Genomic epidemiology of Vibrio cholerae reveals the regional and global spread of two epidemic non-toxigenic lineages

Non-toxigenic Vibrio cholerae isolates have been found associated with diarrheal disease globally, however, the global picture of non-toxigenic infections is largely unknown. Among non-toxigenic V. cholerae, ctxAB negative, tcpA positive (CNTP) isolates have the highest risk of disease. From 2001 to 2012, 71 infectious diarrhea cases were reported in Hangzhou, China, caused by CNTP serogroup O1 isolates. We sequenced 119 V. cholerae genomes isolated from patients, carriers and the environment in Hangzhou between 2001 and 2012, and compared them with 850 publicly available global isolates. We found that CNTP isolates from Hangzhou belonged to two distinctive lineages, named L3b and L9. Both lineages caused disease over a long time period with usually mild or moderate clinical symptoms. Within Hangzhou, the spread route of the L3b lineage was apparently from rural to urban areas, with aquatic food products being the most likely medium. Both lineages had been previously reported as causing local endemic disease in Latin America, but here we show that global spread of them has occurred, with the most likely origin of L3b lineage being in Central Asia. The L3b lineage has spread to China on at least three occasions. Other spread events, including from China to Thailand and to Latin America were also observed. We fill the missing links in the global spread of the two non-toxigenic serogroup O1 V. cholerae lineages that can cause human infection. The results are important for the design of future disease control strategies: surveillance of V. cholerae should not be limited to ctxAB positive strains

Health diplomacy of the European Union and its member states in Central Asia. EL-CSID Policy Brief Issue 2018/5 • April 2018

In the soft power context, health is increasingly seen as an area that generates particular diplomatic benefits because it is ostensibly non-political and can bring both immediate and long-term advantages equally to the donor and the recipient country. Since the European Union’s role in the international affairs is increasing, the EU is expected to play a central role in global health guided by the principles of solidarity, i.e. to provide an equitable and universal access to quality health services. Some commentators point to a lack of coherence and coordination between EU health and other policies1. Also, ambiguities do exist about the scope of national and European competencies in the area of health policy2. The role of the smaller member states may be unusually significant as they "use the health arena to demonstrate their commitment to the multilateral systems that provide them with a voice and allow them a leading role on the global stage”3. Thus, health diplomacy offers an intriguing insight into the dynamics in the EU’s approaches to Central Asia, the region that is incrementally becoming of interest to Europe

Genome-Wide Identification and Expression Analysis of SnRK2 Gene Family in Dormant Vegetative Buds of Liriodendron chinense in Response to Abscisic Acid, Chilling, and Photoperiod

Protein kinases play an essential role in plants’ responses to environmental stress signals. SnRK2 (sucrose non-fermenting 1-related protein kinase 2) is a plant-specific protein kinase that plays a crucial role in abscisic acid and abiotic stress responses in some model plant species. In apple, corn, rice, pepper, grapevine, Arabidopsis thaliana, potato, and tomato, a genome-wide study of the SnRK2 protein family was performed earlier. The genome-wide comprehensive investigation was first revealed to categorize the SnRK2 genes in the Liriodendron chinense (L. chinense). The five SnRK2 genes found in the L. chinense genome were highlighted in this study. The structural gene variants, 3D structure, chromosomal distributions, motif analysis, phylogeny, subcellular localization, cis-regulatory elements, expression profiles in dormant buds, and photoperiod and chilling responses were all investigated in this research. The five SnRK2 genes from L. chinense were grouped into groups (I–IV) based on phylogeny analysis, with three being closely related to other species. Five hormones-, six stress-, two growths and biological process-, and two metabolic-related responsive elements were discovered by studying the cis-elements in the promoters. According to the expression analyses, all five genes were up- and down-regulated in response to abscisic acid (ABA), photoperiod, chilling, and chilling, as well as photoperiod treatments. Our findings gave insight into the SnRK2 family genes in L. chinense and opened up new study options

EGFR-mutated squamous cell lung cancer and its association with outcomes

Background: The therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy. Material and Methods: We consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI-treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed. Results: In total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS. Conclusions: EGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs

Second-Order Weight Distributions

A fundamental property of codes, the second-order weight distribution, is proposed to solve the problems such as computing second moments of weight distributions of linear code ensembles. A series of results, parallel to those for weight distributions, is established for second-order weight distributions. In particular, an analogue of MacWilliams identities is proved. The second-order weight distributions of regular LDPC code ensembles are then computed. As easy consequences, the second moments of weight distributions of regular LDPC code ensembles are obtained. Furthermore, the application of second-order weight distributions in random coding approach is discussed. The second-order weight distributions of the ensembles generated by a so-called 2-good random generator or parity-check matrix are computed, where a 2-good random matrix is a kind of generalization of the uniformly distributed random matrix over a finite filed and is very useful for solving problems that involve pairwise or triple-wise properties of sequences. It is shown that the 2-good property is reflected in the second-order weight distribution, which thus plays a fundamental role in some well-known problems in coding theory and combinatorics. An example of linear intersecting codes is finally provided to illustrate this fact.Comment: 10 pages, accepted for publication in IEEE Transactions on Information Theory, May 201

Global burden of colistin-resistant bacteria : mobilized colistin resistance genes study (1980-2018)

Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of mcr genes, their reservoirs and the potential pathways for human transmission are required to implement control and prevention strategies, yet such data are lacking. Publications from four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases published between 18 November 2015 and 30 December 2018 were identified. In this systematic review and meta-analysis, the prevalence of mcr genes in bacteria isolated from humans, animals, the environment and food products were investigated. A total of 974 publications were identified. 202 observational studies were included in the systematic review and 71 in the meta-analysis. mcr genes were reported from 47 countries across six continents and the overall average prevalence was 4.7% (0.1-9.3%). China reported the highest number of mcr-positive strains. Pathogenic Escherichia coli (54%), isolated from animals (52%) and harboring an IncI2 plasmid (34%) were the bacteria with highest prevalence of mcr genes. The estimated prevalence of mcr-1 pathogenic E. coli was higher in food-animals than in humans and food products, which suggests a role for foodborne transmission. This study provides a comprehensive assessment of prevalence of the mcr gene by source, organism, genotype and type of plasmid

Postfire Phosphorus Enrichment Mitigates Nitrogen Loss in Boreal Forests

Net nitrogen mineralization (Nmin) and nitrification regulate soil N availability and loss after severe wildfires in boreal forests experiencing slow vegetation recovery. Yet, how microorganisms respond to postfire phosphorus (P) enrichment to alter soil N transformations remains unclear in N-limited boreal forests. Here, we investigated postfire N-P interactions using an intensive regional-scale sampling of 17 boreal forests in the Greater Khingan Mountains (Inner Mongolia-China), a laboratory P-addition incubation, and a continental-scale meta-analysis. We found that postfire soils had an increased risk of N loss by accelerated Nmin and nitrification along with low plant N demand, especially during the early vegetation recovery period. The postfire N/P imbalance created by P enrichment acts as a "N retention" strategy by inhibiting Nmin but not nitrification in boreal forests. This strategy is attributed to enhanced microbial N-use efficiency and N immobilization. Importantly, our meta-analysis found that there was a greater risk of N loss in boreal forest soils after fires than in other climatic zones, which was consistent with our results from the 17 soils in the Greater Khingan Mountains. These findings demonstrate that postfire N-P interactions play an essential role in mitigating N limitation and maintaining nutrient balance in boreal forests