Two Subgroups within the GH43_36 α-l-Arabinofuranosidase Subfamily Hydrolyze Arabinosyl from Either Mono-or Disubstituted Xylosyl Units in Wheat Arabinoxylan

Fungal arabinofuranosidases (ABFs) catalyze the hydrolysis of arabinosyl substituents (Ara) and are key in the interplay with other glycosyl hydrolases to saccharify arabinoxylans (AXs). Most characterized ABFs belong to GH51 and GH62 and are known to hydrolyze the linkage of α-(1→2)-Ara and α-(1→3)-Ara in monosubstituted xylosyl residues (Xyl) (ABF-m2,3). Nevertheless, in AX a substantial number of Xyls have two Aras (i.e., disubstituted), which are unaffected by ABFs from GH51 and GH62. To date, only two fungal enzymes have been identified (in GH43_36) that specifically release the α-(1→3)-Ara from disubstituted Xyls (ABF-d3). In our research, phylogenetic analysis of available GH43_36 sequences revealed two major clades (GH43_36a and GH43_36b) with an expected substrate specificity difference. The characterized fungal ABF-d3 enzymes aligned with GH43_36a, including the GH43_36 from Humicola insolens (HiABF43_36a). Hereto, the first fungal GH43_36b (from Talaromyces pinophilus) was cloned, purified, and characterized (TpABF43_36b). Surprisingly, TpABF43_36b was found to be active as ABF-m2,3, albeit with a relatively low rate compared to other ABFs tested, and showed minor xylanase activity. Novel specificities were also discovered for the HiABF43_36a, as it also released α-(1→2)-Ara from a disubstitution on the non-reducing end of an arabinoxylooligosaccharide (AXOS), and it was active to a lesser extent as an ABF-m2,3 towards AXOS when the Ara was on the second xylosyl from the non-reducing end. In essence, this work adds new insights into the biorefinery of agricultural residues.     

Bioinformatics Analysis of RNA-seq Data Reveals Genes Related to Cancer Stem Cells in Colorectal Cancerogenesis

Cancer stem cells (CSC) play one of the crucial roles in the pathogenesis of various cancers, including colorectal cancer (CRC). Although great efforts have been made regarding our understanding of the cancerogenesis of CRC, CSC involvement in CRC development is still poorly understood. Using bioinformatics and RNA-seq data of normal mucosa, colorectal adenoma, and carcinoma (n = 106) from GEO and TCGA, we identified candidate CSC genes and analyzed pathway enrichment analysis (PEI) and protein–protein interaction analysis (PPI). Identified CSC-related genes were validated using qPCR and tissue samples from 47 patients with adenoma, adenoma with early carcinoma, and carcinoma without and with lymph node metastasis and were compared to normal mucosa. Six CSC-related genes were identified: ANLN, CDK1, ECT2, PDGFD, TNC, and TNXB. ANLN, CDK1, ECT2, and TNC were differentially expressed between adenoma and adenoma with early carcinoma. TNC was differentially expressed in CRC without lymph node metastases whereas ANLN, CDK1, and PDGFD were differentially expressed in CRC with lymph node metastases compared to normal mucosa. ANLN and PDGFD were differentially expressed between carcinoma without and with lymph node metastasis. Our study identified and validated CSC-related genes that might be involved in early stages of CRC development (ANLN, CDK1, ECT2, TNC) and in development of metastasis (ANLN, PDGFD).     

Experiences with introduction of the UNICEF program "10 steps for successful breast feeding"

Necrotizing fasciitis is a rapidly progressing, synergistic bacterial infection of fascia with a reported average mortality of about 40%. Fournier's disease, necrotizing fasciitis of the genital sphere, is also included in this study. Seven patients were studied over a one-year period between May 1991 and October 1992. Most commonly, they were infected by perineal diseases, medical procedures and cutaneous ulcers. The local clinical signs are cellulitis, oedema, blisters, necrosis and crepitus; general septic symptoms may also be present. Associated chronic diseases were present in 4 patients. Three infections were polymicrobial. Control of this potentially lethal soft-tissue infection is based on early clinical diagnosis, timely, wide surgical debridements and appropriate antibiotic treatment. The overall mortality rate was 1 of 7 (14%). Death was due to persistent wound sepsis and systemic septic complications, but mainly to delay in surgical treatment. The presence of chronic debilitating diseases (diabetes, alcohol abuse, renal insufficiency, ...) contribute to increase rate of both local and systemic infection.     

Synthetische Alkyllysophospholipide als Antitumormittel - Strukturverwandte des „Platelet Activating Factors”︁

Synthetic Alkyllysophospholipids as Antitumor Drugs - Structural Relation to “Platelet Activating Factor” Alkyllysophospholipids (ALP) are synthetic compounds structurally related to the biologically important platelet activating factor (PAF). In cell culture and animal experiments, ALP and hexadecylphosphocholine show destinct antineoplastic activities. We are now testing hexadecylphosphocholine as a new antitumor drug in clinical phase I trials.