Vulnerability and Growth. Developmental dynamics and differential effects of the loss of an intimate partner in the second half of life. IP 12: Study outline and first results

This working report gives an overview of the Individual Project 12 “Vulnerability and growth. Developmental dynamics and differential effects of the loss of an intimate partner in the second half of life” of the Swiss National Centre of Competence in Research LIVES led by Pasqualina Perrig-Chiello, University of Bern. This longitudinal and interdisciplinary project aims at examining vulnerability and personal growth after a critical life event, namely the break-up of a long-term intimate relationship in the second half of life, be it due to divorce or due to bereavement. In this report we present details about the rationale, the main research questions, the hypotheses and the methods of the study. Special attention is given to the methodological approach. The authors give a first sample description and report on the validity of the data by comparing the sample with Swiss Labour Force Survey and Swiss Health Survey data.

A stratigraphic framework for abrupt climatic changes during the Last Glacial period based on three synchronized Greenland ice-core records: refining and extending the INTIMATE event stratigraphy

Due to their outstanding resolution and well-constrained chronologies, Greenland ice-core records provide a master record of past climatic changes throughout the Last Interglacial–Glacial cycle in the North Atlantic region. As part of the INTIMATE (INTegration of Ice-core, MArine and TErrestrial records) project, protocols have been proposed to ensure consistent and robust correlation between different records of past climate. A key element of these protocols has been the formal definition and ordinal numbering of the sequence of Greenland Stadials (GS) and Greenland Interstadials (GI) within the most recent glacial period. The GS and GI periods are the Greenland expressions of the characteristic Dansgaard–Oeschger events that represent cold and warm phases of the North Atlantic region, respectively. We present here a more detailed and extended GS/GI template for the whole of the Last Glacial period. It is based on a synchronization of the NGRIP, GRIP, and GISP2 ice-core records that allows the parallel analysis of all three records on a common time scale. The boundaries of the GS and GI periods are defined based on a combination of stable-oxygen isotope ratios of the ice (δ18O, reflecting mainly local temperature) and calcium ion concentrations (reflecting mainly atmospheric dust loading) measured in the ice. The data not only resolve the well-known sequence of Dansgaard–Oeschger events that were first defined and numbered in the ice-core records more than two decades ago, but also better resolve a number of short-lived climatic oscillations, some defined here for the first time. Using this revised scheme, we propose a consistent approach for discriminating and naming all the significant abrupt climatic events of the Last Glacial period that are represented in the Greenland ice records. The final product constitutes an extended and better resolved Greenland stratotype sequence, against which other proxy records can be compared and correlated. It also provides a more secure basis for investigating the dynamics and fundamental causes of these climatic perturbations.

Molecular mechanisms of pathogenicity of Mycoplasma mycoides subsp. mycoides SC

Mycoplasma mycoides subsp. mycoides SC, the aetiological agent of contagious bovine pleuropneumonia (CBPP), is considered the most pathogenic of the Mycoplasma species. Its virulence is probably the result of a coordinated action of various components of an antigenically and functionally dynamic surface architecture. The different virulence attributes allow the pathogen to evade the host's immune defence, adhere tightly to the host cell surface, persist and disseminate in the host causing mycoplasmaemia, efficiently import energetically valuable nutrients present in the environment, and release and simultaneously translocate toxic metabolic pathway products to the host cell where they cause cytotoxic effects that are known to induce inflammatory processes and disease. This strategy enables the mycoplasma to exploit the minimal genetic information in its small genome, not only to fulfil the basic functions for its replication but also to damage host cells in intimate proximity thereby acquiring the necessary bio-molecules, such as amino acids and nucleic acid precursors, for its own biosynthesis and survival.

Evaluation of a novel biphasic calcium phosphate in standardized bone defects: a histologic and histomorphometric study in the mandibles of minipigs

OBJECTIVE: A novel biphasic calcium phosphate (CaP) granulate consisting of hydroxyapatite (HA) and beta-tricalciumphosphate (TCP) was compared with pure HA and pure TCP and with autograft as positive control. MATERIALS AND METHODS: Four standardized bone defects were prepared in both mandibular angles of 16 minipigs and grafted with autogenous bone chips, HA, HA/TCP (60% : 40%), or TCP. Histologic and histomorphometric analysis of bone formation and graft degradation followed healing periods of 2, 4, 8, and 24 weeks. RESULTS: 2 weeks: more bone formation in defects filled with autograft than with the three CaP materials (P<0.05). 4 weeks: bone formation differed significantly (P<0.05) between all four materials (autograft>TCP>HA/TCP>HA). 8 weeks: more bone formation in defects with autograft and TCP than with HA/TCP (P<0.05), and HA/TCP had more bone formation than HA (P<0.05). 24 weeks: no difference in bone formation between the groups. Autograft and TCP resorbed quickly and almost completely over 8 weeks, whereas HA/TCP and HA showed limited degradation over 24 weeks. CONCLUSION: All defects healed with mature lamellar bone and intimate contact between bone and the remaining graft material. The rate of bone formation corresponded to the content of TCP in the CaP materials.

Modulation of chemokine gene expression by Shiga-toxin producing Escherichia coli belonging to various origins and serotypes

Infection with Shiga-toxin producing Escherichia coli (STEC) may result in the development of the haemolytic-uremic syndrome (HUS), the main cause of acute renal failure in children. While O157:H7 STEC are associated with large outbreaks of HUS, it is difficult to predict whether a non-O157:H7 isolate can be pathogenic for humans. The mucosal innate immune response plays a central role in the pathogenesis of HUS; therefore, we compared the induction of IL-8 and CCL20 in human colon epithelial cells infected with strains belonging to different serotypes, isolated from cattle or from HUS patients. No correlation was observed between strain virulence and chemokine gene expression. Rather, the genetic background of the strains seems to determine the chemokine gene expression profile. Investigating the contribution of different bacterial factors in this process, we show that the type III secretion system of O157:H7 bacteria, but not the intimate adhesion, is required to stimulate the cells. In addition, H7, H10, and H21 flagellins are potent inducers of chemokine gene expression when synthesized in large amount.

Mental health and quality of life after genetic testing for Huntington disease: a long-term effect study in Germany

Predictive genetic testing for Huntington disease (HD) might cause severe short-term psychological reactions in patients with poor mental health. Very few studies exist on the long-term effects of genetic HD testing. The aim of this study was to assess mental health and quality of life in persons who were tested for HD mutation, to compare mental health depending on the result of the genetic test (non-carriers, gene carriers, and patients with HD) and to identify predictors of mental health and quality of life via linear regression. The data were collected by self-report questionnaires. In total, 121 individuals participated in this study: 52 were non-carriers, 54 were gene carriers, and 15 were gene carriers suffering from HD. Non-carriers and gene carriers showed better mental health and quality of life than HD-patients but did not differ from each other. In non-carriers four variables predicted increased depression and low mental quality of life: low perceived social support, no intimate relationship, female sex and younger age. For gene carriers three predictors were found: low perceived social support, the expectation of an unfavorable genetic test result before the testing procedure and being childless. To prevent detrimental effects of HD testing on mental health and mental quality of life, specific attention should be paid to persons with limited social networks during genetic counseling. Assessment of expectations related to the test result and mental health prior to a genetic testing procedure may help to identify gene carriers at risk of poor coping after an unfavorable test result.

General laboratory diagnostics of eosinophilic GI diseases

Eosinophils and gastrointestinal tract interact in an intimate and enigmatic relationship. Under inflammatory conditions, eosinophil infiltration in the gastrointestinal tract is a common feature of numerous eosinophilic gastrointestinal disorders (EGIDs). EGIDs are disorders, for which the diagnosis is relatively difficult. Nevertheless, some common laboratory techniques are currently used for their diagnosis and disease monitoring. Besides eosinophils, mast cells and T cells have also been suggested to play a role in the pathogenesis of these disorders. Here, we review the pathogenesis and common laboratory approaches applied for their diagnosis, in particular eosinophil and mast cell markers.

Production of interferon-gamma by activated T-cell receptor-alphabeta CD8alphabeta intestinal intraepithelial lymphocytes is required and sufficient for disruption of the intestinal barrier integrity

Maintenance of intestinal epithelial barrier function is of vital importance in preventing uncontrolled influx of antigens and the potentially ensuing inflammatory disorders. Intestinal intraepithelial lymphocytes (IEL) are in intimate contact with epithelial cells and may critically regulate the epithelial barrier integrity. While a preserving impact has been ascribed to the T-cell receptor (TCR)-gammadelta subset of IEL, IEL have also been shown to attenuate the barrier function. The present study sought to clarify the effects of IEL by specifically investigating the influence of the TCR-alphabeta CD8alphabeta and TCR-alphabeta CD8alphaalpha subsets of IEL on the intestinal epithelial barrier integrity. To this end, an in vitro coculture system of the murine intestinal crypt-derived cell-line mIC(cl2) and syngeneic ex vivo isolated IEL was employed. Epithelial integrity was assessed by analysis of transepithelial resistance (TER) and paracellular flux of fluorescein isothiocyanate-conjugated (FITC-) dextran. The TCR-alphabeta CD8alphaalpha IEL and resting TCR-alphabeta CD8alphabeta IEL did not affect TER of mIC(cl2) or flux of FITC-dextran. In contrast, activated TCR-alphabeta CD8alphabeta IEL clearly disrupted the integrity of the mIC(cl2) monolayer. No disrupting effect was seen with activated TCR-alphabeta CD8alphabeta IEL from interferon-gamma knockout mice. These findings demonstrate that secretion of interferon-gamma by activated TCR-alphabeta CD8alphabeta IEL is strictly required and also sufficient for disrupting the intestinal epithelial barrier function.

Action crisis and cost–benefit thinking: A cognitive analysis of a goal-disengagement phase

The present research is based on the notion that disengagement from goals is not a discrete event but a process (Klinger, 1975). A critical phase in this process is when difficulties and setbacks in striving for a goal accumulate. This critical phase is termed here as an action crisis. Given the profound effects that people's thoughts have on their self-regulatory efficiency, it is essential to understand the cognitive correlates of an action crisis. In two experimental lab and two correlational field studies, the hypothesis that goal-related costs and benefits become cognitively highly accessible during an action crisis was tested and supported. Participants who were experiencing an action crisis in such diverse goal areas as intimate relationships, sports, and university studies, thought about goal-related costs and benefits more intensively and frequently in comparison to participants who were not in an action crisis. In an incidental learning task they recognized more of cost–benefit-items and less of implementation-items than the control group. Results are interpreted in terms of action phase specific mindsets (Gollwitzer, 1990, 2012).

New data on the Lateglacial period of SW Europe: a high resolution multiproxy record from Laguna de la Roya (NW Iberia)

High-resolution multiproxy analyses were performed on a 128 cm section of organic sediments accumulated in a small mountain lake in NW Iberia (Laguna de la Roya, 1608 m asl). The pollen stratigraphy together with radiocarbon dating provided the basis for a chronology ranging from 15,600 to 10,500 cal yr BP. Chironomid-inferred July air temperatures suggest a temperature range from 7 to 13 degrees C, also evidencing two well-established cold periods which may be equivalent to the INTIMATE stages GS-2a and GS-1. Furthermore, a number of short cold events (with summer temperatures dropping about 0.5-1 degrees C) appear intercalated within the Lateglacial Interstadial (possibly equivalent to the INTIMATE cold events GI-1d, GI-1c2 and GI-1b) and the early Holocene (possibly equivalent to the 11.2 k event). The temperature variations predicted by our reconstruction allow explaining the changes in local conditions and productivity of the lake inferred from the biological record of the same sediment core. Furthermore, they also agree with the local and regional vegetation dynamics, and the main oscillations deduced for the vegetation belts. Based on its chronology our multiproxy record indicates a similar temperature development in NW Iberia as inferred by the Greenland delta O-18 record, the marine deep-sea records off the Atlantic Iberian Margin, and other chironomid-based Lateglacial temperature reconstructions from Europe. Nevertheless, the impact of most of the less intense Lateglacial/early Holocene cold events in NW Iberia was most probably limited to very sensitive sites that were very close to ecotonal situations. Particularly, our new pollen record indicates that they were represented as three minor environmental crises occurring during the Lateglacial Interestadial in this area. The Older Dryas event (in our usage corresponding to the Aegelsee Oscillation in Central Europe and event GI-1d in central Greenland) has previously been described in this region, but its age and duration (ca 14,250-14050 cal yr BP) is now better constrained. The two subsequent stages, La Roya I (ca 13,600-13,400 cal yr BP) and La Roya II (ca 13,300-12,900 cal yr BP) have been described for first time in NW Iberia. (C) 2013 Elsevier Ltd. All rights reserved.

Transport and uptake of immunogenic lipids

An increasing number of lipid mediators have been identified as key modulators of immunity. Among these is a family of glycolipids capable of cellular uptake, loading onto the MHC-like molecule CD1d and stimulation of NKT cells. NKT cells are particularly interesting because they bridge innate and adaptive immunity by coordinating the early events of dendritic cell maturation, recruitment of NK cells, CD4 and CD8 T cells, and B cells at the site of microbial injury. As such, their therapeutic manipulation could be of the greatest interest in vaccine design or active immunotherapy. However, the use of NKT cells as cellular adjuvant of immunity in the clinic will require a better knowledge of the pharmacology of lipid agonists in order to optimize their action and avoid potential unseen off-target effects. We have been studying extracellular transport and cellular uptake of NKT agonists for the past few years. This field is confronted to a very limited prior knowledge and a small set of usable tools. New technology must be put in place and adapted to answering basic immunology questions related to NKT cells. The intimate link between the pharmacology of glycolipids and lipid metabolism makes us believe that great variations of bioactivity could be seen in the general population when NKT agonists are used therapeutically.

Sanitation in developing countries: A review through a gender lens

Sanitation has evolved from a purely technical discipline to one that includes social, environmental, economic and, increasingly, gender considerations. However, blurry notions of gender are frequently offered in the sanitation literature. Although it has been recognized that gender-responsive sanitation does not mean ‘toilets for women’, substantial alternatives are rarely debated. We structure our review of sanitation in developing countries along three lines: we start by fine-tuning the concept of gender both from the academic and the practitioner's perspective, analyse relevant developments in gender-specific policies and programming, and finally review the most appropriate toilet room and menstrual hygiene technologies. We argue that strategies to make technologies gender-responsive need to be based upon a thorough analysis of the social arrangements of the intimate, and how these are negotiated and institutionalized in a specific context. A lack of robust gender-segregated data on sanitation policies and technologies, along with reductionist framings of gender are to blame for limited progress in verifying the need for, and impact of, gender-responsive sanitation. Technology and policy development and implementation would benefit from gender-considerate interpretations of shame, dignity, safety and status. Further progress could be achieved by improving the translation process between different academic framings of the sanitation crisis. Keywords: appropriate technology; development; gender; menstrual hygiene management (MHM); sanitation

A compilation of Western European terrestrial records 60–8 ka BP: towards an understanding of latitudinal climatic gradients

Terrestrial records of past climatic conditions, such as lake sediments and speleothems, provide data of great importance for understanding environmental changes. However, unlike marine and ice core records, terrestrial palaeodata are often not available in databases or in a format that is easily accessible to the non-specialist. As a consequence, many excellent terrestrial records are unknown to the broader palaeoclimate community and are not included in compilations, comparisons, or modelling exercises. Here we present a compilation of Western European terrestrial palaeo-records covering, entirely or partially, the 60–8-ka INTIMATE time period. The compilation contains 56 natural archives, including lake records, speleothems, ice cores, and terrestrial proxies in marine records. The compilation is limited to include records of high temporal resolution and/or records that provide climate proxies or quantitative reconstructions of environmental parameters, such as temperature or precipitation, and that are of relevance and interest to a broader community. We briefly review the different types of terrestrial archives, their respective proxies, their interpretation and their application for palaeoclimatic reconstructions. We also discuss the importance of independent chronologies and the issue of record synchronization. The aim of this exercise is to provide the wider palaeo-community with a consistent compilation of high-quality terrestrial records, to facilitate model-data comparisons, and to identify key areas of interest for future investigations. We use the compilation to investigate Western European latitudinal climate gradients during the deglacial period and, despite of poorly constrained chronologies for the older records, we summarize the main results obtained from NW and SW European terrestrial records before the LGM.

Response profiles of murine spiral ganglion neurons on multi-electrode arrays.

OBJECTIVE Cochlear implants (CIs) have become the gold standard treatment for deafness. These neuroprosthetic devices feature a linear electrode array, surgically inserted into the cochlea, and function by directly stimulating the auditory neurons located within the spiral ganglion, bypassing lost or not-functioning hair cells. Despite their success, some limitations still remain, including poor frequency resolution and high-energy consumption. In both cases, the anatomical gap between the electrode array and the spiral ganglion neurons (SGNs) is believed to be an important limiting factor. The final goal of the study is to characterize response profiles of SGNs growing in intimate contact with an electrode array, in view of designing novel CI devices and stimulation protocols, featuring a gapless interface with auditory neurons. APPROACH We have characterized SGN responses to extracellular stimulation using multi-electrode arrays (MEAs). This setup allows, in our view, to optimize in vitro many of the limiting interface aspects between CIs and SGNs. MAIN RESULTS Early postnatal mouse SGN explants were analyzed after 6-18 days in culture. Different stimulation protocols were compared with the aim to lower the stimulation threshold and the energy needed to elicit a response. In the best case, a four-fold reduction of the energy was obtained by lengthening the biphasic stimulus from 40 μs to 160 μs. Similarly, quasi monophasic pulses were more effective than biphasic pulses and the insertion of an interphase gap moderately improved efficiency. Finally, the stimulation with an external electrode mounted on a micromanipulator showed that the energy needed to elicit a response could be reduced by a factor of five with decreasing its distance from 40 μm to 0 μm from the auditory neurons. SIGNIFICANCE This study is the first to show electrical activity of SGNs on MEAs. Our findings may help to improve stimulation by and to reduce energy consumption of CIs and thereby contribute to the development of fully implantable devices with better auditory resolution in the future.