Controlling transmembrane protein concentration and orientation in supported lipid bilayers

The trans-membrane protein – proteorhodopsin (pR) has been incorporated into supported lipid bilayers (SLB). In-plane electric fields have been used to manipulate the orientation and concentration of these proteins, within the SLB, through electrophoresis leading to a 25-fold increase concentration of pR

Mechanism of the Interaction between the Intrinsically Disordered C-Terminus of the Pro-Apoptotic ARTS Protein and the Bir3 Domain of XIAP

ARTS (Sept4_i2) is a mitochondrial pro-apoptotic protein that functions as a tumor suppressor. Its expression is significantly reduced in leukemia and lymphoma patients. ARTS binds and inhibits XIAP (X-linked Inhibitor of Apoptosis protein) by interacting with its Bir3 domain. ARTS promotes degradation of XIAP through the proteasome pathway. By doing so, ARTS removes XIAP inhibition of caspases and enables apoptosis to proceed. ARTS contains 27 unique residues in its C-terminal domain (CTD, residues 248–274) which are important for XIAP binding. Here we characterized the molecular details of this interaction. Biophysical and computational methods were used to show that the ARTS CTD is intrinsically disordered under physiological conditions. Direct binding of ARTS CTD to Bir3 was demonstrated using NMR and fluorescence spectroscopy. The Bir3 interacting region in ARTS CTD was mapped to ARTS residues 266–274, which are the nine C-terminal residues in the protein. Alanine scan of ARTS 266–274 showed the importance of several residues for Bir3 binding, with His268 and Cys273 contributing the most. Adding a reducing agent prevented binding to Bir3. A dimer of ARTS 266–274 formed by oxidation of the Cys residues into a disulfide bond bound with similar affinity and was probably required for the interaction with Bir3. The detailed analysis of the ARTS – Bir3 interaction provides the basis for setting it as a target for anti cancer drug design: It will enable the development of compounds that mimic ARTS CTD, remove IAPs inhibition of caspases, and thereby induce apoptosis

Lipid droplets: a classic organelle with new outfits

Lipid droplets are depots of neutral lipids that exist virtually in any kind of cell. Recent studies have revealed that the lipid droplet is not a mere lipid blob, but a major contributor not only to lipid homeostasis but also to diverse cellular functions. Because of the unique structure as well as the functional importance in relation to obesity, steatosis, and other prevailing diseases, the lipid droplet is now reborn as a brand new organelle, attracting interests from researchers of many disciplines

Volunteer Engagement in Housing Co-Operatives – Civil Society “en miniature”

Housing co‐operatives host miniature versions of civil society. They vitalise a social system that is shaped by formal regulations, economic functions, and a population of private housing units. The study examines factors that influence a person’s willingness to volunteer in civic society using a multilevel analysis based on survey data from 32 co‐operatives and 1263 members. To do so, the social exchange theory is extended to include the member value approach, which connects social engagement with the fulfillment of a range of needs, thus going beyond a narrow economic cost benefit analysis. Study results show that volunteer engagement largely depends on the degree to which members can expect to experience their own achievement. This finding provides an explanation for significant differences in the engagement levels beyond factors that have already been determined (age, level of education). On an organizational level, the study reveals that the age of an organization influences volunteer engagement, but that the size and the degree of professionalization do not have an effect on it

Dementia incidence trend over 1992-2014 in the Netherlands: Analysis of primary care data

Background Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands. Methods and findings A dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRNs) across the country. Data regarding dementia incidence were obtained using general-practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 y and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people for the years 1992 to 2014, corresponding to over 4 million person-years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95% CI 0.5% to 3.8%), and incidence rates were 1.08 (95% CI 1.04 to 1.13) times higher for women compared to men. Despite their relatively low numbers of person-years, the highest age groups contributed most to the increasing trend. There was no significant overall change in incidence rates since the start of a national dementia program in 2003 (-0.025; 95% CI -0.062 to 0.011). Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis by general practitioners in electronic health records, and needs to be taken into account when interpreting the data. Conclusions Within the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate a dramatic absolute increase in dementia occurrence over the years to come

Dementia incidence trend over 1992-2014 in the Netherlands:Analysis of primary care data

BackgroundRecent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands.Methods and findingsA dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRNs) across the country. Data regarding dementia incidence were obtained using general-practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 y and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people for the years 1992 to 2014, corresponding to over 4 million person-years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95% CI 0.5% to 3.8%), and incidence rates were 1.08 (95% CI 1.04 to 1.13) times higher for women compared to men. Despite their relatively low numbers of person-years, the highest age groups contributed most to the increasing trend. There was no significant overall change in incidence rates since the start of a national dementia program in 2003 (-0.025; 95% CI -0.062 to 0.011). Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis by general practitioners in electronic health records, and needs to be taken into account when interpreting the data.ConclusionsWithin the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate a dramatic absolute increase in dementia occurrence over the years to come

Sibling species or poecilogony in the polychaete Scoloplos armiger?

In marine invertebrates multiple modes of development, or poecilogony, may occur in a single species. However, after close examination, many of such putative cases turned out to be sibling species. A case in point may be the cosmopolitan orbiniid polychaete Scoloplos armiger, which inhabits marine shallow sediments. In addition to the well-known direct, holobenthic development from egg cocoons, pelagic larvae have also been described. Our culture experiments revealed a spatially segregated source of the two developmental modes. All females of an intertidal population produced egg cocoons and no pelagic larvae. All but 2 out of 15 females of an adjacent subtidal population produced pelagic larvae and no egg cocoons. Based on these results we performed a molecular genetic analysis (RAPD-PCR) on three intertidal and four subtidal populations in the North Sea. Selected samples from all sites were analysed also by the AFLP method. We found significantly higher genetic diversity within subtidal than within intertidal populations. This is consistent with a wider dispersal by pelagic larvae and a smaller effective population size when development is holobenthic. Total genetic divergence is not related to distance but to the intertidal/subtidal division. We suggest that S. armiger actually represents two sibling species