Mammalian Comparative Sequence Analysis of the Agrp Locus

Agouti-related protein encodes a neuropeptide that stimulates food intake. Agrp expression in the brain is restricted to neurons in the arcuate nucleus of the hypothalamus and is elevated by states of negative energy balance. The molecular mechanisms underlying Agrp regulation, however, remain poorly defined. Using a combination of transgenic and comparative sequence analysis, we have previously identified a 760 bp conserved region upstream of Agrp which contains STAT binding elements that participate in Agrp transcriptional regulation. In this study, we attempt to improve the specificity for detecting conserved elements in this region by comparing genomic sequences from 10 mammalian species. Our analysis reveals a symmetrical organization of conserved sequences upstream of Agrp, which cluster into two inverted repeat elements. Conserved sequences within these elements suggest a role for homeodomain proteins in the regulation of Agrp and provide additional targets for functional evaluation

Contested space: The contradictory political dynamics of food banking in the UK

This paper offers a critical reappraisal of the politics of food banking in the UK. Existing work has raised concerns about the institutionalisation of food banks, with charitable assistance apparently – even if inadvertently – undermining collectivist welfare and deflecting attention from fundamental injustices in the food system. This paper presents original ethnographic work that examines the neglected politics articulated within food banks themselves. Conceptualising food banks as potential spaces of encounter where predominantly middle-class volunteers come into contact with ‘poor others’ (Lawson and Elwood, 2013), we illustrate the ways food banks may both reinforce but also rework and generate new, ethical and political attitudes, beliefs and identities. We also draw attention to the limits of these progressive possibilities and examine the ways in which some food banks continue to operate within a set of highly restrictive, and stigmatising, welfare technologies. By highlighting the contradictory dynamics at work in food bank organisations, and among food bank volunteers and clients, we suggest the political role of food banks warrants neither uncritical celebration nor outright dismissal. Rather, food banks represent a highly ambiguous political space still in the making and open to contestatio

Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan

Classifying endometrial hyperplasia (EH) according to the severity of glandular crowding (simple hyperplasia (SH) vs complex hyperplasia (CH)) and nuclear atypia (simple atypical hyperplasia (SAH) vs complex atypical hyperplasia (CAH)) should predict subsequent endometrial carcinoma risk, but data on progression are lacking. Our nested case–control study of EH progression included 138 cases, who were diagnosed with EH and then with carcinoma (1970–2003) at least 1 year (median, 6.5 years) later, and 241 controls, who were individually matched on age, date, and follow-up duration and counter-matched on EH classification. After centralised pathology panel and medical record review, we generated rate ratios (RRs) and 95% confidence intervals (CIs), adjusted for treatment and repeat biopsies. With disordered proliferative endometrium (DPEM) as the referent, AH significantly increased carcinoma risk (RR=14, 95% CI, 5–38). Risk was highest 1–5 years after AH (RR=48, 95% CI, 8–294), but remained elevated 5 or more years after AH (RR=3.5, 95% CI, 1.0–9.6). Progression risks for SH (RR=2.0, 95% CI, 0.9–4.5) and CH (RR=2.8, 95% CI, 1.0–7.9) were substantially lower and only slightly higher than the progression risk for DPEM. The higher progression risks for AH could foster management guidelines based on markedly different progression risks for atypical vs non-atypical EH

Metabolic changes in concussed American football players during the acute and chronic post-injury phases

<p>Abstract</p> <p>Background</p> <p>Despite negative neuroimaging findings many athletes display neurophysiological alterations and post-concussion symptoms that may be attributable to neurometabolic alterations.</p> <p>Methods</p> <p>The present study investigated the effects of sports concussion on brain metabolism using ¹H-MR Spectroscopy by comparing a group of 10 non-concussed athletes with a group of 10 concussed athletes of the same age (mean: 22.5 years) and education (mean: 16 years) within both the acute and chronic post-injury phases. All athletes were scanned 1-6 days post-concussion and again 6-months later in a 3T Siemens MRI.</p> <p>Results</p> <p>Concussed athletes demonstrated neurometabolic impairment in prefrontal and motor (M1) cortices in the acute phase where NAA:Cr levels remained depressed relative to controls. There was some recovery observed in the chronic phase where Glu:Cr levels returned to those of control athletes; however, there was a pathological increase of m-I:Cr levels in M1 that was only present in the chronic phase.</p> <p>Conclusions</p> <p>These results confirm cortical neurometabolic changes in the acute post-concussion phase as well as recovery and continued metabolic abnormalities in the chronic phase. The results indicate that complex pathophysiological processes differ depending on the post-injury phase and the neurometabolite in question.</p

Community food program use in Inuvik, Northwest Territories

Background: Community food programs (CFPs) provide an important safety-net for highly food insecure community members in the larger settlements of the Canadian Arctic. This study identifies who is using CFPs and why, drawing upon a case study from Inuvik, Northwest Territories. This work is compared with a similar study from Iqaluit, Nunavut, allowing the development of an Arctic-wide understanding of CFP use – a neglected topic in the northern food security literature. Methods: Photovoice workshops (n=7), a modified USDA food security survey and open ended interviews with CFP users (n=54) in Inuvik. Results: Users of CFPs in Inuvik are more likely to be housing insecure, female, middle aged (35–64), unemployed, Aboriginal, and lack a high school education. Participants are primarily chronic users, and depend on CFPs for regular food access. Conclusions: This work indicates the presence of chronically food insecure groups who have not benefited from the economic development and job opportunities offered in larger regional centers of the Canadian Arctic, and for whom traditional kinship-based food sharing networks have been unable to fully meet their dietary needs. While CFPs do not address the underlying causes of food insecurity, they provide an important service for communities undergoing rapid change, and need greater focus in food policy herein

HERP, a New Primary Target of Notch Regulated by Ligand Binding

Notch signaling dictates cell fate and critically influences cell proliferation, differentiation, and apoptosis in metazoans. Ligand binding initiates the signal through regulated intramembrane proteolysis of a transmembrane Notch receptor which releases the signal-transducing Notch intracellular domain (NICD). The HES/E(spl) gene family is a primary target of Notch and thus far the only known Notch effector. A newly isolated HERP family, a HES-related basic helix-loop-helix protein family, has been proposed as a potential target of Notch, based on its induction following NICD overexpression. However, NICD is physiologically maintained at an extremely low level that typically escapes detection, and therefore, nonregulated overexpression of NICD—as in transient transfection—has the potential of generating cellular responses of little physiological relevance. Indeed, a constitutively active NICD indiscriminately up-regulates expression of both HERP1 and HERP2 mRNAs. However, physiological Notch stimulation through ligand binding results in the selective induction of HERP2 but not HERP1 mRNA and causes only marginal up-regulation of HES1 mRNA. Importantly, HERP2 is an immediate target gene of Notch signaling since HERP2 mRNA expression is induced even in the absence of de novo protein synthesis. HERP2 mRNA induction is accompanied by specific expression of HERP2 protein in the nucleus. Furthermore, using RBP-Jk-deficient cells, we show that an RBP-Jk protein, a transcription factor that directly activates HES/E(spl) transcription, also is essential for HERP2 mRNA expression and that expression of exogenous RBP-Jk is sufficient to rescue HERP2 mRNA expression. These data establish that HERP2 is a novel primary target gene of Notch that, together with HES, may effect diverse biological activities of Notch

Citizenship for children: By soil, by blood, or by paternalism?

Do states have a right to exclude prospective immigrants as they see fit? According to statists the answer is a qualified yes. For these authors, self-determining political communities have a prima facie right to exclude, which can be overridden by the claims of vulnerable groups such as refugees and children born in the state’s territory. However, there is a concern in the literature that statists have not yet developed a theory that can protect children born in the territory from being excluded from the political community. For if the self-determining political community has the right to decide who should form the self in the first place, then that right should count against both newcomers by immigration and newcomers by birth. Or so the concern goes. In this essay, I defend statism against this line of criticism and provide a liberal justification for the inclusion of children born within the state’s borders. My account leads to some surprising implication for citizenship law, as well as immigration arrangements in the area of asylum and unauthorized immigration