Wnt Pathway Activation Increases Hypoxia Tolerance during Development

Adaptation to hypoxia, defined as a condition of inadequate oxygen supply, has enabled humans to successfully colonize high altitude regions. The mechanisms attempted by organisms to cope with short-term hypoxia include increased ATP production via anaerobic respiration and stabilization of Hypoxia Inducible Factor 1α (HIF-1α). However, less is known about the means through which populations adapt to chronic hypoxia during the process of development within a life time or over generations. Here we show that signaling via the highly conserved Wnt pathway impacts the ability of Drosophila melanogaster to complete its life cycle under hypoxia. We identify this pathway through analyses of genome sequencing and gene expression of a Drosophila melanogaster population adapted over >180 generations to tolerate a concentration of 3.5–4% O₂ in air. We then show that genetic activation of the Wnt canonical pathway leads to increased rates of adult eclosion in low O₂. Our results indicate that a previously unsuspected major developmental pathway, Wnt, plays a significant role in hypoxia tolerance.     

Demonstration of B700 cross-reactive antigens on human and other animal melanomas

B700 is a melanoma-associated antigen originally detected by immunologic and biochemical criteria; it is expressed by several murine melanomas but is not detectable on any normal murine cells, or on murine nonmelanoma neoplasms. We have used antibodies raised against purified B700 to study the presentation of B700 and B700 crossreactive molecules on the surfaces of melanoma cells of various species and origins. The antibodies are shown to bind to all the melanoma cells tested, including five different murine melanoma lines (S91, JB/RH, JB/MS, K1735, and B16), three different B16 sublines (F1, F10, and BL6), three human, one hamster, and two swine melanoma cell lines. These results suggest the candidacy of B700-like molecules as "pan-melanoma" antigens.     

Chromosomal assignment of 46 brain cDNAs.

Expressed sequence tags (ESTs) have been obtained from several hundred brain cDNAs as an initial effort to characterize expressed brain genes. These ESTs will become tools for human genome mapping and they will also provide candidate causative genes for inherited disorders affecting the central nervous system. We have developed a procedure for the rapid chromosomal assignment of these ESTs: cDNA sequences are first analyzed by a computer program to determine regions likely not to be interrupted by introns in the genomic DNA. A pair of oligonucleotide primers is then designed to amplify this region by the polymerase chain reaction using DNA template from human-rodent somatic cell hybrid chromosomal panels. The chromosomal assignment of the cDNA is determined by studying the segregation of the amplified products in these panels. In this paper we describe the mapping of 46 brain ESTs, as well as observations on the amplification of rodent sequences.     

B700 antigen as a component of an antimelanoma vaccine: formalinized extracellular antigens.

Formalin fixation has enjoyed widespread use in the preparation of antibacterial and other vaccines, but rather less use in antitumor vaccines. Previous studies from our laboratories have demonstrated the efficacy of antimelanoma vaccines in mice, produced from formalinized antigens shed by cultured melanoma cells. In this study, we provide evidence that the immunodominant component of that vaccine is the well-characterized B700 melanoma antigen.     

Effect of exercise on muscle function decline with aging.

As people age, changes in muscle occur that are associated with a decrease in strength and endurance. These changes result in decreased functional capacity and quality of life. A substantial portion of this decrease is the result not of aging but of the sedentary life-style so frequently associated with aging. In "healthy old" persons and in older animals in experiments, an appropriate exercise program can result in increased strength and endurance. This is true both in longitudinal and short-term studies. As physical impairment increases, the exercise program must be individualized, and results are not as readily predictable. Much work remains before we may be certain how much exercise can be tolerated in these more impaired persons and what the effects may be.