Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ...ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice specifically lacking estrogen receptor-α (ERα) in serotonin (5-HT) neurons in the dorsal raphe nuclei (DRN). Administration of a recently developed glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate designed to deliver estrogen to GLP1 receptor-enhanced regions effectively targeted bioactive estrogens to the DRN and substantially suppressed binge-like eating in ovariectomized female mice. Administration of GLP-1 alone reduced binge-like eating, but not to the same extent as the GLP-1-estrogen conjugate. Administration of ERα-selective agonist propylpyrazole triol (PPT) to murine DRN 5-HT neurons activated these neurons in an ERα-dependent manner. PPT also inhibited a small conductance Ca2+-activated K+ (SK) current; blockade of the SK current prevented PPT-induced activation of DRN 5-HT neurons. Furthermore, local inhibition of the SK current in the DRN markedly suppressed binge-like eating in female mice. Together, our data indicate that estrogens act upon ERα to inhibit the SK current in DRN 5-HT neurons, thereby activating these neurons to suppress binge-like eating behavior and suggest ERα and/or SK current in DRN 5-HT neurons as potential targets for anti-binge therapies.
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.
Mitochondrial dysfunction has long been implicated in the development of insulin resistance, which is a hallmark of type 2 diabetes. However, recent studies reveal ethnicity-related differences in ...mitochondrial processes, underscoring the need for nuance in studying mitochondrial dysfunction and insulin sensitivity. Furthermore, the higher prevalence of type 2 diabetes among African Americans and individuals of African descent has brought attention to the role of ethnicity in disease susceptibility. In this review, which covers existing literature, genetic studies, and clinical data, we aim to elucidate the complex relationship between mitochondrial alterations and insulin stimulation by considering how mitochondrial dynamics, contact sites, pathways, and metabolomics may be differentially regulated across ethnicities, through mechanisms such as single nucleotide polymorphisms (SNPs). In addition to achieving a better understanding of insulin stimulation, future studies identifying novel regulators of mitochondrial structure and function could provide valuable insights into ethnicity-dependent insulin signaling and personalized care.
Mentoring during Uncertain Times Termini, Christina M.; McReynolds, Melanie R.; Rutaganira, Florentine U.N. ...
Trends in biochemical sciences (Amsterdam. Regular ed.),
20/May , Letnik:
46, Številka:
5
Journal Article
Recenzirano
Odprti dostop
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.
Neuroimmunology of Cardiovascular Disease Zarate, Sara M.; Kirabo, Annet; Hinton Jr, Antentor O. ...
Current hypertension reports,
07/2024, Letnik:
26, Številka:
7
Journal Article
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Odprti dostop
Purpose of Review
Cardiovascular disease (CVD) is a leading cause of death and chronic disability worldwide. Yet, despite extensive intervention strategies the number of persons affected by CVD ...continues to rise. Thus, there is great interest in unveiling novel mechanisms that may lead to new treatments. Considering this dilemma, recent focus has turned to the neuroimmune mechanisms involved in CVD pathology leading to a deeper understanding of the brain’s involvement in disease pathology. This review provides an overview of new and salient findings regarding the neuroimmune mechanisms that contribute to CVD.
Recent Findings
The brain contains neuroimmune niches comprised of glia in the parenchyma and immune cells at the brain’s borders, and there is strong evidence that these neuroimmune niches are important in both health and disease. Mechanistic studies suggest that the activation of glia and immune cells in these niches modulates CVD progression in hypertension and heart failure and contributes to the inevitable end-organ damage to the brain.
Summary
This review provides evidence supporting the role of neuroimmune niches in CVD progression. However, additional research is needed to understand the effects of prolonged neuroimmune activation on brain function.
Purpose of Review
Hypertension is a principal risk factor for cardiovascular morbidity and mortality, with its severity exacerbated by high sodium intake, particularly in individuals with ...salt-sensitive blood pressure. However, the mechanisms underlying hypertension and salt sensitivity are only partly understood. Herein, we review potential interactions in hypertension pathophysiology involving the immune system, endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and proteostasis pathways; identify knowledge gaps; and discuss future directions.
Recent Findings
Recent advancements by our research group and others reveal interactions within and between adaptive and innate immune responses in hypertension pathophysiology. The salt-immune-hypertension axis is further supported by the discovery of the role of dendritic cells in hypertension, marked by isolevuglandin (IsoLG) formation. Alongside these broadened understandings of immune-mediated salt sensitivity, the contributions of T cells to hypertension have been recently challenged by groups whose findings did not support increased resistance of Rag-1-deficient mice to Ang II infusion. Hypertension has also been linked to ER stress and the UPR. Notably, a holistic approach is needed because the UPR engages in crosstalk with autophagy, the ubiquitin proteasome, and other proteostasis pathways, that may all involve hypertension.
Summary
There is a critical need for studies to establish cause and effect relationships between ER stress and the UPR in hypertension pathophysiology in humans and to determine whether the immune system and ER stress function mainly to exacerbate or initiate hypertension and target organ injury. This review of recent studies proposes new avenues for future research for targeted therapeutic interventions.
Informal mentoring affects the development of cell biologists by providing essential career, scientific, and educational guidance to mentees. In this piece, we discuss the importance of formally ...recognizing casual mentorship to encourage this crucial form of mentorship that contributes to the advancement of an inclusive cell biology community.
Sexual dimorphism exists in energy balance, but the underlying mechanisms remain unclear. Here we show that the female mice have more pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of ...hypothalamus than males, and female POMC neurons display higher neural activities, compared to male counterparts. Strikingly, deletion of the transcription factor, TAp63, in POMC neurons confers "male-like" diet-induced obesity (DIO) in female mice associated with decreased POMC neural activities; but the same deletion does not affect male mice. Our results indicate that TAp63 in female POMC neurons contributes to the enhanced POMC neuron functions and resistance to obesity in females. Thus, TAp63 in POMC neurons is one key molecular driver for the sexual dimorphism in energy homeostasis.
The power of saying no Hinton, Antentor O; McReynolds, Melanie R; Martinez, Denise ...
EMBO reports,
03 July 2020, Letnik:
21, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Many students and early‐career scientists too often agree to new tasks and chores and end up overworked. Learning how and when to say “no” is therefore an important part of career development.
Managing technostress in the STEM world Murray, Sandra A.; Shuler, Haysetta D.; Davis, Jamaine S. ...
Trends in biotechnology (Regular ed.),
08/2022, Letnik:
40, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The rapid evolution of technological advancements in the science, technology, engineering, and mathematics (STEM) fields is enabling ever faster progress. However, the rapid pace of change can also ...lead to elevated stress for STEM workers. Here, we provide strategies for coping with and limiting technostress amongst researchers and other STEM professionals.
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