RESUMEN
This study investigated the cervicovaginal microbiome's (CVM's) impact on Chlamydia trachomatis (CT) infection among Black and Hispanic adolescent and young adult women. A total of 187 women with incident CT were matched to 373 controls, and the CVM was characterized before, during, and after CT infection. The findings highlight that a specific subtype of bacterial vaginosis (BV), identified from 16S rRNA gene reads using the molBV algorithm and community state type (CST) clustering, is a significant risk factor for CT acquisition. A microbial risk score (MRS) further identified a network of bacterial genera associated with increased CT risk. Post treatment, the CVM associated with CT acquisition re-emerged in a different subset of cases leading to reinfection. Additionally, the analysis showed a connection between post-treatment CVM and the development of pelvic inflammatory disease (PID) and miscarriage, further underscoring the CVM's contributing role to incident CT natural history and highlighting its consideration as a therapeutic target.
Asunto(s)
Cuello del Útero , Infecciones por Chlamydia , Chlamydia trachomatis , Microbiota , ARN Ribosómico 16S , Vagina , Humanos , Femenino , Chlamydia trachomatis/genética , Chlamydia trachomatis/aislamiento & purificación , Adolescente , Infecciones por Chlamydia/microbiología , Vagina/microbiología , Adulto Joven , ARN Ribosómico 16S/genética , Cuello del Útero/microbiología , Adulto , Vaginosis Bacteriana/microbiología , Factores de Riesgo , Enfermedad Inflamatoria Pélvica/microbiología , Estudios de Casos y Controles , Hispánicos o Latinos/genética , BlancoRESUMEN
Gender inequality in STEM fields remains pervasive and undermines the ability for talented individuals to excel. Despite advances, women still encounter obstacles in pursuing academic careers and reaching leadership positions. This commentary discusses the "scissor-shaped curve" and examines effective strategies to fix it, including data-driven initiatives that we have implemented at our university.
Asunto(s)
Academia , Equidad de Género , Humanos , Femenino , Liderazgo , UniversidadesRESUMEN
Recent studies suggest that human-associated bacteria interact with host-produced steroids, but the mechanisms and physiological impact of such interactions remain unclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, thereby transforming a class of immuno- and metabo-regulatory steroids into a class of sex hormones and neurosteroids. Using comparative genomics, homologous expression, and heterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation. We also uncover an unexpected role for hydrogen gas production by gut commensals in promoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolism in the gut. Levels of certain bacterial progestins, including allopregnanolone, better known as brexanolone, an FDA-approved drug for postpartum depression, are substantially increased in feces from pregnant humans. Thus, bacterial conversion of corticoids into progestins may affect host physiology, particularly in the context of pregnancy and women's health.
Asunto(s)
Microbioma Gastrointestinal , Glucocorticoides , Hidrógeno , Progestinas , Humanos , Progestinas/metabolismo , Hidrógeno/metabolismo , Femenino , Glucocorticoides/metabolismo , Embarazo , Animales , Familia de Multigenes , Heces/microbiología , Pregnanolona/metabolismo , RatonesRESUMEN
Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.
Asunto(s)
Ácidos Grasos , Lactobacillus , Vagina , Vaginosis Bacteriana , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Femenino , Humanos , Vagina/microbiología , Lactobacillus/metabolismo , Ácidos Grasos/metabolismo , Ácido Oléico/metabolismo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Lactobacillus crispatus/metabolismo , Microbiota/efectos de los fármacos , Proteínas Bacterianas/metabolismoRESUMEN
Menopause is the cessation of ovarian function, with loss of reproductive hormone production and irreversible loss of fertility. It is a natural part of reproductive aging. The physiology of the menopause is complex and incompletely understood. Globally, menopause occurs around the age of 49 years, with geographic and ethnic variation. The hormonal changes of the menopause transition may result in both symptoms and long-term systemic effects, predominantly adverse effects on cardiometabolic and musculoskeletal health. The most effective treatment for bothersome menopausal symptoms is evidence-based, menopausal hormone therapy (MHT), which reduces bone loss and may have cardiometabolic benefits. Evidence-based non-hormonal interventions are also available for symptom relief. Treatment should be individualized with shared decision-making. Most MHT regimens are not regulator approved for perimenopausal women. Studies that include perimenopausal women are needed to determine the efficacy and safety of treatment options. Further research is crucial to improve menopause care, along with research to guide policy and clinical practice.
Asunto(s)
Enfermedades Cardiovasculares , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Persona de Mediana Edad , Menopausia , Envejecimiento , BiologíaRESUMEN
Progress in studying sex as a biological variable (SABV) is slow, and the influence of gendered effects of the social environment on biology is largely unknown. Yet incorporating these concepts into basic science research will enhance our understanding of human health and disease. We provide steps to move this process forward.
Asunto(s)
Investigación Biomédica , Femenino , Humanos , Masculino , Medicina de Precisión , Caracteres Sexuales , Factores Sexuales , Salud de la MujerRESUMEN
The lack of racial diversity among the winners of United States biomedical research prizes reflects a chronic problem of the underappreciation of certain groups of biomedical scientists. Asians continue to be severely underrepresented as awardees of United States biomedical research prizes, a trend that shows no obvious recent improvement.
Asunto(s)
Pueblo Asiatico , Distinciones y Premios , Investigación Biomédica , Grupos Minoritarios , Diversidad Cultural , Humanos , National Institutes of Health (U.S.) , Investigadores , Estados Unidos , MujeresRESUMEN
Elle Lett is the winner of the 2021 Rising Black Scientists Award for a post-graduate scholar. For this award, we asked emerging Black scientists to tell us about the experiences that sparked their interest in the life sciences, their vision and goals, and how they want to contribute to a more inclusive scientific community. This is her story.
Asunto(s)
Disciplinas de las Ciencias Biológicas , Bioestadística , Población Negra/psicología , Personal de Laboratorio Clínico/psicología , Justicia Social , Personas Transgénero/psicología , Distinciones y Premios , Educación de Postgrado , Femenino , Objetivos , Humanos , Racismo/psicologíaRESUMEN
Although women experience significantly higher tau burden and increased risk for Alzheimer's disease (AD) than men, the underlying mechanism for this vulnerability has not been explained. Here, we demonstrate through in vitro and in vivo models, as well as human AD brain tissue, that X-linked ubiquitin specific peptidase 11 (USP11) augments pathological tau aggregation via tau deubiquitination initiated at lysine-281. Removal of ubiquitin provides access for enzymatic tau acetylation at lysines 281 and 274. USP11 escapes complete X-inactivation, and female mice and people both exhibit higher USP11 levels than males. Genetic elimination of usp11 in a tauopathy mouse model preferentially protects females from acetylated tau accumulation, tau pathology, and cognitive impairment. USP11 levels also strongly associate positively with tau pathology in females but not males. Thus, inhibiting USP11-mediated tau deubiquitination may provide an effective therapeutic opportunity to protect women from increased vulnerability to AD and other tauopathies.
Asunto(s)
Enfermedad de Alzheimer , Tauopatías , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Animales , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Caracteres Sexuales , Tauopatías/genética , Tauopatías/patología , Tioléster Hidrolasas/genética , Proteasas Ubiquitina-Específicas , Proteínas tau/genéticaRESUMEN
Malaria is a mosquito-borne disease caused by parasites of the obligate intracellular Apicomplexa phylum the most deadly of which, Plasmodium falciparum, prevails in Africa. Malaria imposes a huge health burden on the world's most vulnerable populations, claiming the lives of nearly one million children and pregnant women each year. Although there is keen interest in eradicating malaria, we do not yet have the necessary tools to meet this challenge, including an effective malaria vaccine and adequate vector control strategies. Here we review what is known about the mechanisms at play in immune resistance to malaria in both the human and mosquito hosts at each step in the parasite's complex life cycle with a view toward developing the tools that will contribute to the prevention of disease and death and, ultimately, to the goal of malaria eradication. In so doing, we hope to inspire immunologists to participate in defeating this devastating disease.
Asunto(s)
Culicidae/inmunología , Interacciones Huésped-Patógeno/inmunología , Malaria/inmunología , Plasmodium/inmunología , Animales , Culicidae/parasitología , Humanos , Estadios del Ciclo de Vida , Malaria/parasitología , Malaria/prevención & control , Plasmodium/crecimiento & desarrollo , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/inmunologíaRESUMEN
Our nationwide network of BME women faculty collectively argue that racial funding disparity by the National Institutes of Health (NIH) remains the most insidious barrier to success of Black faculty in our profession. We thus refocus attention on this critical barrier and suggest solutions on how it can be dismantled.
Asunto(s)
Investigación Biomédica/economía , Negro o Afroamericano , Administración Financiera , Investigadores/economía , Humanos , National Institutes of Health (U.S.)/economía , Grupos Raciales , Estados UnidosRESUMEN
Throughout development and aging, human cells accumulate mutations resulting in genomic mosaicism and genetic diversity at the cellular level. Mosaic mutations present in the gonads can affect both the individual and the offspring and subsequent generations. Here, we explore patterns and temporal stability of clonal mosaic mutations in male gonads by sequencing ejaculated sperm. Through 300× whole-genome sequencing of blood and sperm from healthy men, we find each ejaculate carries on average 33.3 ± 12.1 (mean ± SD) clonal mosaic variants, nearly all of which are detected in serial sampling, with the majority absent from sampled somal tissues. Their temporal stability and mutational signature suggest origins during embryonic development from a largely immutable stem cell niche. Clonal mosaicism likely contributes a transmissible, predicted pathogenic exonic variant for 1 in 15 men, representing a life-long threat of transmission for these individuals and a significant burden on human population health.
Asunto(s)
Crecimiento y Desarrollo , Mosaicismo , Espermatozoides/metabolismo , Adolescente , Envejecimiento/sangre , Alelos , Células Clonales , Estudios de Cohortes , Humanos , Masculino , Modelos Biológicos , Mutación/genética , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
This first serious attempt at an autobiographical accounting has forced me to sit still long enough to compile my thoughts about a long personal and scientific journey. I especially hope that my trajectory will be of interest and perhaps beneficial to much younger women who are just getting started in their careers. To paraphrase from Virginia Woolf's writings in A Room of One's Own at the beginning of the 20th century, "for most of history Anonymous was a Woman." However, Ms. Woolf is also quoted as saying "nothing has really happened until it has been described," a harbinger of the enormous historical changes that were about to be enacted and recorded by women in the sciences and other disciplines. The progress in my chosen field of study-the chemical basis of enzyme action-has also been remarkable, from the first description of an enzyme's 3D structure to a growing and deep understanding of the origins of enzyme catalysis.
Asunto(s)
Coenzimas/química , Enzimas/química , Mujeres Trabajadoras/historia , Biocatálisis , Selección de Profesión , Coenzimas/metabolismo , Pruebas de Enzimas , Enzimas/metabolismo , Femenino , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Cinética , Teoría CuánticaRESUMEN
The placental transfer of maternal IgG is critical for infant protection against infectious pathogens. However, factors that modulate the placental transfer of IgG remain largely undefined. HIV-infected women have impaired placental IgG transfer, presenting a unique "disruption model" to define factors that modulate placental IgG transfer. We measured the placental transfer efficiency of maternal HIV and pathogen-specific IgG in US and Malawian HIV-infected mothers and their HIV-exposed uninfected and infected infants. We examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, IgG subclass, and glycan signatures and their association with placental IgG transfer efficiency. Maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcγRIIa and FcγRIIIa, and Fc region glycan profiles were associated with placental IgG transfer efficiency. Our findings suggest that Fc region characteristics modulate the selective placental transfer of IgG, with implications for maternal vaccine design and infant health.
Asunto(s)
Infecciones por VIH/transmisión , VIH/genética , Inmunoglobulina G/sangre , Transmisión Vertical de Enfermedad Infecciosa , Placenta/metabolismo , Complicaciones Infecciosas del Embarazo/virología , Receptores de IgG/metabolismo , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Glicosilación , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Fragmentos Fc de Inmunoglobulinas/metabolismo , Lactante , Recién Nacido , Malaui , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Estados Unidos , Carga Viral/genéticaRESUMEN
Women have been at the forefront of tremendous achievements in immunology in the past decade. However, disparities still exist, limiting upward potential and further advancements. As four NIH intramural women scientists who care deeply about scientific progress and the progress of women in our field, we review ongoing challenges and discuss potential approaches to help advance the promotion of women in the sciences.
Asunto(s)
Alergia e Inmunología/tendencias , Sexismo/tendencias , Derechos de la Mujer/tendencias , Investigación Biomédica/tendencias , Movilidad Laboral , Femenino , Historia del Siglo XXI , Humanos , Tutoría/tendencias , National Institutes of Health (U.S.) , Estados UnidosRESUMEN
African American and other Black individuals (referred to as Black people in this article) have a disproportionate cancer burden, including the lowest survival of any racial or ethnic group for most cancers. Every 3 years, the American Cancer Society estimates the number of new cancer cases and deaths for Black people in the United States and compiles the most recent data on cancer incidence (herein through 2021), mortality (through 2022), survival, screening, and risk factors using population-based data from the National Cancer Institute and the Centers for Disease Control and Prevention. In 2025, there will be approximately 248,470 new cancer cases and 73,240 cancer deaths among Black people in the United States. Black men have experienced the largest relative decline in cancer mortality from 1991 to 2022 overall (49%) and in almost every 10-year age group, by as much as 65%-67% in the group aged 40-59 years. This progress largely reflects historical reductions in smoking initiation among Black teens, advances in treatment, and earlier detections for some cancers. Nevertheless, during the most recent 5 years, Black men had 16% higher mortality than White men despite just 4% higher incidence, and Black women had 10% higher mortality than White women despite 9% lower incidence. Larger inequalities for mortality than for incidence reflect two-fold higher death rates for prostate, uterine corpus, and stomach cancers and for myeloma, and 40%-50% higher rates for colorectal, breast, cervical, and liver cancers. The causes of ongoing disparities are multifactorial, but largely stem from inequalities in the social determinants of health that trace back to structural racism. Increasing diversity in clinical trials, enhancing provider education, and implementing financial incentives to ensure equitable care across the cancer care continuum would help close these gaps.
RESUMEN
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2021) and mortality data collected by the National Center for Health Statistics (through 2022). In 2025, 2,041,910 new cancer cases and 618,120 cancer deaths are projected to occur in the United States. The cancer mortality rate continued to decline through 2022, averting nearly 4.5 million deaths since 1991 because of smoking reductions, earlier detection for some cancers, and improved treatment. Yet alarming disparities persist; Native American people bear the highest cancer mortality, including rates that are two to three times those in White people for kidney, liver, stomach, and cervical cancers. Similarly, Black people have two-fold higher mortality than White people for prostate, stomach, and uterine corpus cancers. Overall cancer incidence has generally declined in men but has risen in women, narrowing the male-to-female rate ratio (RR) from a peak of 1.6 (95% confidence interval, 1.57-1.61) in 1992 to 1.1 (95% confidence interval, 1.12-1.12) in 2021. However, rates in women aged 50-64 years have already surpassed those in men (832.5 vs. 830.6 per 100,000), and younger women (younger than 50 years) have an 82% higher incidence rate than their male counterparts (141.1 vs. 77.4 per 100,000), up from 51% in 2002. Notably, lung cancer incidence in women surpassed that in men among people younger than 65 years in 2021 (15.7 vs. 15.4 per 100,000; RR, 0.98, p = 0.03). In summary, cancer mortality continues to decline, but future gains are threatened by rampant racial inequalities and a growing burden of disease in middle-aged and young adults, especially women. Continued progress will require investment in cancer prevention and access to equitable treatment, especially for Native American and Black individuals.
Asunto(s)
Neoplasias , Humanos , Neoplasias/epidemiología , Neoplasias/mortalidad , Incidencia , Estados Unidos/epidemiología , Femenino , Masculino , Sistema de Registros/estadística & datos numéricos , Persona de Mediana Edad , American Cancer Society , Adulto , Distribución por SexoRESUMEN
The Spanish artist Diego Velázquez created a puzzle-painting 360 years ago that to this day remains unsolved, but still mystifies and intrigues. Unlike artists who get their thrills by creating puzzles that stimulate the imagination, scientists get their kicks by solving puzzles that advance biomedical research.
Asunto(s)
Distinciones y Premios , Investigación Biomédica , Salud de la Mujer , Arte/historia , Historia del Siglo XVII , Historia del Siglo XX , Ciencia , Recursos HumanosRESUMEN
The teleology of sex differences has been argued since at least as early as Aristotle's controversial Generation of Animals more than 300 years BC, which reflects the sex bias of the time to contemporary readers. Although the question "why are the sexes different" remains a topic of debate in the present day in metaphysics, the recent emphasis on sex comparison in research studies has led to the question "how are the sexes different" being addressed in health science through numerous observational studies in both health and disease susceptibility, including blood pressure regulation and hypertension. These efforts have resulted in better understanding of differences in males and females at the molecular level that partially explain their differences in vascular function and renal sodium handling and hence blood pressure and the consequential cardiovascular and kidney disease risks in hypertension. This review focuses on clinical studies comparing differences between men and women in blood pressure over the life span and response to dietary sodium and highlights experimental models investigating sexual dimorphism in the renin-angiotensin-aldosterone, vascular, sympathetic nervous, and immune systems, endothelin, the major renal sodium transporters/exchangers/channels, and the impact of sex hormones on these systems in blood pressure homeostasis. Understanding the mechanisms governing sex differences in blood pressure regulation could guide novel therapeutic approaches in a sex-specific manner to lower cardiovascular risks in hypertension and advance personalized medicine.
Asunto(s)
Hipertensión , Caracteres Sexuales , Animales , Femenino , Humanos , Masculino , Presión Sanguínea/fisiología , Riñón , Hemodinámica , SodioRESUMEN
The normal stress response in humans is governed by the hypothalamic-pituitary-adrenal (HPA) axis through heightened mechanisms during stress, raising blood levels of the glucocorticoid hormone cortisol. Glucocorticoids are quintessential compounds that balance the proper functioning of numerous systems in the mammalian body. They are also generated synthetically and are the preeminent therapy for inflammatory diseases. They act by binding to the nuclear receptor transcription factor glucocorticoid receptor (GR), which has two main isoforms (GRα and GRß). Our classical understanding of glucocorticoid signaling is from the GRα isoform, which binds the hormone, whereas GRß has no known ligands. With glucocorticoids being involved in many physiological and cellular processes, even small disruptions in their release via the HPA axis, or changes in GR isoform expression, can have dire ramifications on health. Long-term chronic glucocorticoid therapy can lead to a glucocorticoid-resistant state, and we deliberate how this impacts disease treatment. Chronic glucocorticoid treatment can lead to noticeable side effects such as weight gain, adiposity, diabetes, and others that we discuss in detail. There are sexually dimorphic responses to glucocorticoids, and women tend to have a more hyperresponsive HPA axis than men. This review summarizes our understanding of glucocorticoids and critically analyzes the GR isoforms and their beneficial and deleterious mechanisms and the sexual differences that cause a dichotomy in responses. We also discuss the future of glucocorticoid therapy and propose a new concept of dual GR isoform agonist and postulate why activating both isoforms may prevent glucocorticoid resistance.