Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo

Development of the heart requires recruitment of cardiovascular progenitor cells (CPCs) to the future heart-forming region. CPCs are the building blocks of the heart, and have the potential to form all the major cardiac lineages. However, little is known regarding what regulates CPC fate and behavior. Activity of GATA4, SMARCD3 and TBX5 - the `cardiac BAF' (cBAF) complex, can promote myocardial differentiation in embryonic mouse mesoderm. Here, we exploit the advantages of the zebrafish embryo to gain mechanistic understanding of cBAF activity. Overexpression of smarcd3b and gata5 in zebrafish results in an enlarged heart, whereas combinatorial loss of cBAF components inhibits cardiac differentiation. In transplantation experiments, cBAF acts cell autonomously to promote cardiac fate. Remarkably, cells overexpressing cBAF migrate to the developing heart and differentiate as cardiomyocytes, endocardium and smooth muscle. This is observed even in host embryos that lack endoderm or cardiac mesoderm. Our results reveal an evolutionarily conserved role for cBAF activity in cardiac differentiation. Importantly, they demonstrate that Smarcd3b and Gata5 can induce a primitive, CPC-like state.     

Simultaneous sludge reduction and nutrient removal (SSRNR) with interaction between Tubificidae and microorganisms: a full-scale study

A symbiotic ecosystem between Tubificidae and microorganisms was established at a full-scale wastewater treatment plant (WWTP). In this ecosystem Tubificidae were inoculated, and then adhered to the outer layers of carrier materials in an oxidation tank. During the long-term treatment of sewage volumes of 20,000 m(3)d(-1), the excess sludge production rate was reduced from 0.21 to 0.051 kg m(-3) and sludge settleability was significantly improved. When the influent concentrations of COD, NH(4)(+)-N, PO(4)(-)-P, and SS were in the ranges of 130.0-459.0 mg L(-1), 14.2-27.5 mg L(-1), 1.6-7.0 mg L(-1), and 60.0-466.0 mg L(-1), respectively, the COD and SS removal efficiency was increased by 8.7% and 13.6% within the symbiotic system compared to the control without Tubificidae. In addition, NH(4)(+)-N and phosphorus removal efficiency can also be improved. The results showed that both sludge reduction and nutrient removal were enhanced simultaneously significantly within the system utilizing the symbiotic interactions of Tubificidae and microorganisms.     

Overlapping role of dynamin isoforms in synaptic vesicle endocytosis

The existence of neuron-specific endocytic protein isoforms raises questions about their importance for specialized neuronal functions. Dynamin, a GTPase implicated in the fission reaction of endocytosis, is encoded by three genes, two of which, dynamin 1 and 3, are highly expressed in neurons. We show that dynamin 3, thought to play a predominantly postsynaptic role, has a major presynaptic function. Although lack of dynamin 3 does not produce an overt phenotype in mice, it worsens the dynamin 1 KO phenotype, leading to perinatal lethality and a more severe defect in activity-dependent synaptic vesicle endocytosis. Thus, dynamin 1 and 3, which together account for the overwhelming majority of brain dynamin, cooperate in supporting optimal rates of synaptic vesicle endocytosis. Persistence of synaptic transmission in their absence indicates that if dynamin plays essential functions in neurons, such functions can be achieved by the very low levels of dynamin 2.     

Consuming un-captured methane from landfill using aged refuse bio-cover

A novel simulated bio-cover was developed to facilitate the biological methane oxidation process using aged refuse and aged sludge from landfill. It was found that 78.7% and 66.9% of CH₄ could be removed, with the aged refuse: aged sludge (w/w%) ratio of 7:3 and 6:4 in bio-cover system, respectively. The maximum CH₄ removal rate could reach 100%, when the aged refuse with the disposal time more than 14 years were applied in bio-cover. Some controlled factors for the methanotrophic activity, i.e. moisture, Eh and organic matter content, were also investigated. It was found that CH₄ oxidation rate increased greatly, when the moisture content and organic matter were increased from 6.0%, 4.8% to 8.0%, 9.5%, respectively. The optimum conditions for this bio-cover system was found to be as follows: aged refuse: aged sludge ratio of 7:3, the moisture content of 8-9%, Eh of 104-108 mV and organic matter of 9.5%.     

Glutaredoxin 2 knockout increases sensitivity to oxidative stress in mouse lens epithelial cells

Glutaredoxin belongs to the oxidoreductase family, with cytosolic glutaredoxin 1 (Grx1) and mitochondrial glutaredoxin 2 (Grx2) isoforms. Of the two isozymes, the function of Grx2 is not well understood. This paper describes the effects of Grx2 deletion on cellular function using primary lens epithelial cell cultures isolated from Grx2 gene knockout (KO) and wild-type (WT) mice. We found that both cell types showed similar growth patterns and morphology and comparable mitochondrial glutathione pool and complex I activity. Cells with deleted Grx2 did not show affected Grx1 or thioredoxin expression but exhibited high sensitivity to oxidative stress. Under treatment with H(2)O(2), the KO cells showed less viability, higher membrane leakage, enhanced ATP loss and complex I inactivation, and weakened ability to detoxify H(2)O(2) in comparison with the WT cells. The KO cells had higher glutathionylation in the mitochondrial proteins, particularly the 75-kDa subunit of complex I. Recombinant Grx2 deglutathionylated complex I and restored most of its activity. We conclude that Grx2 has a function that protects cells against H(2)O(2)-induced injury via its peroxidase and dethiolase activities; particularly, Grx2 prevents complex I inactivation and preserves mitochondrial function.     

Identification of novel pyrrolopyrazoles as protein kinase C β II inhibitors

A novel series of pyrrolopyrazole-based protein kinase C β II inhibitors has been identified from high-throughput screening. Herein, we report our initial structure-activity relationship studies with a focus on optimizing compound ligand efficiency and physicochemical properties, which has led to potent inhibitors with good cell permeability.     

Discovery of benzothiazole-based adenosine A2B receptor antagonists with improved A2A selectivity

The highly potent but modestly selective N-(2-amino-4-methoxy-benzothiazol-7-yl)-N-ethyl-acetamide derivative 2 was selected as the starting point for the design of novel selective A_2B antagonists, due to its excellent potency, and good drug-like properties. A series of compounds containing nonaromatic amides or ureas of five- or six-membered rings, and also bearing an m-trifluoromethyl-phenyl group (shown to impart superior potency) was prepared and evaluated for their selectivity against the A_2A and A₁ receptors. This work resulted in the identification of compound 30, with excellent potency and high selectivity against both A_2A and A₁ receptors.     

Efficient synthesis of trisaccharide saponins and their tumor cell killing effects through oncotic necrosis

To investigate the relationship of cytotoxicity and saponins with varied aglycones, based on the structure of indioside E 1, a natural derived anti-tumor active ingredient from Chinese medicinal plant Solanum indicum L., five novel saponins 2-6 bearing the same trisaccharide moiety together with 1 were efficiently synthesized via a transglycosylation strategy. MTT assay revealed the killing effects to tumor cells of the synthesized saponins are varied with the change of aglycones. Furthermore, time-lapse microscopy, LDH release, PI staining, and immunocytochemical investigations demonstrated that the cell death caused by neosaponin 2 was through oncotic necrosis involving plasma membrane perturbation and destruction of cytoskeleton.     

Sorption and ecotoxicity of pentachlorophenol polluted sediment amended with rice-straw derived biochar

To investigate the feasibility of using biochar to control organic pollutants in sediments, we extracted biochar from rice-straw combustion residues (RBC) and studied its adsorption ability and effect on seed germination ecotoxicity of pentachlorophenol (PCP). The results showed that the Freundlich and dual-mode models could describe all the sorption isotherm data well, and the log K_OC values increased with increasing RBC content. With 50 mg kg⁻¹ PCP in the sediment, a significant seed growth inhibition (P < 0.01) was observed. The addition of 2.0% RBC lowered the PCP concentration in the extraction liquid from 4.53 to 0.17 mg L⁻¹ and increased the germination rate and root length significantly. Furthermore, it was found that the addition of RBC had no toxic but stimulative effect on root elongation. Consequently, RBC could serve as a potential supersorbent for the remediation of organic pollution in situ.