The Contribution of Germline BRCA1 and BRCA2 Mutations to Familial Ovarian Cancer: No Evidence for Other Ovarian Cancer–Susceptibility Genes

To establish the contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer, we have analyzed both genes in DNA samples obtained from an affected individual in each of 112 families containing at least two cases of epithelial ovarian cancer. Germline mutations were found in 43% of the families; BRCA1 mutations were approximately four times more common than BRCA2 mutations. The extent of family history of ovarian and breast cancers was strongly predictive of BRCA1-mutation status. Segregation analysis suggests that a combination of chance clustering of sporadic cases and insensitivity of mutation detection may account for the remaining families; however, the contribution of other genes cannot be excluded. We discuss the implications for genetic testing and clinical management of familial ovarian cancer arising from the data presented in these studies.     

Three‐dimensional reconstruction of the odontophoral cartilages of Caenogastropoda (Mollusca: Gastropoda) using micro‐CT: Morphology and phylogenetic significance

Odontophoral cartilages are located in the molluscan buccal mass and support the movement of the radula during feeding. The structural diversity of odontophoral cartilages is currently known only from limited taxa, but this information is important for interpreting phylogeny and for understanding the biomechanical operation of the buccal mass. Caenogastropods exhibit a wide variety of feeding strategies, but there is little comparative information on cartilage morphology within this group. The morphology of caenogastropod odontophoral cartilages is currently known only from dissection and histology, although preliminary results suggest that they may be structurally diverse. A comparative morphological survey of 18 caenogastropods and three noncaenogastropods has been conducted, sampling most major caenogastropod superfamilies. Three‐dimensional models of the odontophoral cartilages were generated using X‐ray microscopy (micro‐CT) and reconstruction by image segmentation. Considerable morphological diversity of the odontophoral cartilages was found within Caenogastropoda, including the presence of thin cartilaginous appendages, asymmetrically overlapping cartilages, and reflexed cartilage margins. Many basal caenogastropod taxa possess previously unidentified cartilaginous support structures below the radula (subradular cartilages), which may be homologous to the dorsal cartilages of other gastropods. As subradular cartilages were absent in carnivorous caenogastropods, adaptation to trophic specialization is likely. However, incongruence with specific feeding strategies or body size suggests that the morphology of odontophoral cartilages is constrained by phylogeny, representing a new source of morphological characters to improve the phylogenetic resolution of this group. J. Morphol. 2009. © 2008 Wiley‐Liss, Inc.     

Termites Improve the Horizontal Movement of Carbonized Particles: A Step towards Sustainable Utilization of Biochar

Soil amendments containing carbonized materials increase the soil carbon reservoir, influence plant productivity, and, ultimately, help to clean the environment. There is data on the effect of such additions on soil physicochemical properties or plant growth, but few studies have focused on how these carbonized materials are distributed by termite species in the soil ecosystem. It is the first comprehensive study of the transportation of biochar (BC) by termite species under tropical environmental conditions in Pakistan. The present study was carried out to test the hypothesis that if termite species I) were involved in the distribution of biochar particles II) if yes, then how far these particles were transported during the study period (10 days) and III) check their preference between the enriched BC (EBC) and non-enriched BC. BC was enriched with the cattle slurry after its pyrolysis in the study. The results showed that EBC particles were significantly more widely distributed than non-enriched BC particles, but both types of BC were transported more than 4 cm (ring 4) within 10 days (at the end of the experiment). The current study also revealed that EBC was easily attached to the setae, cuticle, and legs of termites, implying that it could potentially be transported over a greater distance. Furthermore, transportation of EBC over larger distances indicated a potential preference of termite species between the EBC and BC particles. During the study, however, the preference among the termite species was also observed. Under the prevailing study conditions, the Coptotermes heimi and Heteroterme indicola species transported the EBC further than Microtermes obesi and Odontotermes obesus. These findings revealed that transportation preferences were observed among the four termite species. In conclusion, the current study found that termites were involved in the distribution of BC particles, with a preference for EBC and that these have the potential to transport BC particles more than 4 cm within 10 days. Furthermore, two species Coptotermes heimi and Heteroterme indicola may be more suitable candidates for EBC transpiration in Pakistani soils. It was necessary to conduct additional research into the effect of temperature on the transportation process.     

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study.

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P<.001), although only 8% of the variance in age at diagnosis could be explained by the specific mutation, and there was no evidence of family-specific effects. When the age at diagnosis of the breast cancer cases was examined by OCCR, cases associated with mutations in the OCCR had a significantly older mean age at diagnosis than was seen in those outside this region (48 years vs. 42 years; P=.0005).     

Ultrastructural Study of the Development of Pleistophora schubergi Zwölfer, 1927 (Protozoa,Microsporida) in Larvae of the Spruce Budworm,Choristoneura fumiferana and Its Subsequent Taxonomic Change to the Genus Endoreticulatus

This study demonstrates that Pleistophora schubergi Zwölfer, 1927, a microsporidium originally isolated from the midgut epithelium of Nygmia phaeorrhoea Don (Euproctis chrysorrhoea L.) and Porthetria dispar L., and subsequently reported in several other insects including the spruce budworm, Choristoneura fumiferana (the host used in this investigation), does not belong in the genus Pleistophora Gurley, 1893. Pleistophora schubergi lacks the major features that are characteristic of Pleistophora typicalis, the type species of this genus. A comparison of ultrastructural observations reported for the type species of the genus Pleistophora, P. typicalis, and our observations of P. schubergi revealed significant differences. A thick (0.5 μm) amorphous coat, derived from parasite secretions and deposited external to the parasite plasmalemma, surrounds all developmental stages in P. typicalis. Double membranes, derived from host rough endoplasmic reticulum cisternae encircle the parasite plasmalemma of all developmental stages in P. schubergi. The sporophorous vesicle encases the spores in P. typicalis, and originates from the parasite-secreted coat that is present around meronts. In P. schubergi, the host endoplasmic reticulum cisternae form the envelope that surrounds the meronts. Moreover, the sporophorous vesicle envelope in P. typicalis persists around groups of spores, while in P. schubergi this envelope breaks easily to release the spores in the host cytoplasm. By comparing the characteristics of the microsporidium found in the spruce budworm with those of the recently created polysporous genera that sporulate within a vesicle, we found that P. schubergi does belong in the new genus Endoreticulatus Brooks et al. 1988, and consequently rename it Endoreticulatus schubergi (Zwölfer, 1927) n. comb.     

Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.

The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.     

The trace fossil Nummipera eocenica from the Tatra Mountains,Poland: morphology and palaeoenvironmental implications

Jach, R., Machaniec, E. & Uchman, A. 2011: The trace fossil Nummipera eocenica from the Tatra Mountains, Poland: morphology and palaeoenvironmental implications. Lethaia, Vol. 45, pp. 342–355. The tubular trace fossil Nummipera eocenica Hölder 1989 occurs in a single stratigraphical horizon in Eocene nummulitic limestones of the Tatra Mountains, Poland. The wall of N. eocenica is built of Discocyclina and Nummulities (larger foraminifera) tests, very rarely of the Ditrupa (Polychaeta) tube fragments, bivalve shell fragments, echinoid spines and coralline algae. Morphotype are distinguished on the basis of wall composition and structure. Morphotype A is dominated by fusiform Discocyclina tests, which were preferentially selected by the trace makers for construction of a well‐constructed and resistant wall. Morphotype B contains more robust tests of Nummulites, while morphotype C is dominated by saddle‐shaped tests of Discocyclina. Nummipera eocenica was produced during a period of seafloor stabilization caused by a deepening. The succession of the morphotypes B, A reflects diminishing energy and increasing water depth. Probably morphotype C represents even lower energy environment than morphotype A. The trace fossil is interpreted as a domichnion, which wall was constructed for protection. The trace maker can be considered between polychaetes and crustaceans; however, comparisons to the closest recent analogues, the polychaete Diopatra cuprea or alpheid shrimps, are not satisfactory. □Bartonian, burrow, Carpathians, large foraminifera, trace fossils.