Tumor start-up: mitochondrial fusion makes it happen.

Whether changes in cellular metabolism precede tumor formation and trigger malignant properties or simply serve as a bioenergetic adaptation of cancer during disease progression remains debated. Bonnay et al (2020) now show that a metabolic reprogramming toward increased oxidative phosphorylation is required for irreversible cell immortalization and subsequent tumor formation.

Retinoic Acid-Mediated Control of Energy Metabolism Is Essential for Lung Branching Morphogenesis.

Lung branching morphogenesis relies on intricate epithelial-mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic acid (RA) signaling influences lung proximal-distal patterning and branching morphogenesis, but its role as a metabolic modulator is unknown. Hence, this study investigates how RA signaling affects the metabolic profile of lung branching. We performed ex vivo lung explant culture of embryonic chicken lungs treated with DMSO, 1 µM RA, or 10 µM BMS493. Extracellular metabolite consumption/production was evaluated by using 1H-NMR spectroscopy. Mitochondrial respiration and biogenesis were also analyzed. Proliferation was assessed using an EdU-based assay. The expression of crucial metabolic/signaling components was examined through Western blot, qPCR, and in situ hybridization. RA signaling stimulation redirects glucose towards pyruvate and succinate production rather than to alanine or lactate. Inhibition of RA signaling reduces lung branching, resulting in a cystic-like phenotype while promoting mitochondrial function. Here, RA signaling emerges as a regulator of tissue proliferation and lactate dehydrogenase expression. Furthermore, RA governs fatty acid metabolism through an AMPK-dependent mechanism. These findings underscore RA's pivotal role in shaping lung metabolism during branching morphogenesis, contributing to our understanding of lung development and cystic-related lung disorders.

Resveratrol and ascorbic acid prevent DNA damage induced by cryopreservation in human semen.

Cryopreservation of human semen can cause DNA damages, which compromise the fertilization and normal embryo development. The present study showed that the antioxidant resveratrol prevents these damages both in fertile and infertile men. The addition of ascorbic acid before cryopreservation can reduce DNA damages only in infertile men. Although further studies are needed, the present work showed that resveratrol could be considered in human cryopreservation procedures to avoid/minimize DNA damages and preserve sperm integrity.

Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility.

The fate and proliferative capacity of stem cells have been shown to strongly depend on their metabolic state. Mitochondria are the powerhouses of the cell being responsible for energy production via oxidative phosphorylation (OxPhos) as well as for several other metabolic pathways. Mitochondrial activity strongly depends on their structural organization, with their size and shape being regulated by mitochondrial fusion and fission, a process known as mitochondrial dynamics. However, the significance of mitochondrial dynamics in the regulation of stem cell metabolism and fate remains elusive. Here, we characterize the role of mitochondria morphology in female germ stem cells (GSCs) and in their more differentiated lineage. Mitochondria are particularly important in the female GSC lineage. Not only do they provide these cells with their energy requirements to generate the oocyte but they are also the only mitochondria pool to be inherited by the offspring. We show that the undifferentiated GSCs predominantly have fissed mitochondria, whereas more differentiated germ cells have more fused mitochondria. By reducing the levels of mitochondrial dynamics regulators, we show that both fused and fissed mitochondria are required for the maintenance of a stable GSC pool. Surprisingly, we found that disrupting mitochondrial dynamics in the germline also strongly affects nurse cells morphology, impairing egg chamber development and female fertility. Interestingly, reducing the levels of key enzymes in the Tricarboxylic Acid Cycle (TCA), known to cause OxPhos reduction, also affects GSC number. This defect in GSC self-renewal capacity indicates that at least basal levels of TCA/OxPhos are required in GSCs. Our findings show that mitochondrial dynamics is essential for female GSC maintenance and female fertility, and that mitochondria fusion and fission events are dynamically regulated during GSC differentiation, possibly to modulate their metabolic profile.

Oxidative stress and hematologic and biochemical parameters in individuals with Down syndrome.

OBJECTIVE: To evaluate the levels of thiobarbituric acid reactive substances (TBARS), uric acid, and seric superoxide dismutase and catalase activities, as well as total serum iron, total iron-binding capacity (TIBC), erythrocyte osmotic fragility, and hemograms in people with Down syndrome. PARTICIPANTS AND METHODS: The study sampled (July to December 2003) 50 people with Down syndrome and 50 individuals without Down syndrome (control group) matched by age and sex. The levels of TBARS were measured by the TBARS method. Serum superoxide dismutase and catalase activities and uric acid levels were determined spectrophotometrically. Erythrocyte osmotic fragility was assessed by the percentage of hemolysis. Hemograms, total serum iron level, and TIBC were determined with automated systems. RESULTS: The results showed that levels of TBARS, uric acid, and seric superoxide dismutase and catalase activities were higher in the Down syndrome group compared with the control group. We also observed a slight increase in erythrocyte osmotic fragility in the Down syndrome group, but the total serum iron levels, TIBC, and hemograms for both groups were within the age-related reference values. CONCLUSION: This was the first time, to our knowledge, that increases in seric superoxide dismutase and catalase activities were observed in people with Down syndrome. Although other studies are necessary, our results add to the understanding of the mechanisms responsible for the increased oxidative stress observed in individuals with Down syndrome and may be useful in supporting future antioxidant therapies that will improve the lives of people with Down syndrome.

Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing.

How different organs in the body sense growth perturbations in distant tissues to coordinate their size during development is poorly understood. Here we mutate an invertebrate orphan relaxin receptor gene, the Drosophila Leucine-rich repeat-containing G protein-coupled receptor 3 (Lgr3), and find body asymmetries similar to those found in insulin-like peptide 8 (dilp8) mutants, which fail to coordinate growth with developmental timing. Indeed, mutation or RNA intereference (RNAi) against Lgr3 suppresses the delay in pupariation induced by imaginal disc growth perturbation or ectopic Dilp8 expression. By tagging endogenous Lgr3 and performing cell type-specific RNAi, we map this Lgr3 activity to a new subset of CNS neurons, four of which are a pair of bilateral pars intercerebralis Lgr3-positive (PIL) neurons that respond specifically to ectopic Dilp8 by increasing cAMP-dependent signalling. Our work sheds new light on the function and evolution of relaxin receptors and reveals a novel neuroendocrine circuit responsive to growth aberrations.

Effects of resveratrol supplementation on cryopreservation medium of human semen.

OBJECTIVE: To analyze oxidative stress markers and seminal standard parameters after using resveratrol (0.1, 1.0, and 10.0 mM), an important antioxidant, in the cryopreservation of human semen. DESIGN: In vitro prospective study. SETTING: Institutional study. PATIENT(S): Infertile and fertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Levels of thiobarbituric acid-reactive species (TBARS), superoxide dismutase (SOD), and catalase (CAT) activities and spermatozoa concentration, motility, and morphology. RESULT(S): Increased TBARS levels were observed in the post-thawing semen in both fertile and infertile men. Infertile men had lower CAT and SOD activities in prefreezing and post-thawing samples when compared with fertile men. The addition of resveratrol in all the concentrations assayed was able to prevent post-thawing lipoperoxidation in both fertile and infertile men. However, this effect was not dose dependent. The cryopreservation process was not able to change sperm concentration or morphology. However, a decrease in sperm motility was observed in both the fertile and infertile men. The addition of resveratrol was not able to prevent this effect. CONCLUSION(S): Resveratrol avoids oxidative damages induced by the cryopreservation of human semen, but it is not able to restore the decrease in sperm motility.

Ponderações sobre o tempo em psicanálise e suas relações com a atualidade / Considerations about time in psychoanalysis and its relationship with the present / Ponderaciones sobre el tiempo en psicoanalisis y su relación con la actualidad

Esta exposição trata de como a questão da temporalidade se apresenta no contemporâneo e como o sujeito responde a isso na singularidade de seu tempo. Para tal, abordaremos os efeitos sociais do discurso capitalista e como o tempo se constitui na clínica psicanalítica e no sujeito sob uma forma alienante ou não. Busca-se encaminhar, na constituição do sujeito, o que se processa como temporalidade lógica, tendo como suporte a teoria lacaniana sobre o tema. Supõe-se que o acesso ao consumo faz com que a relação de objeto, na atualidade, seja uma saída para o sofrimento que advém da falta, castração e da ideia de finitude. As diferenças que, por vezes, encontramos na psicose fornecem uma oposição à massificação da contemporaneidade, o que indica que o discurso capitalista seria uma solução para alguns, mas não para aqueles fora do laço social.

The present article is about how the issue of temporality in contemporary is presented as how the subject responds to the uniqueness of his/her time. We will discuss the social effects of capitalist discourse and how time constitutes itself in the psychoanalitic clinic and within the subject as form of alienation or not. The aim, supported by Lacan's theory on the subject, is routing in the constitution of the subject, which renders as temporal logic. It is assumed that access to consumption makes the object relationship, in the present, is a way of releasing suffering, which arises from want, castration and the idea of finiteness. The differences, which are sometimes found in psychosis, provide an opposition to the massification of contemporary times, which indicates that the capitalist discourse would be a solution for some, but not for those outside the social bond.

La exposición siguiente trata sobre la cuestión de cómo la temporalidad se muestra en lo contemporáneo y como el individuo responde a eso en la singularidad de su tiempo. Para esto, abordamos los efectos sociales del discurso capitalista y cómo el tiempo se constituye en la clínica psicoanalítica y en el individuo bajo una forma alienante o no. La búsqueda es la dirección, en la constitución del sujeto, lo que ocurre como la temporalidad lógica teniendo como su apoyo la teoría lacaniana sobre el tema. Se supone que el acceso al consumo hace que la relación de objeto, en las noticias, sea una salida para el dolor que proviene de la falta, castración y la finitud. Las diferencias que encontramos de vez em cuando en las psicosis nos ofrecem una oposición a la masificación de la contemporaneidad, al mismo tiempo en que nos apunta en ese discurso lo que sería una solución.

A influência das espécies reativas de oxigênio na infertilidade masculina / The influence of reactive oxigen species on male infertility

A infertilidade masculina é uma entidade multifatorial que abrange uma grande variedade de alterações, podendo ser congênita ou adquirida. A infertilidade idiopática pode ser causada pela excessiva produção de espécies reativas de oxigênio no plasma seminal, levando ao estresse oxidativo. Estudos têm demonstrado que os espermatozóides humanos possuem a capacidade de gerar espécies reativas de oxigênio quando incubados em ambiente aeróbio, sendo que as maiores fontes de espécies reativas de oxigênio no sêmen são leucócitos, espermatozóides com citoplasma residual e espermatozóides imaturos. A membrana plasmática dos espermatozóides é rica em ácidos graxos poliinsaturados sendo vulnerável ao processo de peroxidação lipídica, o que pode prejudicar a estrutura celular, motilidade, sobrevivência e funções metabólicas do espermatozóide. O estresse oxidativo pode induzir dano ao DNA espermático, podendo ser responsável pela aceleração do processo de apoptose da célula germinativa, levando a diminuição da concentração de espermatozóides e à aparente deterioração da qualidade seminal observada nas últimas 4 à 5 décadas. Entretanto dois fatores protegem o DNA espermático do ataque oxidativo: a característica de empacotamento do DNA e os antioxidantes presentes no plasma seminal. Consequentemente, as espécies reativas de oxigênio têm efeitos favoráveis ou prejudiciais sobre a função dos espermatozóides de acordo com sua natureza e concentração, assim como o momento e lugar da exposição. Estes achados mostram a importância do equilíbrio adequado entre antioxidantes e baixos níveis de ERO que são necessários para função espermática normal