Experimental investigation of geologically produced antineutrinos with KamLAND

The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained.     

Amphipols: polymeric surfactants for membrane biology research

Membrane proteins classically are handled in aqueous solutions as complexes with detergents. The dissociating character of detergents, combined with the need to maintain an excess of them, frequently results in more or less rapid inactivation of the protein under study. Over the past few years, we have endeavored to develop a novel family of surfactants, dubbed amphipols (APs). APs are amphiphilic polymers that bind to the transmembrane surface of the protein in a noncovalent but, in the absence of a competing surfactant, quasi-irreversible manner. Membrane proteins complexed by APs are in their native state, stable, and they remain water-soluble in the absence of detergent or free APs. An update is presented of the current knowledge about these compounds and their demonstrated or putative uses in membrane biology.     

Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency

Most eukaryotic cell types use a common program to regulate the process of cell division. During mitosis, successful partitioning of the genetic material depends on spatially coordinated chromosome movement and cell cleavage. Here we characterize a zebrafish mutant, retsina (ret), that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia. Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, we show that the ret mutation is in a gene (slc4a1) encoding the anion exchanger 1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. We further show an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic slc4a1 with a variety of mutations show that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis.     

Non-classical receptive field mediates switch in a sensory neuron's frequency tuning

Animals have developed stereotyped communication calls to which specific sensory neurons are well tuned. These communication calls must be discriminated from environmental signals such as those produced by prey. Sensory systems might have evolved neural circuitry to encode both categories. In weakly electric fish, prey and communication signals differ in their spatial extent and frequency content. Here we show that stimuli of different spatial extents mimicking prey and communication signals cause a switch in the frequency tuning and spike-timing precision of electrosensory pyramidal neurons, resulting in the selective and optimal encoding of both stimulus categories. As in other sensory systems, pyramidal neurons respond only to stimuli located within a restricted region of space known as the classical receptive field (CRF). In some systems, stimulation outside the CRF but within a non-classical receptive field (nCRF) can modulate the neural response to CRF stimulation even though nCRF stimulation alone fails to elicit responses. We show that pyramidal neurons possess a nCRF and that it can modulate the response to CRF stimuli to induce this neurobiological switch in frequency tuning.     

DNA reveals high dispersal synchronizing the population dynamics of Canada lynx

Population dynamics of Canada lynx (Lynx canadensis) have been of interest to ecologists for nearly sixty years. Two competing hypotheses concerning lynx population dynamics and large-scale spatial synchrony are currently debated. The first suggests that dispersal is substantial among lynx populations, and the second proposes that lynx at the periphery of their range exist in small, isolated patches that maintain cycle synchrony via correlation with extrinsic environmental factors. Resolving the nature of lynx population dynamics and dispersal is important both to ecological theory and to the conservation of threatened lynx populations: the lack of knowledge about connectivity between populations at the southern periphery of the lynx's geographic range delayed their legal listing in the United States. We test these competing hypotheses using microsatellite DNA markers and lynx samples from 17 collection sites in the core and periphery of the lynx's geographic range. Here we show high gene flow despite separation by distances greater than 3,100 km, supporting the dispersal hypothesis. We therefore suggest that management actions in the contiguous United States should focus on maintaining connectivity with the core of the lynx's geographic range.     

A regular pattern of two types of 100-residue motif in the sequence of titin

Titin is the largest polypeptide yet described (relative molecular mass approximately 3 x 10(6); refs 1, 2) and an abundant protein of striated muscle. Its molecules are string-like and in vivo span from the M to Z-lines. I-band regions of titin are thought to make elastic connections between the thick filament and the Z-line, thereby forming a third type of sarcomere filament. These would centre the A-band in the sarcomere and provide structural continuity in relaxed myofibrils. The A-band region of titin seems to be bound to the thick filament, where it has been proposed to act as a 'molecular ruler' regulating filament length and assembly. Here, we show that partial titin complementary DNAs encode a regular pattern of two types of 100-residue motif, each of which probably folds into a separate domain type. Such motifs are present in several evolutionarily divergent muscle proteins, all of which are likely to interact with myosin. One or both of the domain types is therefore likely to bind to myosin.     

Molecular cloning and expression of cDNAs for the human interleukin-2 receptor

We have purified the human T-cell growth factor (interleukin-2) receptor and have cloned, sequenced and expressed cDNAs corresponding to this receptor. We identify one gene, but two interleukin-2 receptor mRNAs which differ in their polyadenylation signals. We have isolated an additional cDNA that may correspond to an alternatively spliced mRNA that lacks a 216 base segment and appears to encode an altered membrane protein which cannot bind interleukin-2.     

A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS

The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 1986. For the primary vaccination recombinant vaccinia virus (V25) expressing the complete gp160 env protein of the HTLV-IIIB strain of HIV-1 was introduced by scarification. This elicited a weak primary response which we subsequently attempted to enhance by additional immunizations (boosting), using four different immunization protocols. We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results. This individual received second and third boosts of intramuscular gp160 derived from an HTLV-IIIB clone using the hybrid vaccinia virus/bacteriophage T7 expression system. An anamnestic humoral and cellular immune reaction was achieved for over one year after the original vaccination, with high levels of antibodies to the viral envelope, and neutralizing antibodies against divergent HIV-1 strains such as HTLV-IIIB and HTLV-IIIRF (also called HTLV-III HAT) after the first boost. In addition, group-specific cell-mediated immunity and cell-mediated cytotoxicity against infected T4 cells were obtained after the primary vaccine and enhanced by the boosts. Finally, skin tests showed both immediate and delayed hypersensitivity to gp160 in vivo. Although this protocol is not practical for a large scale vaccine trial, our results show for the first time that an immune state against HIV can be obtained in man.