An SCN9A channelopathy causes congenital inability to experience pain

The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit.     

Immunogenicity of formaldehyde and binary ethylenimine inactivated infectious bursal disease virus in broiler chicks

Infectious bursal disease virus (IBDV) was inactivated by two different chemicals—formaldehyde and binary ethylenimine (BEI). Formaldehyde was used at 0.1% and 0.2%, while BEI was used at concentrations of 0.001 and 0.002 mol/L. These four vaccines were tested for their efficiency in generating humoral immune response in different groups of broiler chicks. Both BEI-inactivated vaccines gave relatively higher antibody titers and were almost twice as efficient as formaldehyde-inactivated ones.     

Skeletons of terrestrial cetaceans and the relationship of whales to artiodactyls

Modern members of the mammalian order Cetacea (whales, dolphins and porpoises) are obligate aquatic swimmers that are highly distinctive in morphology, lacking hair and hind limbs, and having flippers, flukes, and a streamlined body. Eocene fossils document much of cetaceans' land-to-water transition, but, until now, the most primitive representative for which a skeleton was known was clearly amphibious and lived in coastal environments. Here we report on the skeletons of two early Eocene pakicetid cetaceans, the fox-sized Ichthyolestes pinfoldi, and the wolf-sized Pakicetus attocki. Their skeletons also elucidate the relationships of cetaceans to other mammals. Morphological cladistic analyses have shown cetaceans to be most closely related to one or more mesonychians, a group of extinct, archaic ungulates, but molecular analyses have indicated that they are the sister group to hippopotamids. Our cladistic analysis indicates that cetaceans are more closely related to artiodactyls than to any mesonychian. Cetaceans are not the sister group to (any) mesonychians, nor to hippopotamids. Our analysis stops short of identifying any particular artiodactyl family as the cetacean sister group and supports monophyly of artiodactyls.     

A data-mining approach to biomarker identification from protein profiles using discrete stationary wavelet transform

Objective： To develop a new bioinformatic tool based on a data-mining approach for extraction of the most informative proteins that could be used to find the potential biomarkers for the detection of cancer. Methods： Two independent datasets from serum samples of 253 ovarian cancer and 167 breast cancer patients were used. The samples were examined by surfaceenhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF MS）. The datasets were used to extract the informative proteins using a data-mining method in the discrete stationary wavelet transform domain. As a dimensionality reduction procedure, the hard thresholding method was applied to reduce the number of wavelet coefficients. Also, a distance measure was used to select the most discriminative coefficients. To find the potential biomarkers using the selected wavelet coefficients, we applied the inverse discrete stationary wavelet transform combined with a two-sided t-test. Results： From the ovarian cancer dataset, a set of five proteins were detected as potential biomarkers that could be used to identify the cancer patients from the healthy cases with accuracy, sensitivity, and specificity of 100%. Also, from the breast cancer dataset, a set of eight proteins were found as the potential biomarkers that could separate the healthy cases from the cancer patients with accuracy of 98.26%, sensitivity of 100%, and specificity of 95.6%. Conclusion： The results have shown that the new bioinformatic tool can be used in combination with the high-throughput proteomic data such as SELDI-TOF MS to find the potential biomarkers with high discriminative power.     

Analysis of Co3O4 /Mildly Oxidized Graphite Oxide (mGO) Nanocomposites of Mild Oxidation Degree for the Removal of Acid Orange 7

In this study,a series of Co_3O_4/ mildly oxidized graphite oxide(mGO) nanocatalysts(Co_3O_4/ mGO-l,Co_3O_4/ mGO-2 and Co_3O_4/mGO-3) were synthesized through solvothermal method and used as a mediator for the heterogeneous peroxymonosulfate(PMS)activation.The performance of CO_3O_4 / mGO/PMS system was investigated using acid orange 7(AO7).Results showed that Co_3O_4/mGO-3 had the best degradation efficiency of AO7 and the removal rate was above 90%in about 6 min.The phenomenon indicated the catalytic activity of Co_3O_4/mGO composites was related to the oxidation degree of graphite oxide(GO).In addition,experiments showed the content of Co_3O_4 had an effect on the catalytic activity.The composites were characterized with X-ray powder diffraction(XRD),FTIR,Raman,X-ray photoelectron spectroscopy(XPS) and transmission electron microscopy(TEM).According to the charactrization and synergistic catalytic mechanism,the generation of Co—OH complexes found to be the initial step to activate PMS in the heterogeneous system of Co_3O_4/mGO hybrid.     

A central role for calcineurin in protein misfolding neurodegenerative diseases

Accumulation of misfolded/unfolded aggregated proteins in the brain is a hallmark of many neurodegenerative diseases affecting humans and animals. Dysregulation of calcium (Ca²⁺) and disruption of fast axonal transport (FAT) are early pathological events that lead to loss of synaptic integrity and axonal degeneration in early stages of neurodegenerative diseases. Dysregulated Ca²⁺ in the brain is triggered by accumulation of misfolded/unfolded aggregated proteins in the endoplasmic reticulum (ER), a major Ca²⁺ storing organelle, ultimately leading to neuronal dysfunction and apoptosis. Calcineurin (CaN), a Ca²⁺/calmodulin-dependent serine/threonine phosphatase, has been implicated in T cells activation through the induction of nuclear factor of activated T cells (NFAT). In addition to the involvement of several other signaling cascades, CaN has been shown to play a role in early synaptic dysfunction and neuronal death. Therefore, inhibiting hyperactivated CaN in early stages of disease might be a promising therapeutic strategy for treating patients with protein misfolding diseases. In this review, we briefly summarize the structure of CaN, inhibition mechanisms by which immunosuppressants inhibit CaN, role of CaN in maintaining neuronal and synaptic integrity and homeostasis and the role played by CaN in protein unfolding/misfolding neurodegenerative diseases.     

Effect of oxygen content on the structural and optical properties of ZnO films grown by atmospheric pressure MOCVD

Atmospheric pressure MOCVD was used to deposit ZnO layers on sapphire and homoepitaxial template under different oxygen flow rates.Oxygen content affects the lattice constant value and texture coefficient of the films as evidenced by the θ-2θ peaks position and their intensity.Films deposited at lower oxygen flow rate possess higher value of strain and stresses.ZnO films deposited at high oxygen flow rates show intense UV emissions while samples prepared under oxygen deficient conditions exhibited defect related emission along with UV luminescence.The results are compared to the ZnO films deposited homoepitaxially on annealed ZnO samples.The data obtained suggest that ZnO stoichiometry is responsible for the structural and optical quality of ZnO films.