381 research outputs found
Adenine Nucleotide Translocase 1 Expression is Coupled to the HSP27-Mediated TLR4 Signaling in Cardiomyocytes
The cardiac-specific overexpression of the adenine nucleotide translocase 1 (ANT1) has cardioprotective effects in various experimental heart disease models. Here, we analyzed the link between ANT1 expression and heat shock protein 27 (HSP27)-mediated toll-like receptor 4 (TLR4) signaling, which represents a novel communication pathway between mitochondria and the extracellular environment. The interaction between ANT1 and HSP27 was identified by co-immunoprecipitation from neonatal rat cardiomyocytes. ANT1 transgenic (ANT1-TG) cardiomyocytes demonstrated elevated HSP27 expression levels. Increased levels of HSP27 were released from the ANT1-TG cardiomyocytes under both normoxic and hypoxic conditions. Extracellular HSP27 stimulated TLR4 signaling via protein kinase B (AKT). The HSP27-mediated activation of the TLR4 pathway was more pronounced in ANT1-TG cardiomyocytes than in wild-type (WT) cardiomyocytes. HSP27-specific antibodies inhibited TLR4 activation and the expression of HSP27. Inhibition of the HSP27-mediated TLR4 signaling pathway with the TLR4 inhibitor oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) reduced the mitochondrial membrane potential (âĎm) and increased caspase 3/7 activity, which are both markers for cell stress. Conversely, treating cardiomyocytes with recombinant HSP27 protein stimulated TLR4 signaling, induced HSP27 and ANT1 expression, and stabilized the mitochondrial membrane potential. The activation of HSP27 signaling was verified in ischemic ANT1-TG heart tissue, where it correlated with ANT1 expression and the tightness of the inner mitochondrial membrane. Our study shows a new mechanism by which ANT1 is part of the cardioprotective HSP27-mediated TLR4 signaling
Teachersâ Beliefs Concerning Teaching Multilingual Learners: A Cross-Cultural Comparison Between the US and Germany
We analysed the beliefs about multilingualism in school of in-service teachers from the US (n = 60) and Germany (n = 65), utilising a survey originally developed in German that was translated and adapted into English. Results show that teachers from both samples, on average, strongly agree that a personâs identity is connected to their language and culture. However, we found significant differences in scale mean values between US teachers and German teachers concerning their beliefs about (1) the interconnected nature of language with culture and identity, (2) language demand in content classrooms, (3) responsibility for language teaching, and (4) valuing multilingualism. Our results provide insight into cross-cultural differences between German and US teachersâ beliefs, as well as a strong instrument in two languages to measure teachersâ beliefs about multilingualism in schools
Qualitative and Quantitative Comparison of LiquidâLiquid Phase Extraction Using Ethyl Acetate and LiquidâSolid Phase Extraction Using Poly-Benzyl-Resin for Natural Products
A key step in the process of isolating microbial natural products is the preparation of an
extract from a culture. This step determines which molecules will be available for detection in the
subsequent chemical and biological analysis of a biodiscovery pipeline. In the present study we
wanted to document potential differences in performance between liquidâliquid extraction using
ethyl acetate and liquidâsolid extraction using a polyâbenzylâresin. For the comparison of the two
extraction protocols, we spiked a culture of Flavobacterium sp. with a diverse selection of natural
products of microbial and plant origin to investigate whether the methods were comparable with
respect to selectivity. We also investigated the efficiency of the two extraction methods quantitaâ
tively, using water spiked with a selection of natural products, and studied the quantitative effect
of different pH levels of the aqueous solutions on the extraction yields of the two methods. The
same compounds were extracted by the two methods, but the solidâphase extract contained more
media components compared with the liquidâphase extract. Quantitatively, the two extraction
methods varied in their recovery rates. We conclude that practical aspects could be more important
when selecting one of the extraction protocols, as their efficiencies in extracting specific compounds
were quite similar
Selective isolation of Arctic marine actinobacteria and a down-scaled fermentation and extraction strategy for identifying bioactive compounds
Actinobacteria are among the most prolific producers of bioactive secondary metabolites. In order to collect Arctic marine bacteria for the discovery of new bioactive metabolites, actinobacteria were selectively isolated during a research cruise in the Greenland Sea, Norwegian Sea and the Barents Sea. In the frame of the isolation campaign, it was investigated how different sample treatments, isolation media and sample-sources, such as animals and sediments, affected the yield of actinobacterial isolates to aid further isolation campaigns. Special attention was given to sediments, where we expected spores of spore forming bacteria to enrich. Beside actinobacteria a high share of bacilli was obtained which was not desired. An experimental protocol for down-scaled cultivation and extraction was tested and compared with an established low-throughput cultivation and extraction protocol. The heat-shock method proved suitable to enrich spore-, or endospore forming bacteria such as bacilli. Finally, a group bioactive compounds could be tentatively identified using UHPLCâMS/MS analysis of the active fractions.publishedVersio
Structural elements in the oxidation process of a single cobalt layer on Ir(100)-(1 Ă 1)
The ordered phases developing in sequence by oxidation of a single monolayer of cobalt deposited on Ir(100)-(1 Ă 1) were investigated by low-energy electron diffraction (LEED), scanning tunneling microscopy, and thermal desorption spectroscopy. It turns out that the structural elements of the different phases observed for increasing oxygen content and analyzed by quantitative LEED are pyramids based on squares or triangles made up by cobalt species and oxygen on top. The Co-O bond lengths are smaller than in the bulk of cobalt oxide owing to the reduced coordination of oxygen. For O:Co ratios of r = 1/4, 1/2, and 5/8, the bonding of the oxide to the iridium substrate is merely by the cobalt species, and at r = 1 it is via both Co and O
The Static and Dynamic Lattice Changes Induced by Hydrogen Adsorption on NiAl(110)
Static and dynamic changes induced by adsorption of atomic hydrogen on the
NiAl(110) lattice at 130 K have been examined as a function of adsorbate
coverage. Adsorbed hydrogen exists in three distinct phases. At low coverages
the hydrogen is itinerant because of quantum tunneling between sites and
exhibits no observable vibrational modes. Between 0.4 ML and 0.6 ML, substrate
mediated interactions produce an ordered superstructure with c(2x2) symmetry,
and at higher coverages, hydrogen exists as a disordered lattice gas. This
picture of how hydrogen interacts with NiAl(110) is developed from our data and
compared to current theoretical predictions.Comment: 36 pages, including 12 figures, 2 tables and 58 reference
Acetylcholine receptors (muscarinic) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Muscarinic acetylcholine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [45]) are GPCRs of the Class A, rhodopsin-like family where the endogenous agonist is acetylcholine. In addition to the agents listed in the table, AC-42, its structural analogues AC-260584 and 77-LH-28-1, N-desmethylclozapine, TBPB and LuAE51090 have been described as functionally selective agonists of the M1 receptor subtype via binding in a mode distinct from that utilized by non-selective agonists [243, 242, 253, 155, 154, 181, 137, 11, 230]. There are two pharmacologically characterised allosteric sites on muscarinic receptors, one defined by it binding gallamine, strychnine and brucine, and the other defined by the binding of KT 5720, WIN 62,577, WIN 51,708 and staurosporine [161, 162]
Acetylcholine receptors (muscarinic) in GtoPdb v.2021.3
Muscarinic acetylcholine receptors (mAChRs) (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [50]) are activated by the endogenous agonist acetylcholine. All five (M1-M5) mAChRs are ubiquitously expressed in the human body and are therefore attractive targets for many disorders. Functionally, M1, M3, and M5 mAChRs preferentially couple to Gq/11 proteins, whilst M2 and M4 mAChRs predominantly couple to Gi/o proteins. Both agonists and antagonists of mAChRs are clinically approved drugs, including pilocarpine for the treatment of elevated intra-ocular pressure and glaucoma, and atropine for the treatment of bradycardia and poisoning by muscarinic agents such as organophosphates
Acetylcholine receptors (muscarinic) in GtoPdb v.2023.1
Muscarinic acetylcholine receptors (mAChRs) (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [53]) are activated by the endogenous agonist acetylcholine. All five (M1-M5) mAChRs are ubiquitously expressed in the human body and are therefore attractive targets for many disorders. Functionally, M1, M3, and M5 mAChRs preferentially couple to Gq/11 proteins, whilst M2 and M4 mAChRs predominantly couple to Gi/o proteins. Both agonists and antagonists of mAChRs are clinically approved drugs, including pilocarpine for the treatment of elevated intra-ocular pressure and glaucoma, and atropine for the treatment of bradycardia and poisoning by muscarinic agents such as organophosphates. Of note, it has been observed that mAChRs dimerise reversibly [134] and that dimerisation/oligomerisation can be affected by ligands [183, 196]
Synthetic biology approaches in drug discovery and pharmaceutical biotechnology
Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology
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