Dynamics of human adipose lipid turnover in health and metabolic disease

Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division

RNA interference (RNAi) is an evolutionarily conserved defence mechanism whereby genes are specifically silenced through degradation of messenger RNAs; this process is mediated by homologous double-stranded (ds)RNA molecules. In invertebrates, long dsRNAs have been used for genome-wide screens and have provided insights into gene functions. Because long dsRNA triggers a nonspecific interferon response in many vertebrates, short interfering (si)RNA or short hairpin (sh)RNAs must be used for these organisms to ensure specific gene silencing. Here we report the generation of a genome-scale library of endoribonuclease-prepared short interfering (esi)RNAs from a sequence-verified complementary DNA collection representing 15,497 human genes. We used 5,305 esiRNAs from this library to screen for genes required for cell division in HeLa cells. Using a primary high-throughput cell viability screen followed by a secondary high content videomicroscopy assay, we identified 37 genes required for cell division. These include several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown. Thus, our study uncovers new aspects of cell division and establishes esiRNA as a versatile approach for genomic RNAi screens in mammalian cells.     

Electrical and band-gap properties of amorphous zinc-indium-tin oxide thin films

Zinc-indium-tin oxide (ZITO) films were grown by pulsed-laser deposition.Three different material compositions were investigated:ZITO-30,ZITO-50 and ZITO-70 in which 30％,50％ and 70％,respectively,of the...     

Detection and imaging of atmospheric radio flashes from cosmic ray air showers

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.     

Forensics: age written in teeth by nuclear tests

Establishing the age at death of individuals is an important step in their identification and can be done with high precision up to adolescence by analysis of dentition, but it is more difficult in adults. Here we show that the amount of radiocarbon present in tooth enamel as a result of nuclear bomb testing during 1955-63 is a remarkably accurate indicator of when a person was born. Age is determined to within 1.6 years, whereas the commonly used morphological evaluation of skeletal remains and tooth wear is sensitive to within 5-10 years in adults.     

Electrical and band-gap properties of amorphous zinc–ind ium–tin oxide thin films

Zinc–indium–tin oxide (ZITO) films were grown by pulsed-laser deposition. Three different material compositions were investigated: ZITO-30, ZITO-50 and ZITO-70 in which 30%,50% and 70%, respectively, of the indium in the In2O3 structure was replaced by substitution with zinc and tin in equal molar proportions (co-substitution): In22xZnxSnxO3, where x=0.3, 0.5, 0.7. All ZITO films grown at room temperature were amorphous. The first evidence of crystallinity was observed at higher deposition-temperature as the degree of co-substitution was increased. A decrease in mobility and conductivity was also observed as the degree of co-substitution was increased. The highest mobility for ZITO-30 and ZITO-50 was observed at deposition temperatures just prior to crystallization. The effect of deposition temperature on carrier concentration was minor compared to the effect of oxygen partial pressure during deposition.     

A precision measurement of the mass of the top quark

The standard model of particle physics contains parameters--such as particle masses--whose origins are still unknown and which cannot be predicted, but whose values are constrained through their interactions. In particular, the masses of the top quark (M(t)) and W boson (M(W)) constrain the mass of the long-hypothesized, but thus far not observed, Higgs boson. A precise measurement of M(t) can therefore indicate where to look for the Higgs, and indeed whether the hypothesis of a standard model Higgs is consistent with experimental data. As top quarks are produced in pairs and decay in only about 10(-24) s into various final states, reconstructing their masses from their decay products is very challenging. Here we report a technique that extracts more information from each top-quark event and yields a greatly improved precision (of +/- 5.3 GeV/c2) when compared to previous measurements. When our new result is combined with our published measurement in a complementary decay mode and with the only other measurements available, the new world average for M(t) becomes 178.0 +/- 4.3 GeV/c2. As a result, the most likely Higgs mass increases from the experimentally excluded value of 96 to 117 GeV/c2, which is beyond current experimental sensitivity. The upper limit on the Higgs mass at the 95% confidence level is raised from 219 to 251 GeV/c2.     

Effect of splenectomy on the in-vitro migration inhibition response to sheep erythrocytes in the lizard,Calotes versicolor

Summary Splenectomy completely erased the PFC response to SRBC in lizards. In contrast, it has very little effect on the degree of MI to all doses ranging from 10⁴ to 10⁹, excepting the lowest dose, 10³ SRBC.Supported by PL-480 (NIH) research grant, No. 01-077.Grateful to Madurai University for the award of Studentship during the tenure of the work and to Dr P. W. Askenase for the gift of capillaries used in this study.