Quantitative Yeast Genetic Interaction Profiling of Bacterial Effector Proteins Uncovers a Role for the Human Retromer in Salmonella Infection.

Intracellular bacterial pathogens secrete a repertoire of effector proteins into host cells that are required to hijack cellular pathways and cause disease. Despite decades of research, the molecular functions of most bacterial effectors remain unclear. To address this gap, we generated quantitative genetic interaction profiles between 36 validated and putative effectors from three evolutionarily divergent human bacterial pathogens and 4,190 yeast deletion strains. Correlating effector-generated profiles with those of yeast mutants, we recapitulated known biology for several effectors with remarkable specificity and predicted previously unknown functions for others. Biochemical and functional validation in human cells revealed a role for an uncharacterized component of the Salmonella SPI-2 translocon, SseC, in regulating maintenance of the Salmonella vacuole through interactions with components of the host retromer complex. These results exhibit the power of genetic interaction profiling to discover and dissect complex biology at the host-pathogen interface.

Management of recurrent pancreatic cancer after surgical resection: a protocol for systematic review, evidence mapping and meta-analysis.

INTRODUCTION: Although recurrence rate among cases of resected pancreatic cancer are as high as 85%, an optimal treatment for recurrent pancreatic cancer (RePC) has not been established. Previous evidence regarding RePC is scarce, and randomised controlled trials (RCTs) are particularly lacking. The evidence mapping (EM) method has been introduced as a tool intended to complement the conventional systematic review (SR) and meta-analysis (MA) and is suitable for this issue. This review aims to investigate the optimal treatment options for RePC, using a newly developed automatic EM tool. METHOD AND ANALYSIS: All study types, including RCTs, non-randomised studies and other forms of observational studies will be included in the SR-EM. The Medline, Embase, Cochrane library and Scopus databases will be searched for reports of five treatment options for local and metastatic recurrences, including re-resection, chemotherapy, radiotherapy, best supportive care and other novel treatments, published from database inception to 30 April 2017. References from relevant studies will be searched manually. If meta-analysis is feasible, the primary outcome measure will be median overall survival. Two independent authors will select the studies and assess the risk of bias, and a third author will resolve discrepancies in consensus meeting. To visualise EM, we will use a novel web-based and open-access mapping programme, Plotting E-Map (PLOEM) (http://plotting-e-map.com). If eligible combinations of interventions for quantitative comparison are identified, we will conduct subgroup MAs using random-effect models and I2 statistics. Publication bias will be visualised using funnel plots. ETHICS AND DISSEMINATION: This study will not use primary data, and therefore formal ethical approval is not required. The findings will be disseminated through peer-reviewed journals and committee conferences. PROSPEROREGISTRATION NUMBER: CRD42016049178.

Systematic Gene-to-Phenotype Arrays: A High-Throughput Technique for Molecular Phenotyping.

We have developed a highly parallel strategy, systematic gene-to-phenotype arrays (SGPAs), to comprehensively map the genetic landscape driving molecular phenotypes of interest. By this approach, a complete yeast genetic mutant array is crossed with fluorescent reporters and imaged on membranes at high density and contrast. Importantly, SGPA enables quantification of phenotypes that are not readily detectable in ordinary genetic analysis of cell fitness. We benchmark SGPA by examining two fundamental biological phenotypes: first, we explore glucose repression, in which SGPA identifies a requirement for the Mediator complex and a role for the CDK8/kinase module in regulating transcription. Second, we examine selective protein quality control, in which SGPA identifies most known quality control factors along with U34 tRNA modification, which acts independently of proteasomal degradation to limit misfolded protein production. Integration of SGPA with other fluorescent readouts will enable genetic dissection of a wide range of biological pathways and conditions.

Genetic interaction analysis of point mutations enables interrogation of gene function at a residue-level resolution: exploring the applications of high-resolution genetic interaction mapping of point mutations.

We have achieved a residue-level resolution of genetic interaction mapping - a technique that measures how the function of one gene is affected by the alteration of a second gene - by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post-translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high-throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure-function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine.

Distribution of schistosome infected snails in Anhui Province / 中国血吸虫病防治杂志

Objective To understand the current distribution of infected snails in Anhui Province.Methods The data of snail survey were collected,the database was set up and the position of environments of infected snails were determined with GPS,the E-map was established with ArcGis 9.1 and the distribution of infected snail was analyzed.Results In 2007,331 environments with infected snails were found in Anhui Province,and 62.5% of them were found in the lake regions and 37.5% in the mountainous areas.The infected snail habitat areas were 682.6 hm2,85.5% of them were distributed in the lake regions and 14.5% in the mountainous areas.The river beach and the canal were the main environments with infected snails in the lake regions and mountainous areas,respectively;and 97.2% of the environments with infected snail were distributed in the infection-uncontrolled villages or villages which reached the criteria of infection control of schistosomiasis.Grassland was the main vegetation with infected snails,and the second was the reeds and trees.Conclusions The current endemic situation of the infection-uncontrolled villages or villages which reached the criteria of infection control of schistosomiasis is severe and should be emphasized for schistosomiasis prevention and control.The distribution of infected snail is connected with the river system.In the lake regions,the infected snails are distributed over the bottomlands of the Yangtze River and tributaries and islets and lakes;in the mountainous areas,the infected snails are distributed in the rivers banks and irrigated areas or special environments.