Review of Self+Culture+Writing: Autoethnography for/as Writing Studies, Rebecca Jackson and Jackie Grutsch McKinney, editors

This volume brings together a compendium of works that explore autoethnography and its emerging applications. A qualitative approach that first appeared in the social sciences, autoethnography has recently gained traction within other disciplines over the last two decades, including rhetoric and composition studies. However, due to its theoretically and methodologically amorphous qualities, over the years researchers have struggled to firmly define autoethnography, especially as the field continues to evolve. Still, many within writing studies have championed the method and now understand it as a recursive tool for studying “the relationship between self and other and all of its dimensions” (Kafar and Ellis 134)

Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.

INTRODUCTION: Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. Areas covered: This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation. Pre-clinical models support GUCY2C ligand supplementation as a novel disease prevention paradigm. With the recent FDA approval of the GUCY2C ligand, linaclotide, and two more synthetic ligands in the pipeline, this strategy can be tested in human trials. In addition to primary tumor prevention, we also review immunotherapies targeting GUCY2C expressed by metastatic lesions, and platforms using GUCY2C as a biomarker for detection and patient staging. Expert commentary: Results of the first GUCY2C targeting schemes in patients will become available in the coming years. The identification of GUCY2C ligand loss as a requirement for colorectal tumorigenesis has the potential to change the treatment paradigm from an irreversible disease of genetic mutation, to a treatable disease of ligand insufficiency

GUCY2C maintains intestinal LGR5+ stem cells by opposing ER stress

Long-lived multipotent stem cells (ISCs) at the base of intestinal crypts adjust their phenotypes to accommodate normal maintenance and post-injury regeneration of the epithelium. Their long life, lineage plasticity, and proliferative potential underlie the necessity for tight homeostatic regulation of the ISC compartment. In that context, the guanylate cyclase C (GUCY2C) receptor and its paracrine ligands regulate intestinal epithelial homeostasis, including proliferation, lineage commitment, and DNA damage repair. However, a role for this axis in maintaining ISCs remains unknown. Transgenic mice enabling analysis of ISCs (Lgr5-GFP) in the context of GUCY2C elimination (Gucy2c-/-) were combined with immunodetection techniques and pharmacological treatments to define the role of the GUCY2C signaling axis in supporting ISCs. ISCs were reduced in Gucy2c-/- mice, associated with loss of active Lgr5+ cells but a reciprocal increase in reserve Bmi1+ cells. GUCY2C was expressed in crypt base Lgr5+ cells in which it mediates canonical cyclic (c) GMPdependent signaling. Endoplasmic reticulum (ER) stress, typically absent from ISCs, was elevated throughout the crypt base in Gucy2c-/- mice. The chemical chaperone tauroursodeoxycholic acid resolved this ER stress and restored the balance of ISCs, an effect mimicked by the GUCY2C effector 8Br-cGMP. Reduced ISCs in Gucy2c-/-mice was associated with greater epithelial injury and impaired regeneration following sub-lethal doses of irradiation. These observations suggest that GUCY2C provides homeostatic signals that modulate ER stress and cell vulnerability as part of the machinery contributing to the integrity of ISCs. © Kraft et al

APC-β-catenin-TCF signaling silences the intestinal guanylin-GUCY2C tumor suppressor axis.

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation eliminates guanylin expression at tumor initiation, silencing GUCY2C signaling which, in turn, dysregulates intestinal homeostatic mechanisms contributing to tumor progression. They expand the mechanistic paradigm for colorectal cancer from a disease of irreversible mutations in APC and β-catenin to one of guanylin hormone loss whose replacement, and reconstitution of GUCY2C signaling, could prevent tumorigenesis

Preventing Teen Pregnancy Among Latinos: Recommendations from Research, Evaluation, and Practitioner Experience

Despite recent and dramatic declines in the rate of childbearing among Latino adolescents, that rate is still the highest among the major racial and ethnic groups in the United States. This fact underscores the need for effective interventions designed specifically to reduce teen pregnancy in this population. Child Trends examined the determinants of early childbearing among Latinos from multiple perspectives to develop a research-based pregnancy prevention approach for Latino adolescents. Specifically, we drew from research studies, program evaluations, and practitioner insights to identify,develop, or adapt promising program models for a Latino population.This brief highlights ways that adolescents' individual attitudes and behaviors, as well as family and parents, peers, and romantic partners, can help or hinder their desires to avoid teen pregnancy. Further, the brief addresses the need for programs and policy makers torecognize these influences and respond accordingly. Based on the findings outlined in this brief, Child Trends developed eight key recommendations for consideration in future intervention efforts

World Health Organization infant and young child feeding indicators and their associations with child anthropometry: a synthesis of recent findings

As the World Health Organization (WHO) infant and young child feeding (IYCF) indicators are increasingly adopted, a comparison of country-specific analyses of the indicators\u27 associations with child growth is needed to examine the consistency of these relationships across contexts and to assess the strengths and potential limitations of the indicators. This study aims to determine cross-country patterns of associations of each of these indicators with child stunting, wasting, height-for-age z-score (HAZ) and weight-for-height z-score (WHZ). Eight studies using recent Demographic and Health Surveys data from a total of nine countries in sub-Saharan Africa (nine), Asia (three) and the Caribbean (one) were identified. The WHO indicators showed mixed associations with child anthropometric indicators across countries. Breastfeeding indicators demonstrated negative associations with HAZ, while indicators of diet diversity and overall diet quality were positively associated with HAZ in Bangladesh, Ethiopia, India and Zambia (P \u3c 0.05). These same complementary feeding indicators did not show consistent relationships with child stunting. Exclusive breastfeeding under 6 months of age was associated with greater WHZ in Bangladesh and Zambia (P \u3c 0.05), although CF indicators did not show strong associations with WHZ or wasting. The lack of sensitivity and specificity of many of the IYCF indicators may contribute to the inconsistent associations observed. The WHO indicators are clearly valuable tools for broadly assessing the quality of child diets and for monitoring population trends in IYCF practices over time. However, additional measures of dietary quality and quantity may be necessary to understand how specific IYCF behaviours relate to child growth faltering

Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations revealed that obesity reversibly silenced guanylin expression through calorie-dependent induction of endoplasmic reticulum stress and the unfolded protein response in intestinal epithelial cells. In transgenic mice, enforcing specific expression of guanylin in intestinal epithelial cells restored GUCY2C signaling, eliminating intestinal tumors associated with a high calorie diet. Our findings show how caloric suppression of the guanylin-GUCY2C signaling axis links obesity to negation of a universal tumor suppressor pathway in colorectal cancer, suggesting an opportunity to prevent colorectal cancer in obese patients through hormone replacement with the FDA-approved oral GUCY2C ligand linaclotide

Differential regulation of gene expression pathways with dexamethasone and ACTH after early life seizures.

Early-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients\u27 quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even been shown to exacerbate injury in a rat model of temporal lobe epilepsy. We hypothesized that ACTH exerted positive effects on cognitive outcomes through beneficial changes to gene expression and proposed that administration of ACTH at seizure induction would return gene-expression in the brain towards the normal pattern of expression in the Control animals whereas Dex would not. Twenty-six Sprague-Dawley rats were randomized into vehicle- Control, and ACTH-, Dex-, and vehicle- ELS. Rat pups were subjected to 60 flurothyl seizures from P5 to P14. After seizure induction, brains were removed and the hippocampus and PFC were dissected, RNA was extracted and sequenced, and differential expression analysis was performed using generalized estimating equations. Differential expression analysis showed that ACTH pushes gene expression in the brain back to a more normal state of expression through enrichment of pathways involved in supporting homeostatic balance and down-regulating pathways that might contribute to excitotoxic cell-damage post-ELS

Vision in an abundant North American bird: The Red-winged Blackbird

Avian vision is fundamentally different from human vision; however, even within birds there are substantial between species differences in visual perception in terms of visual acuity, visual coverage, and color vision. However, there are not many species that have all these visual traits described, which can constrain our ability to study the evolution of visual systems in birds. To start addressing this gap, we characterized multiple traits of the visual system (visual coverage, visual acuity, centers of acute vision, and color vision) of the Red-winged Blackbird (Agelaius phoeniceus), one of the most abundant and studied birds in North America. We found that Red-winged Blackbirds have: wide visual coverage; one center of acute vision per eye (fovea) projecting fronto-laterally with high density of single and double cones, making it the center of both chromatic and achromatic vision; a wide binocular field that does not have the input of the centers of acute vision; and an ultraviolet sensitive visual system. With this information, we parameterized a Red-winged Blackbird-specific perceptual model considering different plumage patches. We found that the male red epaulet was chromatically conspicuous but with minimal achromatic signal, but the male yellow patch had a lower chromatic but a higher achromatic signal, which may be explained by the pigment composition of the feathers. However, the female epaulet was not visually conspicuous in both the chromatic and achromatic dimensions compared with other female feather patches. We discuss the implications of this visual system configuration relative to the foraging, antipredator, mate choice, and social behaviors of Red-winged Blackbirds. Our findings can be used for comparative studies as well as for making more species-specific predictions about different visual behaviors for future empirical testing