Mitochondrial uncoupling protein 2 structure determined by NMR molecular fragment searching

Mitochondrial uncoupling protein 2 (UCP2) is an integral membrane protein in the mitochondrial anion carrier protein family, the members of which facilitate the transport of small molecules across the mitochondrial inner membrane. When the mitochondrial respiratory complex pumps protons from the mitochondrial matrix to the intermembrane space, it builds up an electrochemical potential. A fraction of this electrochemical potential is dissipated as heat, in a process involving leakage of protons back to the matrix. This leakage, or 'uncoupling' of the proton electrochemical potential, is mediated primarily by uncoupling proteins. However, the mechanism of UCP-mediated proton translocation across the lipid bilayer is unknown. Here we describe a solution-NMR method for structural characterization of UCP2. The method, which overcomes some of the challenges associated with membrane-protein structure determination, combines orientation restraints derived from NMR residual dipolar couplings (RDCs) and semiquantitative distance restraints from paramagnetic relaxation enhancement (PRE) measurements. The local and secondary structures of the protein were determined by piecing together molecular fragments from the Protein Data Bank that best fit experimental RDCs from samples weakly aligned in a DNA nanotube liquid crystal. The RDCs also determine the relative orientation of the secondary structural segments, and the PRE restraints provide their spatial arrangement in the tertiary fold. UCP2 closely resembles the bovine ADP/ATP carrier (the only carrier protein of known structure), but the relative orientations of the helical segments are different, resulting in a wider opening on the matrix side of the inner membrane. Moreover, the nitroxide-labelled GDP binds inside the channel and seems to be closer to transmembrane helices 1-4. We believe that this biophysical approach can be applied to other membrane proteins and, in particular, to other mitochondrial carriers, not only for structure determination but also to characterize various conformational states of these proteins linked to substrate transport.     

Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic beta cells

A class I histocompatibility gene, H-2Kb, linked to the rat insulin promoter, is overexpressed in the pancreatic beta cells of transgenic mice. The mice, whether syngeneic or allogeneic to the transgene, develop insulin dependent diabetes without detectable T cell infiltration, suggesting a direct, non-immune role for the transgenic class I molecules in the disease process.     

Nonstructural carbohydrate and element pools in globemallow ( Sphaeralcea ): defoliation effects and seasonal trends

Globemallows ( Sphaeralcea spp.) are arid land forbs suitable for seeding with crested wheatgrass ( Agropyron cristatum [L.] Geartner). However, little is known about the quantitative role of total nonstructural carbohydrates (TNC) in relation to globemallow tolerance of grazing, or about seasonal dynamics of mineral elements. The objectives of this study were to compare TNC and element pools (concentration x biomass) in the roots, crowns, and shoots of clipped versus unclipped S. munroana (Dogl.) Spach. Seedlings of S. munroana were transplanted to a northern Utah field site in 1985. Interplanted crested wheatgrass provided uniform competitive background. One-half of the globemallows were clipped to 5 cm on 10 May 1986 when stems were elongating the root and crown TNC pools were low. The remaining globemallows were not clipped. Root, crown and shoot pools of TNC and elements (N, P, K, Ca, and MG) were determined on 1 May, 20 May, 7 June, 11 July, 22 September, and 5 November 1986, and 29 May 1987. Defoliation did not affect shoot weights during a 1-year period. Experiment-long TNC and element pools also were not affected by clipping. Results indicate that S. munroana shoot recovery from a single spring grazing during a 1-year period would not be impaired by low root and crown TNC pools, and that TNC stored in the roots and crowns would account for only 7% of the regrowth produced. Furthermore, TNC and element pools of roots and crowns were generally constant from May to September but increased from September to November. TNC and element pools in shoots increased from May to September and then generally declined by November. TNC Pools of roots and crowns declined during winter.     

A structural taxonomy of DNA-binding domains

The structures of several classes of DNA-binding domains reveal a variety of designs for recognizing a specific site on DNA.     

Diagnosis of Vocal Cord Paralysis in Anaesthesia

Vocal cord paralysis can occur as a complication o surgery or anaesthesia,if permanent is a significant clinica problem.Early detection is important to optimize the chance o repair,and avoid complications associated with an impaired swallow.An algorithm to detect altered vocal cord function was presented based on wavelet packet analysis(WPA) and suppor vector machines(SVM),and compared with the Hoarseness Diagram method(HDm),which was reported as an objective voice quality evaluation approach and could be u...     

Weakening of tropical Pacific atmospheric circulation due to anthropogenic forcing

Since the mid-nineteenth century the Earth's surface has warmed, and models indicate that human activities have caused part of the warming by altering the radiative balance of the atmosphere. Simple theories suggest that global warming will reduce the strength of the mean tropical atmospheric circulation. An important aspect of this tropical circulation is a large-scale zonal (east-west) overturning of air across the equatorial Pacific Ocean--driven by convection to the west and subsidence to the east--known as the Walker circulation. Here we explore changes in tropical Pacific circulation since the mid-nineteenth century using observations and a suite of global climate model experiments. Observed Indo-Pacific sea level pressure reveals a weakening of the Walker circulation. The size of this trend is consistent with theoretical predictions, is accurately reproduced by climate model simulations and, within the climate models, is largely due to anthropogenic forcing. The climate model indicates that the weakened surface winds have altered the thermal structure and circulation of the tropical Pacific Ocean. These results support model projections of further weakening of tropical atmospheric circulation during the twenty-first century.