Computational biology tools in design of an agrochemical against Xyllela fastidiosa.

Xylella fastidiosa is a Gram-negative, non-flagellated bacterium that causes CVC in citrus and Pierce?s disease in grapevines. The CVC affects 40% of the 200 million orange trees in São Paulo state. It colonizes the xylem vessels of the plants, blocking the water and nutrient flows. PilT protein is a part of the motility system and very important for Xyllela pathogenicity and our protein target for drug design. Computational biology tools were used to design the compound able to inhibit the formation of the PilT hexamer, leading to loss of Xyllela pathogenicity. This approach could be employed in the development of new inhibitors against different targets belonging to the same protein family of PilT

Computational Biology tools in design of an agrochemical against Xylella fastidiosa.

Since its pathogenicity is related to bacterial motility, the protein PilT from the twitching motility system has been chosen as the host target. Using rational drug design, based on a detailed comprehension of the protein host structure, small molecules were designed in order to block the activity of the protein and provoke the loss of the bacterium pathogenicity.C.016

Heavy-tailed kernels reveal a finer cluster structure in t-SNE visualisations

T-distributed stochastic neighbour embedding (t-SNE) is a widely used data visualisation technique. It differs from its predecessor SNE by the low-dimensional similarity kernel: the Gaussian kernel was replaced by the heavy-tailed Cauchy kernel, solving the "crowding problem" of SNE. Here, we develop an efficient implementation of t-SNE for a $t$-distribution kernel with an arbitrary degree of freedom $\nu$, with $\nu\to\infty$ corresponding to SNE and $\nu=1$ corresponding to the standard t-SNE. Using theoretical analysis and toy examples, we show that $\nu<1$ can further reduce the crowding problem and reveal finer cluster structure that is invisible in standard t-SNE. We further demonstrate the striking effect of heavier-tailed kernels on large real-life data sets such as MNIST, single-cell RNA-sequencing data, and the HathiTrust library. We use domain knowledge to confirm that the revealed clusters are meaningful. Overall, we argue that modifying the tail heaviness of the t-SNE kernel can yield additional insight into the cluster structure of the data

Mapping contacts between regulatory domains of skeletal muscle TnC and Tnl by analyses of a single-chain chimeras.

The troponin (Tn) complex is formed by TnC, TnI and TnT and is responsible for the calcium-dependent inhibition of muscle contraction. TnC and TnI interact in an antiparallel fashion in which the N domain of TnC binds in a calcium-dependent manner to the C domain of TnI, releasing the inhibitory effect of the latter on the actomyosin interaction. While the crystal structure of the core cardiac muscle troponin complex has been determined, very little high resolution information is available regarding the skeletal muscle TnITnC complex. With the aim of obtaining structural information regarding specific contacts between skeletal muscle TnC and TnI regulatory domains, we have constructed two recombinant chimeric proteins composed of the residues 191 of TnC linked to residues 98182 or 98147 of TnI. The polypeptides were capable of binding to the thin filament in a calcium-dependent manner and to regulate the ATPase reaction of actomyosin. Small angle X-ray scattering results showed that these chimeras fold into compact structures in which the inhibitory plus the C domain of TnI, with the exception of residues 148182, were in close contact with the N-terminal domain of TnC. CD and fluorescence analysis were consistent with the view that the last residues of TnI (148182) are not well folded in the complex. MS analysis of fragments produced by limited trypsinolysis showed that the whole TnC N domain was resistant to proteolysis, both in the presence and in the absence of calcium. On the other hand the TnI inhibitory and C-terminal domains were completely digested by trypsin in the absence of calcium while the addition of calcium results in the protection of only residues 114137

A pedagogical model for effective online teacher professional development—findings from the Teacher Academy initiative of the European Commission

During their careers, teachers experience change in education policy, societal trends, and cultural shifts in pedagogical thought, requiring continual adaptation and innovation of their practices. Coupled with this is an assumed intrinsic desire to progress, whether as part of their own subject expertise, or with a view to taking on a role as leader in school management or a specialist area. Effective support and opportunities for teachers to develop and apply their competences is crucial for maintaining both motivation and high standards in the profession. However, many teachers across Europe claim to struggle to have access to effective forms of continued professional development coupled with the numerous demands already made on their work. On-site courses with opportunities for peer learning remain popular but demand time and are not financially cost-effective in reaching a large number of teachers, nor are they viable during pandemic restrictions. By exploring the pedagogical model of the online courses of the European Commission's Teacher Academy in the context of these challenges, this article discusses how an effective, collaborative approach to online continued professional development can be developed as a way of addressing both teacher and education system needs

A protocol for fish lipid analysis using nuclear magnetic resonance spectroscopy

This article reports on an easy-to-follow methodology for fish lipids analysis, including the biological sample collection, lipid extraction, sample preparation, nuclear magnetic resonance (NMR) spectroscopy analysis and statistical data analysis, with details on parameters used for the NMR analysis and the care needed in each step execution. As an example of the biological matrix of lipids, for the entire procedure, we have used two Amazonian fish samples. Phenotype factor was taken into account when lipid contents of the Amazonian fish samples were evaluated, such as fish-eating habits in distinct Amazon seasonal periods, the flood and the drought. Results demonstrated the applicability of NMR as a powerful and useful tool for fish oil analysis. The omnivorous (T. elongatus) and the piscivorous (C. monoculus) Amazonian fish differ in composition and distribution of lipids, which show differences not only because of the different eating habits between the two species, but also by the availability and quantity of food along the year, i.e., during the flood and drought Amazon periods. ©2020 Sociedade Brasileira de Químic

Insights in Osteosarcoma by Proton Nuclear Magnetic Resonance Serum Metabonomics

Pediatric osteosarcoma outcomes have improved over the last decades; however, patients who do not achieve a full resection of the tumor, even after aggressive chemotherapy, have the worst prognosis. At a genetic level, osteosarcoma presents many alterations, but there is scarce information on alterations at metabolomic levels. Therefore, an untargeted nuclear magnetic resonance metabonomic approach was used to reveal blood serum alterations, when samples were taken from 21 patients with osteosarcoma aged from 12–20 (18, 86%) to 43 (3, 14%) years before any anticancer therapy were collected. The results showed that metabolites differed greatly between osteosarcoma and healthy control serum samples, especially in lipids, aromatic amino acids (phenylalanine and tyrosine), and histidine concentrations. Besides, most of the loading plots point to protons of the fatty acyls (-CH3 and -CH2-) from very-low- and low-density lipoproteins and cholesterol, as crucial metabolites for discrimination of the patients with osteosarcoma from the healthy samples. The relevance of blood lipids in osteosarcoma was highlighted when analyzed together with the somatic mutations disclosed in tumor samples from the same cohort of patients, where six genes linked to the cholesterol metabolism were found being altered too. The high consistency of the discrimination between osteosarcoma and healthy control blood serum suggests that nuclear magnetic resonance could be successfully applied for osteosarcoma diagnostic and prognostic purposes, which could ameliorate the clinical efficacy of therapy