The X-ray spectra of the flaring and quiescent states of AT Microscopii observed by XMM-Newton

The X-ray spectrum of the late-type M-dwarf binary AT Mic (dM4.5e+dM4.5e) is observed in the wavelength range 1 - 40 Angstrom by means of rgs and epic-mos on board XMM-Newton. During the exposure a flare occured. We have performed a 3-temperature fit and a DEM-modeling to the flaring and quiescent part of the spectrum. We report the coronal temperature distribution, emission measures, and abundances of the flaring and quiescent state of this bright X-ray source. The temperature range stretches from about 1 to 60 MK. The total volume emission measure in this temperature interval is ~12.2*10^51 cm^-3 for the quiescent state and ~19.5*10^51 cm^-3 for the flare state. This difference is due to the contribution of the hot temperature component. The high-resolution spectrum of AT Mic, obtained by rgs, is dominated by the H- and He-like transitions of C, N, O, and Ne and by Fe XVII lines, produced by the plasma with temperatures from 1 to 10 MK. The epic-mos spectrum below 10 Angstrom shows H- and He-like Ne, Si and the iron K-shell transitions. They are produced by the hot component (30 MK). The iron K-shell is more prominent in the flare state. The abundance pattern in the quiescent state of AT Mic shows the depletion of low-FIP elements relative to high-FIP elements, indicating the presence of an I(nverse)FIP effect in this active star. In the flare state, however, some flattening of this IFIP effect is present.Comment: 7 pages, 11 figures ordered as: 1, 2ab, 3, 4abc, 5ab, 6a

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

The thing about replicas - why historic replicas matter

Reproduction of archaeological material was a significant and serious enterprise for antiquarians and museums in the long nineteenth century. Embedding many stories and embodying considerable past human energy, behind their creation, circulation, use and after-life lies a series of specific social networks and relationships that determined why, when and in what circumstances they were valued, or not. Summarising the context of their production, circulation and changing fortunes, this paper introduces the ways in which they are important and the specific benefits and aspects of a biographical approach to their study. Beyond the evidential, the study of existing replicas provides a historical and contemporary laboratory in which to explore the concepts of value and authenticity, and their application in cultural heritage and collections management, offering us a richer insight into the history of ourselves as archaeologists and curators

Maternal and perinatal health research priorities beyond 2015 : an international survey and prioritization exercise

Background: Maternal mortality has declined by nearly half since 1990, but over a quarter million women still die every year of causes related to pregnancy and childbirth. Maternal-health related targets are falling short of the 2015 Millennium Development Goals and a post-2015 Development Agenda is emerging. In connection with this, setting global research priorities for the next decade is now required. Methods. We adapted the methods of the Child Health and Nutrition Research Initiative (CHNRI) to identify and set global research priorities for maternal and perinatal health for the period 2015 to 2025. Priority research questions were received from various international stakeholders constituting a large reference group, and consolidated into a final list of research questions by a technical working group. Questions on this list were then scored by the reference working group according to five independent and equally weighted criteria. Normalized research priority scores (NRPS) were calculated, and research priority questions were ranked accordingly. Results: A list of 190 priority research questions for improving maternal and perinatal health was scored by 140 stakeholders. Most priority research questions (89%) were concerned with the evaluation of implementation and delivery of existing interventions, with research subthemes frequently concerned with training and/or awareness interventions (11%), and access to interventions and/or services (14%). Twenty-one questions (11%) involved the discovery of new interventions or technologies. Conclusions: Key research priorities in maternal and perinatal health were identified. The resulting ranked list of research questions provides a valuable resource for health research investors, researchers and other stakeholders. We are hopeful that this exercise will inform the post-2015 Development Agenda and assist donors, research-policy decision makers and researchers to invest in research that will ultimately make the most significant difference in the lives of mothers and babies.</p

Ancestral Mutation in Telomerase Causes Defects in Repeat Addition Processivity and Manifests As Familial Pulmonary Fibrosis

The telomerase reverse transcriptase synthesizes new telomeres onto chromosome ends by copying from a short template within its integral RNA component. During telomere synthesis, telomerase adds multiple short DNA repeats successively, a property known as repeat addition processivity. However, the consequences of defects in processivity on telomere length maintenance are not fully known. Germline mutations in telomerase cause haploinsufficiency in syndromes of telomere shortening, which most commonly manifest in the age-related disease idiopathic pulmonary fibrosis. We identified two pulmonary fibrosis families that share two non-synonymous substitutions in the catalytic domain of the telomerase reverse transcriptase gene hTERT: V791I and V867M. The two variants fell on the same hTERT allele and were associated with telomere shortening. Genealogy suggested that the pedigrees shared a single ancestor from the nineteenth century, and genetic studies confirmed the two families had a common founder. Functional studies indicated that, although the double mutant did not dramatically affect first repeat addition, hTERT V791I-V867M showed severe defects in telomere repeat addition processivity in vitro. Our data identify an ancestral mutation in telomerase with a novel loss-of-function mechanism. They indicate that telomere repeat addition processivity is a critical determinant of telomere length and telomere-mediated disease

The need to research refractory breathlessness

High-quality research is needed to improve quality of life for people with chronic refractory breathlessness in COP

Anderson's ethical vulnerability: animating feminist responses to sexual violence

Pamela Sue Anderson argues for an ethical vulnerability which “activates an openness to becoming changed” that “can make possible a relational accountability to one another on ethical matters”. In this essay I pursue Anderson’s solicitation that there is a positive politics to be developed from acknowledging and affirming vulnerability. I propose that this politics is one which has a specific relevance for animating the terms of feminist responses to sexual violence, something which has proved difficult for feminist theorists and activists alike. I will demonstrate the contribution of Anderson’s work to such questions by examining the way in which “ethical vulnerability” as a framework can illuminate the intersectional feminist character of Tarana Burke’s grassroots Me Too movement when compared with the mainstream, viral version of the movement. I conclude by arguing that Anderson’s “ethical vulnerability” contains ontological insights which can allay both activist and academic concerns regarding how to respond to sexual violence

Telomerase mutations in families with idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis is progressive and often fatal; causes of familial clustering of the disease are unknown. Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia and pulmonary fibrosis. METHODS: To test the hypothesis that familial idiopathic pulmonary fibrosis may be caused by short telomeres, we screened 73 probands from the Vanderbilt Familial Pulmonary Fibrosis Registry for mutations in hTERT and hTR. RESULTS: Six probands (8%) had heterozygous mutations in hTERT or hTR; mutant telomerase resulted in short telomeres. Asymptomatic subjects with mutant telomerase also had short telomeres, suggesting that they may be at risk for the disease. We did not identify any of the classic features of dyskeratosis congenita in five of the six families. CONCLUSIONS: Mutations in the genes encoding telomerase components can appear as familial idiopathic pulmonary fibrosis. Our findings support the idea that pathways leading to telomere shortening are involved in the pathogenesis of this disease

Microalbuminuria among Type 1 and Type 2 diabetic patients of African origin in Dar Es Salaam, Tanzania

BACKGROUND: The prevalences and risk factors of microalbuminuria are not full described among black African diabetic patients. This study aimed at determining the prevalence of microalbuminuria among African diabetes patients in Dar es Salaam, Tanzania, and relate to socio-demographic features as well as clinical parameters. METHODS: Cross sectional study on 91 Type 1 and 153 Type 2 diabetic patients. Two overnight urine samples per patient were analysed. Albumin concentration was measured by an automated immunoturbidity assay. Average albumin excretion rate (AER) was used and were categorised as normalbuminuria (AER < 20 ug/min), microalbuminuria (AER 20–200 ug/min), and macroalbuminuria (AER > 200 ug/min). Information obtained also included age, diabetes duration, sex, body mass index, blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, triglycerides, serum creatinine, and glycated hemoglobin A(1c). RESULTS: Overall prevalence of microalbuminuria was 10.7% and macroalbuminuria 4.9%. In Type 1 patients microalbuminuria was 12% and macroalbuminuria 1%. Among Type 2 patients, 9.8% had microalbuminuria, and 7.2% had macroalbuminuria. Type 2 patients with abnormal albumin excretion rate had significantly longer diabetes duration 7.5 (0.2–24 yrs) than those with normal albumin excretion rate 3 (0–25 yrs), p < 0.001. Systolic and diastolic blood pressure among Type 2 patients with abnormal albumin excretion rate were significantly higher than in those with normal albumin excretion rate, (p < 0.001). No significant differences in body mass index, glycaemic control, and cholesterol levels was found among patients with normal compared with those with elevated albumin excretion rate either in Type 1 or Type 2 patients. A stepwise multiple linear regression analysis among Type 2 patients, revealed AER (natural log AER) as the dependent variable to be predicted by [odds ratio (95% confidence interval)] diabetes duration 0.090 (0.049, 0.131), p < 0.0001, systolic blood pressure 0.012 (0.003–0.021), p < 0.010 and serum creatinine 0.021 (0.012, 0.030). CONCLUSION: The prevalence of micro and macroalbuminuria is higher among African Type 1 patients with relatively short diabetes duration compared with prevalences among Caucasians. In Type 2 patients, the prevalence is in accordance with findings in Caucasians. The present study detects, however, a much lower prevalence than previously demonstrated in studies from sub-Saharan Africa. Abnormal AER was significantly related to diabetes duration and systolic blood pressure