A total of 11 REF and 9 BRIX studies were available. The meta-analytic methods allowed reporting variation of the true and false positive rate across and among all reported cut-offs. Pooled points estimates (95 % Bayesian credible intervals) for sensitivity (Se) and specificity (Sp) of REF less then 5.5 g/L were 86.1 % (68.5-97.9%) and 76.2 % (65.9-88.4%) whereas BRIX less then 8.4 % was associated with Se of 91.6 % (77.2-99.5%) and Sp of 88.2 % (65.4-99.8%). Interestingly, the accuracy (Se + Sp-1) was generally higher for BRIX than for REF at the reported cut-offs. Besides the benefit of providing pooled estimates for all reported and unreported BRIX and REF thresholds, the general framework used in this study could potentially be used in many veterinary diagnostic tests studies that reported multiple thresholds accounting for potentially different tests distributions in population with and without the target condition.Chemotaxis is the process of sensing chemical gradients and navigating towards favourable conditions. Bacterial chemotaxis is mediated by arrays of trans-membrane chemoreceptor proteins. The most common class of chemoreceptors have periplasmic ligand-binding domains (LBDs) that detect extracellular chemical signs and transduce these signals to the downstream chemotaxis machinery. The repertoire of chemoreceptor proteins in a bacterium determines the range of environmental signals to which it can respond. Pseudomonas syringae pv. actinidiae (Psa) is a plant pathogen which causes bacterial canker of kiwifruit (Actinidia sp.). Compared to many other bacteria, Psa has a large number of chemoreceptors encoded in its genome (43) and most of these remain uncharacterized. A previous study identified PscC as a potential chemoreceptor for l-proline and other amino acid ligands. Here, we have characterized the interaction of PscC-LBD with l-proline using a combination of isothermal titration calorimetry (ITC) and X-ray crystallography. ITC confirmed direct binding of l-proline to PscC-LBD with KD value of 5.0 μM. We determined the structure of PscC-LBD in complex with l-proline. Our structural analysis showed that PscC-LBD adopts similar double-CACHE fold to several other amino acid chemoreceptors. A comparison of the PscC-LDB to other dCACHE structures highlights residues in the binding cavity which contribute to its ligand specificity.Protein kinase CK1δ expression and activity is involved in different pathological situations that include neuroinflammatory and neurodegenerative diseases. For this reason, protein kinase CK1δ has become a possible therapeutic target for these conditions. 5,6-fused bicyclic heteroaromatic systems that resemble adenine of ATP represent optimal scaffolds for the development of a new class of ATP competitive CK1δ inhibitors.  https://www.selleckchem.com/products/nik-smi1.html  In particular, a new series of [1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-a][1,3,5]triazines was developed. Some crucial interactors have been identified, such as the presence of a free amino group able to interact with the residues of the hinge region at the 5- and 7- positions of the [1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-a][1,3,5]triazine scaffolds, respectively; or the presence of a 3-hydroxyphenyl or 3,5-dihydroxyphenyl moiety at the 2- position of both nuclei. Molecular modeling studies identified the key interactions involved in the inhibitor-protein recognition process that appropriately fit with the outlined structure-activity relationship. Considering the fact that the CK1 protein kinase is involved in various pathologies in particular of the central nervous system, the interest in the development of new inhibitors permeable to the blood-brain barrier represents today an important goal in the pharmaceutical field. The best potent compound of the series is the 5-(7-amino-5-(benzylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)benzen-1,3-diol (compound 51, IC50 = 0.18 μM) that was predicted to have an intermediate ability to cross the membrane in our in vitro assay and represents an optimal starting point to both studies the therapeutic value of protein kinase CK1δ inhibition and to develop new more potent derivatives.Small-molecule kinase inhibitors are being continuously explored as new anticancer therapeutics. Kinases are the phosphorylating enzymes which regulate numerous cellular functions such as proliferation, differentiation, migration, metabolism, and angiogenesis by activating several signalling pathways. Kinases have also been frequently found to be deregulated and overexpressed in cancerous tissues. Therefore, modulating the kinase activity by employing small molecules has emerged as a strategic approach for cancer treatment. On the other hand, oxindole motifs have surfaced as privileged scaffolds with significant multi-kinase inhibitory activity. The present review summarises recent advances in the development of oxindole based kinase inhibitors. The role of distinguished structural frameworks of oxindoles, such as 3-alkenyl oxindoles, spirooxindoles, 3-iminooxindoles and similar hydrazone derivatives have been described based on their kinase inhibition potential. Furthermore, the design strategies, mechanism of actions, structure activity relationships (SARs) and their mode of interaction with target protein have been critically highlighted.We describe the use of natural product combretastatin A4 (CA4) as a versatile new payload for the construction of antibody-drug conjugates (ADCs). Cetuximab conjugates consisting of CA4 derivatives were site-specially prepared by disulfide re-bridging approach using cleavable and non-cleavable linkers. These ADCs retained antigen binding and internalization efficiency and exhibited high potencies against cancer cell lines in vitro. The conjugates also demonstrated significant antitumor activities in EGFR-positive xenograft models without observed toxicities. CA4 appears to be a viable payload option for ADCs research and development.Organic aromatic compounds used for dyeing and coloring in the textile industry are persistent and hazardous pollutants that must be treated before they are discharged into rivers and surface waters. Therefore, we investigated the potential of the white rot fungus Phanerochaete velutina to decolorize commonly used reactive dyes. The fungus decolorized in average 55% of Reactive Orange 16 (RO-16) after 14 days at a maximum rate of 0.09 d-1 and a half-life of 8 days. Furthermore, we determined the inhibitory effects of co-present inorganic contaminants Nickel (Ni) and Cobalt (Co) salts on the decolorization potential and determined IC50 values of 5.55 mg l-1 for Co and a weaker inhibition by Ni starting from a concentration of 20 mg l-1. In the decolorization assay for Remazol Brilliant Blue R (RBBR) we observed the interference of a metabolite of P. velutina, which did not allow us to investigate the kinetics of the reaction. The formation of the metabolite, however, could be used to obtain IC50 values of 3.37 mg l-1 for Co and 7.