Calcium channels in planar lipid bilayers: insights into mechanisms of ion permeation and gating

Electrophysiological recordings were used to analyze single calcium channels in planar lipid bilayers after membranes from bovine cardiac sarcolemmal vesicles had been incorporated into the bilayer. In these cell-free conditions, channels in the bilayer showed unitary barium or calcium conductances, gating kinetics, and pharmacological responses that were similar to dihydropyridine-sensitive calcium channels in intact cells. The open channel current varied in a nonlinear manner with voltage under asymmetric (that is, physiological) ionic conditions. However, with identical solutions on both sides of the bilayer, the current-voltage relation was linear. In matched experiments, calcium channels from skeletal muscle T-tubules differed significantly from cardiac calcium channels in their conductance properties and gating kinetics.     

A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytoskeletal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.     

Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes

We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus-related acquired immunodeficiency syndrome and other infectious diseases.     

Proton magnetic resonance of proteins fully deuterated except for 1H-leucine side chains

The fully deuterated proteins C-phycocyanin, C-phycoerythrin, and cytochrome c have been obtained by biosynthesis with the leucine side chains, and only the leucine side chains, of normal ((1)H) isotopic composition. In these (isotopic hybrid) proteins, proton magnetic resonance analysis shows that the (1)H-leucine side chains are in a variety of environments. During protein biosynthesis, the alpha hydrogen of leucine is exchanged with a hydrogen ((2)H) from the aqueous medium.     

Microinjected c-myc as a competence factor

While a number of oncogenes are expressed in a cell cycle-dependent manner, their role in the control of cell proliferation can only be established by a direct functional assay. The c-myc protein, upon microinjection into nuclei of quiescent Swiss 3T3 cells, cooperated with platelet-poor plasma in the stimulation of cellular DNA synthesis. This suggests that c-myc protein, like platelet-derived growth factor (PDGF), may act as a competence factor in the cell cycle to promote the progression of cells to S phase. The presence in the medium of an antibody against PDGF abolished DNA synthesis induced by microinjected PDGF; however, the microinjected c-myc protein stimulated DNA synthesis even when its own antibody was present in the medium. The c-myc protein may act as an intracellular competence factor, while PDGF expresses its biological activity only from outside the cells.     

Diversity of atlantic coastal plain mollusks since the pliocene

About 70 percent of tropical western Atlantic mollusk species have become extinct since the Pliocene, which has led to perceptions of a corresponding decline in diversity. However, a compilation of gastropod species from Plio-Pleistocene faunas of the United States Atlantic coastal plain and from Recent western Atlantic faunas indicates that regional diversity has not changed since the Pliocene. Gastropod diversity in the Pliocene Pinecrest Beds in Florida approximates that seen today on either coast of Florida. Gastropod diversity is not demonstrably different in the Recent tropical western Atlantic than in the Recent tropical eastern Pacific. High extinction rates must have been balanced by high origination rates.     

Wasted fishery resources: discarded by-catch in the USA

Fishery by‐catch, especially discarded by‐catch, is a serious problem in the world's oceans. Not only are the stocks of discarded species affected, but entire trophic webs and habitats may be disrupted at the ecosystem level. This paper reviews discarding in the marine fisheries of the USA; however, the type, diversity and regulatory mechanisms of the fisheries are similar to developed fisheries and management programmes throughout the world. We have compiled current estimates of discarded by‐catch for each major marine fishery in the USA using estimates from existing literature, both published and unpublished. We did not re‐estimate discards or discard rates from raw data, nor did we include data on protected species (turtles, mammals and birds) and so this study covers discarded by‐catch of finfish and fishable invertebrates. For some fisheries, additional calculations were required to transform number data into weight data, and typically length and weight composition data were used. Specific data for each fishery are referenced in Harrington et al. (Wasted Resources: Bycatch and discards in US Fisheries, Oceana, Washington, DC, 2005). Overall, our compiled estimates are that 1.06 million tonnes of fish were discarded and 3.7 million tonnes of fish were landed in USA marine fisheries in 2002. This amounts to a nationwide discard to landings ratio of 0.28, amongst the highest in the world. Regionally, the southeast had the largest discard to landings ratio (0.59), followed closely by the highly migratory species fisheries (0.52) and the northeast fisheries (0.49). The Alaskan and west coast fisheries had the lowest ratios (0.12 and 0.15 respectively). Shrimp fisheries in the southeast were the major contributors to the high discard rate in that region, with discard ratios of 4.56 (Gulf of Mexico) and 2.95 (South Atlantic). By‐catch and discarding is a major component of the impact of fisheries on marine ecosystems. There have been substantial efforts to reduce by‐catch in some fisheries, but broadly based programmes covering all fisheries are needed within the USA and around the world. In response to international agreements to improve fishery management, by‐catch and discard reduction must become a regular part of fishery management planning.