Analysis of antenal sensilla patterns of Rhodnius prolixus from Colombia and Venezuela

Antennal sensilla patterns were used to analyze population variation of domestic Rhodnius prolixus from six departments and states representing three biogeographical regions of Colombia and Venezuela. Discriminant analysis of the patterns of mechanoreceptors and of three types of chemoreceptors on the pedicel and flagellar segments showed clear differentiation between R. prolixus populations east and west of the Andean Cordillera. The distribution of thick and thin-walled trichoids on the second flagellar segment also showed correlation with latitude, but this was not seen in the patterns of other sensilla. The results of the sensilla patterns appear to be reflecting biogeographic features or population isolation rather than characters associated with different habitats and lend support to the idea that domestic R. prolixus originated in the eastern region of the Andes.Fil: Esteban, Lyda. Universidad Industrial de Santander; ColombiaFil: Angulo, Víctor Manuel. Universidad Industrial de Santander; ColombiaFil: Dora Feliciangeli, M.. Universidad de Carabobo; VenezuelaFil: Catala, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; Argentin

An advanced 3D multi-body system model for the human lumbar spine

Series : Mechanisms and machine science, ISSN 2211-0984, vol. 24A novel 3D multi-body system model of the human lumbar spine is presented, allowing the dynamic study of the all set but also to access mechanical demands, characteristics and performance under work of the individual intervertebral discs. An advanced FEM analysis was used for the most precise characterization of the disc 6DOF mechanical behavior, in order to build up a tool capable of predicting and assist in the design of disc recovery strategies – namely in the development of replace-ment materials for the degenerated disc nucleus – as well as in the analysis of variations in the me-chanical properties (disorders) at disc level or kinematic structure (e.g. interbody fusion, pedicle fixa-tion, etc.), and its influence in the overall spine dynamics and at motion segments individual level. Preliminary results of the model, at different levels of its development, are presented

The Kinematic Algebra From the Self-Dual Sector

We identify a diffeomorphism Lie algebra in the self-dual sector of Yang-Mills theory, and show that it determines the kinematic numerators of tree-level MHV amplitudes in the full theory. These amplitudes can be computed off-shell from Feynman diagrams with only cubic vertices, which are dressed with the structure constants of both the Yang-Mills colour algebra and the diffeomorphism algebra. Therefore, the latter algebra is the dual of the colour algebra, in the sense suggested by the work of Bern, Carrasco and Johansson. We further study perturbative gravity, both in the self-dual and in the MHV sectors, finding that the kinematic numerators of the theory are the BCJ squares of the Yang-Mills numerators.Comment: 29 pages, 5 figures. v2: references added, published versio

A selective p53 activator and anticancer agent to improve colorectal cancer therapy

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.We thank PT national funds (FCT/MCTES , Fundação para a Ciência e a Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) through grants UIDB/50006/2020 , UID/BIO/04469/2019 , UIDB/04539/2020 , and UIDP/04539/2020 ( CIBB ); BioTecNorte operation ( NORTE-01-0145-FEDER-000004 ) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S ( Norte-01-0145-FEDER-000008 ) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte ; Masaryk University ( Project MUNI/A/1127/2019 ) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125 ); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC ( IG#18985 , A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences , PD/00016/2012 ). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) via the projects UIDB/50006/2020 ( LAQV/REQUIMTE ), UIDB/00313/2020 , and UIDP/00313/2020 , co-funded by COMPETE2020-UE

Two Distinct Triatoma dimidiata (Latreille, 1811) Taxa Are Found in Sympatry in Guatemala and Mexico

Approximately 10 million people are infected with Trypanosoma cruzi, the causative agent of Chagas disease, which remains the most serious parasitic disease in the Americas. Most people are infected via triatomine vectors. Transmission has been largely halted in South America in areas with predominantly domestic vectors. However, one of the main Chagas vectors in Mesoamerica, Triatoma dimidiata, poses special challenges to control due to its diversity across its large geographic range (from Mexico into northern South America), and peridomestic and sylvatic populations that repopulate houses following pesticide treatment. Recent evidence suggests T. dimidiata may be a complex of species, perhaps including cryptic species; taxonomic ambiguity which confounds control. The nuclear sequence of the internal transcribed spacer 2 (ITS2) of the ribosomal DNA and the mitochondrial cytochrome b (mt cyt b) gene were used to analyze the taxonomy of T. dimidiata from southern Mexico throughout Central America. ITS2 sequence divides T. dimidiata into four taxa. The first three are found mostly localized to specific geographic regions with some overlap: (1) southern Mexico and Guatemala (Group 2); (2) Guatemala, Honduras, El Salvador, Nicaragua, and Costa Rica (Group 1A); (3) and Panama (Group 1B). We extend ITS2 Group 1A south into Costa Rica, Group 2 into southern Guatemala and show the first information on isolates in Belize, identifying Groups 2 and 3 in that country. The fourth group (Group 3), a potential cryptic species, is dispersed across parts of Mexico, Guatemala, and Belize. We show it exists in sympatry with other groups in Peten, Guatemala, and Yucatan, Mexico. Mitochondrial cyt b data supports this putative cryptic species in sympatry with others. However, unlike the clear distinction of the remaining groups by ITS2, the remaining groups are not separated by mt cyt b. This work contributes to an understanding of the taxonomy and population subdivision of T. dimidiata, essential for designing effective control strategies

Phylogeographic pattern and extensive mitochondrial DNA divergence disclose a species complex within the Chagas disease vector Triatoma dimidiata.

ABSTARCT: Previous studies have shown that "bioequivalent" generic products of vancomycin are less effective in vivo against Staphylococcus aureus than the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assess in vivo the impact of exposure to innovator and generic products of vancomycin on S. aureus susceptibility. A clinical methicillin-resistant S. aureus (MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ∼7.0 log(10) CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies than S. aureus ATCC 29213 but without vancomycin-intermediate S. aureus (VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide