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Landfills will likely remain an essential part of integrated solid waste management systems in many developed and developing countries for the foreseeable future. Further improvements are required to model the generated gas from landfills. The literature has not addressed detailed waste characterization in landfill gas (LFG) modeling by a first-order decay model such as LandGEM while using a genetic algorithm. Additionally, little has been done in the literature regarding H2S generation modeling. This paper uses a genetic algorithm to independently fit parameters to a CH4 and H2S generation model based on a modified first-order decay model. In the case of CH4 generation modeling, biodegradable organic waste (OW) was segregated into food waste, yard waste, paper, and wood. In addition to optimizing the OW fractions, key modeling parameters of OW, such as CH4 generation potential (L0) and CH4 decay rate (kCH4), were determined independently for different periods in the landfill’s life. Similarly, in the case of H2S generation modeling, the construction and demolition waste (CD) was classified into fines (FCD) and bulky materials (BCD), and H2S generation potential (S0) and H2S decay rate (kH2S) of FCD and BCD were determined. LFG collection data from a landfill site in the province of Quebec, Canada, was used to validate the LFG generation model. A range of scenarios was analyzed using the validated model, including fourteen scenarios (two benchmark and twelve optimizing) for CH4 and two for H2S modeling. The results showed that the differentiation of more waste types improves the modeling accuracy for CH4. Moreover, within the decade-long lifetime of a landfill, the waste management strategies change, requiring different assumptions for the modeling. Also, the work showed the importance of considering how different landfill sectors are filled over time. Finally, scenario twelve of optimizing scenarios, which assumed four waste types, constant three periodic waste fractions, and six sectors, had the lowest residual sum of squares (RSS) value. For H2S generation modeling, both scenarios, with or without separate fits of S0 and kH2S for FCD and BCD, predicted the generated H2S well and had a very similar RSS value. Further data could improve H2S generation modeling.

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β family, has been shown to act as a negative regulator in cardiac hypertrophy. Ca2+ signaling modulates cardiomyocyte growth; however, the role of Ca2+-dependent mechanisms in mediating the effects of GDF11 remains elusive. Here, we found that GDF11 induced intracellular Ca2+ increases in neonatal rat cardiomyocytes and that this response was blocked by chelating the intracellular Ca2+ with BAPTA-AM or by pretreatment with inhibitors of the inositol 1,4,5-trisphosphate (IP3) pathway. Moreover, GDF11 increased the phosphorylation levels and luciferase activity of Smad2/3 in a concentration-dependent manner, and the inhibition of IP3-dependent Ca2+ release abolished GDF11-induced Smad2/3 activity. To assess whether GDF11 exerted antihypertrophic effects by modulating Ca2+ signaling, cardiomyocytes were exposed to hypertrophic agents (100 nM testosterone or 50 μM phenylephrine) for 24 h. Both treatments increased cardiomyocyte size and [3H]-leucine incorporation, and these responses were significantly blunted by pretreatment with GDF11 over 24 h. Moreover, downregulation of Smad2 and Smad3 with siRNA was accompanied by inhibition of the antihypertrophic effects of GDF11. These results suggest that GDF11 modulates Ca2+ signaling and the Smad2/3 pathway to prevent cardiomyocyte hypertrophy.

In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.

Testosterone induces cardiac hypertrophy through a mechanism that involves a concerted crosstalk between cytosolic and nuclear signaling pathways. Nuclear factor of activated T-cells (NFAT) is associated with the promotion of cardiac hypertrophy, glycogen synthase kinase-3β (GSK-3β) is considered to function as a negative regulator, mainly by modulating NFAT activity. However, the role played by calcineurin-NFAT and GSK-3β signaling in testosterone-induced cardiac hypertrophy has remained unknown. Here, we determined that testosterone stimulates cardiac myocyte hypertrophy through NFAT activation and GSK-3β inhibition. Testosterone increased the activity of NFAT-luciferase (NFAT-Luc) in a time- and dose-dependent manner, with the activity peaking after 24 h of stimulation with 100 nM testosterone. NFAT-Luc activity induced by testosterone was blocked by the calcineurin inhibitors FK506 and cyclosporine A and by 11R-VIVIT, a specific peptide inhibitor of NFAT. Conversely, testosterone inhibited GSK-3β activity as determined by increased GSK-3β phosphorylation at Ser9 and β-catenin protein accumulation, and also by reduction in β-catenin phosphorylation at residues Ser33, Ser37, and Thr41. GSK-3β inhibition with 1-azakenpaullone or a GSK-3β-targeting siRNA increased NFAT-Luc activity, whereas overexpression of a constitutively active GSK-3β mutant (GSK-3βS9A) inhibited NFAT-Luc activation mediated by testosterone. Testosterone-induced cardiac myocyte hypertrophy was established by increased cardiac myocyte size and [3H]-leucine incorporation (as a measurement of cellular protein synthesis). Calcineurin-NFAT inhibition abolished and GSK-3β inhibition promoted the hypertrophy stimulated by testosterone. GSK-3β activation by GSK-3βS9A blocked the increase of hypertrophic markers induced by testosterone. Moreover, inhibition of intracellular androgen receptor prevented testosterone-induced NFAT-Luc activation. Collectively, these results suggest that cardiac myocyte hypertrophy induced by testosterone involves a cooperative mechanism that links androgen signaling with the recruitment of NFAT through calcineurin activation and GSK-3β inhibition.

Background Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake—via AMP-activated protein kinase (AMPK)—after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). Methods Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain ( β-mhc ). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). Results Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc , Hk2 and Pfk2 mRNA levels. Conclusion These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

In Chile, lesbian-parent families have faced legal and social advancements as well as challenges, generating new dynamics through assisted reproduction. The reproductive justice framework allows for an analysis of the inequities and injustices experienced by LGBTIQA+ people in relation to their reproductive rights. Objective: To analyze the narratives of lesbian-parent families who have accessed parenthood through assisted reproduction techniques within the Chilean healthcare system, identifying barriers and facilitators in the process, as well as possible instances of discrimination. Methodology: This research adopted a qualitative approach with a descriptive scope and was based on a constructivist paradigm, utilizing a narrative design and analysis. Four lesbian-parent families participated, selected through purposive or convenience sampling. Results: The findings revealed that the main barriers were related to health insurance coverage and social and geographical factors. Among the key facilitators were support networks, educational level, and healthcare professionals’ guidance. Discussion: The study highlighted the presence of inequalities affecting the exercise of parenthood and the right to form a family, shaped by institutional and social barriers from a reproductive justice framework. Conclusions: The study underscores the need to advance inclusive public policies and systemic changes that recognize and protect family diversity in Chile. Furthermore, it highlights the role of narratives as a tool to make visible and challenge the inequalities surrounding lesbian parenthood.

Autosomal Dominant Optic Atrophy (ADOA), a disease that causes blindness and other neurological disorders, is linked to OPA1 mutations. OPA1, dependent on its GTPase and GED domains, governs inner mitochondrial membrane (IMM) fusion and cristae organization, which are central to oxidative metabolism. Mitochondrial dynamics and IMM organization have also been implicated in Ca 2+ homeostasis and signaling but the specific involvements of OPA1 in Ca 2+ dynamics remain to be established. Here we studied the possible outcomes of OPA1 and its ADOA-linked mutations in Ca 2+ homeostasis using rescue and overexpression strategies in Opa1 -deficient and wild-type murine embryonic fibroblasts (MEFs), respectively and in human ADOA-derived fibroblasts. MEFs lacking Opa1 required less Ca 2+ mobilization from the endoplasmic reticulum (ER) to induce a mitochondrial matrix [Ca 2+ ] rise ([Ca 2+ ] mito ). This was associated with closer ER-mitochondria contacts and no significant changes in the mitochondrial calcium uniporter complex. Patient cells carrying OPA1 GTPase or GED domain mutations also exhibited altered Ca 2+ homeostasis, and the mutations associated with lower OPA1 levels displayed closer ER-mitochondria gaps. Furthermore, in Opa1 −/− MEF background, we found that acute expression of OPA1 GTPase mutants but no GED mutants, partially restored cytosolic [Ca 2+ ] ([Ca 2+ ] cyto ) needed for a prompt [Ca 2+ ] mito rise. Finally, OPA1 mutants’ overexpression in WT MEFs disrupted Ca 2+ homeostasis, partially recapitulating the observations in ADOA patient cells. Thus, OPA1 modulates functional ER-mitochondria coupling likely through the OPA1 GED domain in Opa1 −/− MEFs. However, the co-existence of WT and mutant forms of OPA1 in patients promotes an imbalance of Ca 2+ homeostasis without a domain-specific effect, likely contributing to the overall ADOA progress.

Testosterone is known to induce cardiac hypertrophy through androgen receptor (AR)-dependent and -independent pathways, but the molecular underpinnings of the androgen action remain poorly understood. Previous work has shown that Ca2+/calmodulin-dependent protein kinase II (CaMKII) and myocyte-enhancer factor 2 (MEF2) play key roles in promoting cardiac myocyte growth. In order to gain mechanistic insights into the action of androgens on the heart, we investigated how testosterone affects CaMKII and MEF2 in cardiac myocyte hypertrophy by performing studies on cultured rat cardiac myocytes and hearts obtained from adult male orchiectomized (ORX) rats. In cardiac myocytes, MEF2 activity was monitored using a luciferase reporter plasmid, and the effects of CaMKII and AR signaling pathways on MEF2C were examined by using siRNAs and pharmacological inhibitors targeting these two pathways. In the in vivo studies, ORX rats were randomly assigned to groups that were administered vehicle or testosterone (125 mg⋅kg-1⋅week-1) for 5 weeks, and plasma testosterone concentrations were determined using ELISA. Cardiac hypertrophy was evaluated by measuring well-characterized hypertrophy markers. Moreover, western blotting was used to assess CaMKII and phospholamban (PLN) phosphorylation, and MEF2C and AR protein levels in extracts of left-ventricle tissue from control and testosterone-treated ORX rats. Whereas testosterone treatment increased the phosphorylation levels of CaMKII (Thr286) and phospholambam (PLN) (Thr17) in cardiac myocytes in a time- and concentration-dependent manner, testosterone-induced MEF2 activity and cardiac myocyte hypertrophy were prevented upon inhibition of CaMKII, MEF2C, and AR signaling pathways. Notably, in the hypertrophied hearts obtained from testosterone-administered ORX rats, both CaMKII and PLN phosphorylation levels and AR and MEF2 protein levels were increased. Thus, this study presents the first evidence indicating that testosterone activates MEF2 through CaMKII and AR signaling. Our findings suggest that an orchestrated mechanism of action involving signal transduction and transcription pathways underlies testosterone-induced cardiac myocyte hypertrophy.

In Chile, same-sex couples have faced legal and social barriers that limit their equitable access to the adoption process. Objective: To explore the experiences of three same-sex couples who completed the adoption process in the Chilean public system before implementing the equal marriage law in 2022. Method: A qualitative phenomenological approach was employed, using semi-structured interviews to collect narratives from adoptive families. The information was analyzed using qualitative content analysis, identifying patterns and emerging themes. Results: It was revealed that families identified a market-driven logic within the adoption process, where personal preferences and prejudices influence the adoption decisions of traditional families, from which same-sex couples try to distance themselves. Additionally, significant challenges related to emotional bonding and family adaptation post-adoption were identified. Same-sex couples reported being clearly in a different position compared to traditional families and faced additional difficulties due to a lack of institutional support and insufficient post-adoption follow-up. Discussion and Conclusions: The need for structural reforms in the Chilean adoption system is highlighted to ensure equity and fair treatment for all families, regardless of their composition. The conclusion emphasizes the importance of implementing inclusive policies that recognize and support family diversity, promoting a fairer and more equitable adoption system that ensures the well-being of all children involved.

This study examines the experiences of lesbian-parent families in Chile regarding the civil registry and the registration of their children, highlighting how heteronormative structures persist despite significant legislative advancements. Through semi-structured interviews with lesbian mothers, it explored how the policies and practices occurring at the civil registry affect their rights and legal recognition. The qualitative data analysis revealed significant barriers in the filiation processes due to outdated forms and lack of training among officials, reflecting a disconnect between progressive legislation and its practical implementation. The findings indicate that while there is growing social recognition of family diversity, lesbian-parent families face institutional discrimination, limiting their full participation in society. These barriers not only perpetuate occupational injustices but also negatively affect the emotional and social well-being of these families. This study underscores the need for legislative and administrative reforms to ensure effective inclusion and recognition of lesbian-parent families, recommending policies that update administrative processes to reflect the realities of all families adequately. The research highlights the importance of continuous education and awareness for civil registry workers, ensuring that existing laws are applied fairly and equitably.