Climate change and the resurgence of malaria in the East African highlands

The public health and economic consequences of Plasmodium falciparum malaria are once again regarded as priorities for global development. There has been much speculation on whether anthropogenic climate change is exacerbating the malaria problem, especially in areas of high altitude where P. falciparum transmission is limited by low temperature. The International Panel on Climate Change has concluded that there is likely to be a net extension in the distribution of malaria and an increase in incidence within this range. We investigated long-term meteorological trends in four high-altitude sites in East Africa, where increases in malaria have been reported in the past two decades. Here we show that temperature, rainfall, vapour pressure and the number of months suitable for P. falciparum transmission have not changed significantly during the past century or during the period of reported malaria resurgence. A high degree of temporal and spatial variation in the climate of East Africa suggests further that claimed associations between local malaria resurgences and regional changes in climate are overly simplistic.     

Dinosaurian growth patterns and rapid avian growth rates

Did dinosaurs grow in a manner similar to extant reptiles, mammals or birds, or were they unique? Are rapid avian growth rates an innovation unique to birds, or were they inherited from dinosaurian precursors? We quantified growth rates for a group of dinosaurs spanning the phylogenetic and size diversity for the clade and used regression analysis to characterize the results. Here we show that dinosaurs exhibited sigmoidal growth curves similar to those of other vertebrates, but had unique growth rates with respect to body mass. All dinosaurs grew at accelerated rates relative to the primitive condition seen in extant reptiles. Small dinosaurs grew at moderately rapid rates, similar to those of marsupials, but large species attained rates comparable to those of eutherian mammals and precocial birds. Growth in giant sauropods was similar to that of whales of comparable size. Non-avian dinosaurs did not attain rates like those of altricial birds. Avian growth rates were attained in a stepwise fashion after birds diverged from theropod ancestors in the Jurassic period.     

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.     

Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death

Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes dominantly inherited type 4 long-QT cardiac arrhythmia in humans. Mice heterozygous for a null mutation in ankyrin-B are haploinsufficient and display arrhythmia similar to humans. Mutation of ankyrin-B results in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-trisphosphate receptors (all ankyrin-B-binding proteins), which reduces the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also leads to altered Ca2+ signalling in adult cardiomyocytes that results in extrasystoles, and provides a rationale for the arrhythmia. Thus, we identify a new mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters.     

Evidence for recycled Archaean oceanic mantle lithosphere in the Azores plume

The compositional differences between mid-ocean-ridge and ocean-island basalts place important constraints on the form of mantle convection. Also, it is thought that the scale and nature of heterogeneities within plumes and the degree to which heterogeneous material endures within the mantle might be reflected in spatial variations of basalt composition observed at the Earth's surface. Here we report osmium isotope data on lavas from a transect across the Azores archipelago which vary in a symmetrical pattern across what is thought to be a mantle plume. Many of the lavas from the centre of the plume have lower 187Os/188Os ratios than most ocean-island basalts and some extend to subchondritic 187Os/188Os ratios-lower than any yet reported from ocean-island basalts. These low ratios require derivation from a depleted, harzburgitic mantle, consistent with the low-iron signature of the Azores plume. Rhenium-depletion model ages extend to 2.5 Gyr, and we infer that the osmium isotope signature is unlikely to be derived from Iberian subcontinental lithospheric mantle. Instead, we interpret the osmium isotope signature as having a deep origin and infer that it may be recycled, Archaean oceanic mantle lithosphere that has delaminated from its overlying oceanic crust. If correct, our data provide evidence for deep mantle subduction and storage of oceanic mantle lithosphere during the Archaean era.     

Cloning by functional expression of a member of the glutamate receptor family

We have isolated a complementary DNA clone by screening a rat brain cDNA library for expression of kainate-gated ion channels in Xenopus oocytes. The cDNA encodes a single protein of relative molecular mass (Mr) 99,800 which on expression in oocytes forms a functional ion channel possessing the electrophysiological and pharmacological properties of the kainate subtype of the glutamate receptor family in the mammalian central nervous system.     

Activated CD8 binding to class I protein mediated by the T-cell receptor results in signalling

The CD8 glycoprotein of T cells bind nonpolymorphic regions of class I major histocompatibility complex proteins on target cells and these interactions promote antigen recognition and signalling by the T-cell receptor. Studies using artificial membranes indicated that effective CD8/class I interaction is critical for response by alloantigen-specific cytotoxic T lymphocytes when class I protein is the only ligand on the antigen-bearing surface. But significant CD8-mediated binding of cytotoxic T lymphocytes to non-antigenic class I protein could not be detected in the absence of the alloantigen. These apparently contradictory findings indicate that CD8 binding to class I protein might be activated through the T-cell receptor and the results reported here demonstrate that this is the case. Treatment of cytotoxic T lymphocytes with soluble anti-T-cell receptor antibody activates adhesion of the cytotoxic T lymphocytes to class I, but not class II proteins. The specificity of this binding implies that it is mediated by CD8 and blocking by anti-CD8 antibodies confirmed this. Furthermore, binding of CD8 to class I protein resulted in generation of an additional signal(s) necessary to initiate response at low T-cell receptor occupancy levels.     

Butterfly wing antineoplastic agents

Zusammenfassung Eine Voruntersuchung der Insektengruppe Lepidoptera auf anti-tumor-aktive Stoffe führte zu einer detaillierten chemischen Prüfung der aus Asien stammenden SchmetterlingeCatopsilia crocale Cramer (Pieridae) undPieris rapae cruavora. Ein bedeutender Teil der Anti-Tumor-Aktivität scheint ihren Ursprung in der chemischen Substanz Isoxanthopterin zu besitzen.

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The present contribution represents Part XXVII of the series Antineoplastic Agents. For Part XXVI refer toG. R. Pettit, J. F. Day, J. L. Hartwell andH. B. Wood, Nature, Lond.227, 962 (1970).

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This investigation was supported by Public Health Service Research Grants No. CA-10612-01 to No. CA-10612-04 from the National Cancer Institute, and was presented in part at the American Chemical Society Meeting, Washington, D.C., September 1971. We are also grateful to the National Science Foundation for financial assistance (Grant numbers GB-4939 and GB-6979) used in obtaining the Atlas CH-4B and SM-1B mass spectrometers employed in this study.