Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling.

The Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the activity of several GPCRs involved in the control of food intake and energy expenditure. While MRAP2 was originally thought to exclusively interact with melanocortin receptors we have recently shown that it interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PKR1). In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1. Importantly, like MC4R and PKRs, OX1R is predominately expressed in the brain where it regulates food intake. By demonstrating that MRAP2 modulates the activity of OX1R we further establish the critical role of MRAP2 in the control of energy homeostasis.

Melanocortin Receptor Accessory Proteins (MRAPs): Functions in the melanocortin system and beyond.

G-protein coupled receptors (GPCRs) are regulated by numerous proteins including kinases, G-proteins, ß-arrestins and accessory proteins. Several families of GPCR accessory proteins like Receptor Activity Modifying Proteins, Receptor Transporting Proteins and Melanocortin Receptor Accessory Proteins (MRAPs) have been identified as regulator of receptor trafficking, signaling and ligand specificity. The MRAP family contains two members, MRAP1 and MRAP2, responsible for the formation of a functional ACTH receptor and for the regulation of energy homeostasis respectively. Like all known GPCR accessory proteins, MRAPs are single transmembrane proteins, however, they form a unique structure since they assemble as an anti-parallel homodimer. Moreover, the accepted idea that MRAPs are specific regulators of melanocortin receptors was recently challenged by the discovery that MRAP2 inhibits the activity of prokineticin receptors. Recent studies are starting to explain the role of the unusual structure of MRAPs and to illustrate the importance of MRAP2 for the maintenance of both energy and glucose homeostasis. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.

Factors Affecting Vaccine Attitudes Influenced by the COVID-19 Pandemic.

The development of vaccines has significantly contributed to the success of disease prevention. However, there has been a sharp decline in immunization rates since COVID-19 spread globally. Seemingly overnight, the world shut down and most non-essential medical procedures were postponed. Since the COVID-19 vaccine became available, and the world started going back to normal these vaccine rates have not recovered. In this paper, we review the published literature to explore how convenience factors, perceived risk of vaccination, media or anti-vaccination ideals/movements, and healthcare professionals affect an individual's compliance to be vaccinated to better understand the factors that contribute to the change in overall vaccination rates.

Decrease in Overall Vaccine Hesitancy in College Students during the COVID-19 Pandemic.

The COVID-19 pandemic changed our world as we know it and continues to be a global problem three years since the pandemic began. Several vaccines were produced, but there was a considerable amount of societal turmoil surrounding them that has affected the way people view not only COVID-19 vaccines but all vaccines. We used a survey to compare how attitudes towards vaccination have changed in college students during the pandemic. An initial survey was administered in 2021, then a follow-up in 2022. Out of 316 respondents who answered the first survey, 192 completed the follow-up. The survey was designed to measure trends in changes to vaccine attitudes since the COVID-19 pandemic began. By comparing the first survey in 2021 and the follow-up, we found that roughly 55% of respondents' vaccine attitudes did not change, roughly 44% of respondents' attitudes towards vaccines became more positive, and only about 1% of the respondents' vaccine attitudes became more negative. Improved view of vaccines was associated with political views and increased trust in medicine and the healthcare system. Worsened opinions of vaccines were associated with a belief that the COVID-19 vaccine affected fertility.

Cautious Sexual Attitudes Diminish Intent to Vaccinate Children against HPV in Utah.

Although most Human papillomavirus (HPV) infections are mild and are cleared by the immune system, some high-risk HPV strains can cause various cancers. Vaccines have been developed that protect against high-risk HPV strains. HPV vaccines have been approved for use by the CDC (Centers for Disease Control and Prevention) and are recommended for everyone aged 11-26. Despite the availability of safe and effective vaccines, uptake is low. HPV vaccine uptake has been extensively studied on a national and international level, but less is known about vaccine acceptance on a state or local level. The state of Utah, in the United States of America, has a relatively low HPV vaccination rate. In this study, we identified factors that impact the intent of Utah parents to vaccinate their children against HPV. A survey was distributed electronically to Utah residents. Survey results were analyzed using confirmatory factor analysis, structural equation modeling, and univariate analysis. Knowledge about HPV and positive vaccine attitudes had the greatest positive effect on intent to vaccinate children against HPV. Cautious sexual attitudes and high religious practice were found to have a negative impact on intent to vaccinate. Effective public health messaging will consider the cultural and religious influences of the target population.

Queer in the Heartland: Cancer Risks, Screenings, and Diagnoses among Sexual and Gender Minorities in Iowa.

Little is known about the cancer experiences of sexual and gender minority (SGM) persons in Midwestern areas. In response, a statewide survey of 567 SGM adults in Iowa, a largely rural Midwestern state, assessed cancer prevalence, screening tests, and related risk factors. Skin cancer accounted for nearly half of reported cancers. Individuals assigned female sex at birth reported high levels of lifetime mammograms and Papanicolaou (Pap) tests. In contrast, there were almost no colorectal cancer screenings reported among older (age 50+) respondents, regardless of gender identity or sexual orientation. Current tobacco use was modest overall, and cisgender women were more likely to report heavy drinking than cisgender men. Cisgender men age 40 and younger were less likely to have any human papillomavirus vaccination than cisgender women. The survey identified both strengths to leverage and deficits to address, which may inform future cancer prevention efforts in Iowa and other Midwestern states.

MRAP2 regulates ghrelin receptor signaling and hunger sensing.

Ghrelin is the only known circulating orexigenic hormone. It is primarily secreted by the stomach and acts at its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), in the hypothalamus to signal hunger and promote food intake. The melanocortin receptor accessory protein 2 (MRAP2) was previously shown to regulate energy homeostasis through the modulation of the activity of the melanocortin-4 receptor and prokineticin receptors. In this study we identify MRAP2 as a partner of ghrelin-GHSR1a signaling. We show that MRAP2 interacts with GHSR1a and potentiates ghrelin-stimulated signaling both in vitro and in vivo. We demonstrate that in the absence of MRAP2, fasting fails to activate agouti-related protein neurons. In addition, we show that the orexigenic effect of ghrelin is lost in mice lacking MRAP2. Our results suggest that MRAP2 is an important modulator of the energy homeostasis machinery that operates through the regulation of multiple GPCRs throughout the hypothalamus.Melanocortin receptor accessory protein 2 (MRAP2) is an adaptor protein that contributes to melanocortin-4 receptor and prokineticin receptor 1 signalling. Here the authors show that MRAP2 also regulates ghrelin receptor signalling in the hypothalamus and starvation sensing in mice.