Exploring 5-nitrofuran derivatives against nosocomial pathogens: Synthesis,antimicrobial activity and chemometric analysis

The burden of nosocomial or health care-associated infection (HCAI) is increasing worldwide. According to the World Health Organization (WHO), it is several fold higher in low- and middle-income countries. Considering the multidrug-resistant infections, the development of new and more effective drugs is crucial. Herein, two series (I and II) of 5-nitrofuran derivatives were designed, synthesized and assayed against microorganisms, including Gram-positive and -negative bacteria, and fungi. The pathogens screened was directly related to either the most currently relevant HCAI, or to multidrug-resistant infection caused by MRSA/VRSA strains, for instance. The sets I and II were composed by substituted-[N′-(5-nitrofuran-2-yl)methylene]benzhydrazide and 3-acetyl-5-(substituted-phenyl)-2-(5-nitro-furan-2-yl)-2,3-dihydro-1,3,4-oxadiazole compounds, respectively. The selection of the substituent groups was based upon physicochemical properties, such as hydrophobicity and electronic effect. The compounds have showed better activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. The findings from S. aureus strain, which was more susceptible, were used to investigate the intersamples and intervariables relationships by applying chemometric methods. It is noteworthy that the compound 4-butyl-[N′-(5-nitrofuran-2-yl)methylene]benzhydrazide has showed similar MIC value to vancomycin, which is the reference drug for multidrug-resistant S. aureus infections. Taken the findings together, the 5-nitrofuran derivatives might be indeed considered as promising hits to develop novel antimicrobial drugs to fight against nosocomial infection.     

西部干旱区煤炭开采环境影响研究

大规模煤炭资源开采与干旱脆弱生态环境的空间耦合将会诱发日益严峻的社会、环境问题。分析了我国西部干旱区煤炭地下开采对植被、土壤水、地下水、土壤等关键环境要素影响的研究进展与不足;指出现有研究主要以单一环境要素、局部尺度为主,缺乏多尺度综合的环境要素协同损伤规律与井上下联动响应机理等基础研究。因此,现有成果还无法满足指导煤炭开采技术改进与控制环境损伤的需要。建议从井下到井上,从工作面、矿井、矿区、流域多尺度综合实现地空一体化同步监测,加强对西部干旱矿区各关键环境要素的协同损伤规律研究;加强对井上下环境要素对开采地质条件响应机理研究;建立不同开采条件、不同评价尺度下,矿区开采环境损伤的评价与预测模型。     

山西省医疗机构服务能力分析与评估系统开发与应用

介绍了山西省医疗机构服务能力分析与评估系统开发的必要性,描述了具体的系统设计方案、运行流程、分析方法及应用情况。通过该系统的应用,及时收集全省二级以上医疗机构病案首页数据、门诊患者的诊疗数据与医疗机构经济运行数据,及时分析评估医疗机构的医疗技术服务能力、医疗质量、管理水平、患者费用负担、经济运行状况以及影响全省人群的主要疾病等指标,为卫生行政部门实施医疗卫生体制改革、医疗机构日常监管、全省范围内疾病防控等提供数据支持。     

基于MIMIC数据库的多参数数据D/A回放系统

文中分析了MIMIC多参数智能监护数据库存储文件的识读方法,该数据库公开发表于PhysioNET,还研究及基于STM32和DAC8568的多参数数据D/A回放系统,包括系统硬件工作原理和系统软件工作原理。MIMIC多参数智能监护数据库的数据文件对于变异性较大的生理参数采用连续采样的方式,而对于相对稳定的生理参数采用周期采样的方式,因此,多参数数据各信号的抽样频率不同。系统首先通过VC++编程读取一个多抽样频率数据并在PC机上显示其波形,然后经过D/A硬件设备进行D/A转换后使用示波器输出其波形,实现输出的波形与原始的波形能同时回放。系统可作为模拟信号源,为远程多参数生理监护仪的研制奠定了基础。     

Register-based predictors of violations of animal welfare legislation in dairy herds

The assessment of animal welfare can include resource-based or animal-based measures. Official animal welfare inspections in Denmark primarily control compliance with animal welfare legislation based on resource measures (e.g. housing system) and usually do not regard animal response parameters (e.g. clinical and behavioural observations). Herds selected for welfare inspections are sampled by a risk-based strategy based on existing register data. The aim of the present study was to evaluate register data variables as predictors of dairy herds with violations of the animal welfare legislation (VoAWL) defined as occurrence of at least one of the two most frequently violated measures found at recent inspections in Denmark, namely (a) presence of injured animals not separated from the rest of the group and/or (b) animals in a condition warranting euthanasia still being present in the herd. A total of 25 variables were extracted from the Danish Cattle Database and assessed as predictors using a multivariable logistic analysis of a data set including 73 Danish dairy herds, which all had more than 100 cows and cubicle loose-housing systems. Univariable screening was used to identify variables associated with VoAWL at a P-value<0.2 for the inclusion in a multivariable logistic regression analysis. Backward selection procedures identified the following variables for the final model predictive of VoAWL: increasing standard deviation of milk yield for first lactation cows, high bulk tank somatic cell count (⩾250 000 cells/ml) and suspiciously low number of recorded veterinary treatments (⩽25 treatments/100 cow years). The identified predictors may be explained by underlying management factors leading to impaired animal welfare in the herd, such as poor hygiene, feeding and management of dry or calving cows and sick animals. However, further investigations are required for causal inferences to be established.     

How to estimate variability in affinity relationships in partially observed groups of domestic herbivores?

Animal sociability measurements based on inter-individual distances or nearest-neighbour distributions can be obtained automatically with telemetry collars. So far, all the indices that have been used require the whole group to be observed. Here, we propose an index of the variability in affinity relationships in groups of domestic herbivores, whose definition does not depend on group size and that can be used even if some data are missing. This index and its estimators are based on a function that measures how frequently an animal is closer than another one from a third animal. When no data are missing, we show that our estimator and the variance of the sociability matrixsensu Sibbald (considered as the reference method) are strongly correlated. We then consider two cases of missing data. In the first case, some animals are randomly missing, that is, to account for random breakdown of telemetry collars. Our estimator is unbiased by such missing data and its variance decreases as the number of observation dates increases. In the second case, the same animals are missing at all observation dates, that is, in large herds where there are more individuals to be observed than available telemetry collars. Our estimator of affinity variance within a group is biased by such missing data. Thus, it requires changing animals equipped with telemetry collars regularly during the experiment. Conversely, the estimator remains unbiased at the population level, that is, if several independent groups are being analysed. We finally illustrate how this estimator can be used by investigating changes in the variability of affinities according to group size in grazing heifers.     

MPAgenomics: an R package for multi-patient analysis of genomic markers

Background

Last generations of Single Nucleotide Polymorphism (SNP) arrays allow to study copy-number variations in addition to genotyping measures.

Results

MPAgenomics, standing for multi-patient analysis (MPA) of genomic markers, is an R-package devoted to: (i) efficient segmentation and (ii) selection of genomic markers from multi-patient copy number and SNP data profiles. It provides wrappers from commonly used packages to streamline their repeated (sometimes difficult) manipulation, offering an easy-to-use pipeline for beginners in R.The segmentation of successive multiple profiles (finding losses and gains) is performed with an automatic choice of parameters involved in the wrapped packages. Considering multiple profiles in the same time, MPAgenomics wraps efficient penalized regression methods to select relevant markers associated with a given outcome.

Conclusions

MPAgenomics provides an easy tool to analyze data from SNP arrays in R. The R-package MPAgenomics is available on CRAN.     

A novel approach for multi-domain and multi-gene family identification provides insights into evolutionary dynamics of disease resistance genes in core eudicot plants

Background

Recent advances in DNA sequencing techniques resulted in more than forty sequenced plant genomes representing a diverse set of taxa of agricultural, energy, medicinal and ecological importance. However, gene family curation is often only inferred from DNA sequence homology and lacks insights into evolutionary processes contributing to gene family dynamics. In a comparative genomics framework, we integrated multiple lines of evidence provided by gene synteny, sequence homology and protein-based Hidden Markov Modelling to extract homologous super-clusters composed of multi-domain resistance (R)-proteins of the NB-LRR type (for NUCLEOTIDE BINDING/LEUCINE-RICH REPEATS), that are involved in plant innate immunity.

Results

To assess the diversity of R-proteins within and between species, we screened twelve eudicot plant genomes including six major crops and found a total of 2,363 NB-LRR genes. Our curated R-proteins set shows a 50% average for tandem duplicates and a 22% fraction of gene copies retained from ancient polyploidy events (ohnologs). We provide evidence for strong positive selection and show significant differences in molecular evolution rates (Ka/Ks-ratio) among tandem- (mean = 1.59), ohnolog (mean = 1.36) and singleton (mean = 1.22) R-gene duplicates. To foster the process of gene-edited plant breeding, we report species-specific presence/absence of all 140 NB-LRR genes present in the model plant Arabidopsis and describe four distinct clusters of NB-LRR “gatekeeper” loci sharing syntenic orthologs across all analyzed genomes.

Conclusion

By curating a near-complete set of multi-domain R-protein clusters in an eudicot-wide scale, our analysis offers significant insight into evolutionary dynamics underlying diversification of the plant innate immune system. Furthermore, our methods provide a blueprint for future efforts to identify and more rapidly clone functional NB-LRR genes from any plant species.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-966) contains supplementary material, which is available to authorized users.