Mapping how personal care products may alter timing of puberty

A first-of-its-kind systematic evidence map allows researchers to evaluate studies exploring the link between personal care products (PCPs) and early onset of puberty, according to researchers from the Division of Translational Toxicology.

PCPs contain endocrine-disrupting chemicals (EDCs), including phthalates and phenols, which interfere with hormone function. Early-life exposure to EDCs commonly found in PCPs has been linked to earlier onset of puberty.

The researchers characterized the available human and mammalian animal evidence for the potential relationship between the timing of puberty and PCP exposure. To do so, they conducted a comprehensive literature search and used machine learning to priority-rank studies for screening, which resulted in 98 human and 299 animal studies that covered 96 different chemicals. Phthalates and phenols were the most well-studied chemical classes, and most of this subset of studies examined secondary sex characteristics and changes in estradiol and testosterone levels.

The final data were used to create interactive visuals, which are available for download from an interactive dashboard. This map could support evidence-based decisions by enabling anyone to search, sort, and filter the literature base of puberty-related studies by key concepts, such as specific chemicals or health outcomes. According to the authors, the interactive visualization can be used by researchers and regulators to prioritize and target future research and funding to reduce uncertainties and address data gaps. [Read related article.]

Citation: Taylor KW, Howdeshell KL, Bommarito PA, Sibrizzi CA, Blain RB, Magnuson K, Lemeris C, Tracy W, Baird DD, Jackson CL, Gaston SA, Rider CV, Walker VR, Rooney AA. 2023. Systematic evidence mapping informs a class-based approach to assessing personal care products and pubertal timing. Environ Int 181:108307.

How disordered regions of proteins regulate RNA binding

Intrinsically disordered regions (IDRs) help to mediate interactions between partner proteins to control RNAs, according to NIEHS researchers and their collaborators. IDRs in proteins lack well-defined structures, but they engage in molecular recognition and molecular assembly and play important roles in cellular signaling and regulation. RNA-binding proteins are enriched with IDRs, which can influence RNA-binding activities.

The researchers set out to shed light on how IDRs regulate RNA-binding affinity. They focused on the roles of IDRs in mediating the collaboration between two roundworm proteins called fem-3 binding factor-2 (FBF-2) and lateral signaling target-1 (LST-1). These proteins interact to regulate mRNAs in stem cells.

By determining a crystal structure of FBF-2 and through biochemical studies, the researchers discovered that an IDR at the C-terminus of FBF-2 autoinhibits its RNA-binding affinity. The findings also suggest that LST-1 enhances FBF-2 RNA-binding affinity by displacing its C-terminus, thereby alleviating autoinhibition.

This regulatory mechanism, driven by IDRs, provides a biochemical and biophysical explanation for the interdependence of FBF-2 and LST-1 in stem cell self-renewal. According to the authors, more research is needed to uncover the various ways partner proteins combine different mechanisms to control RNAs.

Citation: Qiu C, Zhang Z, Wine RN, Campbell ZT, Zhang J, Hall TMT. 2023. Intra- and inter-molecular regulation by intrinsically-disordered regions governs PUF protein RNA binding. Nat Commun 14:7323.

Discrimination–related high blood pressure risk may be worse among Black women with higher education

Discrimination-related risk of high blood pressure, also known as hypertension, may disproportionately affect Black or African American women with the highest levels of education, according to NIEHS researchers and their collaborators.

Hypertension is a highly prevalent and strong risk factor for cardiovascular disease, which is the leading cause of death among women in the U.S. The prevalence of hypertension is highest for non-Hispanic Black or African American women. Psychosocial stress related to experiencing racial and ethnic discrimination may increase hypertension risk.

The researchers studied whether educational attainment modifies the relationship between racial and ethnic discrimination and hypertension risk within racial and ethnic groups. Educational attainment modified the link between perceived everyday racial and ethnic discrimination and higher hypertension risk, but only among Black or African American women. Compared to counterparts with some college, Black or African American women with a Bachelor’s degree or higher most frequently reported everyday racial and ethnic discrimination and had higher associated hypertension risk.

Minoritized individuals — particularly Black or African American — with higher compared to lower educational attainment may more frequently encounter exclusion and antagonism in stress-inducing environments, such as professional workplace settings or higher income stores and neighborhoods. According to the authors, assessments of experiences of discrimination and educational attainment may inform hypertension prevention, management, and intervention efforts implemented by health professionals.

Citation: Gaston SA, Forde AT, Green M, Sandler DP, Jackson CL. 2023. Racial and ethnic discrimination and hypertension by educational attainment among a cohort of US women. JAMA Netw Open 6(11):e2344707.

How long-term memories are created during sleep

A brain region called the entorhinal cortex (EC) plays a critical role in forming long-term memories during sleep by generating synchronous neural activity, according to NIEHS researchers and their collaborators.

Long-term memories are formed mainly during sleep through a process called memory consolidation. The process involves a region of the brain called the hippocampus — long-term memories are consolidated during sleep after the initial encoding of short-lasting memories while awake. The EC has intricate connections with the hippocampus and is a region that is severely damaged in Alzheimer’s disease. Yet, its role in memory consolidation is largely unknown.

To address this knowledge gap, the researchers recorded neural activity in the brains of mice. During anesthesia and sleep, there were strong neural oscillations — synchronous activities of multiple neurons — in the temporoammonic (TA) pathway, which are EC neurons that project to the hippocampus. A subpopulation of the TA pathway neurons called sleep cells generated delta oscillations during sleep via HCN channels.

The blockade of these oscillations significantly impaired the consolidation of hippocampus-dependent memory. Together, the findings demonstrated that delta oscillations of TA pathway neurons are critical for the consolidation of newly encoded memory.

Citation: Haam J, Gunin S, Wilson L, Fry S, Bernstein B, Thomson E, Noblet H, Cushman J, Yakel JL. 2023. Entorhinal cortical delta oscillations drive memory consolidation. Cell Rep 42(10):113267.

Why breast cancer incidence varies across the United States

Environmental exposures and neighborhood-level socioeconomic factors may contribute to geographic disparities in breast cancer incidence, according to NIEHS researchers and their collaborators.

Breast cancer is the most diagnosed cancer among women in the U.S. The incidence varies regionally but established demographic and reproductive risk factors do not fully explain this disparity, suggesting that other factors may also play an important role.

To investigate this possibility, the researchers mapped the association between residential location and breast cancer incidence for 44,707 participants across 382 public health regions. They found the risk of breast cancer to be lower in the South and Southeast and greater in the Northwest and certain areas of the Midwest and Northeast. This pattern was evident for all breast cancers and a subtype characterized by estrogen receptor-positive (ER+) tumors.

The level of ambient nitrogen dioxide, outdoor light at night, and the area deprivation index (ADI), which captures census block-level indicators of poverty, education, housing, and employment, accounted for 21.4% of the variation in breast cancer incidence across regions. For ER+ breast cancer, ambient nitrogen dioxide, fine particulate matter chemical composition, outdoor light at night, greenspace, and the ADI explained 63.3% of the spatial variation in incidence.

Together, the results provide additional evidence for a role of environmental exposures in breast cancer incidence and suggest that geographic-based risk factors may vary according to breast cancer subtype.

Citation: Carroll R, Ish JL, Sandler DP, White AJ, Zhao S. 2023. Understanding the role of environmental and socioeconomic factors in the geographic variation of breast cancer risk in the US-wide Sister Study. Environ Res 239(Pt 1):117349.