Expanding the repertoire of ceDAF-12 ligands for modulation of the steroid endocrine system in C. elegans.

Steroid hormones are essential for the biological processes of eukaryotic organisms. The steroid endocrine system of C. elegans, which includes dafachronic acids (DA) and the nuclear receptor ceDAF-12, provides a simple model for exploring the role of steroid hormone signaling pathways in animals. In this study, we show for the first time the feasibility of designing synthetic steroids that can modulate different physiological processes, such as development, reproduction and ageing, in relation to ceDAF-12. Our results not only confirm the conclusions derived from genetic studies linking these processes but also provide new chemical tools to selectively manipulate them, as we found that different compounds produce different phenotypic results. The structures of these compounds are much more diverse than those of endogenous hormones and analogues previously described by other researchers, allowing further development of the chemical modulation of the steroid endocrine system in C. elegans and related nematodes.

Key role of the TM2-TM3 loop in calcium potentiation of the α9α10 nicotinic acetylcholine receptor.

The α9α10 nicotinic cholinergic receptor (nAChR) is a ligand-gated pentameric cation-permeable ion channel that mediates synaptic transmission between descending efferent neurons and mechanosensory inner ear hair cells. When expressed in heterologous systems, α9 and α10 subunits can assemble into functional homomeric α9 and heteromeric α9α10 receptors. One of the differential properties between these nAChRs is the modulation of their ACh-evoked responses by extracellular calcium (Ca2+). While α9 nAChRs responses are blocked by Ca2+, ACh-evoked currents through α9α10 nAChRs are potentiated by Ca2+ in the micromolar range and blocked at millimolar concentrations. Using chimeric and mutant subunits, together with electrophysiological recordings under two-electrode voltage-clamp, we show that the TM2-TM3 loop of the rat α10 subunit contains key structural determinants responsible for the potentiation of the α9α10 nAChR by extracellular Ca2+. Moreover, molecular dynamics simulations reveal that the TM2-TM3 loop of α10 does not contribute to the Ca2+ potentiation phenotype through the formation of novel Ca2+ binding sites not present in the α9 receptor. These results suggest that the TM2-TM3 loop of α10 might act as a control element that facilitates the intramolecular rearrangements that follow ACh-evoked α9α10 nAChRs gating in response to local and transient changes of extracellular Ca2+ concentration. This finding might pave the way for the future rational design of drugs that target α9α10 nAChRs as otoprotectants.

Preimplantation genetic testing: A narrative review.

Preimplantation genetic testing (PGT) is a diagnostic procedure that has become a powerful complement to assisted reproduction techniques. PGT has numerous indications, and there is a wide range of techniques that can be used, each with advantages and limitations that should be considered before choosing the more adequate one. In this article, it is reviewed the indications for PGT, biopsy and diagnostic technologies, along with their evolution, while also broaching new emerging methods.

Mechanochemically Promoted Functionalization of Postconsumer Poly(Methyl Methacrylate) and Poly(α-Methylstyrene) for Bulk Depolymerization.

We describe a methodology of post-polymerization functionalization to enable subsequent bulk depolymerization to monomer by utilizing mechanochemical macro-radical generation. By harnessing ultrasonic chain-scission in the presence of N-hydroxyphthalimide methacrylate (PhthMA), we successfully chain-end functionalize polymers to promote subsequent depolymerization in bulk, achieving up to 81% depolymerization of poly(methyl methacrylate) (PMMA) and poly(α-methylstyrene) (PAMS) within 30 min. This method of depolymerization yields a high-purity monomer that can be repolymerized. Moreover, as compared to the most common methods of depolymerization, this work is most efficient with ultra-high molecular weight (UHMW) polymers, establishing a method with the potential to address highly persistent, non-degradable all-carbon backbone plastic materials. Lastly, we demonstrate the expansion of this depolymerization method to commercial cell cast PMMA, achieving high degrees of depolymerization from post-consumer waste. This work is the first demonstration of applying PhthMA-promoted depolymerization strategies in homopolymer PMMA and PAMS prepared by conventional polymerization methods.

An Aggressive Interaction Rapidly Increases Brain Androgens in a Male Songbird during the Non-breeding Season.

Aggression is a crucial behavior that impacts access to limited resources in different environmental contexts. Androgens synthesized by the gonads promote aggression during the breeding season. However, aggression can be expressed during the non-breeding season, despite low androgen synthesis by the gonads. The brain can also synthesize steroids ("neurosteroids"), including androgens, which might promote aggression during the non-breeding season. Male song sparrows, Melospiza melodia, are territorial year-round and allow the study of seasonal changes in the steroid modulation of aggression. Here, we quantified steroids following a simulated territorial intrusion (STI) for 10 min in wild adult male song sparrows during the breeding and non-breeding seasons. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined 11 steroids: pregnenolone, progesterone, corticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17ß-estradiol, 17α-estradiol, estriol, and estrone. Steroids were measured in blood and 10 microdissected brain regions that regulate social behavior. In both seasons, STI increased corticosterone in the blood and brain. In the breeding season, STI had no rapid effects on androgens or estrogens. Intriguingly, in the non-breeding season, STI increased testosterone and androstenedione in several behaviorally relevant regions, but not in the blood, where androgens remained non-detectable. Also in the non-breeding season, STI increased progesterone in the blood and specific brain regions. Overall, rapid socially modulated changes in brain steroid levels are more prominent during the non-breeding season. Brain steroid levels vary with season and social context in a region-specific manner and suggest a role for neuroandrogens in aggression during the non-breeding season.

The Parallel World of Dyspnea: A Case Report.

Dyspnea can be found as a symptom of a wide range of diseases. Clinical thinking usually leads us to more common or frequent syndromes and diseases. This case report alerts us to keep investigating when faced with therapeutic failure or the arising of new symptoms. The subject in this case had dyspnea as an initial presentation of his disease and was treated initially as a case of heart dysfunction. Nevertheless, because his symptoms did not respond to the treatment and even got worse, he was sent to the emergency room where he was medicated and discharged with the same diagnostic hypothesis. In light of a new characteristic symptom - ptosis - the hospital team expanded its clinical and laboratory investigation to neuromuscular diseases, reaching out the diagnosis of myasthenia gravis.

Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].

Effect of a Territorial Challenge on the Steroid Profile of a Juvenile Songbird.

Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to modulate aggressive interactions, especially in reproductive contexts. In many species, individuals also demonstrate aggression before reaching gonadal maturation. Adult male song sparrows, Melospiza melodia, breed seasonally but maintain territories year-round. Juvenile (hatch-year) males aggressively compete for territory ownership during their first winter when circulating testosterone is low. Here, we characterized the relationship between the steroid milieu and aggressive behavior in free-living juvenile male song sparrows in winter. We investigated the effect of a 10 min simulated territorial intrusion (STI) on behavior and steroid levels in blood, 10 microdissected brain regions, and four peripheral tissues (liver, pectoral muscle, adrenal glands, and testes). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified 12 steroids: pregnenolone, progesterone, corticosterone, 11-dehydrocorticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17ß-estradiol, 17α-estradiol, estrone, and estriol. We found that juvenile males are robustly aggressive, like adult males. An STI increases progesterone and corticosterone levels in blood and brain and increases 11-dehydrocorticosterone levels in blood only. Pregnenolone, androgens, and estrogens are generally non-detectable and are not affected by an STI. In peripheral tissues, steroid concentrations are very high in the adrenals. These data suggest that adrenal steroids, such as progesterone and corticosterone, might promote juvenile aggression and that juvenile and adult songbirds might rely on distinct neuroendocrine mechanisms to support similar aggressive behaviors.

Spatial propagation of temperate phages within and among biofilms.

Bacteria form groups comprised of cells and a secreted polymeric matrix that controls their spatial organization. These groups - termed biofilms - can act as refuges from environmental disturbances and from biotic threats, including phages. Despite the ubiquity of temperate phages and bacterial biofilms, live propagation of temperate phages within biofilms has never been characterized on cellular spatial scales. Here, we leverage several approaches to track temperate phages and distinguish between lytic and lysogenic host infections. We determine that lysogeny within E. coli biofilms initially occurs within a predictable region of cell group packing architecture on the biofilm periphery. Because lysogens are generally found on the periphery of large cell groups, where lytic viral infections also reduce local biofilm cell packing density, lysogens are predisposed to disperse into the passing liquid and are over-represented in biofilms formed from the dispersal pool of the original biofilm-phage system. Comparing our results with those for virulent phages reveals that temperate phages have previously unknown advantages in propagating over long spatial and time scales within and among bacterial biofilms.