Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.     

Identification of adult nephron progenitors capable of kidney regeneration in zebrafish

Loss of kidney function underlies many renal diseases. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.     

Natural history of a saline mound ecosystem

Along the margins of playas in northwestern Nevada, a salt-tolerant plant community occupies mounds that dot a largely unvegetated landscape. In this environment we studied soil development and plant-soil relationships. The mounds, averaging 0.3 m in height, are occupied by the shrubs Allenrolfea occidentalis (iodine bush), Sacrobatus vermiculatus (black greasewood), and Atriplex lentiformis spp. torreyi (Torrey saltbush). Distichlis spicata (desert saltgrass) is the only herbaceous plant occupying this community. Soil salinity decreases with depth in this environment, and content of aqueous-extractable solutes is significantly influenced by site-specific vegetation. Content of silt, clay, and salt in mound surface horizons suggests a chronosequence of mound formation, with the youngest at the barren playa interface and the oldest at the upland vegetation border. Plant demography and mound soil stratigraphy suggest that a pulse of plant recruitment and mound building occurred during a time of neoglacial cooling. As a substrate for plant recruitment, mounds have a limited lifespan because deposition of eolian-transported salts and geochemical cycling by plants quickly render them too saline for seed germination. The apparent productivity of mound formation precludes definitive conclusions regarding those mound characteristics favorable for plant recruitment and survivorship.     

Bats of the Colorado oil shale region

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Conservative and moderate grazing effects on Chihuahuan Desert wildlife sightings

Seasonal wildlife observations were made along transects on 2 pastures conservatively grazed (36% use of perennial grasses) and 2 pastures moderately grazed (47% use of perennial grasses) in south central New Mexico in non-drought (1997) and drought years (1998). Experimental pastures were similar in soils, terrain, spacing of watering points, and brush cover. Average ecological condition score for the conservatively grazed pastures was 60% compared with 64% for moderately grazed pastures. Throughout the study total standing vegetation understory herbage levels were higher ( P P > 0.05) between conservatively and moderately grazed pastures. Black-tailed jackrabbit ( Lepus californicus ) sightings were higher ( P Antilocapra americana ), scaled quail ( Callipepla squamata ), mourning doves ( Zenaida macroura ), and desert cottontails ( Sylvilagus auduboni ) showed no differences ( P > 0.05) between conservatively and moderately grazed pastures. Dry conditions in 1998 depressed total wildlife sightings by > 50% compared to 1997. Both songbird and gamebird (particularly mourning dove) sightings were severely reduced in the dry compared to wet year ( P < 0.05). Our results are consistent with Nelson et al. (1997) that livestock grazing at intermediate levels had no effect on most Chihuahuan Desert upland wildlife species, and that drought years severely depress wildlife sightings.     

Editorial

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