{"title":"A predicted chemo-polypharmacophoric agent comprising (Propeptide-Fc)/MGF peptide mimicking interactive of high free binding energy properties towards Wnt7a/Fzd7 signalling Akt/mTOR anabolic growth IGF-I/PI3K/Akt -I/MAPK/ERK pathways.","authors":"I. Grigoriadis","doi":"10.5281/ZENODO.31276","DOIUrl":"https://doi.org/10.5281/ZENODO.31276","url":null,"abstract":": The insulin-like growth factor-I (IGF-I) is a key regulator of skeletal muscle growth in vertebrates, promoting mitogenic and anabolic effects through the activation of the MAPK/ERK and the PI3K/Akt signaling pathways. Also, these results show that there is a time-dependent regulation of IGF-I plasma levels and its signaling pathways in muscle. The insulin-like growth factor-I (IGF-I) is a key regulatory hormone that controls growth in vertebrates. Particularly, skeletal muscle growth is strongly stimulated by this hormone. IGFI stimulates both proliferation and differentiation of myoblasts, as well as promoting myotube hypertrophy in vitro and in vivo. The mitogenic and anabolic effects of IGF-I on muscle cells are mediated through specific binding with the IGF-I receptor (IGF-IR). This ligand-receptor interaction promotes the activation of two major intracellular signaling pathways, the mitogen-activated protein kinases (MAPKs), specifically the extracellular signal-regulated kinase (ERK), and the phosphatidylinositol 3 kinase (PI3K)/Akt. The MAPK (RAF/MEK/ERK) is a key signaling pathway in skeletal muscle, where its activation is absolutely indispensable for muscle cell proliferation. Biologically active polypeptides derived from the E domain that forms the C-terminus of the insulin-like cells of accuracy. this the and are evaluate IRLC, we first define M the mean conservation score of N residues within a predicted where C is the conservation score representing the of peptide conservation of a residue in position of the neo-ligand like be calculated by any suitable while our experiment, position evaluate we A motif molecule will be as a false prediction if some if much conserved than is contradicts domains which in turn leads to select, fragmenter, identified all of potential fragment-protein interactions. Benchmarking with known drug-protein interactions shows that our proposed methodology outperforms previous methods that exploit either protein sequences or compound structures to predict drug targets, which demonstrates the predictive power of our proposed BiogenetoligandorolTM KNIME-based referenced based GA(M)E-QSAR PDTCD method. We propose a ligand-based approach to the selection of conserved active pharmacophpric fragments with positive contribution to biological immunogenic activity, developed on the basis of the KNIME-BiogenetoligandorolTM-PASS-KNIME-based GA(M)E-QSAR algorithm. The robustness of our novel cluster of chemical iniformatic stochastic low mass algorithm for heterogeneous datasets has been shown earlier. PASS can estimate qualitative (yes/no) prediction of biological activity spectra for over 4000 biological activities and, therefore, provides the basis for the preparation of a fragment library corresponding to multiple criteria. Our novel cluster of algorithms for the prediction of the total free energy interactive binding between the conserved fragment-based pharmacophore top ranked selected has been validated using th","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"67 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115115792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A mechanistic in silico molecular recognized approach for the ligand based generation of a dual N-formyl-Met-Leu-Phe (fMLP), and MMK-1peptide mimetic hyper-agonist fMLP targeted receptor against the PGE2 EP4 pathway chemotherapy-induced alopecia.","authors":"I. Grigoriadis","doi":"10.5281/ZENODO.31283","DOIUrl":"https://doi.org/10.5281/ZENODO.31283","url":null,"abstract":": It has been shown that the Oral administration for 6 days of 100 mg/kg MMK-1, of an agonist peptide selective for the FPRL1 receptor, suppressed alopecia induced by the anticancer drug etoposide in neonatal rats. However, the anti-alopecia effect of orally administered MMK-1 was inhibited by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-23848B, an antagonist of the EP4 receptor for prostaglandin (PG) E2, suggesting involvement of PGE2 release and the EP4 receptor in the oral MMK-1 anti-alopecia mechanism. The anti-alopecia effect of orally administered MMK-1 was also blocked by an inhibitor of nuclear factor-kappaB (NF-kappaB), pyrrolidine dithiocarbamate, suggesting that the oral anti-alopecia effect of MMK-1 may be mediated by activation of NF-kappaB. These results suggested that MMK-1 bound to FPRL1 receptor might suppress etoposide-induced apoptosis of hair follicle cells and alopecia by way of PGE2 release and NF-kappaB activation. Previously, it has also been found that an intraperitoneally administered chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), and MMK-1, functional anti-cancer neo-ligand motif like peptide-mimic molecule motif generally have more accurate human cancer stem cells targeted to functional anti-cancer neo-ligand motif like peptide-mimic molecule -boundaries in terms of residue-level accuracy. In this Scientific Project the optimal α and β are set as 0.8 and 0.6 respectively. To evaluate IRLC, we first define M as the mean conservation score of N residues within a predicted where C i is the conservation score representing the degree of motif-like peptide conservation of a residue in position i of the predicted functional anti-cancer neo-ligand motif like peptide-mimic molecule; C i can be calculated by any suitable scoring metric, while in our experiment, position specific scoring matrix (PSSM) was used to evaluate residue conservation; the conservation score of a residue in the position i' of a sequence was obtained from the corresponding column of the residue in the i'-th row of the PSSM of the sequence. The PSSM of each query sequence was gene human cancer stem cell by three human cancer stem cell regions of PSI-BLAST [40] searches against NCBI non-redundant database with the BLOSUM62 substitution matrix and E-value threshold of 0.001. Second, we define IRLC j as the IRLC score for a flanking residue j: Where the flanking residues are defined as the residues within 5 amino acids away from the predicted functional anti-cancer neo-ligand motif like peptidomimic molecule, and σ represents the standard deviation of the conservation scores of all the residues in the sequence. A functional anticancer neo-ligand motif like peptidomimic molecule prediction will be determined as a false positive prediction if its IRLC score is higher than some threshold value T. The human cancer stem cells regional is that if there is any residue in the flanking region that is much more conserved than the average conservation sco","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125980606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In vivo and in vitro models of bromodomain and extraterminal domain inhibitor-induced intestinal stem cell loss and villous atrophy reveal differential human vs pre-clinal species sensitivity","authors":"P. Newham","doi":"10.5281/ZENODO.31218","DOIUrl":"https://doi.org/10.5281/ZENODO.31218","url":null,"abstract":"","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133675180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rakesh Yadav, A. Kuhad, K. Pandey, Divya Gumber, Radha Sharma, D. Yadav
{"title":"Synthesis and Evaluation of some newer Hybrids of Diclofenac Acid and 1,3,4-Oxadiazole: Reduction of Ulceration with Anti-Inflammatory Activity","authors":"Rakesh Yadav, A. Kuhad, K. Pandey, Divya Gumber, Radha Sharma, D. Yadav","doi":"10.5281/zenodo.31483","DOIUrl":"https://doi.org/10.5281/zenodo.31483","url":null,"abstract":"Inflammation is a tissue reaction to infection, injury, irritation etc. and is a part of host defense mechanism. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain, inflammation and arthritis. In 1971, Vane and coworkers made the landmark observation that NSAIDs acts by blocking generation of certain chemicals such as prostaglandins (PGs) by the enzyme cyclooxygenase (COX). Diclofenac, an aryl-acetic acid derivative a non-steroidal anti-inflammatory (NSAID) drug inhibits PG synthesis. Sodium salt of diclofenac is one of the most frequently used NSAIDs worldwide (5 million prescriptions are filled yearly) and was approved in the US firstly in the year 1988. The presence of free carboxylic acid moiety in the diclofenac is mainly responsible for the associated side effects such as gastric ulceration. Several studies describes the derivatization of the carboxylate function of NSAIDs with less acidic azoles, viz. 1, 3, 4-oxadiazole, etc. which resulted in an increased anti-inflammatory activity with reduced ulcerogenicity. Seven new hybrids of 1,3,4-oxadiazole and diclofenac acid was synthesized to decrease the side effects associated with the acidic function of diclofenac acid such as gastric ulceration to increase the anti-inflammatory activity ( Scheme-1 ). The synthesized derivatives were evaluated for their anti-inflammatory & anti ulcer activity using various animal models. Among the synthesized derivatives, the compound 6c was found to be most active as compared to the standard diclofenac sodium.","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114241891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapid monoclonality verification methods to boost cell line development","authors":"M. McPate, Mio Muelthaler, Wilson Lew","doi":"10.5281/zenodo.31219","DOIUrl":"https://doi.org/10.5281/zenodo.31219","url":null,"abstract":"Figure 2. CloneSelect Imager FL software fluorescence image view of well B1 from the plate in Figure 1. In the middle shows the CellTracker Green fluorescence from a CHO-S cell (circled). On the top right (arrowed), there is a well layout that shows the zoomed image location (boxed) and the location of the cell in the well (red spot). The use of fluorescence and the well layout make it simple to locate the cell within the well.","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133696561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ULTRASENSITIVE MEASUREMENT OF MUTANT HUNTINGTIN IN HUMAN CSF AND RODENT SAMPLES","authors":"V. Fodale","doi":"10.5281/zenodo.31251","DOIUrl":"https://doi.org/10.5281/zenodo.31251","url":null,"abstract":"","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129624099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Computational Methods in GPCR Mechanism Study and Drug Discovery","authors":"Shuguang Yuan","doi":"10.5281/ZENODO.31248","DOIUrl":"https://doi.org/10.5281/ZENODO.31248","url":null,"abstract":"","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"403 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131852118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Kolb, M. Lutolf, A. J. Vlies, Katarzyna A Mosiewicz, N. Gjorevski
{"title":"Microscale hydrogel patterning to manipulate stem cell fate","authors":"Laura Kolb, M. Lutolf, A. J. Vlies, Katarzyna A Mosiewicz, N. Gjorevski","doi":"10.5281/ZENODO.31259","DOIUrl":"https://doi.org/10.5281/ZENODO.31259","url":null,"abstract":"","PeriodicalId":315352,"journal":{"name":"Basel Life Science Week","volume":"41 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133242848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}