Frequency of influenza H3N2 intra-subtype reassortment: attributes and implications of reassortant spread

Background

Increasing evidence suggests that influenza reassortment not only contributes to the emergence of new human pandemics but also plays an important role in seasonal influenza epidemics, disease severity, evolution, and vaccine efficacy. We studied this process within 2091 H3N2 full genomes utilizing a combination of the latest reassortment detection tools and more conventional phylogenetic analyses.

Results

We found that the amount of H3N2 intra-subtype reassortment depended on the number of sampled genomes, occurred with a steady frequency of 3.35%, and was not affected by the geographical origins, evolutionary patterns, or previous reassortment history of the virus. We identified both single reassortant genomes and reassortant clades, each clade representing one reassortment event followed by successful spread of the reassorted variant in the human population. It was this spread that was mainly responsible for the observed high presence of H3N2 intra-subtype reassortant genomes. The successfully spread variants were generally sampled within one year of their formation, highlighting the risk of their rapid spread but also presenting an opportunity for their rapid detection. Simultaneous spread of several different reassortant lineages was observed, and despite their limited average lifetime, second and third generation reassortment was detected, as well as reassortment between viruses belonging to different vaccine-associated clades, likely displaying differing antigenic properties. Some of the spreading reassortants remained confined to certain geographical regions, while others, sharing common properties in amino acid positions of the HA, NA, and PB2 segments, were found throughout the world.

Conclusions

Detailed surveillance of seasonal influenza reassortment patterns and variant properties may provide unique information needed for prediction of spread and construction of future influenza vaccines.

     

Hepatic Deficiency of Augmenter of Liver Regeneration Exacerbates Alcohol-Induced Liver Injury and Promotes Fibrosis in Mice

Why only a subpopulation (about 15%) of humans develops liver cirrhosis due to alcohol is a critical as yet unanswered question. Liver-specific depletion of augmenter of liver regeneration (ALR) protein in mice causes robust steatosis and hepatocyte apoptosis by 2 weeks; these pathologies regress subsequently with return of ALR expression even at lower than control levels, but the mice develop modest steatohepatitis by 8 weeks. We aimed to investigate whether chronic alcohol ingestion promotes excessive hepatic fibrosis in these ALR-deficient mice. Liver-specific ALR-deficient and wild type (WT) female mice (8–10 weeks old) were placed on 4% alcohol-supplemented or isocaloric diet for 4 weeks. Liver sections were examined for histopathology, and parameters of steatosis and fibrosis were quantified. The mRNA expression of alcohol dehydrogenase-1, acetaldehyde dehydrogenase-1 and cytochrome P450-2E1 increased in WT mice but decreased in ALR-deficient mice upon alcohol ingestion. While alcohol induced steatosis and mild inflammation in WT mice, ALR-deficient mice showed minimal steatosis, strong hepatocellular injury and inflammation, prominent ductular proliferation, and robust fibrosis. Compared to the WT mice, alcohol feeding of ALR-deficient mice resulted in significantly greater increase in hepatic TNFα and TGFβ, and oxidative stress; there was also hepatic iron accumulation, robust lipid peroxidation and mitochondrial DNA damage. Importantly, similar to ALR-deficient mice, lower hepatic ALR levels in human alcoholic liver cirrhosis were associated with increased iron content, reduced expression of alcohol dehydrogenase and acetaldehyde dehydrogenase, and elevated fibrogenic markers. We conclude that ALR deficiency or anomaly can play a critical role in alcohol-induced hepatic fibrosis/cirrhosis, mechanisms of which may involve dysregulation of alcohol metabolism and iron homeostasis, mitochondrial damage and oxidative injury.     

Release of Aspartate and Glutamate Caused by Chloride Reduction in Synaptosomal Incubation Media

Release of the amino acid neurotransmitter candidates aspartate and glutamate from synaptosomes can be stimulated by reduction of [Cl-] in the incubation medium by replacement with the impermeant anions propionate and isethionate. Replacement by the permeant anion Br- is without effect on amino acid release. This release offers a biochemical method of studying the Cl-ion channel in CNS membrane.     

Computational Study of Plasmon Interaction in Organic Media: a Comparison Between Analytical and Numerical Model for Dimer

Plasmonics - In the present work, an investigation of wavelength-dependent absorption spectrum of spherical nanoparticles with different arrangements in organic medium using discrete dipole...     

ORIGINAL ARTICLE: Epithelioid hemangioendothelioma in the right auricle of an adult,male Rhesus macaque (Macaca mulatta)

Abstract Background A 9‐year‐old, male castrate, Rhesus macaque was euthanized following a prolonged history of chronic renal failure. Results Necropsy revealed a proliferative lesion within the right cardiac auricle composed of neoplastic epithelioid cells which infiltrated the myocardium and frequently exhibited intracytoplasmic luminae. Cells multifocally exhibited strong cytoplasmic immunoreactivity for Factor VIII‐related protein (von Willebrand’s factor). Conclusions The histological characteristics of this tumor are consistent with a diagnosis of epithelioid hemangioendothelioma, an intermediate‐grade vasoformative neoplasm which has to our knowledge not previously been reported in the heart of a non‐human species.     

Impact of throughfall deposition and its runoff through different land use surfaces on the chemistry of Ganga water,Varanasi

Limnology - The study was conducted to understand the influence of interactions of atmospheric deposition with different land use surfaces and change in water chemistry of river Ganga through...     

Improved BLAST searches using longer words for protein seeding

MOTIVATION: The blastp and tblastn modules of BLAST are widely used methods for searching protein queries against protein and nucleotide databases, respectively. One heuristic used in BLAST is to consider only database sequences that contain a high-scoring match of length at most 5 to the query. We implemented the capability to use words of length 6 or 7. We demonstrate an improved trade-off between running time and retrieval accuracy, controlled by the score threshold used for short word matches. For example, the running time can be reduced by 20-30% while achieving ROC (receiver operator characteristic) scores similar to those obtained with current default parameters. AVAILABILITY: The option to use long words is in the NCBI C and C++ toolkit code for BLAST, starting with version 2.2.16 of blastall. A Linux executable used to produce the results herein is available at: ftp://ftp.ncbi.nlm.nih.gov/pub/agarwala/protein_longwords