The plantation system and the roots of the southern rural mortality penalty in the northern Blackland Prairies of Texas.

In recent decades, public health researchers have observed that the health of rural people has declined relative to the health of urban people in the United States. This disparity in health and life expectancy across the rural/urban divide has been described as the Rural Mortality Penalty. However, public health researchers have also noted that health and life expectancies are not uniform across the rural United States, but vary according to race, sex, gender, and other factors. Rural health disparities also vary geospatially and are especially pronounced in the American South, leading to recent calls for greater attention to the structural factors that shape the health of rural Southerners. In this study, we take an anthropological and historically explicit approach to study the impacts of systemic violence on rural health. Specifically, we focus on farm labor within the plantation system as a context where geospatial, racial, and sexual differences in mortality, often studied in isolation, find a common historical source. Here we analyze vital records data from the post-emancipation period in the Blackland Prairies ecoregion of Texas, a period when emerging forms of plantation labor such as tenant farming, convict leasing, and migrant labor were being developed to maintain the plantation economy after the abolishment of chattel slavery. We find that the plantation system remains a strong predictor of differential mortalities in rural Texas, accounting for nearly all the variation that exists across the rural/urban divide and elucidating the complex interactions of race, sex, labor, and health in the rural South.

What does Juneteenth mean in STEMM?

Juneteenth commemorates the freeing of the last large group of enslaved people in 1865 at the end of the American Civil War. We asked several Black scientists what Juneteenth means to them in the context of science, technology, engineering, mathematics, and medicine (STEMM)? Their answers run the emotional gamut.

Theoretical constraints: Science, caretaking, and the creation of normative ideals.

OBJECTIVES: This review explores the dualism in evolutionary anthropology that both acknowledges a broad range of familial caretaking strategies, while also remaining tethered to theories scaffolded around notions of selfish genes that constrain our understanding of who provides adequate kin care. I examine the process of norm creation in the sciences by investigating how theory may limit which data are collected and how those data are interpreted. METHODS: This paper serves as a literature review and critique of prominent biological, evolutionary, and psychological conceptualizations of parental investment and caretaking in humans, and how these studies shape what is considered normal behavior in scientific literature. RESULTS: Quantification, assessment, and theory building in evolutionary anthropology, and an oversampling of WEIRD communities in other disciplines, have limited our understanding of what constitutes both evolutionarily adaptive behaviors, and culturally specific human behaviors. CONCLUSIONS: A synthetic theoretical model of behavioral norms in childrearing must account for an exchange of psycho-social and cultural resources and skills, the transfer of energetic reserves via gestation and lactation, and the indirect benefits of genetic inheritance. The emphasis on tailoring data collection to fit evolutionary theories of the family has limited our ability to understand the diverse proximate mechanisms that humans employ in taking care of kin as biocultural reproducers.

Navigating cross-cultural research: methodological and ethical considerations.

The intensifying pace of research based on cross-cultural studies in the social sciences necessitates a discussion of the unique challenges of multi-sited research. Given an increasing demand for social scientists to expand their data collection beyond WEIRD (Western, educated, industrialized, rich and democratic) populations, there is an urgent need for transdisciplinary conversations on the logistical, scientific and ethical considerations inherent to this type of scholarship. As a group of social scientists engaged in cross-cultural research in psychology and anthropology, we hope to guide prospective cross-cultural researchers through some of the complex scientific and ethical challenges involved in such work: (a) study site selection, (b) community involvement and (c) culturally appropriate research methods. We aim to shed light on some of the difficult ethical quandaries of this type of research. Our recommendation emphasizes a community-centred approach, in which the desires of the community regarding research approach and methodology, community involvement, results communication and distribution, and data sharing are held in the highest regard by the researchers. We argue that such considerations are central to scientific rigour and the foundation of the study of human behaviour.

Author Correction: Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs.

The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD) efforts. These structures have revealed that GPCRs are highly dynamic macromolecules whose function is dependent on their intrinsic flexibility. Unfortunately, the use of static structures to understand ligand binding can potentially be misleading, especially in systems with an inherently high degree of conformational flexibility. Here, we show that docking a set of dopamine D3 receptor compounds into the existing eticlopride-bound dopamine D3 receptor (D3R) X-ray crystal structure resulted in poses that were not consistent with results obtained from site-directed mutagenesis experiments. We overcame the limitations of static docking by using large-scale high-throughput molecular dynamics (MD) simulations and Markov state models (MSMs) to determine an alternative pose consistent with the mutation data. The new pose maintains critical interactions observed in the D3R/eticlopride X-ray crystal structure and suggests that a cryptic pocket forms due to the shift of a highly conserved residue, F6.52. Our study highlights the importance of GPCR dynamics to understand ligand binding and provides new opportunities for drug discovery.

Residential context, institutional alloparental care, and child growth in Jamaica.

OBJECTIVES: Although children are typically raised in familial care networks, not all children have access to kin. Here, I investigate the growth measures of children living in two different residential contexts in Jamaica: institutional care settings and familial homes. METHODS: This cross-sectional study sampled individuals ranging from 5-18 years old, residing in children's homes (N = 113 participants) and familial homes (N = 103 participants). Anthropometric measurements and interview data were collected from all participants. Height for age z-scores (ZHFA) and weight for age z-scores (ZWFA) were calculated using the 2007 WHO standards. Body fat was estimated from tricep and suprailiac skinfold thickness. Between group comparisons were completed using analysis of covariance (ANCOVA), with age included as a covariate. Significance was accepted at P ≤ 0.05. RESULTS: Context was more predictive of condition among children than adolescents. Both girls and boys ages 5-11 years living with family members had higher mean height and weight for age, and summed skinfold thickness measures, than their peers living in children's homes. Fewer correlations between home setting and growth measurements were found among 12-18 year olds. Notably, although children were randomly assigned to children's homes, boys in a single-sex institution did not differ in growth measurements from boys living with family members. CONCLUSIONS: Younger children who lived with family members had better growth measurements than their peers living in institutional settings. However, improved growth measures for children living in one home were correlated to nonconventional counseling practices, and nutritional policies that mirror some aspects of familial care. Am. J. Hum. Biol. 28:493-502, 2016. © 2015 Wiley Periodicals, Inc.

Survey of academic field experiences (SAFE): trainees report harassment and assault.

Little is known about the climate of the scientific fieldwork setting as it relates to gendered experiences, sexual harassment, and sexual assault. We conducted an internet-based survey of field scientists (N = 666) to characterize these experiences. Codes of conduct and sexual harassment policies were not regularly encountered by respondents, while harassment and assault were commonly experienced by respondents during trainee career stages. Women trainees were the primary targets; their perpetrators were predominantly senior to them professionally within the research team. Male trainees were more often targeted by their peers at the research site. Few respondents were aware of mechanisms to report incidents; most who did report were unsatisfied with the outcome. These findings suggest that policies emphasizing safety, inclusivity, and collegiality have the potential to improve field experiences of a diversity of researchers, especially during early career stages. These include better awareness of mechanisms for direct and oblique reporting of harassment and assault and, the implementation of productive response mechanisms when such behaviors are reported. Principal investigators are particularly well positioned to influence workplace culture at their field sites.

The 5-hydroxytryptamine4 receptor agonists prucalopride and PRX-03140 increase acetylcholine and histamine levels in the rat prefrontal cortex and the power of stimulated hippocampal θ oscillations.

5-Hydroxytryptamine (5-HT)(4) receptor agonists reportedly stimulate brain acetylcholine (ACh) release, a property that might provide a new pharmacological approach for treating cognitive deficits associated with Alzheimer's disease. The purpose of this study was to compare the binding affinities, functional activities, and effects on neuropharmacological responses associated with cognition of two highly selective 5-HT(4) receptor agonists, prucalopride and 6,7-dihydro-4-hydroxy-7-isopropyl-6-oxo-N-[3-(piperidin-1-yl)propyl]thieno[2,3-b]pyridine-5-carboxamide (PRX-03140). In vitro, prucalopride and PRX-03140 bound to native rat brain 5-HT(4) receptors with K(i) values of 30 nM and 110 nM, respectively, and increased cAMP production in human embryonic kidney-293 cells expressing recombinant rat 5-HT(4) receptors. In vivo receptor occupancy studies established that prucalopride and PRX-03140 were able to penetrate the brain and bound to 5-HT(4) receptors in rat brain, achieving 50% receptor occupancy at free brain exposures of 330 nM and 130 nM, respectively. Rat microdialysis studies revealed that prucalopride maximally increased ACh and histamine levels in the prefrontal cortex at 5 and 10 mg/kg, whereas PRX-03140 significantly increased cortical histamine levels at 50 mg/kg, failing to affect ACh release at doses lower than 150 mg/kg. In combination studies, donepezil-induced increases in cortical ACh levels were potentiated by prucalopride and PRX-03140. Electrophysiological studies in rats demonstrated that both compounds increased the power of brainstem-stimulated hippocampal θ oscillations at 5.6 mg/kg. These findings show for the first time that the 5-HT(4) receptor agonists prucalopride and PRX-03140 can increase cortical ACh and histamine levels, augment donepezil-induced ACh increases, and increase stimulated-hippocampal θ power, all neuropharmacological parameters consistent with potential positive effects on cognitive processes.

The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice.

CD40 is a member of the TNF family of receptors that has been shown to play a crucial role in enhancing dendritic cell activity and fostering anti-tumor immune responses. In this study, we demonstrate the in vitro properties and in vivo efficacious activity of the CD40 agonist antibody, CP-870,893. CP-870,893 is a fully human, IgG2 antibody that selectively interacts with CD40 at a site distinct from its ligand-binding region with a KD of 0.4 nM. It enhances the expression of MHC class II, CD54, CD86, and CD23 on human B cells in vitro. CP-870,893 also enhances dendritic cell activity as evidenced by cytokine secretion (IL-12, IL-23, IL-8), the upregulation of CD86 and CD83, and the ability to prime T cells to secrete IFNγ. In SCID-beige mice, a single parenteral injection of CP-870,893 was therapeutically effective against several CD40(pos) human tumors (B-cell lymphoma, breast, colon, and prostate) indicating direct effects on tumor cell survival and/or growth. When mice were co-implanted with human T cells and dendritic cells, the activity of CP-870,893 against CD40(pos) tumors increased, and efficacy was also observed against CD40(neg) and CD40(low) tumors demonstrating the ability of CP-870,893 to enhance anti-tumor immune function in vivo. These studies suggest that CP-870,893 has the potential to be efficacious against a wide range of tumor types through both direct and immune-mediated effects.

The Need for Experimental Methodology in Intimate Partner Violence: Finding Programs That Effectively Prevent IPV.

The lack of rigorous evaluations of intimate partner violence (IPV) programs has severely limited our knowledge about what works. However, IPV programs can be rigorously evaluated through randomized controlled trials (RCTs) conducted ethically and safely. This article provides an example of how a RCT to test an IPV preventive intervention-the Enhanced Nurse Family Partnership Study (ENFPS)-was successfully implemented by a partnership of researchers and practitioners. The article concludes with some recommendations, arrived at by the researchers and practitioners on the ENFPS team, for achieving a successful collaboration thought to be essential in executing a field experiment.

Adult health outcomes and their implications for experiences of childhood nutritional stress in Jamaica.

With insights from the developmental origins of health and disease paradigm (DOHaD), this study explores the impact of childhood nutritional stress on adult health outcomes in Jamaica. Jamaica experienced a lengthy period of political and economic instability beginning in the postcolonial period of the early 1960s. This study tests whether decreased government spending on public resources and limited access to imported food products during the early postcolonial period will be reflected in increased adiposity and body mass index among Jamaican adults. Ethnographic and anthropometric data were collected from individuals born between 1958 and 1988. Variability in health outcomes was assessed using Z-score values for body mass index and summed skinfold thickness measures. Age was employed as both a continuous and categorical independent variable. In partial correlation models controlling for economic status, body mass index values and summed skinfold thickness increased with age. Birth cohort and gender effects were also apparent. Women born between 1959 and 1968 had higher body mass index Z-score values than younger women. Both men and women born between 1959 and 1968 had significantly higher skinfold thickness measures than younger individuals. Individuals born between 1959 and 1968 were children during the immediate postcolonial era in Jamaica. Experiences of nutritional stress during critical developmental periods may have contributed to the observed age-related increases in adipose tissue and body mass index values. This study informs our understanding of the ways that fluctuations in the sociopolitical environment during development can mediate and contribute to poor adult health outcomes.

Essential role of CCR6 in directing activated T cells to the skin during contact hypersensitivity.

CCR6 is expressed in a number of dermatological inflammatory diseases. Here, we report that mice sensitized with the hapten oxazolone had increased numbers of CCR6+ T cells in the draining lymph nodes. Using CCR6-/- mice, we assessed the role of CCR6 on the development of contact hypersensitivity. After hapten sensitization and re-challenge, ear swelling in CCR6-/- animals was reduced 80% as compared with wild-type (WT) control mice. This decreased level of inflammation was not related to an inhibition in T-cell activation, because CCR6-/- lymph node cells from sensitized mice produced threefold higher levels of IFN-gamma in culture than cells from sensitized WT mice and, when these cells were directly injected into the site of hapten challenge, induced a robust inflammatory response. However, intravenous injection of CCR6-/- lymph node cells from sensitized mice were unable to prime naive mice to re-challenge whereas cells from primed WT mice were able to sensitize animals. These results suggest that CCR6 plays an important role in directing the trafficking of activated T cells into the skin and suggests that a CCR6 antagonist could be useful to treat skin-mediated inflammatory reactions.

The human specific CCR1 antagonist CP-481,715 inhibits cell infiltration and inflammatory responses in human CCR1 transgenic mice.

We previously described the in vitro characteristics of the potent and selective CCR1 antagonist, CP-481,715. In addition to being selective for CCR1 vs other chemokine receptors, CP-481,715 is also specific for human CCR1 (hCCR1), preventing its evaluation in classical animal models. To address this, we generated mice whereby murine CCR1 was replaced by hCCR1 (knockin) and used these animals to assess the anti-inflammatory properties of CP-481,715. Cells isolated from hCCR1 knockin mice were shown to express hCCR1 and migrate in response to both murine CCR1 and hCCR1 ligands. Furthermore, this migration is inhibited by CP-481,715 at dose levels comparable to those obtained with human cells. In animal models of cell infiltration, CP-481,715 inhibited CCL3-induced neutrophil infiltration into skin or into an air pouch with an ED50 of 0.2 mg/kg. CP-481,715 did not inhibit cell infiltration in wild-type animals expressing murine CCR1. In a more generalized model of inflammation, delayed-type hypersensitivity, CP-481,715 significantly inhibited footpad swelling and decreased the amount of IFN-gamma and IL-2 produced by isolated spleen cells from sensitized animals. It did not, however, induce tolerance to a subsequent challenge. These studies illustrate the utility of hCCR1 knockin animals to assess the activity of human specific CCR1 antagonists; demonstrate the ability of the CCR1 antagonist CP-481,715 to inhibit cell infiltration, inflammation, and Th1 cytokine responses in these animals; and suggest that CP-481,715 may be useful to modulate inflammatory responses in human disease.

Experimental Leishmania major infection suppresses HIV-1 DNA vaccine induced cellular immune response.

The AIDS epidemic in the developing world represents a major global crisis and an effective vaccine is imperative. However, many parasites are common in developing countries and can result in a state of chronic immune activation that is polarized towards a Th2 profile and which can potentially impair responses to vaccines or other infectious challenges. In this study we demonstrate that experimental Leishmania major infection of BALB/c mice inhibits responses to a DNA-based HIV-1 gag vaccine. L. major infection in BALB/c results in a polarized Th2 immune response. In this study naïve BALB/c mice immunized with the HIV-1 gag DNA vaccine mounted a cellular immune response against the vaccine antigen, HIV-1 gag. CD8+ T lymphocytes were able to respond in vitro to HIV-1 gag stimulation and secrete interferon (IFN)-gamma. However, L. major-infected, vaccinated BALB/c mice had a significantly reduced number of IFN-gamma-producing CD8+ T cells following in vitro stimulation with gag antigen. These data suggest that parasitic infection, which results in a Th2 profile, reduces the efficacy of DNA vaccines that are designed to induce antiviral CD8+ T cell responses.

Parasitic infection and the polarized Th2 immune response can alter a vaccine-induced immune response.

The AIDS epidemic in the Developing World represents a major global crisis. It is imperative that we develop an effective vaccine. Vaccines are economically the most efficient means of controlling viral infections. However, the development of a vaccine against HIV-1 has been a formidable task, and in developing countries chronic parasitic infection adds another level of complexity to AIDS vaccine development. Helminthic and protozoan infections, common in developing countries, can result in a constant state of immune activation that is characterized by a dominant Th2 type of cytokine profile, high IgE levels, and eosinophilia. Such an immune profile may have an adverse impact on the efficacy of vaccines, in particular, an HIV-1 vaccine. Indeed, the CD8 cellular immune response and the corresponding Th1 type cytokines that enhance the CD8 cellular immune response are important for clearing many viral infections. It is believed that an antigen specific CD8 cellular immune response will be an important component of an HIV-1 vaccine.