Testing of thin-walled steel joints fabricated by spot welding and plug welding

Selected methods of joining which can be used for manufacturing and repairing of car bodies by means of welding are presented in this article. Three kinds of 1 mm-thick steel sheets were used in the tests: deep drawing steel (DC04) and two-phase steels of increased high strength (DP600 and DP800). The comparative connections were carried out by means of resistance spot welding and with plug joints made by means of the MAG method and through braze welding. Comparative assessment of the strength and geometrical parameters of the test joints was then conducted.     

Effect of thymol on microbial diversity in the porcine jejunum

Thirty two weaned pigs (24 d-old) were fed a diet without or with 1% (w/w) thymol. Pigs from each dietary treatment remained unchallenged or were challenged with Salmonella enterica serovar typhimurium. Jejunal content was collected and molecular microbial diversity was investigated using 16S rRNA gene polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Shannon index analysis showed no differences in diversity but Pearson coefficient analysis showed clear clustering of profiles, which delineated thymol fed and control groups irrespective of Salmonella challenge. Moreover, absence of bands corresponding to Actinobacillus minor (98-99% identity) was observed in thymol groups. A band corresponding to Citrobacter freundii (98% identity) was observed in almost all pigs from thymol groups, and only in 4 samples from pigs fed no thymol in the diet. Supplementation of pig diet with thymol caused clear changes in small intestine microbacterial community. Surprisingly, Salmonella infection caused no major perturbations to the community structure.     

Activation of dispersed PtSn/C nanoparticles by tungsten oxide matrix towards more efficient oxidation of ethanol

A novel electrocatalytic system for oxidation of ethanol, in which carbon-supported PtSn nanoparticles were modified with ultra-thin films/deposits of tungsten oxide, was proposed, fabricated and characterized here using electrochemical as well as spectroscopic (X-ray diffraction) and microscopic (transmission electron) techniques. The enhancement effect was evident from comparative diagnostic electrochemical experiments utilizing WO₃-modified and bare (unmodified) PtSn nanoparticles in acid medium (0.5 mol dm⁻³ H₂SO₄) at room temperature in the presence of ethanol. It is noteworthy that, the chronoamperometric electrocatalytic currents measured at potentials as low as 0.3 V (vs. RHE) were significantly larger for WO₃-modified PtSn/C relative to bare PtSn/C. In another diagnostic “stripping” experiment, it was found that oxidation of CO-adsorbate occurred in the presence of WO₃ at potentials almost 100 mV lower in comparison to the unmodified system. The overall activation effect may have origin in interactions of tungsten oxide with tin (from PtSn alloy nanoparticles) leading to stabilization of the catalytic tin oxo species. WO₃ may also provide large population of reactive oxo groups at the Pt/Sn-based electrocatalytic interface.     

The Mutation in wbaP cps Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of Klebsiella pneumoniae

Klebsiella pneumoniae is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting K. pneumoniae against the immune response and thus may be targeted by phage-based therapeutics such as polysaccharides-degrading enzymes. Since the emergence of resistance to antibacterials is generally considered undesirable, in this study, the genetic and phenotypic characteristics of resistance to the phage-borne CPS-degrading depolymerase and its effect on K. pneumoniae virulence were investigated. The K63 serotype targeting depolymerase (KP36gp50) derived from Klebsiella siphovirus KP36 was used as the selective agent during the treatment of K. pneumoniae 486 biofilm. Genome-driven examination combined with the surface polysaccharide structural analysis of resistant mutant showed the point mutation and frameshift in the wbaP gene located within the cps gene cluster, resulting in the loss of the capsule. The sharp decline in the yield of CPS was accompanied by the production of a larger amount of smooth LPS. The modification of the surface polysaccharide layers did not affect bacterial fitness nor the insensitivity to serum complement; however, it made bacteria more prone to phagocytosis combined with the higher adherence and internalization to human lung epithelial cells. In that context, it was showed that the emerging resistance to the antivirulence agent (phage-borne capsule depolymerase) results in beneficial consequences, i.e., the sensitization to the innate immune response.     

Role of RNA Motifs in RNA Interaction with Membrane Lipid Rafts: Implications for Therapeutic Applications of Exosomal RNAs

RNA motifs may promote interactions with exosomes (EXO-motifs) and lipid rafts (RAFT-motifs) that are enriched in exosomal membranes. These interactions can promote selective RNA loading into exosomes. We quantified the affinity between RNA aptamers containing various EXO- and RAFT-motifs and membrane lipid rafts in a liposome model of exosomes by determining the dissociation constants. Analysis of the secondary structure of RNA molecules provided data about the possible location of EXO- and RAFT-motifs within the RNA structure. The affinity of RNAs containing RAFT-motifs (UUGU, UCCC, CUCC, CCCU) and some EXO-motifs (CCCU, UCCU) to rafted liposomes is higher in comparison to aptamers without these motifs, suggesting direct RNA-exosome interaction. We have confirmed these results through the determination of the dissociation constant values of exosome-RNA aptamer complexes. RNAs containing EXO-motifs GGAG or UGAG have substantially lower affinity to lipid rafts, suggesting indirect RNA-exosome interaction via RNA binding proteins. Bioinformatics analysis revealed RNA aptamers containing both raft- and miRNA-binding motifs and involvement of raft-binding motifs UCCCU and CUCCC. A strategy is proposed for using functional RNA aptamers (fRNAa) containing both RAFT-motif and a therapeutic motif (e.g., miRNA inhibitor) to selectively introduce RNAs into exosomes for fRNAa delivery to target cells for personalized therapy.     

Blockade of Serotonin 5-HT6 Receptor Constitutive Activity Alleviates Cognitive Deficits in a Preclinical Model of Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a common inherited disorder caused by mutations of the NF1 gene that encodes the Ras-GTPase activating protein neurofibromin, leading to overactivation of Ras-dependent signaling pathways such as the mTOR pathway. It is often characterized by a broad range of cognitive symptoms that are currently untreated. The serotonin 5-HT₆ receptor is a potentially relevant target in view of its ability to associate with neurofibromin and to engage the mTOR pathway to compromise cognition in several cognitive impairment paradigms. Here, we show that constitutively active 5-HT₆ receptors contribute to increased mTOR activity in the brain of Nf1^+/− mice, a preclinical model recapitulating some behavioral alterations of NF1. Correspondingly, peripheral administration of SB258585, a 5-HT₆ receptor inverse agonist, or rapamycin, abolished deficits in long-term social and associative memories in Nf1^+/− mice, whereas administration of CPPQ, a neutral antagonist, did not produce cognitive improvement. These results show a key influence of mTOR activation by constitutively active 5-HT₆ receptors in NF1 cognitive symptoms. They provide a proof of concept that 5-HT₆ receptor inverse agonists already in clinical development as symptomatic treatments to reduce cognitive decline in dementia and psychoses, might be repurposed as therapies alleviating cognitive deficits in NF1 patients.     

Small-Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer

The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the N⁶ atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high-throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3.     

Long-term cyclability of nanostructured LiFePO4

Amorphous LiFePO₄ was obtained by lithiation of FePO₄ synthesized by spontaneous precipitation from equimolar aqueous solutions of Fe(NH₄)₂(SO₄)₂·6H₂O and NH₄H₂PO₄, using hydrogen peroxide as oxidizing agent. Nano-crystalline LiFePO₄ was obtained by heating amorphous nano-sized LiFePO₄ for different periods of time. The materials were characterized by TG, DTA, X-ray powder diffraction, scanning electron microscopy (SEM) and BET. All materials showed very good electrochemical performance in terms of energy and power density. Upon cycling, a capacity fading affected the materials, thus reducing the electrochemical performance. Nevertheless, the fading decreased upon cycling and after the 200th cycle the cell was able to cycle for more than 500 cycles without further fading.