Karyotype characterization of Eurysternus caribaeus: the smallest diploid number among Scarabaeidae (Coleoptera: Scarabaeoidea)

Eurysternus caribaeus was analyzed cytologically by conventional chromosomal staining. The species presents a diploid number of 2n=8, chromosomes with two arms and an XY sex determining mechanism. This is the first karyotype described for the genus Eurysternus and the tribe Eurysternini, and is also the smallest diploid number observed in the family Scarabaeidae and superfamily Scarabaeoidea.     

Antiplasmodial Drugs in the Gas Phase: A CID and DFT Study of Quinolon-4(1H)-Imine Derivatives

The gas-phase behavior of 12 quinolon-4(1H)-imine derivatives with antiplasmodial activity was investigated using electrospray ionization tandem mass spectrometry together with collision induced dissociation and density functional theory (DFT) calculations. The most probable protonation site was predicted by calculating the proton affinity (PA) values for each possible protonation site and it was found to be the imine nitrogen for all compounds under study. Fragmentation pathways of the protonated molecules were proposed and the assignment of product ion structures was performed taking into account theoretical calculations. The nature of the quinoline substituent was found to influence the gas-phase behavior of the compounds under study. The data acquired allowed to bracket the proton affinity of the quinolin-4-imine scaffold, which can be a useful starting point to choose appropriate references for determining PA values of this scaffold. Figure

?     

Polymeric biocomposites of poly (butylene adipate-co-terephthalate) reinforced with natural Munguba fibers

In this work, polymeric biocomposites of poly (butylene adipate-co-terephthalate), PBAT, were reinforced with Munguba fibers (Pseudobombax munguba). This tree is found in great abundance in the marshy areas of the Amazon forest. The motivation for using this fiber in polymer composites comes from the fact that although research for this fiber has not been reported in the scientific literature, it is commonly used by the local population because its bark is strong and flexible. Most important is that the extraction of Munguba fibers does not damage the supplier tree because as it is extracted from the bark, its regeneration starts as it is removed. The fibers were chemically treated by mercerization/acetylation and evaluated by Fourier transform infrared spectroscopy, thermogravimetric analysis and tensile tests. The Munguba fiber presented mechanical properties similar to those of other natural fibers traditionally used in composites, and the chemical treatment provided improvements of its thermal stability and stiffness. The biocomposites showed a better elastic modulus in relation to the pure PBAT. The addition of fibers caused changes in the T _g, T _m and T _c of PBAT as observed by differential scanning calorimetry analysis. The Russel, Halpin-Tsai and Maxwell models were employed to provide the theoretical elastic modulus of the biocomposites.     

Geometric finite-time inner-outer loop trajectory tracking control strategy for quadrotor slung-load transportation

Nonlinear Dynamics - This paper presents a geometric finite-time inner-outer loop control strategy for slung payload transportation using a quadrotor. The underactuated nature of the quadrotor in...     

Indoxyl sulfate- and P-cresol-induced monocyte adhesion and migration is mediated by integrin-linked kinase-dependent podosome formation

Cardiovascular disease is an important cause of death in patients with chronic kidney disease (CKD). Protein-bound uremic toxins, such as p-cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction and leukocyte extravasation. These processes can be related to dynamic adhesion structures called podosomes. Several studies have indicated the role of integrin-linked kinase (ILK) in the accumulation of integrin-associated proteins in podosomes. Here, we investigated the involvement of ILK and podosome formation in the adhesion and extravasation of monocytes under p-cresol (pc) and IS exposure. Incubation of THP-1 human monocyte cells with these toxins upregulated ILK kinase activity. Together, both toxins increased cell adhesion, podosome formation, extracellular matrix degradation, and migration of THP-1 cells, whereas ILK depletion with specific small interfering RNAs suppressed these processes. Interestingly, F-actin colocalized with cortactin in podosome cores, while ILK was colocalized in podosome rings under toxin stimulation. Podosome Wiskott-Aldrich syndrome protein (WASP)-interacting protein (WIP) and AKT protein depletion demonstrated that monocyte adhesion depends on podosome formation and that the ILK/AKT signaling pathway is involved in these processes. Ex vivo experiments showed that both toxins induced adhesion and podosome formation in leukocytes from wild-type mice, whereas these effects were not observed in leukocytes of conditional ILK-knockdown animals. In summary, under pc and IS stimulation, monocytes increase podosome formation and transmigratory capacity through an ILK/AKT signaling pathway-dependent mechanism, which could lead to vascular injury. Therefore, ILK could be a potential therapeutic target for the treatment of vascular damage associated with CKD.Subject terms: Experimental models of disease, Atherosclerosis, Mechanisms of disease, Integrins, End-stage renal disease     

Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development,Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literature. In this review, we discuss the development of proteasome inhibitors and the mechanisms of innate and acquired resistance to their activity—a major challenge in preclinical and clinical therapeutics. An improved understanding of these mechanisms is crucial to guiding the design of new and more effective drugs to tackle these devastating diseases. In addition, we provide a comprehensive overview of proteasome inhibitors used in combination with other chemotherapeutic agents, as this is a key strategy to combat resistance.     

Characterization of Collagen/Lipid Nanoparticle–Curcumin Cryostructurates for Wound Healing Applications

Curcumin‐loaded collagen cryostructurates have been devised for wound healing applications. Curcumin displays strong antioxidant, antiseptic, and anti‐inflammatory properties, while collagen is acknowledged for promoting cell adhesion, migration and differentiation. However, when curcumin is loaded directly into collagen hydrogels, it forms large molecular aggregates and clogs the matrix pores. A double‐encapsulation strategy is therefore developed by loading curcumin into lipid nanoparticles (LNP), and embedding these particles inside collagen scaffolds. The resulting collagen/LNP cryostructurates have an optimal fibrous structure with ≈100 µm average pore size for sustaining cell migration. Results show that collagen is structurally unaltered and that nanoparticles are homogeneously distributed amidst collagen fibers. Hydrogels soaked in saline buffer release about 20 to 30% of their nanoparticles content within 24 h, while achieved 100% release after 25 days. When exposed to NIH 3T3 fibroblasts, these hydrogels provide a satisfactory scaffold for cell interaction as early as 4 h after seeding, with no cytotoxic counter effect. These positive features make the collagen/lipid cryostructurates a promising material for further use in wound healing.