterns are also being discerned in how the post-WGD signalling networks are reconfigured in human cancers and neurological conditions. It is fascinating to unpick how ancient genomic events impact on complexity, variety and disease in modern life

Transcriptome analyses throughout chili pepper fruit development reveal novel insights into the domestication process

Chili pepper (Capsicum spp.) is an important crop, as well as a model for fruit development studies and domestication. Here, we performed a time-course experiment to estimate standardized gene expression profiles with respect to fruit development for six domesticated and four wild chili pepper ancestors. We sampled the transcriptomes every 10 days from flowering to fruit maturity, and found that the mean standardized expression profiles for domesticated and wild accessions significantly differed. The mean standardized expression was higher and peaked earlier for domesticated vs. wild genotypes, particularly for genes involved in the cell cycle that ultimately control fruit size. We postulate that these gene expression changes are driven by selection pressures during domestication and show a robust network of cell cycle genes with a time shift in expression, which explains some of the differences between domesticated and wild phenotypes

Folistatina, resistencia a la insulina y composición corporal en adultos colombianos

Introducción: La folistatina es una proteína capaz de neutralizar varias hormonas de la familia del TGF-?, tales como la activina, las proteínas morfogénicas del hueso y la miostatina. Al inactivar la activina y la folistatina reduce la secreción de FSH. La folistatina se produce además de en el ovario en muchos otros tejidos, por ello se sospecha que tiene otros efectos. En ratones, la deleción genética de la folistatina se acompaña de resistencia a la insulina (RI). Sin embargo, la asociación entre la folistatina plasmática y RI medida directamente no ha sido evaluada en humanos. Métodos: En 81 participantes entre 30 y 69 años (56% mujeres, 54% con sobrepeso, 13% con obesidad), determinamos antropometría, composición corporal, factores de riesgo cardiovascular y múltiples índices de RI: Área incremental bajo la curva de insulina, índice de sensibilidad a la insulina según Gutt, Homeostatic Model Assessment – Insulin Resistance (HOMA-IR) e insulinemia en ayuno. Un subgrupo de 21 participantes se sometió además a un clamp hiperinsulinémico-euglucémico. La folistatina y la miostatina se midieron en plasma de ayuno, empleando técnicas inmunométricas. Resultados: La concentración promedio de folistatina fue 2.517±830 pg/mL, sin diferencia entre sexos (p=0,55). La folistatina tuvo una tendencia a correlación positiva con el porcentaje de masa magra (r=0,19, p=0,088) y negativa con el porcentaje de grasa corporal (r= -0,19, p=0,097). La folistatina no se correlacionó con índices de RI derivados de la PTOG pero sí con la captación corporal de glucosa en el clamp (r=0,42, p=0,031). No se halló asociación entre las concentraciones de folistatina y miostatina plasmáticas. Conclusión: Los niveles de folistatina mostraron una tendencia hacia una correlación positiva con la masa muscular y negativa con adiposidad corporal. Esto concuerda con el efecto inhibitorio de la folistatina sobre la miostatina. Aunque la folistatina no correlacionó con índices indirectos de RI, sí lo hizo con la determinación directa de sensibilidad a la insulina en el clamp hiperinsulinémico-euglucémico

EVALUACIÓN DE DOS DESCOMPACTADORES EN SIEMBRA DIRECTA

Background: No tillage is a widely used tillage system in Argentinean extensive grain production. Despite their benefits, the risk of soil compaction is still a critical point. Deep tillage is a valid option to solve compaction problems and several types of deep tillage agricultural equipment are available. Nevertheless, accurate knowledge on their energetic performance rates and agricultural parameters is still limited. Objectives: a) determine energy requirements of different subsoiling equipment, b) evaluate the effect of different subsoilers on physical soil properties and c) analyze the recompaction of subsoiled soil. Methods: A field experiment in a direct drill system (Typical Argiudol soil type) was carried out. Treatments were: a) without decompaction, b) paratill and c) chisel with flexible and rigid shanks. Traction, soil disturbance and specific resistance were measured. After tillage, physical soil properties were assessed. Results: Traction and specific resistance were 5,5% and 11,5% greater in chisel. In general, soil density and penetration resistance were reduced by subsoiling but these benefits do not persist after 18 months. Conclusions: Paratill performance in direct-drilled soils is higher than chisel performance. Subsoiling of direct-drilled soils improve soil physical properties.&nbsp;Antecedentes: La siembra directa se ha generalizado en los sistemas de producción de cultivos extensivos en Argentina. Esta técnica presenta varias ventajas, aunque uno de sus aspectos críticos lo constituye el riesgo de compactación. La labranza vertical profunda es una alternativa viable para solucionar los problemas de compactación. Existen numerosas opciones de descompactadores, sin que se disponga, para la mayoría de ellos, de información sobre sus prestaciones, en términos energéticos y agronómicos. Objetivos: a) determinar los requerimientos de energía de diferentes equipamientos de descompactación, b) valorar el efecto de distintos diseños de descompactadores sobre las propiedades físicas del suelo, c) analizar la recompactación de suelos descompactados. Métodos: Se realizó un experimento sobre un suelo Argiudol típico, contrastándose tres tratamientos: a) sin descompactar, b) descompactado con paratill y c) descompactado con cincel de arcos rígidos y flexibles. Se cuantificó el esfuerzo de tracción, el área de suelo removida y la resistencia específica al laboreo. Luego de realizadas las labores se evaluaron las propiedades físicas del suelo. Resultados: El cincel demandó un 5,5% más de esfuerzo de tracción y tuvo 11,2% más de resistencia específica al laboreo. El subsolado disminuyó la densidad aparente y la resistencia a la penetración, aunque esas diferencias se pierden a los 18 meses. Conclusiones: La descompactación de suelos en siembra directa con paratill es energéticamente más eficiente que con cincel. Las labores de descompactado, ya sea por medio del cincel como del paratill, realizadas sobre un suelo con historia en siembra directa, mejoran las propiedades físicas del suelo: densidad aparente y resistencia a la penetración

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940