Molecular farming of recombinant antibodies in plants

Antibodies represent a large proportion of therapeutic drugs currently in development. In most cases, they are produced in mammalian cell lines or transgenic animals because these have been shown to fold and assemble the proteins correctly and generate authentic glycosylation patterns. However, such expression systems are expensive, difficult to scale up and there are safety concerns due to potential contamination with pathogenic organisms or oncogenic DNA sequences. Plants represent an inexpensive, efficient and safe alternative for the production of recombinant antibodies. Research over the last 10 years has shown that plants can produce a variety of functional antibodies and there is now intense interest in scaling up production to commercial levels. In this review, we discuss the advantages of plants over traditional expression systems, describe how antibody expression in plants is achieved and optimized and then consider the practical issues concerning large-scale molecular farming in plants. The first plant-produced therapeutic antibodies are already in clinical trials, and, given the economic benefits of this production system, we are likely to see many more recombinant antibodies produced in this manner in the future.     

Break-up of the Atlantic deep western boundary current into eddies at 8 degrees S

The existence in the ocean of deep western boundary currents, which connect the high-latitude regions where deep water is formed with upwelling regions as part of the global ocean circulation, was postulated more than 40 years ago. These ocean currents have been found adjacent to the continental slopes of all ocean basins, and have core depths between 1,500 and 4,000 m. In the Atlantic Ocean, the deep western boundary current is estimated to carry (10-40) x 10(6) m3 s(-1) of water, transporting North Atlantic Deep Water--from the overflow regions between Greenland and Scotland and from the Labrador Sea--into the South Atlantic and the Antarctic circumpolar current. Here we present direct velocity and water mass observations obtained in the period 2000 to 2003, as well as results from a numerical ocean circulation model, showing that the Atlantic deep western boundary current breaks up at 8 degrees S. Southward of this latitude, the transport of North Atlantic Deep Water into the South Atlantic Ocean is accomplished by migrating eddies, rather than by a continuous flow. Our model simulation indicates that the deep western boundary current breaks up into eddies at the present intensity of meridional overturning circulation. For weaker overturning, continuation as a stable, laminar boundary flow seems possible.     

High-resolution record of Northern Hemisphere climate extending into the last interglacial period

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.     

Chlorine isotope homogeneity of the mantle, crust and carbonaceous chondrites

Chlorine in the Earth is highly depleted relative to carbonaceous chondrites and solar abundances. Knowledge of the Cl concentrations and distribution on Earth is essential for understanding the origin of these depletions. Large differences in the stable chlorine isotope ratios of meteoritic, mantle and crustal materials have been used as evidence for distinct reservoirs in the solar nebula and to calculate the relative proportions of Cl in the mantle and crust. Here we report that large isotopic differences do not exist, and that carbonaceous chondrites, mantle and crust all have the same 37Cl/35Cl ratios. We have further analysed crustal sediments from the early Archaean era to the Recent epoch and find no systematic isotopic variations with age, demonstrating that the mantle and crust have always had the same delta37Cl value. The similarity of mantle, crust and carbonaceous chondrites establishes that there were no nebular reservoirs with distinct isotopic compositions, no isotopic fractionation during differentiation of the Earth and no late (post-core formation) Cl-bearing volatile additions to the crustal veneer with a unique isotopic composition.     

原子结构计算的进展

1IntroductionThe error in a non-relativistic Hartree-Fock(HF)wavefunctionis due to correlationinthe motion of theelectrons.For this reason,the error in the energy is referred to as the correlation energy.For fewelectronsystems,this correlation can beinclu…     

Defective planar cell polarity in polycystic kidney disease

Morphogenesis involves coordinated proliferation, differentiation and spatial distribution of cells. We show that lengthening of renal tubules is associated with mitotic orientation of cells along the tubule axis, demonstrating intrinsic planar cell polarization, and we demonstrate that mitotic orientations are significantly distorted in rodent polycystic kidney models. These results suggest that oriented cell division dictates the maintenance of constant tubule diameter during tubular lengthening and that defects in this process trigger renal tubular enlargement and cyst formation.     

Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2

We identified loss-of-function mutations in ATP6V0A2, encoding the a2 subunit of the V-type H+ ATPase, in several families with autosomal recessive cutis laxa type II or wrinkly skin syndrome. The mutations result in abnormal glycosylation of serum proteins (CDG-II) and cause an impairment of Golgi trafficking in fibroblasts from affected individuals. These results indicate that the a2 subunit of the proton pump has an important role in Golgi function.