Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

Empatía en estudiantes de medicina procedentes de Brasil y Argentina: diferencias por sexo y nivel en la carrera / Empathy in medicine students from Brazil and Argentina: differences by sex and career level

La presente investigación tuvo como objetivo comparar Empatía Médica y el impacto que sobre ella tienen las variables Sexo y Nivel en que se encontraban en la carrera, en dos grupos de estudiantes de Medicina (provenientes de países diferentes). La muestra comprendió a 391 estudiantes de la misma universidad argentina (IUCS Fundación H.A. Barceló), 212 provenientes de Brasil y 179 del entorno local. Se administró una encuesta para datos personales y académicos y la Escala de Empatía Médica de Jefferson. Se compararon ambos grupos en el puntaje total de la escala y en sus 3 (tres) factores y se analizaron las interacciones mediante diseños factoriales. Los resultados evidenciaron que los grupos presentaron diferencias significativas en sus respuestas al Puntaje total de Empatía y en el factor Ponerse en el lugar del otro. Se observaron efectos de interacción de País de procedencia con sexo, pero no con nivel en la carrera(AU)

The objective of this research was to compare Medical Empathy and the impact that the variables Sex and Level in which they are in the career had on it, in two groups of Medicine students (from different countries). The sample included 391 students from the same Argentine university (IUCS Fundación H.A. Barceló), 212 from Brazil and 179 from the local environment. A survey was administered for personal and academic data and the Jefferson Medical Empathy Scale. Both groups were compared in the total score of the scale and in its 3 (three) factors and the interactions were analyzed using factorial designs. The results showed that the groups presented significant differences in their responses to the Total Empathy Score and the factor Putting themselves in the place of the other. Interaction effects of country of origin with sex were observed, but not with career level(AU)

Glucose tolerance and insulin sensitivity define adipocyte transcriptional programs in human obesity.

OBJECTIVE: Although debated, metabolic health characterizes 10-25% of obese individuals and reduces risk of developing life-threatening co-morbidities. Adipose tissue is a recognized endocrine organ important for the maintenance of whole-body metabolic health. Adipocyte transcriptional signatures of healthy and unhealthy obesity are largely unknown. METHODS: Here, we used a small cohort of highly characterized obese individuals discordant for metabolic health, characterized their adipocytes transcriptional signatures, and cross-referenced them to mouse phenotypic and human GWAs databases. RESULTS AND CONCLUSIONS: Our study showed that glucose intolerance and insulin resistance co-operate to remodel adipocyte transcriptome. We also identified the Nuclear Export Mediator Factor (NEMF) and the Ectoderm-Neural Cortex 1 (ENC1) as novel potential targets in the management of metabolic health in human obesity.

Production of High Amounts of Hepatotoxin Nodularin and New Protease Inhibitors Pseudospumigins by the Brazilian Benthic Nostoc sp. CENA543.

Nostoc is a cyanobacterial genus, common in soils and a prolific producer of natural products. This research project aimed to explore and characterize Brazilian cyanobacteria for new bioactive compounds. Here we report the production of hepatotoxins and new protease inhibitors from benthic Nostoc sp. CENA543 isolated from a small, shallow, saline-alkaline lake in the Nhecolândia, Pantanal wetland area in Brazil. Nostoc sp. CENA543 produces exceptionally high amounts of nodularin-R. This is the first free-living Nostoc that produces nodularin at comparable levels as the toxic, bloom-forming, Nodularia spumigena. We also characterized pseudospumigins A-F, which are a novel family of linear tetrapeptides. Pseudospumigins are structurally related to linear tetrapeptide spumigins and aeruginosins both present in N. spumigena but differ in respect to their diagnostic amino acid, which is Ile/Leu/Val in pseudospumigins, Pro/mPro in spumigins, and Choi in aeruginosins. The pseudospumigin gene cluster is more similar to the spumigin biosynthetic gene cluster than the aeruginosin gene cluster. Pseudospumigin A inhibited trypsin (IC50 4.5 µM after 1 h) in a similar manner as spumigin E from N. spumigena but was almost two orders of magnitude less potent. This study identifies another location and environment where the hepatotoxic nodularin has the potential to cause the death of eukaryotic organisms.

Short- and long-term (final height) data in children with normal variant short stature treated with growth hormone.

UNLABELLED: Seventeen children with normal variant short stature and a predicted height below -2 SDS were treated with growth hormone (GH) six times a week for a period of 5 years. Patients were randomly selected to receive three different doses of GH, group 1 (n = 6) 3 IU/m2 per day, group 2 (n = 6) 4.5 IU/m2 per day and group 3 (n=5) 3 IU/m2 per day in the 1st year and 4.5 IU/m2 per day thereafter. There was a significant increase in height after 1 and 2 years for all patients and for all subgroups. However, this increase was not dependent on GH dose. The decrease in height velocity during the 2nd year was not prevented by the increase of GH dose in group 3. The change of predicted height after 2 years was +0.75 SDS (according to Tanner Whitehouse). Fourteen children have been treated for 4 years and 8 children for 5 years without a further change in height prediction. Nine patients have reached final height which was 2.4 cm (+0.41 SDS) above pretreatment height prediction. Final height was nearly identical to predicted height after 1 year of therapy. CONCLUSION: An increment in height prediction was observed during the first 2 years of GH treatment and maintained thereafter. However, there was only a minor increase in final height over predicted height which does not justify the general use of GH in children with normal variant short stature.