Actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human epidermal keratinocytes in culture

Summary In humans, the skin is a particularly sensitive target for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and certain halogenated analogs. Reported lesions include a thickening of the epidermis (acanthosis), hyperkeratosis, and squamous metaplasia of the epithelial lining of the sebaceous glands. In this report we describe ongoing studies on the actions of TCDD on cultured human epidermal cells. This system has been established as an in vitro model for interfollicular epidermal hyperkeratinization. Treatment of newly confluent cultures with TCDD results in enhanced differentiation as judged by histologic examination of the cultures, a decrease in the number of basal proliferating cells, and an increase in the number of envelope competent (differentiating) cells and terminally differentiated cells with highly cross-linked cornified envelopes. Changes in the differentiation program are preceded by a decrease in epidermal growth factor (EGF) binding. The concentration dependence and stereospecificity for these responses suggest the involvement of theAh receptor. We propose that TCDD modulates normal patterns of epidermal differentiation through direct actions on proliferating basal cells, modulating the responsiveness of these cells to growth factors such as EGF. This paper was presented at the Session-In-Depth on In Vitro Applications in Toxicology at the 34th Annual Meeting of the Tissue Culture Association, Orlando, FL, June 12–16, 1983. Rosemarie Osborne was a Chemical Industry Institute of Toxicology Postdoctoral Fellow.     

Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining

In S and G2 phase mammalian cells DNA double strand breaks (DSBs) can potentially be repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ). Results of several studies suggest that these two mechanistically distinct repair pathways can compete for DNA ends. Because HR and NHEJ differ with respect to error susceptibility, generation of chromosome rearrangements, which are potentially carcinogenic products of DSB repair, may depend on the pathway choice. To investigate this hypothesis, the influence of HR and NHEJ inhibition on the frequencies of chromosome aberrations in G2 phase cells was investigated. SW-1573 and RKO cells were treated with mild (41 °C) hyperthermia in order to disable HR and/or NU7441/cisplatin to inactivate NHEJ and frequencies of chromosomal fragments (resulting from unrepaired DSBs) and translocations (products of erroneous DSB rejoining) were studied using premature chromosome condensation (PCC) combined with fluorescence in situ hybridization (FISH).It is shown here that temporary inhibition of HR by hyperthermia results in increased frequency of ionizing-radiation (IR)-induced chromosomal translocations and that this effect is abrogated by NU7441- or cisplatin-mediated inhibition of NHEJ. The results suggest that in the absence of HR, DSB repair is shifted to the error-prone NHEJ pathway resulting in increased frequencies of chromosomal rearrangements. These results might be of consequence for clinical cancer treatment approaches that aim at inhibition of one or more DSB repair pathways.     

'Candidatus Liberibacter europaeus' sp. nov. that is associated with and transmitted by the psyllid Cacopsylla pyri apparently behaves as an endophyte rather than a pathogen

'Candidatus Liberibacter spp.' cause serious plant diseases. 'Candidatus Liberibacter asiaticus', 'Ca. L. americanus' and 'Ca. L. africanus' are the aetiological agents of citrus greening (Huanglongbing) in Asia, America and Africa. 'Candidatus Liberibacter solanacearum' causes diseases in Solanaceae in America and New Zealand. All four species are vectored by psyllid insects of different genera. Here, we show that the pear psyllid pest Cacopsylla pyri (L.) hosts a novel liberibacter species that we named 'Ca. Liberibacter europaeus'. It can bloom to high titres in the psyllid host, with more than 10(9) 16S rRNA gene copies per individual. Fluorescent in situ hybridization experiments showed that 'Ca. L. europaeus' is present in the host midgut lumen, salivary glands and Malpighian tubules. 'Candidatus L. europaeus' has a relatively high prevalence (> 51%) in C. pyri from different areas in the Piedmont and Valle d'Aosta regions in Italy and can be transmitted to pear plants in experimental transmission trials. However, even though high titres of the bacterium (more than 10(8) 16S rRNA gene copies g(-1) of pear plant tissue) could be detected, in the pear tissues no specific disease symptoms could be observed in the infected plants over a 6-month period. Despite liberibacters representing potential quarantine organisms, 'Ca. L. europaeus', first described in Italy and Europe, apparently behaves as an endophyte rather than a pathogen.     

Family caregivers' experiences of involuntary psychiatric hospital admissions of their relatives--a qualitative study

Background

Family caregivers of people with mental disorders are frequently involved in involuntary hospital admissions of their relatives.

Objective

To explore family caregivers'' experience of involuntary admission of their relative.

Method

30 in-depth interviews were conducted with family caregivers of 29 patients who had been involuntarily admitted to 12 hospitals across England. Interviews were analysed using thematic analysis.

Results

Four major themes of experiences were identified: relief and conflicting emotions in response to the relative''s admission; frustration with a delay in getting help; being given the burden of care by services; and difficulties with confidentiality.Relief was a predominant emotion as a response to the relative''s admission and it was accompanied by feelings of guilt and worry. Family caregivers frequently experienced difficulties in obtaining help from services prior to involuntary admission and some thought that services responded to crises rather than prevented them. Family caregivers experienced increased burden when services shifted the responsibility of caring for their mentally unwell relatives to them. Confidentiality was a delicate issue with family caregivers wanting more information and a say in decisions when they were responsible for aftercare, and being concerned about confidentiality of information they provided to services.

Conclusion

Compulsory admission of a close relative can be a complex and stressful experience for family caregivers. In order for caregivers to be effective partners in care, a balance needs to be struck between valuing their involvement in providing care for a patient and not overburdening them.     

Evolutionary Psychology��s Place in Evolutionary Studies: a Tale of Promise and Challenge

The Evolutionary Studies (EvoS) Consortium and the academic programs born from its creation have been wildly successful in their initial ventures. These achievements are marked by feedback from across the EvoS campuses, the resultant scholarly work produced by participating students, and faculty collaborations spurred by exposure to the organization. The success of EvoS is probably best marked by the recent National Science Foundation grant (CCLI Award #0817337), awarded jointly to SUNY New Paltz and Binghamton University, with the purpose of expanding EvoS beyond the bounds of these two institutions. A particularly noteworthy element of many EvoS programs is the role of Evolutionary Psychology (EP), a perspective in the behavioral sciences that addresses questions of human behavior from the perspective of evolution. In light of several forms of data, including analyses of a variety of disciplines drawn on from evolutionary psychologists in their work, we argue that evolutionary psychologists may well be the most naturally interdisciplinary scholars within the behavioral sciences, making them highly appropriate for inclusion in EvoS. But our research shows not only promise regarding the relationship between EP and EvoS—challenges are raised as well. We present additional data showing that EP is currently represented disproportionately within the EvoS world—a fact that clearly shows that there are currently limitations to the potential impact of EvoS in modern academia. Scholars from other disciplines, particularly within the humanities and social sciences, seem to be missing the evolution revolution. Implications regarding how EvoS can broaden its scope to be even more powerful in its integrative scope are discussed.     

Comparison of printed glycan array, suspension array and ELISA in the detection of human anti-glycan antibodies

Anti-glycan antibodies represent a vast and yet insufficiently investigated subpopulation of naturally occurring and adaptive antibodies in humans. Recently, a variety of glycan-based microarrays emerged, allowing high-throughput profiling of a large repertoire of antibodies. As there are no direct approaches for comparison and evaluation of multi-glycan assays we compared three glycan-based immunoassays, namely printed glycan array (PGA), fluorescent microsphere-based suspension array (SA) and ELISA for their efficacy and selectivity in profiling anti-glycan antibodies in a cohort of 48 patients with and without ovarian cancer. The ABO blood group glycan antigens were selected as well recognized ligands for sensitivity and specificity assessments. As another ligand we selected P(1), a member of the P blood group system recently identified by PGA as a potential ovarian cancer biomarker. All three glyco-immunoassays reflected the known ABO blood groups with high performance. In contrast, anti-P(1) antibody binding profiles displayed much lower concordance. Whilst anti-P(1) antibody levels between benign controls and ovarian cancer patients were significantly discriminated using PGA (p=0.004), we got only similar results using SA (p=0.03) but not for ELISA. Our findings demonstrate that whilst assays were largely positively correlated, each presents unique characteristic features and should be validated by an independent patient cohort rather than another array technique. The variety between methods presumably reflects the differences in glycan presentation and the antigen/antibody ratio, assay conditions and detection technique. This indicates that the glycan-antibody interaction of interest has to guide the assay selection.     

Structure of surface layer homology (SLH) domains from Bacillus anthracis surface array protein

Surface (S)-layers, para-crystalline arrays of protein, are deposited in the envelope of most bacterial species. These surface organelles are retained in the bacterial envelope through the non-covalent association of proteins with cell wall carbohydrates. Bacillus anthracis, a Gram-positive pathogen, produces S-layers of the protein Sap, which uses three consecutive repeats of the surface-layer homology (SLH) domain to engage secondary cell wall polysaccharides (SCWP). Using x-ray crystallography, we reveal here the structure of these SLH domains, which assume the shape of a three-prong spindle. Each SLH domain contributes to a three-helical bundle at the spindle base, whereas another α-helix and its connecting loops generate the three prongs. The inter-prong grooves contain conserved cationic and anionic residues, which are necessary for SLH domains to bind the B. anthracis SCWP. Modeling experiments suggest that the SLH domains of other S-layer proteins also fold into three-prong spindles and capture bacterial envelope carbohydrates by a similar mechanism.     

Coral-rudist bioconstructions in the Upper Cretaceous Haidach section (Gosau Group; Northern Calcareous Alps, Austria)

Summary In the area of Haidach (Northern Calcareous Alps, Austria), coral-rudist mounds, rudist biostromes, and bioclastic limestones and marls constitute an Upper Cretaceous shelf succession approximately 100 meters thick. The succession is part of the mixed siliciclasticcarbonate Gosau Group that was deposited at the northern margin of the Austroalpine microplate. In its lower part, the carbonate succession at Haidach comprises two stratal packages that each consists, from bottom to top, of a coral-rudist mound capped by a rudist biostrome which, in turn, is overlain by bioclastic limestones and, locally, marls. The coral-rudist mounds consist mainly of floatstones. The coral assemblage is dominated by Fungiina, Astreoina, Heterocoeniina andAgathelia asperella (stylinina). From the rudists, elevators (Vaccinites spp., radiolitids) and recumbents (Plagioptychus) are present. Calcareous sponges, sclerosponges, and octocorals are subordinate. The elevator rudists commonly are small; they settled on branched corals, coral heads, on rudists, and on biolastic debris. The rudists, in turn, provided settlement sites for corals. Predominantly plocoid and thamnasteroid coral growth forms indicate soft substrata and high sedimentation rates. The mounds were episodically smothered by carbonate mud. Many corals and rudists are coated by thick and diverse encrustations that indicate high nutrient level and/or turbid waters. The coral-rudist mounds are capped byVaccinites biostromes up to 5 m thick. The establishment of these biostromes may result from unfavourable environmental conditions for corals, coupled with the potential of the elevator rudists for effective substrate colonization. TheVaccinites biostromes are locally topped by a thin radiolitid biostrome. The biostromes, in turn, are overlain by bioclastic limestones; these are arranged in stratal packages that were deposited from carbonate sand bodies. Approximately midsection, an interval of marls with abundantPhelopteria is present. These marls were deposited in a quiet lagoonal area where meadows of sea grass or algae, coupled with an elevated nutrient level, triggered the mass occurrence ofPhelopteria. The upper part of the Haidach section consists of stratal packages that each is composed of a rudist biostrome overlain by bioclastic wackestones to packstones with diverse smaller benthic foraminifera and calcareous green algae. The biostromes are either built by radiolitids,Vaccinites, andPleurocora, or consist exclusively of radiolitids (mainlyRadiolites). Both the biostromes and the bioclastic limestones were deposited in a low-energy lagoonal environment that was punctuated by high-energy events.In situ-rudist fabrics typically have a matrix of mudstone to rudistclastic wackestone; other biogens (incl. smaller benthic foraminifera) are absent or very rare. The matrix of rudist fabrics that indicate episodic destruction by high-energy events contain a fossil assemblage similar to the vertically associated bioclastic limestones. Substrata colonized by rudists thus were unfavourable at least for smaller benthic foraminifera. The described succession was deposited on a gently inclined shelf segment, where coral-rudist mounds and hippuritid biostromes were separated by a belt of bioclastic sand bodies from a lagoon with radiolitid biostromes. The mounds document that corals and Late Cretaceous elevator rudists may co-occur in close association. On the scale of the entire succession, however, mainly as a result of the wide ecologic range of the rudists relative to corals, the coral-dominated mounds and the rudist biostromes are vertically separated.