Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy.

Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness. We have identified 15 different missense mutations resulting in 14 different amino acid changes. The missense mutations in ACTA1 are distributed throughout all six coding exons, and some involve known functional domains of actin. Approximately half of the patients died within their first year, but two female patients have survived into their thirties and have children. We identified dominant mutations in all but 1 of 14 families, with the missense mutations being single and heterozygous. The only family showing dominant inheritance comprised a 33-year-old affected mother and her two affected and two unaffected children. In another family, the clinically unaffected father is a somatic mosaic for the mutation seen in both of his affected children. We identified recessive mutations in one family in which the two affected siblings had heterozygous mutations in two different exons, one paternally and the other maternally inherited. We also identified de novo mutations in seven sporadic probands for which it was possible to analyse parental DNA.     

The chicken B locus is a minimal essential major histocompatibility complex.

Here we report the sequence of the region that determines rapid allograft rejection in chickens, the chicken major histocompatibility complex (MHC). This 92-kilobase region of the B locus contains only 19 genes, making the chicken MHC roughly 20-fold smaller than the human MHC. Virtually all the genes have counterparts in the human MHC, defining a minimal essential set of MHC genes conserved over 200 million years of divergence between birds and mammals. They are organized differently, with the class III region genes located outside the class II and class I region genes. The absence of proteasome genes is unexpected and might explain unusual peptide-binding specificities of chicken class I molecules. The presence of putative natural killer receptor gene(s) is unprecedented and might explain the importance of the B locus in the response to the herpes virus responsible for Marek's diseases. The small size and simplicity of the chicken MHC allows co-evolution of genes as haplotypes over considerable periods of time, and makes it possible to study the striking MHC-determined pathogen-specific disease resistance at the molecular level.     

Quantum teleportation between light and matter

Quantum teleportation is an important ingredient in distributed quantum networks, and can also serve as an elementary operation in quantum computers. Teleportation was first demonstrated as a transfer of a quantum state of light onto another light beam; later developments used optical relays and demonstrated entanglement swapping for continuous variables. The teleportation of a quantum state between two single material particles (trapped ions) has now also been achieved. Here we demonstrate teleportation between objects of a different nature--light and matter, which respectively represent 'flying' and 'stationary' media. A quantum state encoded in a light pulse is teleported onto a macroscopic object (an atomic ensemble containing 10 caesium atoms). Deterministic teleportation is achieved for sets of coherent states with mean photon number (n) up to a few hundred. The fidelities are 0.58 +/- 0.02 for n = 20 and 0.60 +/- 0.02 for n = 5--higher than any classical state transfer can possibly achieve. Besides being of fundamental interest, teleportation using a macroscopic atomic ensemble is relevant for the practical implementation of a quantum repeater. An important factor for the implementation of quantum networks is the teleportation distance between transmitter and receiver; this is 0.5 metres in the present experiment. As our experiment uses propagating light to achieve the entanglement of light and atoms required for teleportation, the present approach should be scalable to longer distances.     

Labelling of insect spermatozoa by adenine-8-14C

Résumé La technique de marquage avec de l'adénine-8-¹⁴C des spermatozoïdes mûres du coléoptèrePtinus hirtellus et deDrosophila melanogaster est décrite. L'isotope était administré par injection dans les larves dePtinus et par bouche dans celles deDrosophila.

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Research Worker of the British Empire Cancer Campaign.     

Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility

Ath1 is a quantitative trait locus on mouse chromosome 1 that renders C57BL/6 mice susceptible and C3H/He mice resistant to diet-induced atherosclerosis. The quantitative trait locus region encompasses 11 known genes, including Tnfsf4 (also called Ox40l or Cd134l), which encodes OX40 ligand. Here we report that mice with targeted mutations of Tnfsf4 had significantly (P 相似文献   

A comprehensive linkage analysis for myocardial infarction and its related risk factors

Coronary artery disease and myocardial infarction (MI) are leading causes of death in the western world. Numerous studies have shown that risk factors such as diabetes mellitus, arterial hypertension and hypercholesterolemia contribute to the development of the disease. Although each risk factor by itself is partly under genetic control, a positive family history is an independent predictor, which suggests that there are additional susceptibility genes. We have scanned the whole genome in 513 families to identify chromosomal regions linked to myocardial infarction and related risk factors that are known to be under genetic control. Here we show, by using variance component analysis and incorporating risk factors, that risk of myocardial infarction maps to a single region on chromosome 14 with a significant lod score of 3.9 (pointwise P=0.00015, genome-wide P<0.05), providing evidence of a principal MI locus. To characterize this locus we analyzed each risk factor by itself. Serum concentrations of lipoprotein (a) show linkage to both the apolipoprotein (a) locus (lod score 26.99) and a new locus on chromosome 1 (lod score 3.8). There is suggestive linkage for diabetes mellitus on chromosome 6 (lod score 2.96), for hypertension on chromosomes 1 and 6, for high-density and low-density lipoprotein cholesterol on chromosomes 1 and 17, and for triglyceride concentrations on chromosome 9. Although some of these risk factors overlap with previously identified loci, none overlaps with the newly identified susceptibility locus for myocardial infarction and coronary artery disease.     

Effect of testosterone propionate on the urogenital organs of immature crocodileCrocodylus palustris lesson

Zusammenfassung Nicht geschlechtsreifen, zweijährigen Krokodilen aus gleicher Brut wurden je 25 mg (Gesamtdosis) Testosteronpropionat verabreicht. Sektionsbefund 7 Tage nach der letzten Injektion: Spermatogenese und entwickelte Spermien, Rückbildung des interstitiellen Gewebes. Penis und Klitoris hypertrophisch. Nierenvergrösserung, Ovarien und Müllersche Gänge unverändert. Kontrollen ohne Spermatogenese, jedoch mit Vermehrung der Leydigschen Zellen.

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Investigation made possible from a grant from the Ford Foundation, New Delhi.     

Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage

Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are members of the phosphoinositide-3-kinase-related protein kinase (PIKK) family, and are rapidly activated in response to DNA damage. ATM and DNA-PKcs respond mainly to DNA double-strand breaks, whereas ATR is activated by single-stranded DNA and stalled DNA replication forks. In all cases, activation involves their recruitment to the sites of damage. Here we identify related, conserved carboxy-terminal motifs in human Nbs1, ATRIP and Ku80 proteins that are required for their interaction with ATM, ATR and DNA-PKcs, respectively. These motifs are essential not only for efficient recruitment of ATM, ATR and DNA-PKcs to sites of damage, but are also critical for ATM-, ATR- and DNA-PKcs-mediated signalling events that trigger cell cycle checkpoints and DNA repair. Our findings reveal that recruitment of these PIKKs to DNA lesions occurs by common mechanisms through an evolutionarily conserved motif, and provide direct evidence that PIKK recruitment is required for PIKK-dependent DNA-damage signalling.