Ablation of Gadd45β ameliorates the inflammation and renal fibrosis caused by unilateral ureteral obstruction

The growth arrest and DNA damage‐inducible beta (Gadd45β) protein have been associated with various cellular functions, but its role in progressive renal disease is currently unknown. Here, we examined the effect of Gadd45β deletion on cell proliferation and apoptosis, inflammation, and renal fibrosis in an early chronic kidney disease (CKD) mouse model following unilateral ureteral obstruction (UUO). Wild‐type (WT) and Gadd45β‐knockout (KO) mice underwent either a sham operation or UUO and the kidneys were sampled eight days later. A histological assay revealed that ablation of Gadd45β ameliorated UUO‐induced renal injury. Cell proliferation was higher in Gadd45β KO mouse kidneys, but apoptosis was similar in both genotypes after UUO. Expression of pro‐inflammatory cytokines after UUO was down‐regulated in the kidneys from Gadd45β KO mice, whereas UUO‐mediated immune cell infiltration remained unchanged. The expression of pro‐inflammatory cytokines in response to LPS stimulation decreased in bone marrow‐derived macrophages from Gadd45β KO mice compared with that in WT mice. Importantly, UUO‐induced renal fibrosis was ameliorated in Gadd45β KO mice unlike in WT mice. Gadd45β was involved in TGF‐β signalling pathway regulation in kidney fibroblasts. Our findings demonstrate that Gadd45β plays a crucial role in renal injury and may be a therapeutic target for the treatment of CKD.     

The structure and antimicrobial potential of wasp and hornet (Vespidae) mastoparans: A review

Wasp venom is a complex mixture of biologically active components, including high molecular weight proteins, small peptides, bioactive amines, and amino acids. Peptides comprise up to 70% of dried venom. In social wasp venoms, three of the major peptide types are mastoparans, which cause mast cell degranulation, chemotactic peptides, which promote chemotaxis of polymorphonucleated leukocytes, and kinin‐related peptides, which are known to produce pain and increase vascular permeability. Among these, the bioactive tridecapeptide mastoparan is the most common and may even have antimicrobial activity. Herein we summarize the results of studies on vespid mastoparans, focusing on hornets (Vespa spp.) identified following a systematic literature search for mastoparans of hornets in the genus Vespa, the most active mastoparan research taxon. The common features of hornet mastoparans are C‐terminal amidation, amphipathic helical structure, and multiple functions such as mast cell degranulation and hemolysis, as well as membrane permeabilization. Most interestingly, all tested hornet mastoparans have strong antimicrobial activities, suggesting that they can provide useful insights into and opportunities for development of novel antibacterial peptides.     

Evolution of ecospace occupancy by Mesozoic marine tetrapods

Ecology and morphology are different, and yet in comparative studies of fossil vertebrates the two are often conflated. The macroevolution of Mesozoic marine tetrapods has been explored in terms of morphological disparity, but less commonly using ecological‐functional categories. Here we use ecospace modelling to quantify ecological disparity across all Mesozoic marine tetrapods. We document the explosive radiation of marine tetrapod groups in the Triassic and their rapid attainment of high ecological disparity. Late Triassic extinctions led to a marked decline in ecological disparity, and the recovery of ecospace and ecological disparity was sluggish in the Early Jurassic. High levels of ecological disparity were again achieved by the Late Jurassic and maintained during the Cretaceous, when the ecospace became saturated by the Late Cretaceous. Sauropterygians, turtles and ichthyosauromorphs were the largest contributors to ecological disparity. Throughout the Mesozoic, we find that established groups remained ecologically conservative and did not explore occupied or vacant niches. Several parts of the ecospace remained vacant for long spans of time. Newly evolved, radiating taxa almost exclusively explored unoccupied ecospace, suggesting that abiotic releases are needed to empty niches and initiate diversification. In the balance of evolutionary drivers in Mesozoic marine tetrapods, abiotic factors were key to initiating diversification events, but biotic factors dominated the subsequent generation of ecological diversity.     

Tissue distribution and subcellular localization of the family of Kidney Ankyrin Repeat Domain (KANK) proteins

Kidney Ankyrin Repeat-containing Proteins (KANKs) comprise a family of four evolutionary conserved proteins (KANK1 to 4) that localize to the belt of mature focal adhesions (FAs) where they regulate integrin-mediated adhesion, actomyosin contractility, and link FAs to the cortical microtubule stabilization complex (CMSC). The human KANK proteins were first identified in kidney and have been associated with kidney cancer and nephrotic syndrome. Here, we report the distributions and subcellular localizations of the four Kank mRNAs and proteins in mouse tissues. We found that the KANK family members display distinct and rarely overlapping expression patterns. Whereas KANK1 is expressed at the basal side of epithelial cells of all tissues tested, KANK2 expression is mainly observed at the plasma membrane and/or cytoplasm of mesenchymal cells and KANK3 exclusively in vascular and lymphatic endothelial cells. KANK4 shows the least widespread expression pattern and when present, overlaps with KANK2 in contractile cells, such as smooth muscle cells and pericytes. Our findings show that KANKs are widely expressed in a cell type-specific manner, which suggests that they have cell- and tissue-specific functions.     

The protein kinase 2 inhibitor CX-4945 regulates osteoclast and osteoblast differentiation In vitro

Drug repositioning can identify new therapeutic applications for existing drugs, thus mitigating high R&D costs. The Protein kinase 2 (CK2) inhibitor CX-4945 regulates human cancer cell survival and angiogenesis. Here we found that CX-4945 significantly inhibited the RANKL-induced osteoclast differentiation, but enhanced the BMP2-induced osteoblast differentiation in a cell culture model. CX-4945 inhibited the RANKL-induced activation of TRAP and NFATc1 expression accompanied with suppression of Akt phosphorylation, but, in contrast, it enhanced the BMP2-mediated ALP induction and MAPK ERK1/2 phosphorylation. CX-4945 is thus a novel drug candidate for bone-related disorders such as osteoporosis.     

Frammenti cotiledonari di Aesculus hippocastanum L. coltivati in vitro. Primi dati sul comportamento dell'amido e dell'escina

Abstract

Fragments of Aesculus hippocastanum L. cotyledons grown in vitro. First results about starch and aescin characteristic features.—Cotyledon fragments of Aesculus hippocastanum grown in vitro in different media have been able to form callus and roots. The starch granules in the new cells are compound in structure and morphologically different from the simple cotyledon granules, whereas they are similar to the granules of the other parts of the plant in toto. Moreover, the callus has no aescin even though it originates from the cotyledor tissues.     

Isolation and characterization of BTEX tolerant and degrading Pseudomonas putida BCNU 106

Bacterial strains growing in river sediments were screened to identify an organic solvent-tolerant strain of Pseudomonas. Using this screen, Pseudomonas sp. BCNU 106 was isolated on the basis of its ability to grow on benzene, toluene, ethylbenzene, and three xylene isomers, o-, m- and p-xylene, as its sole carbon source. BCNU 106 was identified as a gram-negative, rod-shaped aerobic and mesophilic bacterium, which grew in liquid media containing high concentrations of organic solvents. 16S rDNA analysis classified BCNU 106 as a new member of the genus Pseudomonas. BCNU 106 was distinguishable from other Pseudomonas strains that are tolerant to organic solvents in that the isolate had the ability to utilize all three xylene isomers as well as benzene, toluene and ethylbenzene. The unique properties of the isolate such as solvent-tolerance and the ability to degrade xylene isomers may have important implications for the efficient treatment of solvent wastes.