Single-Cell Heterogeneity Analysis and CRISPR Screen Identify Key β-Cell-Specific Disease Genes

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内皮祖细胞对急性肺损伤保护作用的研究进展

内皮祖细胞（EPC）是一种多潜能细胞,主要来源于骨髓。外周血EPC可以参与修复多种血管内皮细胞损伤的疾病。目前研究证实EPC通过动员、迁移、归巢和分化等步骤在受损的肺组织处参与内皮细胞修复,调节失控的炎症反应,增强抗氧化能力,对修复和维持肺泡毛细血管屏障的完整性起着重要作用。EPC在心血管疾病和组织工程领域应用研究的成功,为EPC在急性肺损伤的治疗提供了新的思路。     

Scale-down model qualification of ambr® 250 high-throughput mini-bioreactor system for two commercial-scale mAb processes

Recent advances in high-throughput (HTP) automated mini-bioreactor systems have significantly improved development timelines for early-stage biologic programs. Automated platforms such as the ambr® 250 have demonstrated the ability, using appropriate scale-down approaches, to provide reliable estimates of process performance and product quality from bench to pilot scale, but data sets comparing to large-scale commercial processes (>10,000 L) are limited. As development moves toward late stages, specifically process characterization (PC), a qualified scale-down model (SDM) of the commercial process is a regulatory requirement as part of Biologics License Application (BLA)-enabling activities. This work demonstrates the qualification of the ambr® 250 as a representative SDM for two monoclonal antibody (mAb) commercial processes at scales >10,000 L. Representative process performance and product quality associated with each mAb were achieved using appropriate scale-down approaches, and special attention was paid to pCO₂ to ensure consistent performance and product quality. Principal component analysis (PCA) and univariate equivalence testing were utilized in the qualification of the SDM, along with a statistical evaluation of process performance and product-quality attributes for comparability. The ambr® 250 can predict these two commercial-scale processes (at center-point condition) for cell-culture performance and product quality. The time savings and resource advantages to performing PC studies in a small-scale HTP system improves the potential for the biopharmaceutical industry to get products to patients more quickly.     

Comparison of Arterial Spin Labeling and Dynamic Susceptibility Contrast Perfusion MRI in Patients with Acute Stroke

Background

The aim of this study was to evaluate whether arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) can reliably quantify perfusion deficit as compared to dynamic susceptibility contrast (DSC) perfusion MRI.

Methods

Thirty-nine patients with acute ischemic stroke in the anterior circulation territory were recruited. All underwent ASL and DSC MRI perfusion scans within 30 hours after stroke onset and 31 patients underwent follow-up MRI scans. ASL cerebral blood flow (CBF) and DSC time to maximum (T_max) maps were used to calculate the perfusion defects. The ASL CBF lesion volume was compared to the DSC T_max lesion volume by Pearson''s correlation coefficient and likewise the ASL CBF and DSC T_max lesion volumes were compared to the final infarct sizes respectively. A repeated measures analysis of variance and least significant difference post hoc test was used to compare the mean lesion volumes among ASL CBF, DSC T_max >4–6 s and final infarct.

Results

Mean patient age was 72.6 years. The average time from stroke onset to MRI was 13.9 hours. The ASL lesion volume showed significant correlation with the DSC lesion volume for T_max >4, 5 and 6 s (r = 0.81, 0.82 and 0.80; p<0.001). However, the mean lesion volume of ASL (50.1 ml) was significantly larger than those for T_max >5 s (29.2 ml, p<0.01) and T_max >6 s (21.8 ml, p<0.001), while the mean lesion volumes for T_max >5 or 6 s were close to mean final infarct size.

Conclusion

Quantitative measurement of ASL perfusion is well correlated with DSC perfusion. However, ASL perfusion may overestimate the perfusion defects and therefore further refinement of the true penumbra threshold and improved ASL technique are necessary before applying ASL in therapeutic trials.     

SGD: Saccharomyces Genome Database.

The Saccharomyces Genome Database (SGD) provides Internet access to the complete Saccharomyces cerevisiae genomic sequence, its genes and their products, the phenotypes of its mutants, and the literature supporting these data. The amount of information and the number of features provided by SGD have increased greatly following the release of the S.cerevisiae genomic sequence, which is currently the only complete sequence of a eukaryotic genome. SGD aids researchers by providing not only basic information, but also tools such as sequence similarity searching that lead to detailed information about features of the genome and relationships between genes. SGD presents information using a variety of user-friendly, dynamically created graphical displays illustrating physical, genetic and sequence feature maps. SGD can be accessed via the World Wide Web at http://genome-www.stanford.edu/Saccharomyces/     

Resource conversion: a generalizable mechanism for resource-mediated positive species interactions

Positive species interactions are ubiquitous in natural communities, but the mechanisms through which they operate are poorly understood. One proposed mechanism is resource conversion – the conversion by a benefactor species of a resource from a resource state that is inaccessible to a potential beneficiary species into a resource state that is accessible. Such conversion often occurs as a byproduct of resource consumption, and sometimes in exchange for non-resource benefits to the benefactor species. At least five known classes of interactions, including both facilitative and mutualistic ones, may be classified as resource conversion interactions. We formulated a generalizable mathematical model for resource conversion interactions and examined two model variants that represent processing chain and nurse plant interactions. We examined the conditions under which these conformed to the stress-gradient hypothesis (SGH), which predicts increased interaction benefits in more stressful environments. These yielded four key insights: 1) resource conversion interactions can be positive (towards the resource recipient) only when facilitator-mediated resource conversion is more efficient than the baseline, spontaneous, facilitator-independent resource conversion; 2) the sign of resource conversion interaction outcomes never switches (e.g. from net positive to net negative) with changing levels of resource availability, when all other parameters are kept constant; 3) processing chain interactions at equilibrium can never be positive in a manner that conforms to the SGH; 4) nurse plant interactions can be positive and conform to the SGH, although the manner in which they do depends largely on how resource stress is defined, and the environmental supply rate of surface soil moisture. The first two insights are likely to be generalizable across all resource conversion interactions. The general agreement of the model with empirical studies suggest that resource conversion is the mechanism underlying the aforementioned interactions, and an ecologically meaningful way of classifying these previously unassociated positive species interactions.     

红树林源白骨壤链霉菌中多环稠合大环内酰胺类化合物的结构多样性研究

【目的】通过基因组挖掘的方法,研究红树林来源白骨壤链霉菌Streptomyces avicenniae 9-9中多环稠合大环内酰胺(PTMs)类化合物的结构多样性。【方法】通过生物信息学分析白骨壤链霉菌基因组序列,寻找PTMs类化合物的生物合成相关基因;利用UPLC-MS/MS技术对该菌的次级代谢产物进行分析。【结果】在白骨壤链霉菌基因组中发现PTMs生物合成基因簇(aviA-D);从菌液提取物中鉴定出5个PTMs类化合物,其中包括ikarugamycin(化合物1)和capsimycin B(化合物2);基于PTMs类化合物5-6-5环类型的MS/MS碎裂规律,对化合物3–5的结构进行了推测。【结论】红树林来源白骨壤链霉菌S.avicenniae 9-9具有产生5-6-5环类型的PTMs类化合物的能力。     

Vaginal microbiome variances in sample groups categorized by clinical criteria of bacterial vaginosis

Background

One of the most common and recurrent vaginal infections is bacterial vaginosis (BV). The diagnosis is based on changes to the “normal” vaginal microbiome; however, the normal microbiome appears to differ according to reproductive status and ethnicity, and even among individuals within these groups. The Amsel criteria and Nugent score test are widely used for diagnosing BV; however, these tests are based on different criteria, and so may indicate distinct changes in the vaginal microbial community. Nevertheless, few studies have compared the results of these test against metagenomics analysis.

Methods

Vaginal flora samples from 77 participants were classified according to the Amsel criteria and Nugent score test. The microbiota composition was analyzed using 16S ribosome RNA gene amplicon sequencing. Bioinformatics analysis and multivariate statistical analysis were used to evaluate the microbial diversity and function.

Results

Only 3 % of the participants diagnosed BV negative using the Amsel criteria (A−) were BV-positive according to the Nugent score test (N+), while over half of the BV-positive patients using the Amsel criteria (A+) were BV-negative according to the Nugent score test (N−). Thirteen genera showed significant differences in distribution among BV status defined by BV tests (e.g., A − N−, A + N− and A + N+). Variations in the four most abundant taxa, Lactobacillus, Gardnerella, Prevotella, and Escherichia, were responsible for most of this dissimilarity. Furthermore, vaginal microbial diversity differed significantly among the three groups classified by the Nugent score test (N−, N+, and intermediate flora), but not between the Amsel criteria groups. Numerous predictive microbial functions, such as bacterial chemotaxis and bacterial invasion of epithelial cells, differed significantly among multiple BV test, but not between the A− and A+ groups.

Conclusions

Metagenomics analysis can greatly expand our current understanding of vaginal microbial diversity in health and disease. Metagenomics profiling may also provide more reliable diagnostic criteria for BV testing.