关键词： colorectal cancer   microexon   PTBP1   RBFOX2   splicing  

摘要： The splicing of microexons (very small exons) is frequently dysregulated in the brain of individuals with autism spectrum disorder. However, little is known of the patterns, regulatory mechanisms and roles of microexon splicing in cancer. We here examined the transcriptome-wide profile of microexon splicing in matched colorectal cancer (CRC) and normal tissue specimens. Out of 1492 microexons comprising 3 to 15 nucleotides, 21 (1%) manifested differential splicing between CRC and normal tissue. The 21 genes harboring the differentially spliced microexons were enriched in gene ontology terms related to cell adhesion and migration. RNA interference-mediated knockdown experiments identified two splicing factors, RBFOX2 and PTBP1, as regulators of microexon splicing in CRC cells. RBFOX2 and PTBP1 were found to directly bind to microexon-containing pre-mRNAs and to control their splicing in such cells. Differential microexon splicing was shown to be due, at least in part, to altered expression of RBFOX2 and PTBP1 in CRC tissue compared to matched normal tissue. Finally, we found that changes in the pattern of microexon splicing were associated with CRC metastasis. Our data thus suggest that altered expression of RBFOX2 and PTBP1 might influence CRC metastasis through the regulation of microexon splicing.

关键词： alternative splicing   chromatin   dna   methylation   rna   rna splicing factors  

摘要： The well-established functions of UHRF1 converge to DNA biological processes, as exemplified by DNA methylation maintenance and DNA damage repair during cell cycles. However, the potential effect of UHRF1 on RNA metabolism is largely unexplored. Here, we revealed that UHRF1 serves as a novel alternative RNA splicing regulator. The protein interactome of UHRF1 identified various splicing factors. Among them, SF3B3 could interact with UHRF1 directly and participate in UHRF1-regulated alternative splicing events. Furthermore, we interrogated the RNA interactome of UHRF1, and surprisingly, we identified U snRNAs, the canonical spliceosome components, in the purified UHRF1 complex. Unexpectedly, we found H3R2 methylation status determines the binding preference of U snRNAs, especially U2 snRNAs. The involvement of U snRNAs in UHRF1-containing complex and their binding preference to specific chromatin configuration imply a finely orchestrated mechanism at play. Our results provided the resources and pinpointed the molecular basis of UHRF1-mediated alternative RNA splicing, which will help us better our understanding of the physiological and pathological roles of UHRF1 in disease development.

关键词： Biodegradability   Bioenergy   Enzymatic treatment   Life cycle assessment (LCA)   Starchy effluents   Wastewater treatment  

摘要： Enzymatic processes offer an option for the treatment of rich-starch effluents from the industrial processing of potatoes, which has been usually provided by means coagulation-flocculation units followed by settling, filtering or mechanical separation stages. Pre-treatment of these effluents with amylase enzymes increases the biodegradable-soluble COD fraction (bsCOD) by hydrolysis of starch and other complex molecules therein present. For this reason, it has been thought the coupling of an enzymatic pre-treatment with a combined biological process (anaerobic + aerobic) as an alternative treatment for these starchy liquid streams. This "enzymatic biological" concept would allow valuable biogas for its own operational needs and to reduce relevant environmental impacts regarding to the typical physicochemical processes, such as elevated consumption of energy and chemicals, as well the production of hardly biodegradable sludge. The apparent environmental advantages claimed by the enzymatic-biological treatment concept (alternative scenario) have been elucidated through a comparative life cycle assessment (LCA) against a solely physicochemical-based treatment (baseline scenario). Inventory data for the enzymatic pre-treatment were obtained and fitted from lab-scale tests, whilst average operational data were assumed for the anaerobic and aerobic units, as well for the baseline scenario. Environmental benefits have been unfolded by evaluating three mid-point environmental categories prioritized in this study, namely, global power warming, eutrophication potential and non-renewable energy consumption. The LCA results suggest the possible replacement of the physicochemical-based approach to treat starchy streams by applying the alternative enzymatic-biological process proposed in this study.

关键词： Biological sludge   Alternative adsorbents   Circular economy   Tertiary treatment of effluents   Adsorption wastewater treatment   Waste-to-resource  

摘要： The purpose of this study was to investigate pulp mill by-products valorization through activated carbon (AC) production and its application in wastewater treatment. Bio-sludge is a known promising precursor for AC production. The mill's chemical recovery stage generates an effluent (electrostatic precipitator ash leachate - EPAL) with high levels of potassium and sodium, which motivate studies regarding its viability as a chemical source for carbon activation. Bio-sludge and EPAL are problematic by-products and this research line would allow their return to the productive chain, as an adsorbent for the wastewater treatment. Two carbonization heating rates (3.5, 15 degrees C/min), three activation agents (NaOH, KOH, EPAL) and two activator:bio-sludge ratios (1:1, 2:1) were used for AC production. The best ACs in terms of surface area were those produced at 3.5 degrees C/min, with KOH or EPAL in 2:1 proportion. ACs produced under these conditions and commercial activated carbon (CAC) were used in adsorption tests with industrial wastewater. For color removal, KOH-activated carbon presented the greatest efficiency (80.45 %), followed by CAC (76.74 %) and EPAL-activated carbon (70.13 %). For COD removal, EPAL-activated carbon presented greater efficiency (53.49 %), followed by CAC (40.84 %) and KOH-activated carbon (36.86 %). Freundlich's model best described the experimental adsorption data. The KOH results were expected to be satisfactory, since KOH is proven to be effective for carbon activation. The EPAL-activated carbon results were remarkable, especially for COD removal, showing that EPAL can be used as an activator and that the by-products have potential for valorization according to the circular economy principles.

摘要： Motivation: Gene alternative splicing plays an important role in development, tissue specialization and disease and differences in splicing patterns can reveal important factors for phenotypic differentiation. While multiple computational methods exist to determine splicing differences, there is a need for user-friendly visualizations that present an intuitive view of the data and work across methods. Results: We developed a toolkit, Jutils, for visualizing differential splicing events at the intron (splice junction) level. Jutils is method-agnostic, converting individual tools' output into a unified representation and using it to create visualizations. Jutils creates three types of visualizations, namely heatmaps of absolute and Z-score normalized splice ratios, sashimi plots and Venn diagrams of results from multiple comparisons. Jutils is lightweight, relying solely on the unified data file for visualizations.

关键词： African catfish   Animal ingredients   Plant ingredients   Digestible amino acids   Feeding level  

摘要： Apparent digestibility coefficients (ADC) of nutrients and individual amino acids (AA) for 13 feed ingredients as affected by feeding level were determined for African catfish, a species of economic importance in Africa. Results from two trials are reported. In each trial, ADC were determined using a reference diet and test diets with yttrium oxide as indicator. Juvenile African catfish (averaging 53.9 g, trial 1;40.4 g, trial 2) were stocked in tanks connected to a common recirculation aquaculture system. Ingredients tested included hydrolysed feather meal (HFM), fishmeal (FM), insect meal (IM), soybean meal (SBM), sunflower meal (SFM), poultry meal (PM), corn dried distillers grains with solubles (CDDGS), faba beans (FB), lupine meal (LM), pea protein (PP), guar meal (GM), canola meal (CM) and yeast meal (YM). The effect of feeding level on ADC was determined by feeding fish restrictively (80% satiation) for 5 weeks and subsequently to apparent satiation for 2 weeks. Inclusion of yeast meal at 30% resulted in low palatability. ADC of nutrients were significantly affected by feeding level (except for fat and carbohydrate), but the effect was ingredient-dependent. African catfish was able to digest protein very effectively in almost all tested ingredients with ADC values ranging from 85.6 to 105.1% across feeding periods. Several ingredients tested, including animal protein ingredients and YM had similar high ADC for dry matter as FM. However, the ADC of AA differ among ingredients, indicating a need for digestible amino acid profile data. Methionine (Met) was the first limiting essential amino acid in HFM, FB, and LM with values ranging from 5-6 g/kg, expressed as digestible Met (dMet) per unit of digestible protein (DP), compared to FM (27 g dMet/kg DP). IM had comparable and sometimes higher overall digestible essential AA values compared to FM, except for methionine and lysine. For oilseeds and legumes, SBM tended to be the best quality AA source, as it had the

关键词： SWAT   Precipitation   Climate   CFSR   TRMM   APHRODITE  

摘要： Alternative climate products, such as gauge-based gridded data, ground-based weather radar, satellite precipitation and climate reanalysis products, are being increasingly applied for hydrological modelling. This review aims to summarize the studies that have evaluated alternative climate products within Soil and Water Assessment Tool (SWAT) applications and to propose future research directions, primarily for modelers who wish to study limited gauge, ungauged or transnational river basins. A total of 126 articles have been identified since 2004, the majority of which have been published within the last five years. About 58% of the studies were conducted in Asia, mostly in China and India, while another 14% were reported for United States studies. CFSR and TRMM are the most popular applied products in SWAT modelling, followed by PERSIANN, CMADS, APHRODITE, CHIRPS and NEXRAD. Generally, the performance of climate products is region-dependent;e.g., CFSR typically performs well in the United States and South America, but performs more poorly for Asia, Africa and mountainous basin conditions, as compared to other products. In contrast, the CMADS, TRMM, APRHODITE and NEXRAD have shown the strongest capability for supporting SWAT modelling in these regions. However, most of the evaluated products contain only precipitation input;therefore, merging reliable precipitation with CFSR-temperature is recommended for hydro-climatic modelling. Future research directions include: (1) examination of optimal combinations;e.g. CHIRPS-precipitation and CFSR-temperature, for simulating streamflow in different types of river basins;(2) development of a standardized validation scheme which incorporates the commonly accepted products, statistical approaches and temperature variables;(3) further evaluation of existing climate data products to accurately capture extreme events, pattern and indices as well as WGEN statistics;(4) improvement of climate data in terms of averaging approach, bia

摘要： The complement system is an important part of innate immunity. Complement activation leads to formation of convertase enzymes, switch of their specificity from C3 to C5 cleavage, and generation of lytic membrane attack complexes (C5b-9) on surfaces of pathogens. Most C5 cleavage occurs via the complement alternative pathway (AP). The regulator properdin promotes generation and stabilization of AP convertases. However, its role in C5 activation is not yet understood. In this work, we showed that serum properdin is essential for LPS-and zymosan-induced C5b-9 generation and C5b-9-mediated lysis of rabbit erythrocytes. Furthermore, we demonstrated its essential role in C5 cleavage by AP convertases. To this end, we developed a hemolytic assay in which AP convertases were generated on rabbit erythrocytes by using properdin-depleted serum in the presence of C5 inhibitor (step 1), followed by washing and addition of purified C5-C9 components to allow C5b-9 formation (step 2). In this assay, addition of purified properdin to properdin-depleted serum during convertase formation (step 1) was required to restore C5 cleavage and C5b-9-mediated hemolysis. Importantly, C5 convertase activity was also fully restored when properdin was added together with C5b-9 components (step 2), thus after convertase formation. Moreover, with C3-depleted serum, not capable of forming new convertases but containing properdin, in step 2 of the assay, again full C5b-9 formation was observed and blocked by addition of properdin inhibitor Salp20. Thus, properdin is essential for the convertase specificity switch toward C5, and this function is independent of properdin's role in new convertase formation.

关键词： Daphnia magna   Shed carapace length   Alternative growth endpoint  

摘要： Daphnia magna is an important organism for exposure studies in ecotoxicology. Body length measurement of a daphnid is a useful endpoint that represents the adverse effects of exposed chemicals or conditions on growth. This study questioned whether stress on body length measurement conditions while maintaining Daphnia magna on a slide glass results in any impact to antioxidant enzyme activity or growth. At the same time, the shed carapace length was tested to see if it could predict body length and be used as an alternative endpoint. The measured catalase (CAT) activity decreased as the exposure time to the on-slide conditions increased from 30 s to 120 s, although glutathione-S-transferase (GST) activity was not affected. On the other hand, regression between body length and two parameters of shed carapace length showed R-2 values, 0.869 and 0.924. Growth measured for each molting for three weeks was not affected by the exposure to the on-slide conditions. Finally, this study confirmed potential oxidative stress based on the exposure time dependent CAT activity in Daphnia magna under microscopic observation. More importantly, the shed carapace length was validated to reflect body length and it implies applicability of the new parameters to sublethal effect measurement using Daphnia magna. This study suggests potential interference is possible with the traditional growth measurement method on antioxidant enzyme activity in Daphnia magna and proposes better experimental practices to avoid the interference. (C) 2021 Elsevier B.V. All rights reserved.

关键词： Road transportation   GHG emission Reduction   Cost-effectiveness analysis   Low-carbon policy   Mixed policy  

摘要： This study analyzed the greenhouse gas (GHG) reduction potential and cost of urban road transportation policies from a boarder perspective including tank-to-wheel (TTW) and well-to-wheel (WTW) assessments, with Chongqing in China taken as the case city. Three policies and two mixed policies, including improving the fuel economy of passenger cars, promoting electric vehicles (EVs), and promoting natural gas vehicles (NGVs), are analyzed in this study. The two groups of mixed policies are developed to analyze the interaction between the policies. The results indicate that all the policies will reduce TTW and WTW fuel consumption and GHG emissions from 2016 to 2035. During this period, promoting an NGV policy will have the smallest marginal abatement cost (MAC) but the smallest GHG reduction potential, and promoting an EV policy will have the largest MAC but the largest GHG reduction potential from TTW. However, considering the GHG emissions from upstream energy consumption, the GHG emission reduction from promoting the EV policy is reduced and that of improving the fuel economy via the motor vehicle policy will increase significantly, resulting in a larger MAC from WTW than from TTW. With the mixed policies, hedging effects impact fuel savings, GHG emission reductions, and MACs. We put forward some policy suggestions to provide a reference for the formulation and adjustment of China's urban road transportation policies to cost-effectively mitigate GHG emissions in the future.