Emergence and development of H7N9 influenza viruses in China

The occurrence of human infections with avian H7N9 viruses since 2013 demonstrates the continuing pandemic threat posed by the current influenza ecosystem in China. Influenza surveillance and phylogenetic analyses showed that these viruses were generated by multiple interspecies transmissions and reassortments among the viruses resident in domestic ducks and the H9N2 viruses enzootic in chickens. A large population of domestic ducks hosting diverse influenza viruses provided the precondition for these events to occur, while acquiring internal genes from enzootic H9N2 influenza viruses in chickens promoted the spread of these viruses. Human infections effectively act as sentinels, reflecting the intensity of the activity of these viruses in poultry.postprin

Missing Lead and High 3He/4He in Ancient Sulfides Associated with Continental Crust Formation

Major terrestrial reservoirs have Pb isotopes more radiogenic than the bulk silicate Earth. This requires a missing unradiogenic Pb reservoir, which has been argued to reside in the lower continental crust or dissolved in the core. Chalcophile element studies indicate that continent formation requires the formation of sulfide-bearing mafic cumulates in arcs. Because Pb, but not U, partitions into sulfides, we show that continent formation must have simultaneously generated time-integrated unradiogenic Pb reservoirs composed of sulfide-bearing cumulates, now recycled back into the mantle or stored deep in the continental lithosphere. The generation of such cumulates could also lead to coupled He-Pb isotopic systematics because 4He is also produced during U-Th-Pb decay. Here, we show that He may be soluble in sulfide melts, such that sulfide-bearing cumulates would be enriched in both Pb and He relative to U and Th, “freezing” in He and Pb isotopes of the ambient mantle at the time of sulfide formation. This implies that ancient sulfide-bearing cumulates would be characterized by unradiogenic Pb and He isotopes (high-3He/4He). These primitive signatures are usually attributed to primordial, undifferentiated mantle, but in this case, they are the very imprint of mantle differentiation via continent formation

Application of large-scale sequencing and data analysis to research on emerging infectious diseases

Many human diseases are caused by emerging pathogens, such as the SARS and MERS coronaviruses. Timely understanding of the behaviors of these pathogens plays an important role in helping doctors and scientists in searching for treatment methods and designing vaccines. The development of next-generation sequencing (NGS) has led to significant breakthroughs in the production of large amount of unbiased DNA sequence data from field and human clinical samples, providing the capacity to identify the sources of infection, and the virus evolution as well as host/virus interaction. In our study, using 454/Illumina sequencing, we have obtained large amount of whole genome sequences. We designed a preliminary bioinformatics analysis pipeline to classify these NGS reads. First we mapped our nucleotide reads to GenBank reference sequences using BLAST, and classified them by their taxonomic family, such as host, virus and unclassified. Then, for a specific type of virus (e.g. influenza virus, MERS coronavirus), we conducted de novo and reference based assembly of the reads to obtain the full genome sequences for further phylogenetic study. In the future, through advanced bioinformatics tools, we hope to get more detailed information from our large amount of NGS sequences of field/clinical samples, experimental data, especially in the following areas: (i) finding novel pathogens in unclassified sequences; (ii) virus/virus interactions; (iii) pathogen/host interaction.published_or_final_versio

SWATH-MS Quantitative analysis of proteins in the rice inferior and superior spikelets during grain filling

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Evolution of influenza A(H7N9) viruses from waves I to IV

The H7N9 influenza virus that emerged in East China in early 2013 has caused 736 human infections with a fatality rate of 38.5%, through four outbreak waves. Our previous studies revealed that this virus was generated by reassortment between viruses from wild bird H7 and N9 viruses (surface genes) and poultry H9N2 viruses (internal genes), and that while the H7N9 wave I viruses had highly similar surface genes, the surface genes of the wave II viruses developed into regionally distinct clades. The H7N9 viruses continued to reassort with different H9N2 viruses to obtain internal gene segments, thereby generating multiple variants or genotypes. Our ongoing surveillance suggests that the H7N9 virus has become enzootic in chickens, and disseminated to most regions of China during waves III and IV of the outbreak. In this study, we have generated more than 800 H7N9 virus full genome sequences, and are analyzing these together with all genomes available in public databases. We are exploring the following scientific questions: (i) what is the continuing evolutionary behavior of the H7N9 virus lineage; (ii) what are the interactions or gene transfers between circulating H7N9 viruses and other enzootic influenza viruses, and the changes in genotypes over the four waves; (iii) what are the interactions among sub-lineages or clades, i.e. predominance and/or sub-lineage replacement; and (iv) what is the development and dissemination of the H7N9 viruses from a phylogeographic perspective. We hope that the information generated by this project will provide insights into methods to manage the development of the H7N9 outbreak and help to avert similar situations from arising.published_or_final_versio

Ocular fundus pathology and chronic kidney disease in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Previous study indicated a high prevalence of ocular fundus pathology among patients with chronic kidney disease (CKD), while the relationship between them has never been explored in a Chinese Population.</p> <p>Methods</p> <p>This cross-sectional study included 9 670 participants enrolled in a medical screening program. Ocular fundus examination was performed by ophthalmologists using ophthalmoscopes. The presence of eGFR less than 60 mL/min/1.73 m²and/or proteinuria was defined as CKD.</p> <p>Results</p> <p>Compared to participants without CKD, participants with CKD had higher prevalence of retinopathy (28.5% vs. 16.3%, P < 0.001), glaucoma suspect (3.1% vs. 1.8%, P = 0.004), age-related macular degeneration (1.7% vs. 0.9%, P = 0.01) and overall eye pathology (32.0% vs. 19.4%, P < 0.001). After adjusting for potential confounders, the odds ratio of proteinuria for overall eye pathology and retinopathy was 1.29 (95% confidence interval [CI] 1.07-1.55) and 1.37 (95% CI 1.12-1.67), respectively. The results were robust after excluding participants with hypertension or with diabetes.</p> <p>Conclusions</p> <p>Ocular fundus pathology is common among Chinese patients with CKD. Regular eye exam among persons with proteinuria is warranted.</p

The emergence of the 2013 H7N9 and related viruses in China

Promising Investigator ScholarshipPoster Session: News and Views from the H7N9 OutbreakBackground: The novel H7N9 influenza A virus first detected in March 2013 has caused more than 130 cases of human infection in China, resulting in 39 deaths. This virus is a reassortant of H7, N9 and H9N2 avian influenza viruses and carries some amino acids linked to mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully understood. Materials and Methods: Following the initial reports of H7N9 influenza infection in humans, field surveillance was conducted during 4th-18th April in Zhejiang, Shandong and Guangdong provinces. Pairs of oropharyngeal and cloacal samples from chickens and other poultry, together with faecal and water samples from live poultry markets (LPMs), farms and wetlands were collected for virus isolation and whole genomic sequencing. H7, N9, N7 and H9N2 archived isolates, obtained during previous influenza surveillance between 2000-2013 in southern China, were also sequenced and phylogenetically analyzed to pinpoint the genesis of the H7N9 and a related H7N7 virus. The infectivity and pathology of H7N9 and H7N7 viruses were tested in a ferret model. Results: Through a combination of active surveillance, screening of virus archives, and evolutionary analyses, we found that H7 viruses have independently transferred from domestic ducks to chickens in China on at least two occasions. Subsequently they reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related but previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at LPMs that appear to be the immediate source of human infections. In ferrets this virus caused a productive infection and pneumonia. Virus was shed via the nasal route and transmitted to physical contact and some airborne-exposed animals. Like the H7N9 virus, the H7N7 virus was also mainly isolated from chickens at LPMs and it could efficiently infect ferrets, be shed via the nasal and rectal routes, and cause severe pneumonia. Conclusions: These findings provide a clear picture showing how the current H7N9 human viruses emerged. Domestic ducks act as primary vectors to acquire and maintain diversified viruses from migratory birds, and facilitate different subtype combinations between H7 and N9 or N7 viruses and interspecies transmissions to chickens. After being introduced, the H7N9 or H7N7 viruses reassorted with enzootic H9N2 viruses and formed the current reassortant H7N9 or H7N7 viruses seen in chickens. This likely led to outbreaks in chickens, resulting in the rapid spread of the novel reassortant H7N9 virus through LPMs, which then became the source of human infections. Whether the H7N9 outbreak lineage will, or has, become enzootic in China needs further investigation. Our results also indicate that H7 viruses pose a broader threat than the current H7N9 virus. Continued prevalence of this family of H7 viruses in poultry could lead to further sporadic human infections, with an ongoing risk that the virus might acquire efficient human-to-human transmissibility.published_or_final_versio

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation