A 1000-Year Carbon Isotope Rainfall Proxy Record from South African Baobab Trees (Adansonia digitata L.)

A proxy rainfall record for northeastern South Africa based on carbon isotope analysis of four baobab (Adansonia digitata L.) trees shows centennial and decadal scale variability over the last 1,000 years. The record is in good agreement with a 200-year tree ring record from Zimbabwe, and it indicates the existence of a rainfall dipole between the summer and winter rainfall areas of South Africa. The wettest period was c. AD 1075 in the Medieval Warm Period, and the driest periods were c. AD 1635, c. AD 1695 and c. AD1805 during the Little Ice Age. Decadal-scale variability suggests that the rainfall forcing mechanisms are a complex interaction between proximal and distal factors. Periods of higher rainfall are significantly associated with lower sea-surface temperatures in the Agulhas Current core region and a negative Dipole Moment Index in the Indian Ocean. The correlation between rainfall and the El Niño/Southern Oscillation Index is non-static. Wetter conditions are associated with predominantly El Niño conditions over most of the record, but since about AD 1970 this relationship inverted and wet conditions are currently associated with la Nina conditions. The effect of both proximal and distal oceanic influences are insufficient to explain the rainfall regime shift between the Medieval Warm Period and the Little Ice Age, and the evidence suggests that this was the result of a northward shift of the subtropical westerlies rather than a southward shift of the Intertropical Convergence Zone.     

Mucin secretion by the human colon cell line LS174T is regulated by bile salts

We recently reported that bile salts play a role in the regulation of mucin secretion by cultured dog gallbladder epithelial cells. In this study we have examined whether bile salts also influence mucin secretion by the human epithelial colon cell line LS174T. Solutions of bile salts were applied to monolayers of LS174T cells. Mucin secretion was quantified by measuring the secretion of [3H]GlcNAc labeled glycoproteins. Both unconjugated bile salts as well as taurine conjugated bile salts stimulated mucin secretion by the colon cells in a dose-dependent fashion. Hydrophobic bile salts were more potent stimulators than hydrophilic bile salts. Free (unconjugated) bile salts were more stimulatory compared with their taurine conjugated counterparts. Stimulation of mucin secretion by LS174T cells was found to occur at much lower bile salt concentrations than in the experiments with the dog gallbladder epithelial cells. The protein kinase C activators PMA and PDB had no stimulatory effect on mucin secretion. We conclude that mucin secretion by the human colon epithelial cell line LS174T is regulated by bile salts. We suggest that regulation of mucin secretion by bile salts might be a common mechanism, by which different epithelia protect themselves against the detergent action of bile salts, to which they are exposed throughout the gastrointestinal tract.      

Molecular characterization and expression analysis of Mtmr2, mouse homologue of MTMR2, the Myotubularin-related 2 gene, mutated in CMT4B

Charcot-Marie-Tooth type 4B (CMT4B) is caused by mutations in the myotubularin-related 2 gene, MTMR2, on chromosome 11q22. To date, six loss of function mutations and one missense mutation have been demonstrated in CMT4B patients. It remains to be determined how dysfunction of a ubiquitously expressed phosphatase causes a demyelinating neuropathy. An animal model for CMT4B would provide insights into the pathogenesis of this disorder. We have therefore characterized the mouse homologue of MTMR2 by reconstructing the full-length Mtmr2 cDNA as well as the genomic structure. The 1932 nucleotide open reading frame corresponds to 15 coding exons, spanning a genomic region of approximately 55 kilobases, on mouse chromosome 9 as demonstrated by fluorescence in situ hybridization analysis. A comparison between the mouse and human genes revealed a similar genomic structure, except for the number of alternatively spliced exons in the 5'-untranslated region, two in mouse and three in man. In situ hybridization analysis of mouse embryos showed that Mtmr2 was ubiquitously expressed during organogenesis at E9.5, with some areas of enriched expression. At E14.5, Mtmr2 mRNA was more abundant in the peripheral nervous system, including in dorsal root ganglia and spinal roots.     

Arylamine N-acetyltransferase-1 is highly expressed in breast cancers and conveys enhanced growth and resistance to etoposide in vitro

Comparative two-dimensional proteome analysis was used to identify proteins differentially expressed in multiple clinical normal and breast cancer tissues. One protein, the expression of which was elevated in invasive ductal and lobular breast carcinomas when compared with normal breast tissue, was arylamine N-acetyltransferase-1 (NAT-1), a Phase II drug-metabolizing enzyme. NAT-1 overexpression in clinical breast cancers was confirmed at the mRNA level and immunohistochemical analysis of NAT-1 in 108 breast cancer donors demonstrated a strong association of NAT-1 staining with estrogen receptor-positive tumors. Analysis of the effect of active NAT-1 overexpression in a normal luminal epithelial-derived cell line demonstrated enhanced growth properties and etoposide resistance relative to control cells. Thus, NAT-1 may not only play a role in the development of cancers through enhanced mutagenesis but may also contribute to the resistance of some cancers to cytotoxic drugs.     

Patient vs. physician as the target of educational outreach about screening for an inherited susceptibility to colorectal cancer

Are patients identified from a cancer registry better educated directly or via their physician about screening for an inherited susceptibility for colorectal cancer? Of 974 patients diagnosed with colorectal cancer at < or = 60 years from 1987 to 1999 in a five-county area including Rochester, the physicians of 651 patients (67%) forwarded a cancer family history survey to their patient; 459 (71%) completed the survey. Of these 459, 167 (36%) reported having at least one first- or second-degree relative with colon cancer and were sent a set of questionnaires and a more detailed family cancer history form. Of the 167, a total of 101 (60%) continued to qualify by returning the questionnaires. These 101 qualifying patients were randomized to either the patient-education or physician-education group. Of the 101, a total of 47 (47%) came for a free genetic evaluation. Individuals were more likely to accept evaluation if they were parents (p = 0.001), had more cancers of all kinds in their families (p = 0.02), and had a larger social network (p = 0.04). Of the 47 counseled, 36 (77%) chose to have DNA testing at no cost. Of these 47, individuals were more likely to choose DNA testing if they had more cancers in the family (p = 0.04) and fewer symptoms of depression (p = 0.05). Of the 36 tested patients, 6 (20%) were found to have mutations. In summary, acceptance of genetic services was related to the magnitude of the threat (more cancers in the family), perceived ability to deal with the threat (perceived good health and a supportive network), and a desire to inform relatives (being a parent). The two approaches to educating patients, viz. direct patient education vs. education via their physician, did not significantly differ in terms of percentages of patients receiving counseling (42% vs. 51%, respectively) or the percentage choosing DNA testing (32% vs. 37%, respectively).     

Amphibian Diversity in East African Biodiversity Hotspots: Altitudinal and latitudinal Patterns

The Eastern Arc mountain chain and adjoining coastal forests of Tanzania and Kenya have been listed as world biodiversity hotspots. We report on an ongoing attempt to estimate amphibian diversity on the three best studied mountains of the Eastern Arc, the East Usambara, Uluguru and Udzungwa mountains of Tanzania, complemented by an estimate of diversity on the adjoining coastal lowland. This proves to be a complex task, which introduces a note of caution into evaluating global biodiversity estimates. Most amphibian species in eastern Tanzania occur on the coastal lowlands and are widely distributed, extending at least north or south of Tanzania and, to a variable extent, westwards to the elevated interior. Diversity patterns along the length of the lowlands are complex, with the presence of a Sahelian element in the extreme north. On the three Eastern Arc mountains studied, species turnover associated with rising altitude is greater than turnover associated with latitudinal distance between the mountain blocks, leading to greater altitudinal than latitudinal diversity in this equatorial region. A long-standing divergence is indicated between montane and lowland endemics. Although forest-associated species are not the largest contributor to the eastern Tanzanian total species diversity (some 48%), the uniqueness of these species both in lowland and montane forests, combined with their evident vulnerability to disturbance, makes them a subject for particular conservation concern, and justifies hotspot status for both montane and lowland forests.