The MICOS Complex Regulates Mitochondrial Structure and Oxidative Stress During Age-Dependent Structural Deficits in the Kidney.

The kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease. Dysfunction in mitochondria and cristae, the inner folds of mitochondria, is a hallmark of aging. Therefore, age-related kidney function decline could be due to changes in mitochondrial ultrastructure, increased reactive oxygen species (ROS), and subsequent alterations in metabolism and lipid composition. We sought to understand if there is altered mitochondrial ultrastructure, as marked by 3D morphological changes, across time in tubular kidney cells. Serial block facing-scanning electron microscope (SBF-SEM) and manual segmentation using the Amira software were used to visualize murine kidney samples during the aging process at 3 months (young) and 2 years (old). We found that 2-year mitochondria are more fragmented, compared to the 3-month, with many uniquely shaped mitochondria observed across aging, concomitant with shifts in ROS, metabolomics, and lipid homeostasis. Furthermore, we show that the mitochondrial contact site and cristae organizing system (MICOS) complex is impaired in the kidney due to aging. Disruption of the MICOS complex shows altered mitochondrial calcium uptake and calcium retention capacity, as well as generation of oxidative stress. We found significant, detrimental structural changes to aged kidney tubule mitochondria suggesting a potential mechanism underlying why kidney diseases occur more readily with age. We hypothesize that disruption in the MICOS complex further exacerbates mitochondrial dysfunction, creating a vicious cycle of mitochondrial degradation and oxidative stress, thus impacting kidney health. Translational Statement: Due to aging, the efficiency of kidney functions begins to decrease and the risk of kidney diseases may increase, but specific regulators of mitochondrial age-related changes are poorly explained. This study demonstrates the MICOS complex may be a target for mitigating age-related changes in mitochondria. The MICOS complex can be associated with oxidative stress and calcium dysregulation, which also arise in many kidney pathologies.

Quantitative Assessment of Morphological Changes in Lipid Droplets and Lipid-Mito Interactions with Aging in Brown Adipose.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LD) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. Particularly, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Analysis showed reductions in LD volume, area, and perimeter in aged samples compared to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for mitochondria interacting with LD lipids. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology and mitochondrial functionality, metabolism, and bioactivity in aged BAT.

Myeloid Cell Glucocorticoid, Not Mineralocorticoid Receptor Signaling, Contributes to Salt-Sensitive Hypertension in Humans via Cortisol.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality, yet the etiology is poorly understood. We previously found that serum/glucocorticoid-regulated kinase 1 (SGK1) and epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel (ENaC)-dependent sodium entry into monocyte-derived antigen-presenting cells (APCs) and activation of NADPH oxidase, leading to the formation of isolevuglandins (IsoLGs) in SSBP. Whereas aldosterone via the mineralocorticoid receptor (MR) activates SGK1 leading to hypertension, our past findings indicate that levels of plasma aldosterone do not correlate with SSBP, and there is little to no MR expression in APCs. Thus, we hypothesized that cortisol acting via the glucocorticoid receptor (GR), not the MR in APCs mediates SGK1 actions to induce SSBP. METHODS: We performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) analysis on peripheral blood mononuclear cells of humans rigorously phenotyped for SSBP using an inpatient salt loading/depletion protocol to determine expression of MR, GR, and SGK1 in immune cells. In additional experiments, we performed bulk transcriptomic analysis on isolated human monocytes following in vitro treatment with high salt from a separate cohort. We then measured urine and plasma cortisol, cortisone, renin, and aldosterone. Subsequently, we measured the association of these hormones with changes in systolic, diastolic, mean arterial pressure and pulse pressure as well as immune cell activation via IsoLG formation. RESULTS: We found that myeloid APCs predominantly express the GR and SGK1 with no expression of the MR. Expression of the GR in APCs increased after salt loading and decreased with salt depletion in salt-sensitive but not salt-resistant people and was associated with increased expression of SGK1 . Moreover, we found that plasma and urine cortisol/cortisone but not aldosterone/renin correlated with SSBP and APCs activation via IsoLGs. We also found that cortisol negatively correlates with EETs. CONCLUSION: Our findings suggest that renal cortisol signaling via the GR but not the MR in APCs contributes to SSBP via cortisol. Urine and plasma cortisol may provide an important currently unavailable feasible diagnostic tool for SSBP. Moreover, cortisol-GR-SGK1-ENaC signaling pathway may provide treatment options for SSBP. Novelty and Relevance: What Is New?: Although salt sensitivity is a major risk factor for cardiovascular morbidity and mortality, the mechanisms underlying the salt sensitivity of blood pressure (SSBP) are poorly understood.High salt modifies glucocorticoid-receptor expression in antigen-presenting cells (APCs), suggesting a critical role of glucocorticoids in SSBP. Elevated glucocorticoid receptor (GR) expression compared to mineralocorticoid receptor (MR) expression in APCs provides evidence for a GR-dependent pathway to SSBP. Isolevuglandins (IsoLGs) increased in APCs in vitro after hydrocortisone treatment compared to aldosterone treatment, indicating that cortisol was the predominant driver of IsoLG production in these cells. Our studies suggest a mechanism for SGK1 expression through GR activation by cortisol that differs from the currently accepted mechanism for SSBP pathogenesis. What Is Relevant?: Although aldosterone has been used to study SSBP, there has been no consideration of cortisol as a major driver of the condition.Understanding alternative inflammatory pathways that affect SSBP may provide insights into the mechanism of SSBP and suggest a range of therapeutic targets.Our studies may provide a practical approach to understanding and treating salt-sensitive hypertension.Clinical/Pathophysiological Implications?: Our findings firmly support a GR-dependent signaling pathway for activating SSBP via SGK1 expression. A cortisol-driven mechanism could provide a practical approach for targeted treatments for salt-sensitive hypertension. Moreover, it could pave the way for a diagnostic approach.

Methods to Utilize Pulse Wave Velocity to Measure Alterations in Cerebral and Cardiovascular Parameters.

Alzheimer's Disease (AD) is a global health issue, affecting over 6 million in the United States, with that number expected to increase as the aging population grows. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. However, the study of cerebrovascular techniques for AD is still evolving. Here, we provide reproducible methods to measure impedance-based pulse wave velocity (PWV), a marker of arterial stiffness, in the systemic vascular (aortic PWV) and in the cerebral vascular (cerebral PWV) systems. Using aortic impedance and this relatively novel technique of cerebral impedance to comprehensively describe the systemic vascular and the cerebral vascular systems, we examined the sex-dependent differences in 5x transgenic mice (5XFAD) with AD under normal and high-fat diet, and in wild-type mice under a normal diet. Additionally, we validated our method for measuring cerebrovascular impedance in a model of induced stress in 5XFAD. Together, our results show that sex and diet differences in wildtype and 5XFAD mice account for very minimal differences in cerebral impedance. Interestingly, 5XFAD, and not wildtype, male mice on a chow diet show higher cerebral impedance, suggesting pathological differences. Opposingly, when we subjected 5XFAD mice to stress, we found that females showed elevated cerebral impedance. Using this validated method of measuring impedance-based aortic and cerebral PWV, future research may explore the effects of modifying factors including age, chronic diet, and acute stress, which may mediate cardiovascular risk in AD.

A review of undergraduate research programs aimed at underrepresented students.

It is well-understood that the science, technology, engineering, and mathematics (STEM) fields have unique challenges that discourage recruiting and retaining underrepresented minorities. Research programs aimed at undergraduates have arisen as a critical mechanism for fostering innovation and addressing the challenges faced by underrepresented minorities. Here, we review various undergraduate research programs designed to provide exposure to undergraduates, with a focus on underrepresented minorities in STEM disciplines. We provide insight into selected programs' objectives, key features, potential limitations, and outcomes. We also offer recommendations for future improvements of each research program, particularly in the context of mentorship. These programs range from broad-reaching initiatives (e.g., Leadership Alliance) to more specific programs targeting underrepresented students. By offering a nuanced understanding of each program's structure, we seek to provide a brief overview of the landscape of diversity-focused STEM initiatives and a guide on how to run a research program effectively.

Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes.

The sorting and assembly machinery (SAM) Complex is responsible for assembling ß-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block-face-scanning electron microscopy and computer-assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50-deficient myotubes from mice and humans with wild-type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography-Mass Spectrometry-based metabolomics to explore differential changes in WT and Sam50-deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50-deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß-Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50-deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50-deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle.

Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments.

HIV infection and antiretroviral therapy alter mitochondrial function, which can progressively lead to mitochondrial damage and accelerated aging. The interaction between persistent HIV reservoirs and mitochondria may provide insight into the relatively high rates of cardiovascular disease and mortality in persons living with HIV. In this review, we explore the intricate relationship between HIV and mitochondrial function, highlighting the potential for novel therapeutic strategies in the context of cardiovascular diseases. We reflect on mitochondrial dynamics, mitochondrial DNA, and mitochondrial antiviral signaling protein in the context of HIV. Furthermore, we summarize how toxicities related to early antiretroviral therapy and current highly active antiretroviral therapy can contribute to mitochondrial dysregulation, chronic inflammation, and poor clinical outcomes. There is a need to understand the mechanisms and develop new targeted therapies. We further consider current and potential future therapies for HIV and their interplay with mitochondria. We reflect on the next-generation antiretroviral therapies and HIV cure due to the direct and indirect effects of HIV persistence, associated comorbidities, coinfections, and the advancement of interdisciplinary research fields. This includes exploring novel and creative approaches to target mitochondria for therapeutic intervention.

Cytokine and Chemokine Receptor Profiles in Adipose Tissue Vasculature Unravel Endothelial Cell Responses in HIV.

Chronic systemic inflammation contributes to a substantially elevated risk of myocardial infarction in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis that contribute to cardiovascular disease. Our objective was to study the effects of plasma from PLWH on endothelial cell (EC) function, with the hypothesis that cytokines and chemokines are major drivers of EC activation. We first broadly phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in adipose tissue in the subcutaneous adipose tissue of 59 PLWH using single cell transcriptomic analysis. We used CellChat to predict cell-cell interactions between ECs and other cells in the adipose tissue and Spearman correlation to measure the association between ECs and plasma cytokines. Finally, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk sequencing to study the direct effects ex-vivo. We observed that arterial and capillary ECs expressed higher interferon and tumor necrosis factor (TNF) receptors. Venous ECs had more interleukin (IL)-1R1 and ACKR1 receptors, and VSMCs had high significant IL-6R expression. CellChat predicted ligand-receptor interactions between adipose tissue immune cells as senders and capillary ECs as recipients in TNF-TNFRSF1A/B interactions. Chemokines expressed largely by capillary ECs were predicted to bind ACKR1 receptors on venous ECs. Beyond the adipose tissue, the proportion of venous ECs and VSMCs were positively plasma IL-6. In ex-vivo experiments, HAECs cultured with plasma-conditioned media from PLWH expressed transcripts that enriched for the TNF-α and reactive oxidative phosphorylation pathways. In conclusion, ECs demonstrate heterogeneity in cytokine and chemokine receptor expression. Further research is needed to fully elucidate the role of cytokines and chemokines in EC dysfunction and to develop effective therapeutic strategies.

How to design a broad mindfulness program: One approach to introducing mindfulness to a STEM commumity within a university setting.

Mindfulness has become popular in recent decades as a tool for psychological well-being. However, mindfulness has yet to find a solid footing as a routine practice within the Science, Technology, Engineering, and Mathematics (STEM) field. Here, we discuss the design of an introductory mindfulness program that provides the STEM community with a broad overview of various mindfulness methods. We also discuss delivery implementation methods and other considerations when designing mindfulness programming. This article provides resources for those interested in incorporating mindfulness into the STEM field, especially within the university setting.

Running a successful STEMM summer program: A week-by-week guide.

While some established undergraduate summer programs are effective across many institutions, these programs may only be available to some principal investigators or may not fully address the diverse needs of incoming undergraduates. This article outlines a 10-week science, technology, engineering, mathematics, and medicine (STEMM) education program designed to prepare undergraduate students for graduate school through a unique model incorporating mentoring dyads and triads, cultural exchanges, and diverse activities while emphasizing critical thinking, research skills, and cultural sensitivity. Specifically, we offer a straightforward and adaptable guide that we have used for mentoring undergraduate students in a laboratory focused on mitochondria and microscopy, but which may be customized for other disciplines. Key components include self-guided projects, journal clubs, various weekly activities such as mindfulness training and laboratory techniques, and a focus on individual and cultural expression. Beyond this unique format, this 10-week program also seeks to offer an intensive research program that emulates graduate-level experiences, offering an immersive environment for personal and professional development, which has led to numerous achievements for past students, including publications and award-winning posters.

ATF4-dependent increase in mitochondrial-endoplasmic reticulum tethering following OPA1 deletion in skeletal muscle.

Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein- and lipid-enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca2+, lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle-specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin-2, a known MERC protein. In the present study, we tested the hypothesis that Opa1 downregulation in skeletal muscle cells alters MERC formation by evaluating multiple myocyte systems, including from mice and Drosophila, and in primary myotubes. Our results revealed that OPA1 deficiency induced tighter and more frequent MERCs in concert with a greater abundance of MERC proteins involved in calcium exchange. Additionally, loss of OPA1 increased the expression of activating transcription factor 4 (ATF4), an integrated stress response (ISR) pathway effector. Reducing Atf4 expression prevented the OPA1-loss-induced tightening of MERC structures. OPA1 reduction was associated with decreased mitochondrial and sarcoplasmic reticulum, a specialized form of ER, calcium, which was reversed following ATF4 repression. These data suggest that mitochondrial stress, induced by OPA1 deficiency, regulates skeletal muscle MERC formation in an ATF4-dependent manner.

Disparities in funding for Nobel Prize awards in medicine and physiology across nationalities, races, and gender.

Since 1901, the Nobel Prize in Physiology and Medicine has been awarded to numerous individuals for their outstanding contributions. This article presents a comprehensive analysis of the Nobel Prize recipients, focusing on gender, race, and nationality. We observe that an alarming disparity emerges when we examine the underrepresentation of Black scientists among Nobel laureates. Furthermore, trends in nationalities show how Americans make up the majority of Nobel Prize winners, while there is a noticeable lack of gender and racial minority winners of the Nobel Prize in Physiology and Medicine. Together, this highlights the importance of diversity and inclusion in scientific achievement. We offer suggestions and techniques, including funding opportunities and expanding nominators, to improve the gender, racial, and geographical diversity of Nobel Prizes.

Speaking up for the invisible minority: First-generation students in higher education.

A first-generation college student is typically defined as a student whose biological parent(s) or guardian(s) never attended college or who started but did not finish college. However, "first-generation" can represent diverse family education situations. The first-generation student community is a multifaceted, and intersectional group of individuals who frequently lack educational/financial resources to succeed and, consequently, require supportive environments with rigorous mentorship. However, first-generation students often do not make their identity as first-generation students known to others due to several psychosocial and academic factors. Therefore, they are often "invisible minorities" in higher education. In this paper, we describe the diverse family situations of first-generation students, further define "first-generation," and suggest five actions that first-generation trainees at the undergraduate/graduate stages can engage in to succeed in an academic climate. We also provide suggestions for mentors to accommodate first-generation students' unique experiences and equip them with tools to deliver intentional mentoring practices. We hope that this paper will help promote first-generation student success throughout the academic pipeline.

A workshop to showcase the diversity of scientists to middle school students.

Identity matters in science, technology, engineering, mathematics, and medicine (STEMM) because it can affect an individual's long-term sense of belonging, which may in turn affect their persistence in STEMM. Early K-12 science classes often teach students about the foundational discoveries of the field, which have been predominately made, or at least published, by White men. This homogeneity can leave underrepresented individuals in STEMM feeling isolated, and underrepresented K-12 students may feel as though they cannot enter STEMM fields. This study aimed to examine these feelings of inclusivity in STEMM through an interactive workshop that asked middle schoolers to identify scientists from images of individuals with various racial and gender identities. We found that a plurality of students had a positive experience discussing diversity in science and recognizing underrepresented individuals as scientists.NEW & NOTEWORTHY We observed positive sentiments from middle school students following a workshop that showcased diversity in science. This workshop uniquely encourages students to recognize that physiologists and scientists today are much more diverse than textbooks typically demonstrate and can be adapted for middle schoolers, high schoolers, and college students.

Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy.

Hypertension is the primary modifiable risk factor for cardiovascular, renal, and cerebrovascular diseases and is considered the main contributing factor to morbidity and mortality worldwide. Approximately 50% of hypertensive and 25% of normotensive people exhibit salt sensitivity of blood pressure, which is an independent risk factor for cardiovascular disease. Human and animal studies demonstrate that the immune system plays an important role in the etiology and pathogenesis of salt sensitivity of blood pressure, kidney damage, and vascular diseases. Antigen-presenting and adaptive immune cells are implicated in salt-sensitive hypertension and salt-induced renal and vascular injury. Elevated sodium activates antigen-presenting cells to release proinflammatory cytokines including IL (interleukin) 6, tumor necrosis factor-α, IL-1ß, and accumulate isolevuglandin-protein adducts. In turn, these activate T cells release prohypertensive cytokines including IL-17A. Moreover, high-salt intake is associated with gut dysbiosis, leading to inflammation, oxidative stress, and blood pressure elevation but the mechanistic contribution to salt-sensitivity of blood pressure is not clearly understood. Here, we discuss recent advances in research investigating the cause, potential biomarkers, and therapeutic targets for salt-sensitive hypertension as they pertain to the gut microbiome, immunity, and inflammation.

3D Mitochondrial Structure in Aging Human Skeletal Muscle: Insights into MFN-2 Mediated Changes.

Age-related atrophy of skeletal muscle, is characterized by loss of mass, strength, endurance, and oxidative capacity during aging. Notably, bioenergetics and protein turnover studies have shown that mitochondria mediate this decline in function. Although exercise has been the only therapy to mitigate sarcopenia, the mechanisms that govern how exercise serves to promote healthy muscle aging are unclear. Mitochondrial aging is associated with decreased mitochondrial capacity, so we sought to investigate how aging affects mitochondrial structure and potential age-related regulators. Specifically, the three-dimensional (3D) mitochondrial structure associated with morphological changes in skeletal muscle during aging requires further elucidation. We hypothesized that aging causes structural remodeling of mitochondrial 3D architecture representative of dysfunction, and this effect is mitigated by exercise. We used serial block-face scanning electron microscopy to image human skeletal tissue samples, followed by manual contour tracing using Amira software for 3D reconstruction and subsequent analysis of mitochondria. We then applied a rigorous in vitro and in vivo exercise regimen during aging. Across 5 human cohorts, we correlate differences in magnetic resonance imaging, mitochondria 3D structure, exercise parameters, and plasma immune markers between young (under 50 years) and old (over 50 years) individuals. We found that mitochondria we less spherical and more complex, indicating age-related declines in contact site capacity. Additionally, aged samples showed a larger volume phenotype in both female and male humans, indicating potential mitochondrial swelling. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age-related losses. Exercise stimulation restored mitofusin 2 (MFN2), one such of these mitochondrial dynamic proteins, which we show is required for the integrity of mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved as Marf, the MFN2 ortholog in Drosophila, knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age-related structural changes in mitochondria and further suggest that exercise may mitigate age-related structural decline through modulation of mitofusin 2.

Defining Mitochondrial Cristae Morphology Changes Induced by Aging in Brown Adipose Tissue.

Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content and abundance. The physiological function and bioenergetic capacity of mitochondria are connected to the structure, folding, and organization of its inner-membrane cristae. During the aging process, mitochondrial dysfunction is observed, and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells. Therefore, it is hypothesized that significant morphological changes in BAT mitochondria and cristae will be present with aging. A quantitative 3D electron microscopy approach is developed to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, the 3D morphology of mitochondrial cristae is investigated in adult (3-month) and aged (2-year) murine BAT tissue via serial block face-scanning electron microscopy (SBF-SEM) and 3D reconstruction software for manual segmentation, analysis, and quantification. Upon investigation, an increase is found in mitochondrial volume, surface area, and complexity and decreased sphericity in aged BAT, alongside significant decreases in cristae volume, area, perimeter, and score. Overall, these data define the nature of the mitochondrial structure in murine BAT across aging.

Human Heart Failure Alters Mitochondria and Fiber 3D Structure Triggering Metabolic Shifts.

This study, utilizing SBF-SEM, reveals structural alterations in mitochondria and myofibrils in human heart failure (HF). Mitochondria in HF show changes in structure, while myofibrils exhibit increased cross-sectional area and branching. Metabolomic and lipidomic analyses indicate concomitant dysregulation in key pathways. The findings underscore the need for personalized treatments considering individualized structural changes in HF.

A pilot study on our non-traditional, varied writing accountability group for historically excluded and underrepresented persons in STEMM.

Underrepresented faculty have higher burnout rates and lower grant attainment rates when compared with their non-minority counterparts. Many in science, technology, engineering, mathematics, and medicine (STEMM) disciplines, including underrepresented individuals, often have difficulty dedicating time to the writing process, with trainees often being relegated to laboratory tasks in their training years, resulting in a lack of practice in academic writing. Notably, past studies have shown that grant attainment rates of underrepresented individuals are lower than their majority counterparts. Here, we sought to consider a mechanism targeted to underrepresented individuals, although applicable to everyone, to help overcome traditional barriers to writing in STEMM. The authors have hosted a writing accountability group (WAG) that uniquely provides a format focused on physical activity and different forms of writing to strengthen both career development and award/funding attainment. Our objectives were to evaluate this unique format, thus creating a resource for individuals and institutions to learn about WAGs and expand upon the framework to formulate their own WAG. To do this, we performed a small pilot study (n = 21) to investigate attitudes towards the WAG. We present the results of a survey conducted among underrepresented WAG participants, which spanned different career stages and was highly diverse demographically. Our results show that following attendance of our WAG, individuals did not note a significant change in scales pertaining to John Henryism (high-effort coping), resilience, sense of belonging, or grit. However, significant increases were noted in the self-perceived ability to handle stress, confidence in applying for awards, appreciation for mentoring, and satisfaction of WAGs. Taken together, the results of this study suggest that our unique WAG format can have some positive results as a career and writing development opportunity and may be able to support underrepresented individuals in attaining funding at higher education institutions.

3D reconstruction of murine mitochondria reveals changes in structure during aging linked to the MICOS complex.

During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block-face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase-quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age-related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age-related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue-dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals.