Asian Americans in STEM are not a monolith.

Despite tremendous diversity, Asian Americans in STEM are grouped and viewed as a homogeneous monolith, facing stereotypes and disparities. We propose solutions that include disaggregating the Asian American grouping and recognizing the diverse individual ethnic subgroups that comprise Americans of Asian ancestry to implement change within the STEM field.

Patching the Leaks: Revitalizing and Reimagining the STEM Pipeline.

We identify problematic areas throughout the Science, Technology, Engineering and Mathematics (STEM) pipeline that perpetuate racial disparities in academia. Distinct ways to curtail these disparities include early exposure and access to resources, supportive mentoring networks and comprehensive training programs specifically for racially minoritized students and trainees at each career stage. These actions will revitalize the STEM pipeline.

Diversity, Equity and Inclusion in the Laboratory: Strategies to Enhance Inclusive Laboratory Culture.

Building a diverse laboratory that is equitable is critical for the retention of talent and the growth of trainees professionally and personally. Here, we outline several strategies including enhancing understanding of cultural competency and humility, establishing laboratory values, and developing equitable laboratory structures to create an inclusive laboratory environment to enable trainees to achieve their highest success.

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.

Mentoring during Uncertain Times.

Scientific success is mainly supported by mentoring, which often occurs through face-to-face interactions. Changes to the research environment incurred by the Coronavirus 2019 (COVID-19) pandemic have necessitated mentorship adaptations. Here, we describe how mentors can broaden their mentorship to support trainee growth and provide reassurance about trainee development amid uncertain circumstances.

DRP1 mutations associated with EMPF1 encephalopathy alter mitochondrial membrane potential and metabolic programs.

Mitochondria and peroxisomes are dynamic signaling organelles that constantly undergo fission, driven by the large GTPase dynamin-related protein 1 (DRP1; encoded by DNM1L). Patients with de novo heterozygous missense mutations in DNM1L present with encephalopathy due to defective mitochondrial and peroxisomal fission (EMPF1) - a devastating neurodevelopmental disease with no effective treatment. To interrogate the mechanisms by which DRP1 mutations cause cellular dysfunction, we used human-derived fibroblasts from patients who present with EMPF1. In addition to elongated mitochondrial morphology and lack of fission, patient cells display lower coupling efficiency, increased proton leak and upregulation of glycolysis. Mitochondrial hyperfusion also results in aberrant cristae structure and hyperpolarized mitochondrial membrane potential. Peroxisomes show a severely elongated morphology in patient cells, which is associated with reduced respiration when cells are reliant on fatty acid oxidation. Metabolomic analyses revealed impaired methionine cycle and synthesis of pyrimidine nucleotides. Our study provides insight into the role of mitochondrial dynamics in cristae maintenance and the metabolic capacity of the cell, as well as the disease mechanism underlying EMPF1.

Disruption of nucleotide biosynthesis reprograms mitochondrial metabolism to inhibit adipogenesis.

A key organismal response to overnutrition involves the development of new adipocytes through the process of adipogenesis. Preadipocytes sense changes in the systemic nutrient status and metabolites can directly modulate adipogenesis. We previously identified a role of de novo nucleotide biosynthesis in adipogenesis induction, whereby inhibition of nucleotide biosynthesis suppresses the expression of the transcriptional regulators PPARγ and C/EBPα. Here, we set out to identify the global transcriptomic changes associated with the inhibition of nucleotide biosynthesis. Through RNA sequencing (RNAseq), we discovered that mitochondrial signatures were the most altered in response to inhibition of nucleotide biosynthesis. Blocking nucleotide biosynthesis induced rounded mitochondrial morphology, and altered mitochondrial function, and metabolism, reducing levels of tricarboxylic acid cycle intermediates, and increasing fatty acid oxidation (FAO). The loss of mitochondrial function induced by suppression of nucleotide biosynthesis was rescued by exogenous expression of PPARγ. Moreover, inhibition of FAO restored PPARγ expression, mitochondrial protein expression, and adipogenesis in the presence of nucleotide biosynthesis inhibition, suggesting a regulatory role of nutrient oxidation in differentiation. Collectively, our studies shed light on the link between substrate oxidation and transcription in cell fate determination.

How to design a broad mindfulness program: One approach to introducing mindfulness to a STEM community 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.

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.

Cytokine and chemokine receptor profiles in adipose tissue vasculature unravel endothelial cell responses in HIV.

Chronic systemic inflammation significantly increases myocardial infarction risk in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis, contributing to cardiovascular disease. We aimed to characterize endothelial cell (EC) chemokines, cytokine, and chemokine receptors of PLWH, hypothesizing that in our cohort, glucose intolerance contributes to their differential expression implicated in endothelial dysfunction. Using single-cell transcriptomic analysis, we phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in subcutaneous adipose tissue of 59 PLWH with and without glucose intolerance. Our results show that arterial and capillary ECs express significantly higher interferon and tumor necrosis factor (TNF) receptors than venous ECs and VSMCs. Venous ECs exhibited more interleukin (IL)1R1 and ACKR1 receptors, and VSMCs showed significant IL6R expression than arterial and capillary ECs. When stratified by group, arterial ECs from PLWH with glucose intolerance expressed significantly higher IL1R1, IL6R, CXCL12, CCL14, and ICAM2 transcripts than arterial ECs from PLWH without diabetes. Of the different vascular cell types studied, arterial ECs as a proportion of all ECs in adipose tissue were positively correlated with plasma fasting blood glucose. In contrast, venous ECs and VSMCs were positively correlated with plasma IL6. To directly assess the effect of plasma from PLWH on endothelial function, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk RNA sequencing. Plasma from PLWH stimulated ECs with the upregulation of genes that enrich for the oxidative phosphorylation and the TNF-α via NFK-ß pathways. In conclusion, ECs in PLWH show heterogeneous cytokine and chemokine receptor expression, and arterial ECs were the most influenced by glucose intolerance. Further research must explicate cytokine and chemokine roles in EC dysfunction and identify biomarkers for disease progression and therapeutic response.

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.

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.

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.

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.

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 (LDs) 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. For example, 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 the 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. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison 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 the mitochondria interacting with LDs. 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 with mitochondrial function, metabolism, and bioactivity in aged BAT.

A workshop to enrich physiological understanding through hands-on learning about mitochondria-endoplasmic reticulum contact sites.

Physiology is an important field for students to gain a better understanding of biological mechanisms. Yet, many students often find it difficult to learn from lectures, resulting in poor retention. Here, we utilize a learning workshop model to teach students at different levels ranging from middle school to undergraduate. We specifically designed a workshop to teach students about mitochondria-endoplasmic reticulum contact (MERC) sites. The workshop was implemented for middle school students in a laboratory setting that incorporated a pretest to gauge prior knowledge, instructional time, hands-on activities, interactive learning from experts, and a posttest. We observed that the students remained engaged during the session of interactive methods, teamed with their peers to complete tasks, and delighted in the experience. Implications for the design of future physiological workshops are further offered.NEW & NOTEWORTHY This manuscript offers a design for a workshop that utilizes blended learning to engage middle school, high school, and undergraduate students while teaching them about mitochondria-endoplasmic reticulum contact sites.

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.

Three-dimensional mitochondria reconstructions of murine cardiac muscle changes in size across aging.

With sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria breakdown and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress. The roles of key mitochondrial complexes that dictate the ultrastructure, such as the mitochondrial contact site and cristae organizing system (MICOS), in aging cardiac muscle are poorly understood. To better understand the cause of age-related alteration in mitochondrial structure in cardiac muscle, we used transmission electron microscopy (TEM) and serial block facing-scanning electron microscopy (SBF-SEM) to quantitatively analyze the three-dimensional (3-D) networks in cardiac muscle samples of male mice at aging intervals of 3 mo, 1 yr, and 2 yr. Here, we present the loss of cristae morphology, the inner folds of the mitochondria, across age. In conjunction with this, the three-dimensional (3-D) volume of mitochondria decreased. These findings mimicked observed phenotypes in murine cardiac fibroblasts with CRISPR/Cas9 knockout of Mitofilin, Chchd3, Chchd6 (some members of the MICOS complex), and Opa1, which showed poorer oxidative consumption rate and mitochondria with decreased mitochondrial length and volume. In combination, these data show the need to explore if loss of the MICOS complex in the heart may be involved in age-associated mitochondrial and cristae structural changes.NEW & NOTEWORTHY This article shows how mitochondria in murine cardiac changes, importantly elucidating age-related changes. It also is the first to show that the MICOS complex may play a role in outer membrane mitochondrial structure.

A workshop on mitochondria for students to improve understanding of science and hypothesis forming.

There remains a clear deficiency in recruiting middle school students in science, technology, engineering, mathematics, and medicine fields, especially for those students entering physiology from underrepresented backgrounds. A large part of this may be arising from a disconnect between how science is typically practiced at a collegiate and K-12 level. Here, we have envisioned mitochondria and their diverse subcellular structures as an involver for middle school students. We present the framework for a workshop that familiarizes students with mitochondria, employing three-dimensional visual-spatial learning and real-time critical thinking and hypothesis forming. This workshop had the goal of familiarizing middle school students with the unique challenges the field currently faces and better understanding the actuality of being a scientist through critical analysis including hypothesis forming. Findings show that middle school students responded positively to the program and felt as though they had a better understanding of mitochondria. Future implications for hands-on programs to involve underrepresented students in science are discussed, as well as potential considerations to adapt it for high school and undergraduate students.NEW & NOTEWORTHY Here we employ a workshop that utilizes blended and tactile learning to teach middle schoolers about mitochondrial structure. By creating an approachable and fun workshop that can be utilized for middle school students, we seek to encourage them to join a career in physiology.

Mentoring minority trainees: Minorities in academia face specific challenges that mentors should address to instill confidence.

A toolkit for mentoring minority students and trainees in science.