A single amino acid substitution in the alpha 3 domain of an H-2 class I molecule abrogates reactivity with CTL.

We previously described a somatic cell expressing a variant H-2Dd molecule that did not serve as a target for alloreactive anti-Dd CTL. The mutant cell line had been isolated by its failure to express a serological epitope present on the H-2Dd alpha 3 domain. In the present study the alpha 3 domain of the Dd molecule of this somatic cell variant was sequenced and a single nucleotide change resulting in a glutamic acid to lysine substitution at residue 227 was identified. This change was reproduced in the cloned H-2Dd gene by oligonucleotide-directed mutagenesis. Cells transfected with this mutant gene were not killed by anti-H-2Dd CTL. Because previous studies using hybrid H-2 class I molecules had established that the alpha 3 domain does not express allele-specific determinants recognized by CTL, our results raise the possibility that residues in the alpha 3 domain of H-2 class I molecules are critical for CTL recognition and constitute a conserved (or monomorphic) determinant recognized by CTL

‘Bring back Hitler’s gas chambers’: asylum seeking, Nazis and facebook – a discursive analysis

In this article, we explore how talk about Nazis is used in Internet discussions regarding asylum seeking, and the issue of whether or not opposition to asylum seeking is racist. Discursive analysis was conducted on discussions about asylum seeking from the social networking website Facebook, where references to Nazis were made. Three strategies were identified: (1) people supporting asylum seeking accuse asylum opponents of being racist by referring to Nazis; (2) opponents of asylum seeking deal with such accusations by arguing that the debate is being suppressed because of references to Nazis; (3) in the final, and most striking, strategy, opponents of asylum draw upon ideas associated with the Nazis and Hitler to bring about their anti-asylum position. These findings are discussed in relation to how the link between Nazis and racism is emerging in the asylum debat

Long Term Prognostic Impact of Sex-specific Longitudinal Changes in Blood Pressure. The EPIC-Norfolk Prospective Population Cohort Study

AIMS: We aimed to determine the sex differences in longitudinal systolic and diastolic blood pressure (SBP and DBP) trajectories in mid-life and delineate the associations between these and mortality (all-cause, cardiovascular, and non-cardiovascular) and incident cardiovascular disease (CVD) in old age. METHODS AND RESULTS: Participants were selected from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) cohort study. Sex-specific trajectories were determined using group-based trajectory models using three clinic BP measurements acquired between 1993 and 2012 (mean exposure ∼12.9 years). Multivariable Cox regressions determined the associations between trajectories and incident outcomes over the follow-up (median follow-up 9.4 years). A total of 2897 men (M) and 3819 women (F) were included. At baseline, women were younger (F-55.5, M-57.1), had a worse cardiometabolic profile and were less likely to receive primary CVD prevention including antihypertensive treatment (F-36.0%, M-42.0%). Over the exposure period, women had lower SBP trajectories while men exhibited more pronounced SBP decreases over this period. Over the follow-up period, women had lower mortality (F-11.9%, M-20.5%) and CVD incidence (F-19.8%, M-29.6%). Compared to optimal SBP (≤120 mmHg) and DBP (≤70 mmHg) trajectories, hypertensive trajectories were associated with increased mortality and incident CVD in both men and women during follow-up at univariable level. These associations were nevertheless not maintained upon extensive confounder adjustment including antihypertensive therapies. CONCLUSION: We report sex disparities in CVD prevention which may relate to worse cardiometabolic profiles and less pronounced longitudinal SBP decreases in women. Effective anti-hypertensivetherapy may offset the adverse outcomes associated with prolonged exposure to high blood pressure

The Discursive Denial of Racism by Finnish Populist Radical Right Politicians Accused of Anti-Muslim Hate-Speech

This chapter explores Finnish populist radical right politicians’ discursive denials of racism against Muslims following the 2015 European “refugee crisis”. The critical discursive psychological analysis of the politicians’ Facebook accounts identifies four ways in which racism was denied: first, through constructing the statements as mere displays of undisputable facts and common-sense; second, through personal narratives and ontological gerrymandering that acted as ‘proof’ of the politician’s non-racist disposition; third, through transferring the discussion from issues about race to concern matters of cultural threats; and, fourth, through reversing racism to the politicians’ political antagonists. The analyses show that in their discursive denial of racist hate-speech against Muslims, the Finnish politicians relied more on cultural arguments than welfare-protectionist ones. That is, the denials were primarily warranted through nostalgic references to Finnish national identity, people and values, and rhetorical promises that the hope of saving these rests on resisting the cultural threat posed by Islam.Peer reviewe

Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment.

Journal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a clinical isolate of P. asymbiotica at different temperatures in order to identify proteins relevant to the infection of the two different hosts. RESULTS: A comparison of the proteins secreted by a clinical isolate of P. asymbiotica at simulated insect (28 degrees C) and human (37 degrees C) temperatures led to the identification of a small and highly abundant protein, designated Pam, that is only secreted at the lower temperature. The pam gene is present in all Photorhabdus strains tested and shows a high level of conservation across the whole genus, suggesting it is both ancestral to the genus and probably important to the biology of the bacterium. The Pam protein shows limited sequence similarity to the 13.6 kDa component of a binary toxin of Bacillus thuringiensis. Nevertheless, injection or feeding of heterologously produced Pam showed no insecticidal activity to either Galleria mellonella or Manduca sexta larvae. In bacterial colonies, Pam is associated with an extracellular polysaccharide (EPS)-like matrix, and modifies the ability of wild-type cells to attach to an artificial surface. Interestingly, Surface Plasmon Resonance (SPR) binding studies revealed that the Pam protein itself has adhesive properties. Although Pam is produced throughout insect infection, genetic knockout does not affect either insect virulence or the ability of P. luminescens to form a symbiotic association with its host nematode, Heterorhabditis bacteriophora. CONCLUSIONS: We studied a highly abundant protein, Pam, which is secreted in a temperature-dependent manner in P. asymbiotica. Our findings indicate that Pam plays an important role in enhancing surface attachment in insect blood. Its association with exopolysaccharide suggests it may exert its effect through mediation of EPS properties. Despite its abundance and conservation in the genus, we find no evidence for a role of Pam in either virulence or symbiosis.BBSRCWellcome TrustEMBEK

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

Dieting practices, weight perceptions, and body composition: A comparison of normal weight, overweight, and obese college females

BACKGROUND: Of concern to health educators is the suggestion that college females practice diet and health behaviors that contradict the 2005 dietary guidelines for Americans. In this regard, there remain gaps in the research related to dieting among college females. Namely, do normal weight individuals diet differently from those who are overweight or obese, and are there dieting practices used by females that can be adapted to promote a healthy body weight? Since it is well recognized that females diet, this study seeks to determine the dieting practices used among normal, overweight, and obese college females (do they diet differently) and identify dieting practices that could be pursued to help these females more appropriately achieve and maintain a healthy body weight. METHODS: A total of 185 female college students aged 18 to 24 years participated in this study. Height, weight, waist and hip circumferences, and skinfold thickness were measured to assess body composition. Surveys included a dieting practices questionnaire and a 30-day physical activity recall. Participants were classified according to body mass index (BMI) as normal weight (n = 113), overweight (n = 35), or obese (n = 21). Data were analyzed using JMP IN® software. Descriptive statistics included means, standard deviations, and frequency. Subsequent data analysis involved Pearson X(2 )and one-way analysis of variance with comparison for all pairs that were significantly different using Tukey-Kramer honestly significant difference test. RESULTS: Outcomes of this study indicate the majority of participants (83%) used dieting for weight loss and believed they would be 2% to 6% greater than current weight if they did not diet; normal weight, overweight, and obese groups perceived attractive weight to be 94%, 85%, and 74%, respectively, of current weight; 80% of participants reported using physical activity to control weight, although only 19% exercised at a level that would promote weight loss; only two of 15 dieting behaviors assessed differed in terms of prevalence of use among groups, which were consciously eating less than you want (44% normal weight, 57% overweight, 81% obese) and using artificial sweeteners (31% normal weight and overweight, 5% obese); and the most prevalent explicit maladaptive weight loss behavior was smoking cigarettes (used by 9% of participants) and most unhealthy was skipping breakfast (32%). CONCLUSION: Collectively, results indicate female college students, regardless of weight status, would benefit from open discussions with health educators regarding healthy and effective dieting practices to achieve/maintain a healthy body weight. The results are subject to replication among high school, middle-aged, and older females