Immunity to colon cancer assessed by antigen-induced inhibition of mixed mononuclear cell migration

A purified preparation of mixed human peripheral blood lymphocytes and monocytes was used in an inhibition-of-migration assay for cell-mediated immunity to cancer of the colon. This preparation was reproducibly antigen-responsive and migrated with greater reliability than did a more complex cell mixture. Of 27 patients with this disease, cells from 24 showed inhibited migratio in response to colon carcinoma antigen. Uninhibited migration patterns were found in each of the 52 cancer-free controls, including eight patients with nonmalignant disease initially diagnosed as cancer of the colon, and in nine patients with surgically cured adenocarcinoma of the colon.     

Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice

Class IA phosphoinositide 3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that generate second messenger signals downstream of tyrosine kinases, thereby controlling cell metabolism, growth, proliferation, differentiation, motility, and survival. Mammals express three class IA catalytic subunits: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta(D910A)) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity.     

SNARE function analyzed in synaptobrevin/VAMP knockout mice

SNAREs (soluble NSF-attachment protein receptors) are generally acknowledged as central components of membrane fusion reactions, but their precise function has remained enigmatic. Competing hypotheses suggest roles for SNAREs in mediating the specificity of fusion, catalyzing fusion, or actually executing fusion. We generated knockout mice lacking synaptobrevin/VAMP 2, the vesicular SNARE protein responsible for synaptic vesicle fusion in forebrain synapses, to make use of the exquisite temporal resolution of electrophysiology in measuring fusion. In the absence of synaptobrevin 2, spontaneous synaptic vesicle fusion and fusion induced by hypertonic sucrose were decreased approximately 10-fold, but fast Ca2+-triggered fusion was decreased more than 100-fold. Thus, synaptobrevin 2 may function in catalyzing fusion reactions and stabilizing fusion intermediates but is not absolutely required for synaptic fusion.     

Metabolic detoxification: mechanism of insect resistance to plant psoralens

Larvae of the black swallowtail butterfly, Papilio polyxenes Stoll, forage successfully on plants that contain high levels of photosensitizing psoralens. These insects rapidly detoxify psoralens, particularly in the midgut tissue prior to absorption, with the result that appreciable levels of unmetabolized phototoxin do not enter the body circulation where deleterious light-induced interactions with dermal or subdermal tissues would occur.     

Mass spectrometric imaging of highly curved membranes during Tetrahymena mating

Biological membrane fusion is crucial to numerous cellular events, including sexual reproduction and exocytosis. Here, mass spectrometry images demonstrate that the low-curvature lipid phosphatidylcholine is diminished in the membrane regions between fusing Tetrahymena, where a multitude of highly curved fusion pores exist. Additionally, mass spectra and principal component analysis indicate that the fusion region contains elevated amounts of 2-aminoethylphosphonolipid, a high-curvature lipid. This evidence suggests that biological fusion involves and might in fact be driven by a heterogeneous redistribution of lipids at the fusion site.     

SynCAM,a synaptic adhesion molecule that drives synapse assembly

Synapses, the junctions between nerve cells through which they communicate, are formed by the coordinated assembly and tight attachment of pre- and postsynaptic specializations. We now show that SynCAM is a brain-specific, immunoglobulin domain-containing protein that binds to intracellular PDZ-domain proteins and functions as a homophilic cell adhesion molecule at the synapse. Expression of the isolated cytoplasmic tail of SynCAM in neurons inhibited synapse assembly. Conversely, expression of full-length SynCAM in nonneuronal cells induced synapse formation by cocultured hippocampal neurons with normal release properties. Glutamatergic synaptic transmission was reconstituted in these nonneuronal cells by coexpressing glutamate receptors with SynCAM, which suggests that a single type of adhesion molecule and glutamate receptor are sufficient for a functional postsynaptic response.     

An X chromosome gene, WTX, is commonly inactivated in Wilms tumor

Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1 tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for DNA copy-number alterations in Wilms tumor, we identified somatic deletions targeting a previously uncharacterized gene on the X chromosome. This gene, which we call WTX, is inactivated in approximately one-third of Wilms tumors (15 of 51 tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a restricted temporal and spatial expression pattern in normal renal precursors. In contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is inactivated by a monoallelic "single-hit" event targeting the single X chromosome in tumors from males and the active X chromosome in tumors from females.