Suppression of in vitro haematopoiesis following human immunodeficiency virus infection

Viral infections are frequently associated with haematological disorders. Abnormalities including leukopenia, anaemia and thrombocytopenia are commonly observed in patients with the acquired immune deficiency syndrome (AIDS) or the AIDS-related complex (ARC). The underlying cause of these haematological abnormalities is poorly understood. We report here that bone marrow progenitors isolated from AIDS or ARC patients are responsive to recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) and recombinant erythropoietin. Antibodies present in the serum of patients infected with the human immunodeficiency virus (HIV), however, could suppress the growth of these progenitors, but not the growth of progenitors from HIV seronegative controls. A component of this immune-mediated suppression appears to be antibodies directed towards the envelope glycoprotein (gp120) of HIV.     

Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.     

Peat record reflecting Holocene climatic change in the Zoigê Plateau and AMS radiocarbon dating

Through the use of reliable AMS dating of high resolution (15–30 years) peat and the establishment of monsoon climate proxies sequence, we have been able to recognize several cold, dry events in the Tibetan Plateau during the Holocene. The more obvious ones occurred around 12800, 11300, 10200, 9580, 8900, 6400, 4400, 3700, 2800 and 1500 cal. aBP. These events correlate well with both ice rafting events recorded in high latitude North Atlantic Ocean sediment cores and cooling events in the low latitude SST. Spectral analysis indicates high frequency climate variation on centennial-millennial time scale during the Holocene. This further reflects Holocene climate instability and the existence of centennial-millenium scale rhythm in mid latitude areas as well.     

Peat record reflecting Holocene climatic change in the Zoige Plateau and AMS radiocarbon dating

Through the use of reliable AMS dating of high resolution (15-30 years) peat and the establishment of monsoon climate proxies sequence, we have been able to recognize several cold, dry events in the Tibetan Plateau during the Holocene. The more obvious ones occurred around 12800, 11300, 10200, 9580, 8900, 6400, 4400, 3700, 2800 and 1500 cal. aBP. These events correlate well with both ice rafting events recorded in high latitude North Atlantic Ocean sediment cores and cooling events in the low latitude SST. Spectral analysis indicates high frequency climate variation on centennial-millennial time scale during the Holocene. This further reflects Holocene climate instability and the existence of centennial-millenium scale rhythm in mid latitude areas as well.     

Optical detection of meteoroidal impacts on the Moon

Impacts of meteoroids on the Moon should cause detectable optical flashes, but the population of objects that are big enough is very low, and hitherto no unambiguous impact flashes have been recorded. The flux of meteoroids associated with the Leonid meteor shower of 18 November 1999 was predicted to produce observable flashes on the night side of the Moon. Here we report the unambiguous detection of five such impact flashes, three of which were seen simultaneously by other observers. We also observed a possible impact flash on 16 July 1999. All of the flashes were of very brief duration (<0.02 s), as expected for high-speed impacts.     

Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF

Certain proteins are known to play an important part in the proliferation, differentiation and functional activation of haematopoietic progenitor cells in vitro. These proteins include erythropoietin and various colony-stimulating factors (CSFs), one of which is granulocyte-macrophage colony-stimulating factor (GM-CSF). Recently, both murine and human GM-CSF have been purified to homogeneity and complementary DNAs encoding them have been cloned. Although the in vitro activity of recombinant human GM-CSF has been investigated intensively, little is known about the functional activity of this protein in vivo. There is strong evidence that colony-stimulating activities produced by various human and murine tumour tissues and cell lines can stimulate granulopoiesis in mice, as can human urinary extracts. A partially purified preparation of human urinary colony-stimulating factor, however, proved only marginally effective in stimulating granulopoiesis in humans. All these studies suffer from the lack of a homogeneous preparation of colony-stimulating factor. It has recently been shown that recombinant murine multi-CSF or interleukin-3 can stimulate haematopoiesis in mice in vivo. Large-scale production of recombinant human GM-CSF now permits us to examine its effects in vivo using a primate model. We find that the continuous infusion of GM-CSF in healthy monkeys rapidly elicits a dramatic leukocytosis and a substantial reticulocytosis. A similar effect has been observed in one pancytopenic, immunodeficient rhesus macaque. These results suggest that GM-CSF could prove useful in several clinical situations.     

A low-temperature origin for the planetesimals that formed Jupiter

The four giant planets in the Solar System have abundances of 'metals' (elements heavier than helium), relative to hydrogen, that are much higher than observed in the Sun. In order to explain this, all models for the formation of these planets rely on an influx of solid planetesimals. It is generally assumed that these planetesimals were similar, if not identical, to the comets from the Oort cloud that we see today. Comets that formed in the region of the giant planets should not have contained much neon, argon and nitrogen, because the temperatures were too high for these volatile gases to be trapped effectively in ice. This means that the abundances of those elements on the giant planets should be approximately solar. Here we show that argon, krypton and xenon in Jupiter's atmosphere are enriched to the same extent as the other heavy elements, which suggests that the planetesimals carrying these elements must have formed at temperatures lower than predicted by present models of giant-planet formation.     

Equilibrium bed—concentration of nonuniform sediment

Knowledge of the equilibrium bed-concentration is vital to mathematical modeling of the river-bed deformation associated with suspended load but previous investigations only daelt with the reference concentra-tion of uniform sediment because of difficulties in observation of the bed-concentration.This work is a first at-tempe to develop a theoretical formula for the equilibrium bed-concentration of any fraction of nonumiform sedi-ment defined at the bed-surface.The formula is based on a stochastic-mechanistic model for the exchange of nonumiform sediment near the bed,and described as a function of incipient motion probability,non-ceasing probability,pick-up probability,and the ratio of the average single-step continuous motion time to static time.Comparison of bed-concentration calculated from the proposed formula with the measured data showed satisfac-tory agreement,indicating the present formula can be used for solving the differential equation governing the notion of suspended load.     

Mapping and sequencing of structural variation from eight human genomes

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.