Slower rescue of ER homeostasis by the unfolded protein response pathway associated with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia and recurrent infections. Herein we addressed the role of unfolded protein response (UPR) in the pathogenesis of the disease. Augmented unspliced X-box binding protein 1 (XBP-1) mRNA concurrent with co-localization of IgM and BiP/GRP78 were found in one CVID patient. At confocal microscopy analysis this patient`s cells were enlarged and failed to present the typical surface distribution of IgM, which accumulated within an abnormally expanded endoplasmic reticulum. Sequencing did not reveal any mutation on XBP-1, neither on IRE-1 alpha that could potentially prevent the splicing to occur. Analysis of spliced XBP-1, IRE-1 alpha and BiP messages after LPS or Brefeldin A treatment showed that, unlike healthy controls that respond to these endoplasmic reticulum (ER) stressors by presenting waves of transcription of these three genes, this patient`s cells presented lower rates of transcription, not reaching the same level of response of healthy subjects even after 48 h of ER stress. Treatment with DMSO rescued IgM and IgG secretion as well as the expression of spliced XBP-1. Our findings associate diminished splicing of XBP-1 mRNA with accumulation of IgM within the ER and lower rates of chaperone transcription, therefore providing a mechanism to explain the observed hypogammaglobulinemia. (C) 2008 Elsevier Ltd. All rights reserved.

Naturally acquired inhibitory antibodies to Plasmodium vivax Duffy binding protein are short-lived and allele-specific following a single malaria infection

The Duffy binding protein of Plasmodium vivax (DBP) is a critical adhesion ligand that participates in merozoite invasion of human Duffy-positive erythrocytes. A small outbreak of P. vivax malaria, in a village located in a non-malarious area of Brazil, offered us an opportunity to investigate the DBP immune responses among individuals who had their first and brief exposure to malaria. Thirty-three individuals participated in the five cross-sectional surveys, 15 with confirmed P. vivax infection while residing in the outbreak area (cases) and 18 who had not experienced malaria (non-cases). In the present study, we found that only 20% (three of 15) of the individuals who experienced their first P. vivax infection developed an antibody response to DBP; a secondary boosting can be achieved with a recurrent P. vivax infection. DNA sequences from primary/recurrent P. vivax samples identified a single dbp allele among the samples from the outbreak area. To investigate inhibitory antibodies to the ligand domain of the DBP (cysteine-rich region II, DBP(II)), we performed in vitro assays with mammalian cells expressing DBP(II) sequences which were homologous or not to those from the outbreak isolate. In non-immune individuals, the results of a 12-month follow-up period provided evidence that naturally acquired inhibitory antibodies to DBP(II) are short-lived and biased towards a specific allele.

THE POINCARE-BENDIXSON THEOREM ON THE KLEIN BOTTLE FOR CONTINUOUS VECTOR FIELDS

We present a version of the Poincare-Bendixson Theorem on the Klein bottle K(2) for continuous vector fields. As a consequence, we obtain the fact that K(2) does not admit continuous vector fields having a omega-recurrent injective trajectory.

Sediment deformation in Miocene and post-Miocene strata, Northeastern Brazil: Evidence for paleoseismicity in a passive margin

Stratigraphic intervals characterized by varied and complex styles of soft-sediment deformation structures are well preserved in Miocene and Late Pleistocene to Holocene deposits of a sedimentary basin located in Northeastern Brazil. The Miocene strata, represented by the Barreiras Formation, record only brittle structures, including numerous faults and fractures with straight and high angle-dipping planes that are often filled with sands derived from overlying beds. Folds consisting of broad anticlines and synclines are also present in this unit. The late Pleistocene to Holocene deposits, named Post-Barreiras Sediments, contain an indurated sandy package with a large variety of ductile and brittle deformation structures (i.e., massive sandstones with isolated sand fragments and breccias, undulatory strata, sand dykes and diapirs, sinks and bowls, pebbly pockets, plunged sediment mixtures, fitted sand masses, cone-shaped cracks, fault grading and sedimentary enclaves). These features, confined to sharp-based stratigraphic horizons that progressively grade downward into undisturbed deposits, are related to seismic shocks of high surface-wave magnitude (i.e., Ms>5 or 6). Amalgamated seismites suggest that previously formed seismites were affected by subsequent seismic-wave propagation. Seismic waves caused by activity along one, or most likely, several tectonic structures would have propagated throughout the depositional environment, producing laterally extensive seismites. The close proximity to earthquake epicenters would have promoted pervasive re-sedimentation due to pore overpressure, resulting high volumes of massive sandstones and breccia. The similarity between deposits with correlatable strata from many other areas along the Brazilian coast allows raise the hypothesis that the seismic episodes might have affected sedimentation patterns in a large (i.e., extension of several hundreds of kilometers) geographic area. Thus, the modern seismicity recorded along Northeastern Brazil was recurrent during the Quaternary and, perhaps, also in the Pliocene. The estimated high magnitude of the seismic events and the great regional extent of the affected area demonstrate that the Brazilian coast experienced tectonic stress through the last geological episodes of its evolution, which would have favored sediment accumulation and penecontemporaneous re-sedimentation. This geological context is unexpected in a passive margin, inducing to revisit the debate on how active is a passive margin. (C) 2010 Elsevier B.V. All rights reserved.

Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability

The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp. We observed the absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity. The patients had suffered from recurrent episodes of meningitis and other less severe infections. Sera from these patients were unable to mediate hemolytic activity either by the classical or alternative pathways and presented extremely low levels of C5 protein (13, 0.9 and 1.0 mu g/ml-normal range: 45-190 mu g/ml). Hemolytic activity could be restored by the addition of purified C5 to deficient serum. Sequencing of sibling C5 cDNA revealed a homozygous 153 bp deletion that corresponds precisely to exon 30. The parents carried the same deletion but only in one allele. Sequencing of the corresponding region in the genomic DNA revealed a C to C substitution within intron 30 and, most significantly, the substitution of GAG(4028) for GAA(4028) at the 3` end of exon 30 which is most likely responsible for skipping of exon 30. The resulting in-frame deletion in the C5 mRNA codes for a mutant C5 protein lacking residues 1289-1339. These residues map to the CUB and C5d domains of the C5 alpha chain. This deletion is expected to produce a non-functional and unstable C5 protein which is more susceptible to degradation. (C) 2009 Published by Elsevier Ltd.

Alteration of purinergic P2X(4) and P2X(7) receptor expression in rats with temporal-lobe epilepsy induced by pilocarpine

Although ATP and P2X receptor activity have been lately associated with epilepsy, little is known regarding their exact roles in epileptogenesis. Temporal-lobe epilepsy (TLE) in rat was induced by pilocarpine in order to study changes of hippocampal P2X(2), P2X(4) and P2X(7) receptor expression during acute, latent or chronic phases of epilepsy. During acute and chronic phases increased P2X(7) receptor expression was principally observed in glial cells and glutamatergic nerve terminals, suggesting participation of this receptor in the activation of inflammatory and excitotoxic processes during epileptogenesis. No significant alterations of hippocampal P2X(2) and P2X(4) receptor expression was noted during the acute or latent phase when compared to the control group, indicating that these receptors are not directly involved with the initiation of epilepsy. However, the reduction of hippocampal P2X(4) receptor immunostaining in the chronic phase could reflect neuronal toss or decreased GABAergic signaling. (C) 2008 Elsevier B.V. All rights reserved.

Developing Box-Pushing Behaviours Using Evolutionary Robotics

The context of this report and the IRIDIA laboratory are described in the preface. Evolutionary Robotics and the box-pushing task are presented in the introduction.The building of a test system supporting Evolutionary Robotics experiments is then detailed. This system is made of a robot simulator and a Genetic Algorithm. It is used to explore the possibility of evolving box-pushing behaviours. The bootstrapping problem is explained, and a novel approach for dealing with it is proposed, with results presented.Finally, ideas for extending this approach are presented in the conclusion.

Solar Collectors for Historic Homes : Linking consumption to perceptions of space

Reduction of household energy consumption is one of the top issues in contemporary discussions on sustainable consumption. This chapter concerns one way through which consumption of purchased energy for house heating can be reduced; by having a solar thermal system added to one's house. However, the fact that one of the components - the solar collector - usually is situated on the roof or the facade of a building, is a recurrent impediment to such installations. In certain contexts, these attributes may melt into the building, while in others, they may be perceived as problematic. The latter may particularly be the case when the appearance of the building is of major imiportance, as with houses deemed worthy of preservation for coming generations. This chapter draws upon a study carried out in Visby Town, a walled Hanseatic town and a World Heritage site on the island of Gotland, Sweden.

Passive crosslaminated timber buildings : Final report Cerbof-project no. 76

In this project, Stora Enso’s newly developed building system has been further developed to allow building to the Swedish passive house standard for the Swedish climate. The building system is based on a building framework of CLT (Cross laminated timber) boards. The concept has been tested on a small test building. The experience gained from this test building has also been used for planning a larger building (two storeys with the option of a third storey) with passive house standard with this building system. The main conclusions from the project are:  It is possible to build airtight buildings with this technique without using traditional vapour barriers. Initial measurements show that this can be done without reaching critical humidity levels in the walls and roof, at least where wood fibre insulation is used, as this has a greater capacity for storing and evening out the moisture than mineral wool. However, the test building has so far not been exposed to internal generation of moisture (added moisture from showers, food preparation etc.). This needs to be investigated and this will be done during the winter 2013-14.  A new fixing method for doors and windows has been tested without traditional fibre filling between them and the CLT panel. The door or window is pressed directly on to the CLT panel instead, with an expandable sealing strip between them. This has been proved to be successful.  The air tightness between the CLT panels is achieved with expandable sealing strips between the panels. The position of the sealing strips is important, both for the air tightness itself and to allow rational assembly.  Recurrent air tightness measurements show that the air tightness decreased somewhat during the first six months, but not to such an extent that the passive house criteria were not fulfilled. The reason for the decreased air tightness is not clear, but can be due to small movements in the CLT construction and also to the sealing strips being affected by changing outdoor temperatures.  Long term measurements (at least two years) have to be carried out before more reliable conclusions can be drawn regarding the long term effect of the construction on air tightness and humidity in the walls.  An economic analysis comparing using a concrete frame or the studied CLT frame for a three storey building shows that it is probably more expensive to build with CLT. For buildings higher than three floors, the CLT frame has economic advantages, mainly because of the shorter building time compared to using concrete for the frame. In this analysis, no considerations have been taken to differences in the influence on the environment or the global climate between the two construction methods.

La confrontation de la laideur avec la beauté dans lesromans Mercure et Attentat. Une étude sur lareprésentation de la dualité thématique laideur-beautéchez Amélie Nothomb. : "Where there is Quasimodo, there is also Esmeralda." The confrontationbetween ugliness and beauty in the novels Mercure and Attentat. Astudy on the representation of the duality beauty-ugliness in the worksof Amélie Nothomb.

This paper studies one of the recurrent topics of writing found in Amélie Nothomb’snovels: beauty and ugliness. The novels Mercure and Attentat are analyzed in detail,with respect to figures of speech used to describe the extreme physical appearance ofthe protagonists and the role of the duality beauty-ugliness in the advancement of theplot.

Den kroppsliga differentieringens praktik : övervikt och nätdejting på intimitetens marknad

The practice of bodily differentiation: Overweight and internet dating on the market of intimacy With the emergence of Internet dating, the procedure for choosing a partner has been radically changed. Given the initial invisibility of the body when Internet dating, one might presume that looks become less important when searching for partners online. Unfortunately, this is far from the truth. Based on twelve interviews with Internet daters of which six define themselves as overweight, the reproduction of bodily distinction in both mediated and direct communication is here being studied. A recurrent theme among the interviewees is the disappointment of the first date face to face. Ironically the importance of looks (or bodily capital) appears to be even more vital when dating on Internet than when building relationships “in real life”. Besides the disappointment of the first date in real life, the obese women in this study could also gather information of their value on the market of intimacy through being met by serious harassments and in exclusively being treated as sexual objects. Despite its strong association with the physical body, bodily capital can sometimes be difficult to distinguish from other forms of capital. From this point of view, the possibility of less repressive forms of intimacy is discussed.

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania : an open label prospective study

Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. Methods: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p <= 0.046). Conclusions: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

Natthärbärget som vandrande lösning

The shelter as a recurrent solution to homelessness During most of the 20th century shelters for the homeless has been criticized as being of too low standard and an unworthy way of living in a welfare society. During the 1960s and 1970s most shelters in Sweden were shut down and replaced with other forms of housing for the homeless. Since the late 1980s and early 1990s the issue of homelessness has returned to the political agenda as an existing social problem in Sweden. In this period we have also experienced a return of the shelters. These newly opened shelters are in many ways based on the same ideas like the old shelters described in stories of poverty and deprivation from the 19th century. In our article we raise the question how a system that has been rejected and condemned from both ethical and ideological standpoints as an unworthy way of living can be “remodernized” and considered again as a (temporary) solution to homelessness. We examine how shelters are justified in the 21st century and what functions they fill. We also discuss the fact that the shelters are almost exclusively run by (religious) voluntary organizations.

Lanseringen och etableringen av ett socialt problem : En analys av debatten om ledarkulturen inom svensk landslagsgymnastik i Dagens Nyheter 2012–2013

The launching and establishment of a social problem: An analysis of the debate on Swedish national level gymnastics in Dagens Nyheter 2012-2013 In 2012 Sweden’s largest daily newspaper, Dagens Nyheter, published a number of articles on the state of affairs in Swedish national level gymnastics. In these articles, ex-gymnasts, coaches, parents and physicians stepped forward and testified about recurrent wrongdoings and abuse against young (particularly) female gymnasts. In response to the criticism, the accused coaches and representatives of the Swedish Gymnastics Federation downsized or dismissed the criticism as inaccurate. This being said, and using discursive psychology and a qualitative design, this article sheds light upon this debate – by viewing it as a struggle between a hegemonic discourse of ”the goodness” of sports, on the one hand, a number of unfavorable and negative testimonies of the state of affairs in Swedish national level gymnastics on the other. More concretely, this struggle has been analyzed with regard to the discursive and rhetoric resources the involved parties’ used to pursue their claims about the state of affairs in Swedish national level gymnastics and the impact these resources had for their credibility and legitimacy. Questions were: Who is entitled ”to spell out” their view on the state of affairs within Swedish national level gymnastics? What is mediated and how? How are descriptions and accounts about reality constructed as credible and factual? It is concluded that social problems are launched via co-production; in this process, the gymnastics community, the research community, single individuals, and the media – were co-actors. 

Pregnancy-related low back pain and pelvic girdle pain approximately 14 months after pregnancy : pain status, self-rated health and family situation

Background: Pelvic girdle pain (PGP) in pregnancy is distinct from pregnancy-related low back pain (PLBP). However, women with combined PLBP and PGP report more serious consequences in terms of health and function. PGP has been estimated to affect about half of pregnant women, where 25% experience serious pain and 8% experience severe disability. To date there are relatively few studies regarding persistent PLBP/PGP postpartum of more than 3 months, thus the main objective was to identify the prevalence of persistent PLBP and PGP as well as the differences over time in regard to pain status, self-rated health (SRH) and family situation at 12 months postpartum. Methods: The study is a 12 month follow-up of a cohort of pregnant women developing PLBP and PGP during pregnancy, and who experienced persistent pain at 6 month follow-up after pregnancy. Women reporting PLBP/PGP (n = 639) during pregnancy were followed up with a second questionnaire at approximately six month after delivery. Women reporting recurrent or persistent LBP/PGP at the second questionnaire (n = 200) were sent a third questionnaire at 12 month postpartum. Results: A total of 176 women responded to the questionnaire. Thirty-four women (19.3%) reported remission of LBP/PGP, whereas 65.3% (n = 115) and 15.3% (n = 27), reported recurrent LBP/PGP or continuous LBP/PGP, respectively. The time between base line and the 12 months follow-up was in actuality 14 months. Women with previous LBP before pregnancy had an increased odds ratio (OR) of reporting 'recurrent pain' (OR = 2.47) or 'continuous pain' (OR = 3.35) postpartum compared to women who reported 'no pain' at the follow-up. Women with 'continuous pain' reported statistically significant higher level of pain at all measure points (0, 6 and 12 months postpartum). Non-responders were found to report a statistically significant less positive scoring regarding relationship satisfaction compared to responders. Conclusions: The results from this study demonstrate that persistent PLBP/PGP is a major individual and public health issue among women 14 months postpartum, negatively affecting their self-reported health. However, the perceived relationship satisfaction seems to be stable between the groups.