A Comprehensive Curation Shows the Dynamic Evolutionary Patterns of Prokaryotic CRISPRs

Motivation. Clustered regularly interspaced short palindromic repeat (CRISPR) is a genetic element with active regulation roles for foreign invasive genes in the prokaryotic genomes and has been engineered to work with the CRISPR-associated sequence (Cas) gene Cas9 as one of the modern genome editing technologies. Due to inconsistent definitions, the existing CRISPR detection programs seem to have missed some weak CRISPR signals. Results. This study manually curates all the currently annotated CRISPR elements in the prokaryotic genomes and proposes 95 updates to the annotations. A new definition is proposed to cover all the CRISPRs. The comprehensive comparison of CRISPR numbers on the taxonomic levels of both domains and genus shows high variations for closely related species even in the same genus. The detailed investigation of how CRISPRs are evolutionarily manipulated in the 8 completely sequenced species in the genus Thermoanaerobacter demonstrates that transposons act as a frequent tool for splitting long CRISPRs into shorter ones along a long evolutionary history

Water Recharge of Jinan Karst Springs, Shandong, China

As the main scavenge port of groundwater in the karst water system, most of the karst springs affected by human activities experienced discharge attenuation phenomenon in the north of China. Whilst artificial replenishment measures have been taken to keep water spewing, the results are not ideal in many karst springs. This is mainly because of poor understanding about the recharging water sources. This paper used the Jinan Spring region as an example to discuss about different spring water supply sources. Based on a wide range of methods (e.g., dynamic observation of spring water level, real-time monitoring of water temperature and electrical conductivity (EC), tracer test, and frequency analysis), this study obtained several findings. First, the maximum karst-fractured water proportion that Cambrian Zhangxia Formation contribute to the Zhenzhu Spring is 57–59%, and the Heihu Spring only recharges 25–31%. Second, the proportion of fracture-karst water to the Heihu Spring from the Fengshan Formation to the Sanshanzi Formation of the Ordovician is 69–75%, while the proportion of the Tanxi spring is 15–17%. Third, the Baotu Spring and Heihu Spring mainly receive karst-fractured water from the Cambrian Zhangxia Formation and fracture-karst water from the Cambrian Fengshan Formation to the Ordovician Sanshanzi Formation. The supply sources of the Zhenzhu Spring and Tanxi Spring are more diverse, including karst-fractured water of the Cambrian Zhangxia Formation and fracture-karst water of the Cambrian Fengshan Formation to the Ordovician Sanshanzi Formation, as well as a small amount of pore water and fissure water, artificial recharge water supply. Fourth, the frequency analysis of spring water temperature indicated that the Zhenzhu Spring and Tanxi Spring are mainly in deep circulation, while the Baotu Spring and Heihu Spring are predominantly in shallow circulation. The differences in the sources of the four largest spring groups suggest that the karst water movement in Jinan has heterogeneous characteristics. The determination of the mixing ratio of the sources of spring water supplies provides a scientific basis for the protection of spring water, and the implementation of artificial recharge projects

Integrating Inflammation-Responsive Prodrug with Electrospun Nanofibers for Anti-Inflammation Application

Chronic inflammation plays a side effect on tissue regeneration, greatly inhibiting the repair or regeneration of tissues. Conventional local delivery of anti-inflammation drugs through physical encapsulation into carriers face the challenges of uncontrolled release. The construction of an inflammation-responsive prodrug to release anti-inflammation drugs depending on the occurrence of inflammation to regulate chronic inflammation is of high need. Here, we construct nanofiber-based scaffolds to regulate the inflammation response of chronic inflammation during tissue regeneration. An inflammation-sensitive prodrug is synthesized by free radical polymerization of the indomethacin-containing precursor, which is prepared by the esterification of N-(2-hydroxyethyl) acrylamide with the anti-inflammation drug indomethacin. Then, anti-inflammation scaffolds are constructed by loading the prodrug in poly(ε-caprolactone)/gelatin electrospun nanofibers. Cholesterol esterase, mimicking the inflammation environment, is adopted to catalyze the hydrolysis of the ester bonds, both in the prodrug and the nanofibers matrix, leading to the generation of indomethacin and the subsequent release to the surrounding. In contrast, only a minor amount of the drug is released from the scaffold, just based on the mechanism of hydrolysis in the absence of cholesterol esterase. Furthermore, the inflammation-responsive nanofiber scaffold can effectively inhibit the cytokines secreted from RAW264.7 macrophage cells induced by lipopolysaccharide in vitro studies, highlighting the great potential of these electrospun nanofiber scaffolds to be applied for regulating the chronic inflammation in tissue regeneration

Additional file 1: Figure S1. of McTwo: a two-step feature selection algorithm based on maximal information coefficient

Comparison of the binary classification accuracy Acc between the two algorithms McTwo and McOne. Figure S2. Comparison of the binary classification accuracy Acc among the four algorithms, McTwo, CFS, PAM and RRF. Figure S3. Comparison of the binary classification accuracy Acc among the four algorithms, McTwo, TRank, WRank and RCORank. Table S1. Comparison of the binary classification accuracy Acc between the two algorithms McTwo and McOne. Table S2. Comparison of McTwo with the three individual ranking algorithms. Table S3. Statistical significance of the comparison triplets of McTwo with the other feature selection algorithms. (PDF 931 kb