Localization of complement factor H gene expression and protein distribution in the mouse outer retina.

To determine the localization of complement factor H (Cfh) mRNA and its protein in the mouse outer retina.Quantitative real-time PCR (qPCR) was used to determine the expression of Cfh and Cfh-related (Cfhr) transcripts in the RPE/choroid. In situ hybridization (ISH) was performed using the novel RNAscope 2.0 FFPE assay to localize the expression of Cfh mRNA in the mouse outer retina. Immunohistochemistry (IHC) was used to localize Cfh protein expression, and western blots were used to characterize CFH antibodies used for IHC.Cfh and Cfhr2 transcripts were detected in the mouse RPE/choroid using qPCR, while Cfhr1, Cfhr3, and Cfhrc (Gm4788) were not detected. ISH showed abundant Cfh mRNA in the RPE of all mouse strains (C57BL/6, BALB/c, 129/Sv) tested, with the exception of the Cfh(-/-) eye. Surprisingly, the Cfh protein was detected by immunohistochemistry in photoreceptors rather than in RPE cells. The specificity of the CFH antibodies was tested by western blotting. Our CFH antibodies recognized purified mouse Cfh protein, serum Cfh protein in wild-type C57BL/6, BALB/c, and 129/Sv, and showed an absence of the Cfh protein in the serum of Cfh(-/-) mice. Greatly reduced Cfh protein immunohistological signals in the Cfh(-/-) eyes also supported the specificity of the Cfh protein distribution results.Only Cfh and Cfhr2 genes are expressed in the mouse outer retina. Only Cfh mRNA was detected in the RPE, but no protein. We hypothesize that the steady-state concentration of Cfh protein is low in the cells due to secretion, and therefore is below the detection level for IHC

T-duality and Generalized Complex Geometry

We find the explicit T-duality transformation in the phase space formulation of the N=(1,1) sigma model. We also show that the T-duality transformation is a symplectomorphism and it is an element of O(d,d). Further, we find the explicit T-duality transformation of a generalized complex structure in this model. We also show that the extended supersymmetry of the sigma model is preserved under the T-duality.Comment: 18 pages; added references; published versio

Adolescent self-harm in Ghana: a qualitative interview-based study of first-hand accounts

Background: Recent prevalence studies suggest that self-harm among adolescents in sub-Saharan Africa is as common as it is in high income countries. However, very few qualitative studies exploring first-person accounts of adolescent self-harm are available from sub-Saharan Africa. We sought to explore the experiences and first-person perspectives of Ghanaian adolescents reporting self-harm - for deeper reflections on the interpretive repertoires available in their cultural context for making sense of self-harm in adolescents. Methods: Guided by a semi-structured interview protocol, we interviewed one-to-one 36 adolescents (24 in-school adolescents and 12 street-connected adolescents) on their experiences of self-harm. We applied experiential thematic analysis to the data. Results: Adolescents’ description of the background to their self-harm identified powerlessness in the family context and unwanted adultification in the family as key factors leading up to self-harm among both in-school and street-connected adolescents. Adolescents’ explanatory accounts identified the contradictory role of adultification as a protective factor against self-harm among street-connected adolescents. Self-harm among in-school adolescents was identified as a means of “enactment of tabooed emotions and contestations”, as a “selfish act and social injury”, as “religious transgression”, while it was also seen as improving social relations. Conclusions: The first-person accounts of adolescents in this study implicate familial relational problems and interpersonal difficulties as proximally leading to self-harm in adolescents. Self-harm in adolescents is interpreted as an understandable response, and as a strong communicative signal in response to powerlessness and family relationship difficulties. These findings need to be taken into consideration in the planning of services in Ghana and are likely to be generalisable to many other countries in sub-Saharan Africa

Suicidality and depression among adult patients admitted in general medical facilities in Kenya

<p>Abstract</p> <p>Aim</p> <p>To document Beck Depression Inventory (BDI) II suicidal symptoms among patients admitted to Kenyan non-psychiatric general medical facilities</p> <p>Methods</p> <p>All consenting adults admitted within a period of 4 weeks at 10 general medical facilities in Kenya were interviewed for suicidal symptoms and depression using the BDI-II.</p> <p>Results</p> <p>In all, 2,780 patients responded to item 9 (suicidal symptoms of the BDI-II). The prevalence of all BDI-II suicidal symptoms combined was 10.5%. Thoughts of 'killing oneself but have not carried them out' accounted for 9% of the suicidal symptoms. The younger age group had the highest prevalence of suicidal symptoms and the oldest age group had the least prevalence of suicidal symptoms. The more depressed the patients were on the overall BDI-II score, the higher the prevalence of suicidal symptoms.</p> <p>Conclusion</p> <p>On average 1 out of 10 of the patients had suicidal symptoms, more so in younger than the older people and in the more depressed. These symptoms had not been clinically recognised and therefore not managed. This calls for clinical practice that routinely enquires for suicidal symptoms in general medical wards.</p

Repetition and severity of suicide attempts across the life cycle: a comparison by age group between suicide victims and controls with severe depression

<p>Abstract</p> <p>Background</p> <p>Suicide attempts have been shown to be less common in older age groups, with repeated attempts generally being more common in younger age groups and severe attempts in older age groups. Consistently, most studies have shown an increased suicide risk after attempts in older age. However, little is known about the predictive value of age on repeated and severe suicide attempts for accomplished suicide. The aim of the present study was to investigate the reduced incidence for initial, repeated, or severe suicide attempts with age in suicide victims and controls by gender.</p> <p>Methods</p> <p>The records of 100 suicide victims and matched controls with severe depression admitted to the Department of Psychiatry, Lund University Hospital, Sweden between 1956 and 1969, were evaluated and the subjects were monitored up to 2006. The occurrence of suicide attempts (first, repeated, or severe, by age group) was analysed for suicide victims and controls, with gender taken into consideration.</p> <p>Results</p> <p>There was a reduced risk for an initial suicide attempt by older age in females (suicide victims and controls) and male controls (but not suicide victims). The risk for repeated suicide attempts appeared to be reduced in the older age groups in female controls as compared to female suicide victims. The risk for severe suicide attempts seemed reduced in the older age groups in female suicide victims. This risk was also reduced in male controls and in male controls compared to male suicide victims.</p> <p>Conclusion</p> <p>In the older age groups repeated attempts appeared to be predictive for suicide in women and severe attempts predictive in men.</p

Recasting the cancer stem cell hypothesis: Unification using a continuum model of microenvironmental forces

Purpose of review Here, we identify shortcomings of standard compartment-based mathematical models of cancer stem-cells, and propose a continuous formalism which includes the tumor microenvironment. Recent findings Stem-cell models of tumor growth have provided explanations for various phenomena in oncology including, metastasis, drug- and radio-resistance, and functional heterogeneity in the face of genetic homogeneity. While some of the newer models allow for plasticity, or de-differentiation, there is no consensus on the mechanisms driving this. Recent experimental evidence suggests that tumor microenvironment factors like hypoxia, acidosis, and nutrient deprivation have causative roles. Summary To settle the dissonance between the mounting experimental evidence surrounding the effects of the microenvironment on tumor stemness, we propose a continuous mathematical model where we model microenvironmental perturbations like forces, which then shape the distribution of stemness within the tumor. We propose methods by which to systematically measure and characterize these forces, and show results of a simple experiment which support our claims

Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer

Recent studies have linked expression of lectin-like ox-LDL receptor 1 (OLR1) to tumorigenesis. We analyzed microarray data from Olr1 knockout (KO) and wild type (WT) mice for genes involved in cellular transformation and evaluated effects of OLR1 over-expression in normal mammary epithelial cells (MCF10A) and breast cancer cells (HCC1143) in terms of gene expression, migration, adhesion and transendothelial migration. Twenty-six out of 238 genes were inhibited in tissues of OLR1 KO mice; the vast majority of OLR1 sensitive genes contained NF-κB binding sites in their promoters. Further studies revealed broad inhibition of NF-kB target genes outside of the transformation-associated gene pool, with enrichment themes of defense response, immune response, apoptosis, proliferation, and wound healing. Transcriptome of Olr1 KO mice also revealed inhibition of de novo lipogenesis, rate-limiting enzymes fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd1) and ELOVL family member 6 (Elovl6), as well as lipolytic phospholipase A2 group IVB (Pla2g4b). In studies comparing MCF10A and HCC1143, the latter displayed 60% higher OLR1 expression. Forced over-expression of OLR1 resulted in upregulation of NF-κB (p65) and its target pro-oncogenes involved in inhibition of apoptosis (BCL2, BCL2A1, TNFAIP3) and regulation of cell cycle (CCND2) in both cell lines. Basal expression of FASN, SCD1 and PLA2G4B, as well as lipogenesis transcription factors PPARA, SREBF2 and CREM, was higher in HCC1143 cells. Over-expression of OLR1 in HCC1143 cells also enhanced cell migration, without affecting their adherence to TNFα-activated endothelium or transendothelial migration. On the other hand, OLR1 neutralizing antibody inhibited both adhesion and transmigration of untreated HCC1143 cells. We conclude that OLR1 may act as an oncogene by activation of NF-kB target genes responsible for proliferation, migration and inhibition of apoptosis and de novo lipogenesis genes

How adolescents who cut themselves differ from those who take overdoses

The aims of this study were to identify in what ways adolescents who cut themselves differ from those who take overdoses, and to investigate the role of contagion in these behaviours. Data from an anonymous self-report questionnaire survey of 6,020 adolescents in 41 schools were analysed. Comparison of 220 adolescents who reported self-cutting in the previous year with 86 who had taken overdoses in the previous year as the sole method of deliberate self-harm (DSH) showed that far more of those who cut themselves had friends who had also engaged in DSH in the same period (OR 2.84, 95% CI 1.5–5.3, P < 0.001), and fewer had sought help from friends before cutting (OR 0.5, 95% CI 0.3–0.9, P < 0.02). Self-cutting usually involved less premeditation. Analyses at both the individual and school level showed that the association between engaging in DSH and exposure to DSH amongst peers was largely confined to girls who cut themselves. There are important differences between adolescents who cut themselves and those who take overdoses. Contagion may be an important factor in DSH by adolescents, especially in girls who cut themselves. These findings are relevant to the design of prevention and treatment programmes