‘Inverted’ analogs of the antibiotic gramicidin S with an improved biological profile

A series of gramicidin S derivatives 4–15 are presented that have four ornithine residues as polar protonated side chains and two central hydrophobic amino acids with unaltered turn regions. These peptides were screened against human erthrocytes and our standard panel of Gram negative- and Gram positive bacteria, including four MRSA strains. Based on the antibacterial- and hemolytic data, peptides 13 and 14 have an improved biological profile compared to the clinically applied topical antibiotic gramicidin S.     

Calcareous dinoflagellate cyst distributions in surface sediments from upwelling areas off NW Africa, and their relationships with environmental parameters of the upper water column

Only very few studies have focussed on the spatial distribution and ecology of calcareous dinoflagellate cysts (dinocysts) in upwelling areas. Here, distributions of individual calcareous dinocyst species in surface sediment samples from the coastal upwelling zone off NW Africa and their relationships with known environmental parameters of the (sub-)surface waters have been analysed in order to enhance our knowledge on their modern distribution patterns and to determine the ecological significance and palaeoenvironmental reconstruction potential of each calcareous dinocyst species within this exemplary high-productivity region. In addition to calculating relative cyst abundances, well-constrained sedimentation rates have allowed the calculation of dinocyst accumulation rates (cysts cm^− 2 ka^− 1) for most of the surface sample positions, thus providing a much more accurate estimation of actual calcareous dinocyst production in the upper water column than could be warranted in similar studies so far. Distinct differences in the geographic distribution patterns of nine species were observed. In general, high accumulation rates of calcareous dinocysts were found around and south of 29°N and offshore the westernmost Canary Island La Palma, with slightly lower accumulation rates in the upwelling-influenced areas off Cape Yubi and in the upwelling filament area off Cape Ghir. Multivariate ordination techniques were applied in order to compare the cyst accumulation rates of individual species with physical parameters (temperature, salinity, density, mixed layer depth) and the trophic state (nitrate, phosphate and chlorophyll concentrations) of the overlying (sub-)surface waters. All species were found to relate significantly to one or more of the environmental parameters, partly confirming previous results on cyst ecology but also providing new information which will be useful for future palaeoenvironmental reconstructions within upwelling areas.     

Construction of helper plasmid-mediated dual-display phage for autoantibody screening in serum

M13 filamentous bacteriophage has been used in displaying disease-specific antibodies, biomarkers, and peptides. One of the major drawbacks of using phage in diagnostic assays is the aspecific adsorption of proteins leading to a high background signal and decreasing sensitivity. To deal with this, we developed a genetically pure, exchangeable dual-display phage system in which biomarkers and streptavidin-binding protein (SBP) are displayed at opposite ends of the phage. This approach allows for sample purification, using streptavidin-coated magnetic beads resulting in a higher sensitivity of signal detection assays. Our dual-display cassette system approach also allows for easy exchange of both the anchor protein (SBP) and the displayed biomarker. The presented principle is applied for the detection of antibody reactivity against UH-RA.21 which is a good candidate biomarker for rheumatoid arthritis (RA). The applicability of dual-display phage preparation using a helper plasmid system is demonstrated, and its increased sensitivity in phage ELISA assays using patient serum samples is shown.     

Cultural Identity Among Afghan and Iraqi Traumatized Refugees: Towards a Conceptual Framework for Mental Health Care Professionals

Cultural identity in relation with mental health is of growing interest in the field of transcultural psychiatry. However, there is a need to clarify the concept of cultural identity in order to make it useful in clinical practice. The purpose of this study is to unravel the complexity and many layers of cultural identity, and to assess how stress and acculturation relate to (changes in) cultural identity. As part of a larger study about cultural identity, trauma, and mental health, 85 patients from Afghanistan and Iraq in treatment for trauma-related disorders were interviewed with a Brief Cultural Interview. The interviews were analysed through qualitative data analysis using the procedures of grounded theory. The analysis resulted in three domains of cultural identity: personal identity, ethnic identity and social identity. Within each domain relationships with stress and acculturation were identified. The results offer insight into the intensity of changes in cultural identity, caused by pre-and post-migration stressors and the process of acculturation. Based on the research findings recommendations are formulated to enhance the cultural competency of mental health workers.     

Microbial communities and electrochemical performance of titanium-based anodic electrodes in a microbial fuel cell

Four types of titanium (Ti)-based electrodes were tested in the same microbial fuel cell (MFC) anodic compartment. Their electrochemical performances and the dominant microbial communities of the electrode biofilms were compared. The electrodes were identical in shape, macroscopic surface area, and core material but differed in either surface coating (Pt- or Ta-coated metal composites) or surface texture (smooth or rough). The MFC was inoculated with electrochemically active, neutrophilic microorganisms that had been enriched in the anodic compartments of acetate-fed MFCs over a period of 4 years. The original inoculum consisted of bioreactor sludge samples amended with Geobacter sulfurreducens strain PCA. Overall, the Pt- and Ta-coated Ti bioanodes (electrode-biofilm association) showed higher current production than the uncoated Ti bioanodes. Analyses of extracted DNA of the anodic liquid and the Pt- and Ta-coated Ti electrode biofilms indicated differences in the dominant bacterial communities. Biofilm formation on the uncoated electrodes was poor and insufficient for further analyses. Bioanode samples from the Pt- and Ta-coated Ti electrodes incubated with Fe(III) and acetate showed several Fe(III)-reducing bacteria, of which selected species were dominant, on the surface of the electrodes. In contrast, nitrate-enriched samples showed less diversity, and the enriched strains were not dominant on the electrode surface. Isolated Fe(III)-reducing strains were phylogenetically related, but not all identical, to Geobacter sulfurreducens strain PCA. Other bacterial species were also detected in the system, such as a Propionicimonas-related species that was dominant in the anodic liquid and Pseudomonas-, Clostridium-, Desulfovibrio-, Azospira-, and Aeromonas-related species.     

Attending the breast screening programme after breast cancer treatment: A population-based study

IntroductionIn the Netherlands, breast cancer patients are treated and followed at least 5 years after diagnosis. Furthermore, all women aged 50–74 are invited biennially for mammography by the nationwide screening programme. The relation between the outpatient follow-up (follow-up visits in the outpatient clinic for 5 years after treatment) and the screening programme is not well established and attending the screening programme as well as outpatient follow-up is considered undesirable. This study evaluates potential factors influencing women to attend the screening programme during their outpatient follow-up (overlap) and the (re-)attendance to the screening programme after 5 years of outpatient follow-up.MethodsData of breast cancer patients aged 50–74 years, treated for primary breast cancer between 1996 and 2007 were selected from the Netherlands Cancer Registry and linked to the National Breast Cancer Screening Programme in the Northern region. Cox regression analyses were used to study women (re-)attending the screening programme over time, possible overlap with the outpatient follow-up and factors influencing this.ResultsIn total 11 227 breast cancer patients were included, of whom 19% attended the screening programme after breast cancer treatment, 4.4% within 5 years and 15.4% after more than 5 years. Factors that independently influenced attendance within 5 years as well as more than 5 years after treatment were: interval tumours (HR 0.77; 95%CI 0.61–0.97 and HR 0.69; 95%CI 0.53–0.88, ref: screen-detected tumours), receiving adjuvant radiotherapy (HR 0.65; 95%CI 0.47–0.90 and HR 0.66; 95%CI 0.47–0.93; ref: none) and diagnosis of in situ tumours (HR 1.67; 95%CI 1.25–2.23 and HR 1.39; 95%CI 1.05–1.85; ref: stage I tumours). Non-screen related tumours (HR 0.41; 95%CI 0.29–0.58) and recent diagnosis (HR 0.89 per year; 95%CI 0.86–0.92) were only associated with attendance within 5 years after treatment.ConclusionThe interrelation between outpatient follow-up and screening should be improved to avoid overlap and low attendance to the screening programme after outpatient follow-up. Breast cancer patients should be informed that attending the screening programme during the outpatient follow-up is not necessary.     

Mouse model of split hand/foot malformation type I

Split hand/foot malformation type I (SHFM1) disease locus maps to chromosome 7q21.3-q22, a region that includes the distal-less-related (dll) genes DLX5 and DLX6. However, incomplete penetrance, variable expressivity, segregation distortion, and syndromic association with other anomalies have so far prevented the identification of the SHFM1 gene(s) in man. Here we show that the targeted double inactivation of Dlx5 and Dlx6 in the mouse causes in homozygous mutant animals bilateral ectrodactyly with a severe defect of the central ray of the hindlimbs, a malformation typical of SHFM1. This is the first evidence that the role of dll/Dlx genes in appendage development is conserved from insects to mammals and proves their involvement in SHFM1.     

Comparative genetics of a highly divergent DRB microsatellite in different macaque species

The DRB region of the major histocompatibility complex (MHC) of cynomolgus and rhesus macaques is highly plastic, and extensive copy number variation together with allelic polymorphism makes it a challenging enterprise to design a typing protocol. All intact DRB genes in cynomolgus monkeys (Mafa) appear to possess a compound microsatellite, DRB-STR, in intron 2, which displays extensive length polymorphism. Therefore, this STR was studied in a large panel of animals, comprising pedigreed families as well. Sequencing analysis resulted in the detection of 60 Mafa-DRB exon 2 sequences that were unambiguously linked to the corresponding microsatellite. Its length is often allele specific and follows Mendelian segregation. In cynomolgus and rhesus macaques, the nucleotide composition of the DRB-STR is in concordance with the phylogeny of exon 2 sequences. As in humans and rhesus monkeys, this protocol detects specific combinations of different DRB-STR lengths that are unique for each haplotype. In the present panel, 22 Mafa-DRB region configurations could be defined, which exceeds the number detected in a comparable cohort of Indian rhesus macaques. The results suggest that, in cynomolgus monkeys, even more frequently than in rhesus macaques, new haplotypes are generated by recombination-like events. Although both macaque species are known to share several identical DRB exon 2 sequences, the lengths of the corresponding microsatellites often differ. Thus, this method allows not only fast and accurate DRB haplotyping but may also permit discrimination between highly related macaque species.