Examining the impact of a symbiotic lifestyle on the fecundity of the marine gastropod Crepidula plana

The marine gastropod Crepidula plana has an extensive latitudinal range along the eastern coast of the United States. It is usually found living within gastropod shells occupied by hermit crabs, although individuals can sometimes also be found living on rocks and on the exposed surfaces of shells. Our study sought to determine the extent to which residing inside periwinkle (Littorina littorea) shells occupied by the hermit crab Pagurus longicarpus at a study site in coastal Massachusetts compromises the fecundity of C. plana, through size limitation. The egg masses of symbiotic and free‐living females of C. plana included comparable numbers of egg capsules and embryos per female despite the smaller sizes of the symbionts; symbiotic females compensated for their smaller size by producing significantly more embryos per milligram of female body tissue than their free‐living counterparts. These data raise interesting questions about why—unlike its congener C. fornicata—C. plana has not yet become a successful invasive species.     

Intratumor heterogeneity of biomarker expression in breast carcinomas

Small biopsy samples are used increasingly to assess the biomarker expression for prognostic information and for monitoring therapeutic responses prior to and during neoadjuvant therapy. The issue of intratumor heterogeneity of expression of biomarkers, however, has raised questions about the validity of the assessment of biomarker expression based on limited tissue samples. We examined immunohistochemically the expression of HER-2neu (p185^erbB-2), epidermal growth factor receptor (EGFR), Bcl-2, p53, and proliferating cell nuclear antigen (PCNA) in 30 breast carcinomas using archived, paraffin embedded tissue and determined the extent of intratumor heterogeneity. Each section was divided into four randomly oriented discrete regions, each containing a portion of the infiltrating carcinoma. For each tumor, the entire lesion and four regions were analyzed for the expression of these markers. Scores of both membrane and cytoplasmic staining of HER-2neu and EGFR, scores of cytoplasmic staining of Bcl-2, and scores of nuclear staining of both p53 and PCNA were recorded. The intensity of staining and the proportion of immunostained cells were determined. A semiquantitative immunoscore was calculated by determining the sum of the products of the intensity and corresponding proportion of stained tumor cells. We analyzed both invasive (IDC) and in situ (DCIS) carcinomas. The Wilcoxon signed-rank test was used for paired comparisons between overall and regional immunoscores and between overall and regional percentages of stained cells. Spearman's correlation coefficients were used to assess the level of agreement of overall biomarker expression with each of the regions. Generalized linear models were used to assess overall and pair-wise differences in the absolute values of percent changes between overall and regional expression of biomarkers. For IDCs, there were no statistically significant differences in the expression of the biomarkers in terms of either the percentage of cells staining or the immunoscores when comparing the entire tumor with each region except for the lower EGFR expression of arbitrarily selected region 1 and lower p53 expression of region 1 compared to that of the entire tumor section. For DCIS, there were no statistically significant differences in the expression of the biomarkers between the entire tumor and each region except in PCNA of region 2 compared to that of entire tumor section. Positive correlation of immunoscores was observed between the entire tumor and each region as well as across all four regions for IDC. Similar observations were noted with DCIS except for HER-2neu and PCNA. No statistically significant differences were observed in the absolute values of percent changes of biomarker expression between overall and the four regions for both DCIS and IDC. Therefore, no significant intratumor heterogeneity in the expression of HER-2neu, Bcl-2, and PCNA was observed in IDC. Minor regional variations were observed for EGFR and p53 in IDC. Similarly, no significant regional variation in the expression of markers was observed in DCIS except for PCNA.     

Phylogeny and character evolution in the jelly fungi (Tremellomycetes, Basidiomycota, Fungi)

The Tremellomycetes (Agaricomycotina, Basidiomycota, Fungi) are a nutritionally heterogeneous group comprising saprotrophs, animal parasites, and fungicolous species (fungal-inhabiting, including lichen-inhabiting). The relationships of many species, particularly those with a lichenicolous habit, have never been investigated by molecular methods. We present a phylogeny of the Tremellomycetes based on three nuclear DNA ribosomal markers (nSSU, 5.8S and nLSU), representing all main taxonomic groups and life forms, including lichenicolous taxa. The Cystofilobasidiales, Filobasidiales, Holtermanniales, and Tremellales (including the Trichosporonales) are recovered as monophyletic, but this is not the case for the Tremellomycetes. We suggest, however, that the Cystofilobasidiales tentatively continue to be included in the Tremellomycetes. As currently circumscribed, the Filobasidiaceae, Sirobasidiaceae, Syzygosporaceae and Tremellaceae are non-monophyletic. Cuniculitremaceae, Sirobasidiaceae and Tetragoniomycetaceae are nested within Tremellaceae. The lichenicolous species currently included within the Tremellomycetes belong in this group, distributed across the Filobasidiales and Tremellales. Lichen-inhabiting taxa do not form a monophyletic group; they are distributed in several clades and sometimes intermixed with taxa of other nutritional habits. Character state reconstruction indicates that two morphological traits claimed to characterize groups in the Tremellomycetes (the basidium habit and basidium septation) are highly homoplastic. Comparative phylogenetic methods suggest that the transitions between single and catenulate basidia in the Tremellales are consistent with a punctuational model of evolution whereas basidium septation is likely to have evolved under a graduational model in the clade comprising the Holtermanniales, Filobasidiales, and Tremellales.     

Age as a Criterion for Setting Priorities in Health Care? A Survey of the German Public View

Although the German health care system has budget constraints similar to many other countries worldwide, a discussion on prioritization has not gained the attention of the public yet. To probe the acceptance of priority setting in medicine, a quantitative survey representative for the German public (n = 2031) was conducted. Here we focus on the results for age, a highly disputed criterion for prioritizing medical services. This criterion was investigated using different types of questionnaire items, from abstract age-related questions to health care scenarios, and discrete choice settings, all performed within the same sample. Several explanatory variables were included to account for differences in preference; in particular, interviewee''s own age but also his or her sex, socioeconomic status, and health status. There is little evidence that the German public accepts age as a criterion to prioritize health care services.     

Phorbol ester regulation of the human gamma-glutamyltransferase gene promoter

In the present study the molecular mechanisms underlying tetradecanoylphorbol-13-acetate (TPA) mediated regulation of the human gamma-glutamyltransferase (GGT) gene were examined. TPA challenge of HeLa cells resulted in an increase of GGT mRNA and enzyme activity. Deletion analysis of the promoter revealed that the -348 to +60 fragment was able to mediate TPA induced expression. Gel shift and supershift analyses showed that TPA treatment increased nuclear protein binding to a putative AP-1 site (-225 to -214) and that c-Jun was part of the complex. This AP-1 element, when cloned either in its native arrangement or as tandem repeat 5' of the minimal thymidine kinase promoter, mediated a significant increase of luciferase activity after TPA treatment of transfected HeLa cells, while its mutated counterpart abolished the induction. The same AP-1 element was able to mediate TPA induced expression in HepG2 cells. Collectively these results indicate that like other GSH metabolising enzymes, GGT too is a target for AP-1 mediated regulation.     

Semipreparative enantioseparation of Tröger base derivatives by HPLC

We describe the enantioseparation of functionalized derivatives of the Tr?ger base by HPLC on commercially available chiral stationary phases. Cellulose-derived Chiralcel OJ and brush-type Whelk O1 are demonstrated to be complementary to each other in their scope. On the basis of the results obtained, the separation of selected compounds was successfully transferred onto semipreparative columns. We believe that the availability of enantiopure functionalized derivatives of the Tr?ger base will stimulate the further use of this interesting molecular scaffold in molecular recognition, asymmetric catalysis, and related areas of research and technology.     

Chromatin-modifying agents in anti-cancer therapy

Epigenetic alterations are involved in every step of carcinogenesis. The development of chromatin-modifying agents (CMAs) has provided the ability to fight cancer by reversing these alterations. Currently, four CMAs have been approved for cancer treatment; two DNA demethylating agents and two deacetylase inhibitors. A number of promising CMAs are undergoing clinical trials in several cancer types. Moreover, already approved CMAs are still under clinical investigation to improve their efficacy and to extend their use to a broader panel of cancers. Combinatorial treatments with CMAs are already considered a promising strategy to improve clinical benefits and to limit side effects. The real mechanisms by which these CMAs allow the improvement and remission of patients are still obscure. A deeper analysis of the molecular features expressed by responding patients should be performed to reveal this information. In this review, we focus on clinical trials with CMAs, discussing the success and the pitfalls of this new class of anti-cancer drugs.