Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

Summary The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were supporessed with sublethal to acutely lethal dosages (20, 30 and 40 g/kg, s.c.) during the acute excitatory phase of intoxication and at 6–8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 g/kg soman whereas there was a protracted increase with 30 g/kg. Corticosterone was not significantly elevated with 40 g/kg, but death occurred at 13±4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.Supported by US Army Medical Research and Development Command Contract DAMD 17-81-C-1202.     

A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron

Molecular self-assembly offers a means of spontaneously forming complex and well-defined structures from simple components. The specific bonding between DNA base pairs has been used in this way to create DNA-based nanostructures and to direct the assembly of material on the subnanometre to micrometre scale. In principle, large-scale clonal production of suitable DNA sequences and the directed evolution of sequence lineages towards optimized behaviour can be realized through exponential DNA amplification by polymerases. But known examples of three-dimensional geometric DNA objects are not amenable to cloning because they contain topologies that prevent copying by polymerases. Here we report the design and synthesis of a 1,669-nucleotide, single-stranded DNA molecule that is readily amplified by polymerases and that, in the presence of five 40-mer synthetic oligodeoxynucleotides, folds into an octahedron structure by a simple denaturation-renaturation procedure. We use cryo-electron microscopy to show that the DNA strands fold successfully, with 12 struts or edges joined at six four-way junctions to form hollow octahedra approximately 22 nanometres in diameter. Because the base-pair sequence of individual struts is not repeated in a given octahedron, each strut is uniquely addressable by the appropriate sequence-specific DNA binder.     

New fossil elaterid (Coleoptera: Polyphaga: Elateridae) from Yixian Formation of western Liaoning, China

A new species of the elaterid genus Cryptocoelus Dolin and Nel, 2002 from the Late Jurassic to Early Cretaceous Yixian Formation in the western Liaoning, China is described. Diagnosis of the genus is revised, and the systematic position of the genus is briefly discussed. Because the elaterids originated in the Early to Mid-Jurassic, this new material from the Late Jurassic-Early Cretaceous will enhance our understanding of the transition between ancient elaterids and extant ones, bridge the gap of cryptic relationships between the Mesozoic cupedids and elaterids, and expand our knowledge of their evolutionary history.     

The ras oncogene product p21 is not a regulatory component of adenylate cyclase

Harvey (Ha-MSV) and Kirsten (Ki-MSV) murine sarcoma viruses induce tumours in animals and transform various cells in culture because of the expression of the ras oncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily and activated ras oncogenes have been detected in many human cancers. Whether c-ras oncogenes are directly responsible for human carcinogenesis is uncertain; however, it is clear that p21 mediates virus-induced transformation, although by an unknown mechanism. Epithelial and fibroblast cell lines transformed with Ha-MSV and Ki-MSV express p21 (ref. 8) and exhibit reduced adenylate cyclase activity. Like the guanine nucleotide regulatory proteins, Ns and Ni, which mediate stimulation and inhibition, respectively, of adenylate cyclase, p21 is a membrane-associated GTP binding protein, which exhibits GTPase activity. These similarities suggest that p21 and the adenylate cyclase regulatory proteins are related in cellular function, and that p21 depresses adenylate cyclase by inhibiting the activity of Ns or acting as Ni. We have therefore now examined the structural and functional similarities between p21 and Ns and Ni and find no evidence that p21 regulates adenylate cyclase activity by acting as one of these regulatory proteins.     

Clonal selection drives genetic divergence of metastatic medulloblastoma

Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.     

Torsional Models of Two - ply Yarn

In this paper,the vector equation of a generaliseddoubly wound helix was derived.Treloar's pliedyarn geometry could be obtained as a special case ofthe generalised doubly wound helix.The shortest fi-bre length around the surface of a helical tube(formed by fibre helices)was determined by apply-ing variational principles.The fibre length as calcu-lated by using Treloar's geometry was compared in-directly with the shortest possible fibre length at dif-ferent levels of yarn deformation when some of Tre-loar's rigid geometrical constraints were relaxed.Anew idea based on non-concentric circles was intro-duced to approximate the fibre helix movement in atwo-ply yarn.A torsional model of two-ply yarnwas developed and the theoretical predictions werecompared with some preliminary experimental re-sults.     

Inactivation of the p53 pathway in retinoblastoma

Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.     

Investigation of newly developed added damping and stiffness device with low yield strength steel

Energy dissipators, isolated-resistant and specific structural forms for earthquake resistance are popular topics in the research to improve shock-resistance. In this work, experimental methods were used to investigate the property of low yield strength steel. Carbon content in LYS material is lower than that in other steels; the ultimate stress is three times the yield stress. The ultimate elongation rate is about 62% and the ductility is 2-3 times that of A36 steel. In order to overcome some defects of ordinary use metallic dampers, the mechanical characteristic of low yield strength steel is used to develop added damping and stiffness for rhombic steel plate absorber. Test of the energy dissipation behavior for this newly developed device indicated that LYS could stably dissipate or absorb the input energy of earthquake. Then, the analytical model for the hysteretic behavior of this new device is proposed. Comparison of experimental data and numerical simulation results showed that this analytical model is suitable for simulating the hysteretic energy behavior of this new device.     

New fossil elaterid (Coleoptera: Polyphaga: Elateridae) from Yixian Formation of western Liaoning, China

A new species of the elaterid genus Cryptocoelus Dolin and Nel, 2002 from the Late Jurassic to Early Cretaceous Yixian Formation in the western Liaoning, China is described. Diagnosis of the genus is revised, and the systematic position of the genus is briefly discussed. Because the elaterids originated in the Early to Mid-Jurassic, this new material from the Late Jurassic-Early Cretaceous will enhance our understanding of the transition between ancient elaterids and extant ones, bridge the gap of cryptic relationships between the Mesozoic cupedids and elaterids, and expand our knowledge of their evolutionary history.     

A pigment-binding protein essential for regulation of photosynthetic light harvesting

Photosynthetic light harvesting in plants is regulated in response to changes in incident light intensity. Absorption of light that exceeds a plant's capacity for fixation of CO2 results in thermal dissipation of excitation energy in the pigment antenna of photosystem II by a poorly understood mechanism. This regulatory process, termed nonphotochemical quenching, maintains the balance between dissipation and utilization of light energy to minimize generation of oxidizing molecules, thereby protecting the plant against photo-oxidative damage. To identify specific proteins that are involved in nonphotochemical quenching, we have isolated mutants of Arabidopsis thaliana that cannot dissipate excess absorbed light energy. Here we show that the gene encoding PsbS, an intrinsic chlorophyll-binding protein of photosystem II, is necessary for nonphotochemical quenching but not for efficient light harvesting and photosynthesis. These results indicate that PsbS may be the site for nonphotochemical quenching, a finding that has implications for the functional evolution of pigment-binding proteins.