The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage

A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species. We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013. These duck viruses have genetic background distinct from the zoonotic H7N9 lineage. We found that the introduction of PB2 mutation with K at 627 but not K at 591 or N at 701 to the duck H7N9 virus led to increased pathogenicity in mice. We also found that the induction of pro-inflammatory cytokines including TNF-α, IP-10, MCP-1 and MIP-1α were associated with increased severity of infection. We conclude that introduction of the mammalian adaptation mutations into the PB2 gene of duck H7N9 viruses, which are genetically unrelated to the zoonotic H7N9 lineage, can also enhance pathogenicity in mice.published_or_final_versio

Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages.published_or_final_versio

The number of tree species on Earth

One of the most fundamental questions in ecology is how many species inhabit the Earth. However, due to massive logistical and financial challenges and taxonomic difficulties connected to the species concept definition, the global numbers of species, including those of important and well-studied life forms such as trees, still remain largely unknown. Here, based on global ground-sourced data, we estimate the total tree species richness at global, continental, and biome levels. Our results indicate that there are ∼73,000 tree species globally, among which ∼9,000 tree species are yet to be discovered. Roughly 40% of undiscovered tree species are in South America. Moreover, almost one-third of all tree species to be discovered may be rare, with very low populations and limited spatial distribution (likely in remote tropical lowlands and mountains). These findings highlight the vulnerability of global forest biodiversity to anthropogenic changes in land use and climate, which disproportionately threaten rare species and thus, global tree richness

Prevalence of respiratory function abnormalities in asymptomatic Chinese patients with juvenile onset systemic lupus erythematosus

Objectives: To determine the prevalence and features of respiratory function alterations in asymptomatic Chinese patients with juvenile onset systemic erythematosus (JSLE) and to assess its relationship with clinical and immunological parameters. Methods: Twenty-two Chinese patients with JSLE followed up at our Rheumatology Clinic were recruited. Each underwent pulmonary function test (PFT) and completed a respiratory questionnaire. Four were excluded because of past history of pulmonary disease. Abnormal respiratory function findings if present would be correlated with the disease duration, disease activity, organ involvement, clinical features and immunological findings using multiple regression analysis. Results: All 18 patients analysed were totally free of pulmonary symptoms and disease. Thirteen patients (72%) had abnormal PFT results. Ten patients (56%) had decreased diffusion capacity of the lung (DLCO). Among them, 2 had restrictive lung pattern and one had mixed pattern while 7 had isolated DLCO impairment. Disease duration and renal involvement were both found to be significantly associated with decreased DLCO (p=0.037 and p=0.035 respectively). However, both factors became insignificant after multiple regression analysis. Neurological lupus was significantly associated with decreased FEF 25-75% and FEF 75% (p value 0.03 and p<0.001 respectively). Conclusion: Asymptomatic Chinese patients with JSLE and no prior pulmonary involvement showed frequent PFT abnormalities with decreased DLCO being the most common impairment. Neurological involvement was the only factor found to be significantly associated with abnormal lung function parameters. We speculate that decreased DLCO could be related to high occurrence of SLE-associated pulmonary hypertension in Chinese. Further in-depth evaluation and long term follow up study is warranted.link_to_subscribed_fulltex

Amino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts

A novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells in vitro. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation

A multicenter phase II study of sorafenib, capecitabine, and oxaliplatin (SECOX) in patients with advanced hepatocellular carcinoma: final results of Hong Kong-Singapore Hepatocellular Carcinoma Research Collaborative Group study

Open Access JournalGeneral Poster Session - Gastrointestinal (Noncolorectal) Cancer: abstract no. 4117BACKGROUND: This is a single arm, multi-center, phase II study to assess the efficacy and tolerability of sorafenib, oxaliplatin and capecitabine combination for the treatment of advanced hepatocellular carcinoma (HCC) pat...link_to_OA_fulltex