We describe the discovery of a novel, 20 kDa, secreted human protein named mesencephalic astrocyte-derived neurotrophic factor, or MANF. The homologous, native molecule was initially derived from a rat mesencephalic type-1 astrocyte cell line and recombinant MANF subcloned from a cDNA encoding human arginine-rich protein. MANF selectively protects nigral dopaminergic neurons, versus GABAergic or serotonergic neurons. The discovery of MANF marks a more systematic approach in the search for astrocyte-derived, secreted proteins that selectively protect specific neuronal phenotypes. Compared to glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), MANF was more selective in the protection of dopaminergic neurons at lower (0.05-0.25 ng/mL) and middle (0.5-2.5 ng/mL) concentrations: MANF>GDNF>BDNF. GDNF was more selective at higher concentrations (25-50 ng/ml): GDNF>MANF>BDNF. Two domains in MANF of 39-AA and 109-AA respectively, and eight cysteines are conserved from C. elegans to man. MANF is encoded by a 4.3 Kb gene with 4 exons, and is located on the short arm of human chromosome 3. The secondary structure is dominated by alpha-helices (47%) and random coils (37%). Studies to determine the localization of MANF in the brains of rat, monkey, and man, as well as the receptor, signaling pathways, and biologically active peptide mimetics are in progress. The selective, neuroprotective effect of MANF for dopaminergic neurons suggests that it may be indicated for the treatment of Parkinson's disease.

An understanding of the distribution of North American green sturgeon Acipenser medirostris in coastal waters is crucial to minimize impacts on this vulnerable species from various fisheries. To determine migratory patterns, we tagged 213 subadult and adult green sturgeon in spawning rivers and summer aggregation areas with uniquely coded ultrasonic pingers and observed their coastal movements with arrays of automated hydrophones deployed along the West Coast of North America from southeast Alaska to Monterey Bay, California. Green sturgeon exhibited an annual migration along the continental shelf from U.S. to Canadian waters in the fall and an apparent return migration in the spring. Peak migration rates exceeded 50 km/d during the springtime southward migration. Large numbers of green sturgeon were detected near Brooks Peninsula on northwest Vancouver Island, British Columbia, during May‐June and October‐November. A single fish was detected in southeast Alaska in December. This pattern of detections suggests that important overwintering grounds may be north of Vancouver Island and south of Cape Spencer, Alaska. A high frequency of detection allowed us to estimate that annual survival of tagged green sturgeon was 0.83 in 2004. The rapid, frequent long‐distance migrations by these fish may make them vulnerable to bycatch in bottom trawl fisheries on the shelf waters of western North America.

No abstract

Background: Mammalian cells are becoming the prevailing expression system for the production of recombinant proteins because of their capacity for proper protein folding, assembly, and posttranslational modifications. These systems currently allow high volumetric production of monoclonal recombinant antibodies in the range of grams per litre. However their use for largescale expression of cytokines typically results in much lower volumetric productivity.

Adult green sturgeon, Acipenser medirostris, were collected in San