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Avian influenza A (H5N6) has been found to infect humans, and has resulted in ten cases with six deaths in China since 2014. Here, we describe the systematic post-mortem pathology of a patient fatally infected with H5N6 virus and evaluate the associated pathogenesis compared with H1N1 pdm09 fatal cases. The most prominent histopathological features were diffuse alveolar damage and pulmonary vasculitis in the lungs of the patient. The virus disseminated to extrapulmonary organs, including the brain. Compared with H1N1 pdm09 fatal infection, H5N6 infection induced a more exacerbated immune response involving overt pulmonary inflammation, which led to alveolar damage and respiratory failure., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Sub-Angstrom transmission electron microscopy has been achieved at the National Center for Electron Microscopy (NCEM) by a one-Angstrom microscope (OAM) project using software and enhanced hardware developed within a Brite-Euram project (Ultramicroscopy 64 (1996) 1). The NCEM OAM provides materials scientists with transmission electron microscopy at a resolution better than 1 A by using extensive image reconstruction to exploit the significantly higher information limit of an FEG-TEM over its Scherzer resolution limit. Reconstruction methods chosen used off-axis holograms and focal series of underfocused images. Measured values of coherence parameters predict an information limit of 0.78 A. Images from a [1 1 0] diamond test specimen show that sub-Angstrom resolution of 0.89 A has been achieved with the OAM using focal series reconstruction.

Severe infection causes marked derangements in the flow of glutamine among organs, and these changes are accompanied by significant alterations in regional cell membrane transport and intracellular glutamine metabolism. Skeletal muscle, the major repository of glutamine, exhibits a twofold increase in glutamine release during infection, which is associated with a significant increase in endogenous glutamine biosynthesis. Despite an increase in glutamine synthetase activity in skeletal muscle, the intracellular glutamine pool becomes depleted, indicating that release rates exceed rates of synthesis. Simultaneously, the circulating pool of glutamine does not increase, indicating accelerated uptake by other organs. The liver appears to be the major organ of glutamine uptake in severe infection; studies in endotoxemic rodents have shown net hepatic glutamine uptake to increase by as much as 8- to 10-fold. This increase is due partially to increases in liver blood flow, but also to a three- to fourfold increase in hepatocyte System N activity in the liver. Cytokines and glucocorticoids mediate the increased uptake of glutamine by the liver in septic states as well as other compounds. Sepsis does not appear to induce an increase in System N gene expression, indicating that the increase in hepatic glutamine transport observed during severe infection is probably regulated at the protein level. The bowel displays a decrease in glutamine utilization during sepsis, a response that may be related to the decrease in circulating insulin-like growth factor-1 (IGF-1) levels that is characteristic of sepsis. Recent studies suggest that IGF-1 has a direct effect on stimulating glutamine transport across the gut lumen and thus may represent a therapeutic avenue for improving gut nutrition during severe infection. The cells of the immune system (lymphocytes, macrophages) are also major glutamine consumers during inflammatory states in which cell proliferation is increased. Under these conditions, glutamine availability can become rate limiting for key cell functions, such as phagocytosis and antibody production.

Nonprotein amino acids from nine species of cycad seeds were analyzed as N-ethoxycarbonyl ethyl ester (ECEE) derivatives by positive chemical-ionization gas chromatography-mass spectrometry. Based on the retention times and mass spectrometry analyses, 12 nonprotein amino acids were identified in these seeds. In addition to the excitatory and putative neurotoxin beta-N-methylamino-L-alanine (BMAA), the known neurotoxin beta-N-oxalylamino-L-alanine (BOAA) was detected from the seeds of Macrozamia moorei and M. communis, and delta-N-oxalyl-ornithine was obtained from the Cycas revoluta seeds. A novel nonprotein amino acid named cycasindene, previously reported from C. revoluta, was also found in the seeds of members of the C. angulata and C. rumphii complex. Eight additional known nonprotein amino acids were also identified. This is the first report of the neurotoxin BOAA from cycad seeds.

Two nonprotein amino acids, cycasindene and cycasthioamide, along with eight known nonprotein amino acids, were isolated from the seeds of Cycas revoluta Thunb. The structures of cycasindene and cycasthioamide were elucidated as 3-[3'-amino-indenyl-2]-alanine (1) and N-[glycinyl-alaninyl-11-thio]-5-one-pipecolic acid (2) by chemical and spectral methods.

The intestinal epithelium metabolism of glutamine plays a critical role in inter-organ nitrogen flow. Although it is known that glutamine is the primary oxidative energy source and nucleotide precursor in intestinal cells, the luminal uptake of glutamine by the apical surface of enterocytes is poorly understood. In this study we have uncovered the sodium-dependent transporter system responsible for L-glutamine uptake by the apical membrane of a human intestinal epithelial cell line. The sodium-dependent Michaelis constant (Km) = 247 +/- 45 microM glutamine, and Jmax = 4.44 +/- 0.65 x 10(-9) mole min-1(mg protein)-1 (37 degrees C). Glutamine shares the transporter with alanine, as demonstrated by unlabeled glutamine inhibition of [3H]alanine uptake kinetics with a purely competitive-type inhibition pattern, and glutamine inhibition Ki = 205 +/- 18 microM by Dixon analysis. The inhibition pattern for a series of amino acid analogs indicated that this intestinal apical membrane sodium-dependent transporter for glutamine is distinct from any other transport system found in membranes of non-intestinal cells.

Dyskeratosis congenita is a rare X-linked recessive disease, characterized by mucosal leukokeratosis, nail dystrophy, telangiectasia, reticulated hyperpigmentation, pancytopenia, and a heightened susceptibility to infection and malignancy. We exposed cultured fibroblasts and peripheral leukocytes from normal persons and from 2 unrelated young adult men with dyskeratosis congenita to 4,5',8-trimethylpsoralen and ultraviolet light. We than compared certain of their responses. Labeled DNA from fibroblasts exposed to 4,5',8-trimethylpsoralen and ultraviolet light showed fast-sedimenting DNA, a pattern we interpreted as evidence that cross-linking, psoralen-DNA photoadducts had been formed by the treatment. Fast-sedimenting DNA persisted for 24 hr in dyskeratosis congenita cells but disappeared from normal cells during a 24-hr repair period. Cultured peripheral blood leukocytes from persons with this syndrome similarly exposed to 4,5',8-trimethylpsoralen and ultraviolet light developed more sister chromatid exchanges than did cells from normal persons. These data suggest that a heightened susceptibility in DNA cross-links may be of fundamental importance in the etiology of dyskeratosis congenita.