This is supplementary files of a full publication. In the publication, we reported the discovery of a 9-bp nucleotide sequence that enables the efficient translation of more than one protein from a polycistronic mRNA in yeasts and filamentous fungi. Coupling polycistronic expression to multiplexed, markerless, CRISPR/Cas9-based genome editing, we developed a strategy termed “HACKing” (Highly efficient and Accessible system by CracKing genes into the genome) for the assembly of multigene pathways in these organisms. HACKing allows the expression level of each enzyme to be precalibrated by linking their translation to those of host proteins with predetermined abundances under the desired fermentation conditions. We validated HACKing by rapidly constructing highly efficient S. cerevisiae cell factories that express 13 biosynthetic genes, and produce model endogenous (1,090.41±80.92 mg L-1 squalene) or heterologous (1.04±0.02 mg L-1 mogrol) terpenoid products in shake flask fermentations. Thus, HACKing addresses the need of synthetic biology for predictability, simplicity, scalability, and speed upon fungal pathway engineering for valuable metabolites.
Gallstone disease affects more than 6 % of the global population. Initially, it often presents asymptomatically, but the risk of complications increases over time. One rare complication of gallstone disease is intestinal obstruction caused by the blockage of the intestinal lumen, also referred to in foreign literature as “gallstone ileus”. According to international sources on Pubmed, Google Scholar, and Web Of Science, the frequency of “gallstone ileus” is 0.5 % of all gastrointestinal complications. We present a clinical case of a patient with clinical and diagnostic evidence of intestinal obstruction. Patient V., aged 86, was diagnosed with CT signs of a sigmoid neoplasm and a polyp in the cecum, along with intestinal obstruction during an outpatient examination. The patient was referred for intraintestinal stenting. During an attempt to perform a video colonoscopy, multiple diverticula with signs of diverticulitis and narrowing of the lumen of the sigmoid colon were observed in the distal parts of the sigmoid colon. A black foreign body (stone) was found in the area of narrowing. After displacing the stone, a flow of liquid stool was obtained, and 2.5 liters of liquid stool were aspirated. The foreign body was captured using a 4.5 cm Retrieval Net and, with difficulty, removed in the area of narrowing. Following this, a control video colonoscopy showed that the patency of the sigmoid colon was restored.
Conference paper written by Istvan Molnar, Laszlo Lubloy, Andras Bako, László Gáspár and Gyula Kolozsi presented at IABSE Symposium: Towards a Better Built Environment - Innovation, Sustainability, Information Technology, Melbourne, Australia, 11-13 September 2002.
Abstract Argentatins A–C (1–3) , the major cycloartane-type triterpenoids of guayule resin, a byproduct of commercial rubber production, were converted into their pyrimidine (7–12) , thiazole (13–15) , and indole (16–18) analogues by a molecular hybridization approach. The cytotoxic activities of these fused heterocyclic analogues 7–18 were compared with those of argentatins A–C (1–3) against a panel of three sentinel human cancer cell lines [NCI-H460 (non-small cell lung), MCF-7 (breast adenocarcinoma), and SF-268 (central nervous system glioma)], and normal human fibroblast (WI-38) cells. The cytotoxicity data suggest that the pyrimidine analogues 7 and 8 (derived from 1), 9 and 10 (derived from 2), and 12 (derived from 3 ) had significantly enhanced activity compared to the parent compounds or their thiazole (13–15) and indole (16–18) analogues. These findings indicate that triterpenoid constituents of guayule resin may be exploited to obtain value-added products with potential applications in anticancer drug discovery.
Introduction: Oncothermia (OTM) is based on electromagnetic interactions with the living organism.Its nano-targeting approach [established a newer paradigm, which could be applied not only in case of malignancies but in any other diseases, when the non-selective conditions are existing.This technique by now is well proven from the simple laboratory level to the several different clinical applications.Oncothermia method ignites the natural processes to rescue them from the system, re-establishing the better communication harmony between the cells of organism.This method will lead us to the treatment of some non-malignant diseases too to try delaying their development or offering earlier recovery.Our aim was to use OTM on the common basis of equilibrium demand; and use the recognition of the deviations from the complex harmony of the organism or its part for selection to act properly. Study protocol and Method:Oncothermia was successfully applied for non malignant conditions like Lyme disease, for non-specific lowback pain, for Peyronie disease, and for Dupuytren's contracture, too.We made more extended study, proving in details the applicability of the OTM in these diseases, especially in the situations when traditional Chinese Medicine (TCM) is also applicable (acupuncture, permanent needle techniques).Our special permanent acupuncture method was proven previously and well fits to the complementary applications. Results & Discussion:The synergy of the ancient knowledge -application of heat energy -and the high-tech state-of-art of the medical knowledge could be established with our research.Recognition of the distortions in the healthy tissue have some common principles and possibilities in TCM and OTM: the left complexity of the living organization is recognized by both the methods.OTM application is a useful, harmless additional complementary treatment for management of selected diseases.Our topic is giving western trained physicians clinical applications of modern (Oncothermia-Booster) as a physiotherapeutic -equipment to accommodate accelerating interests in modern complex treatment of chronic low back pain and Dupuytren's contracture. Conclusion:In recent study data verified the relevant end-points of the study: the safety, the quality of life (QoL), the shortened rest time, duration of painless state, cost/benefit ratio.
Precursor-directed biosynthesis was used to produce analogues of the cyclic depsipeptide mycotoxin beauvericin (1) using the filamentous fungus Beauveria bassiana ATCC 7159. Feeding 30 analogues of d-2-hydroxyisovalerate and l-phenylalanine, the natural 2-hydroxycarboxylic acid and amino acid precursors of beauvericin, led to the biosynthesis of novel beauvericins. Six of these were isolated and characterized, and their cytotoxicity and directional cell migration (haptotaxis) inhibitory activity against the metastatic prostate cancer cell line PC-3M were evaluated. Replacement of one, two, or all three of the d-2-hydroxyisovalerate constituents in beauvericin (1) with 2-hydroxybutyrate moieties (beauvericins G1–3, compounds 2–4) caused a parallel decline of cell migration inhibitory activity and cytotoxicity, suggesting a requirement for a branched side chain for both of these biological activities at the corresponding positions of beauvericins. Replacement of one, two, or all three N-methyl-l-phenylalanine residues of beauvericin with N-methyl-l-3-fluorophenylalanine moieties (beauvericins H1–3, compounds 5–7) increased cytotoxicity without affecting antihaptotactic activity.
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