Yeast and other lower eukaryotic organisms for studies of Vps13 proteins in health and disease

Human Vps13 proteins are associated with several diseases, including the neurodegenerative disorder Chorea-acanthocytosis (ChAc). However, the biology of these proteins is relatively poorly understood. Studies in lower eukaryotic models, such as Saccharomyces cerevisiae and Dictyostelium discoideum, point to the involvement of Vps13 in many key cellular processes, the actin cytoskeleton organization, vesicular trafficking, regulation of membrane contact sites, mitochondrial functioning and autophagy. Recent findings revealed that yeast Vps13 binds phosphatidylinositol lipids via at least four different lipid binding regions. Modelling of ChAc-associated mutations in yeast has revealed that particular amino acid substitutions give rise to specific phenotypes. Noteworthy, a mutation in the APT1 domain of Vps13 results in diminished lipid binding and disturbances of all processes studied, including the actin cytoskeleton organization, vacuolar transport, endocytosis and sporulation. This review describes the great potential of simple eukaryotes to decipher disease mechanisms and highlights novel insights into the pathological role of Vps13 towards ChAc

Long-term performance of magnetic force microscopy tips grown by focused electron beam induced deposition

High-resolution micro- and nanostructures can be grown using Focused Electron Beam Induced Deposition (FEBID), a direct-write, resist-free nanolithography technology which allows additive patterning, typically with sub-100 nm lateral resolution, and down to 10 nm in optimal conditions. This technique has been used to grow magnetic tips for use in Magnetic Force Microscopy (MFM). Due to their high aspect ratio and good magnetic behavior, these FEBID magnetic tips provide several advantages over commercial magnetic tips when used for simultaneous topographical and magnetic measurements. Here, we report a study of the durability of these excellent candidates for high-resolution MFM measurements. A batch of FEBID-grown magnetic tips was subjected to a systematic analysis of MFM magnetic contrast for 30 weeks, using magnetic storage tape as a test specimen. Our results indicate that these FEBID magnetic tips operate effectively over a long period of time. The magnetic signal was well preserved, with a maximum reduction of 60% after 21 weeks of recurrent use. No significant contrast degradation was observed after 30 weeks in storage

Increments in cytokines and matrix metalloproteinases in skeletal muscle after injection of tissue-damaging toxins from the venom of the snake Bothrops asper.

Envenomations by the snake Bothrops asper are characterized by prominent local tissue damage (i.e. myonecrosis), blistering, hemorrhage and edema. Various phospholipases A2 and metalloproteinases that induce local pathological alterations have been purified from this venom. Since these toxins induce a conspicuous inflammatory response, it has been hypothesized that inflammatory mediators may contribute to the local pathological alterations described. This study evaluated the local production of cytokines and matrix metalloproteinases (MMPs) as a consequence of intramuscular injections of an Asp-49 myotoxic phospholipase A2 (myotoxin III (MT-III)) and a P-I type hemorrhagic metalloproteinase (BaP1) isolated from B. asper venom. Both enzymes induced prominent tissue alterations and conspicuous increments in interleukin (IL)-1beta, IL-6 and a number of MMPs, especially gelatinase MMP-9, rapidly after injection. In contrast, no increments in tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma were detected. In agreement, MT-III and BaP1 did not induce the synthesis of TNF-alpha by resident peritoneal macrophages in vitro. Despite the conspicuous expression of latent forms of MMPs in muscle, evidenced by zymography, there were no increments in activated MMP-2 and only a small increase in activated MMP-9, as detected by a functional enzymatic assay. This suggests that MMP activity was regulated by a highly controlled activation of latent forms and, probably, by a concomitant synthesis of MMP inhibitors. Since no hemorrhage nor dermonecrosis were observed after injection of MT-III, despite a prominent increase in MMP expression, and since inflammatory exudate did not enhance hemorrhage induced by BaP1, it is suggested that endogenous MMPs released in the tissue are not responsible for the dermonecrosis and hemorrhage characteristic of B. asper envenomation. Moreover, pretreatment of mice with the peptidomimetic MMP inhibitor batimastat did not reduce myotoxic nor edema-forming activities of MT-III, suggesting that MMPs do not play a prominent role in the pathogenesis of these effects in this experimental model. It is concluded that MT-III and BaP1 induce a local inflammatory response associated with the synthesis of IL-1beta, IL-6 and MMPs. MMPs do not seem to play a prominent role in the acute local pathological alterations induced by these toxins in this experimental model

Supplementary data for article: Villalta-Romero, F.; Borro, L.; Mandić, B.; Escalante, T.; Rucavado, A.; Gutierrez, J. M.; Neshich, G.; Tasic, L. Discovery of Small Molecule Inhibitors for the Snake Venom Metalloprotease BaP1 Using in Silico and in Vitro Tests. Bioorganic and Medicinal Chemistry Letters 2017, 27 (9), 2018–2022. https://doi.org/10.1016/j.bmcl.2017.03.007

Supplementary material for: [ https://doi.org/10.1016/j.bmcl.2017.03.007]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2449]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3001

Metaloproteinasas dependientes de Zinc: Protagonistas centrales en la Fisiopatología de Envenenamientos por Serpientes de la familia Viperidae

Se presenta y discute el papel que juegan las metaloproteinasas de los venenos de serpientes (SVMPs) de la familia Viperidae en la fisiopatología de los envenenamientos inducidos por mordeduras de estos reptiles. Se hace especial énfasis en los mecanismos mediante los cuales estas enzimas inducen hemorragia. Así mismo, se discuten otros efectos que resultan de la acción de estas enzimas, tales como la necrosis muscular, la formación de ampollas y flictenas, y la coagulopatía. Finalmente, se analiza el rol que juegan las SVMPs en la deficiente regeneración de tejido muscular que caracteriza estos envenenamientos.The role played by snake venom metalloproteinases (SVMPs) in the pathophysiology of envenomings induced by snakes of the family Viperidae is discussed. The mechanisms involved in the ability of these enzymes to generate hemorrhage are presented, together with an analysis of other pathological effects induced by SVMPs, such as myonerosis, blistering and coagulopathy. Finally, the role played by these enzymes in the poor skeletal muscle regeneration characteristic of viperid snakebite envenomings is analyzed.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Los estilos de aprendizaje en la construcción de tutores inteligentes : Una revisión bibliográfica

En este trabajo se introducen conceptos de los campos en los que incursiona esta investigación, como son: los estilos de aprendizaje en estudiantes y los Tutores Inteligentes (TI). Se presenta una revisión bibliográfica de proyectos o estudios que consideran estilos de aprendizaje en la enseñanza para la construcción de Tutores Inteligentes. Así mismo se detallan las características consideradas esenciales en un prototipo de tutor inteligente. Este sistema se constituye en una herramienta complementaria del proceso de enseñanza aprendizaje en estudiantes de Ingeniería para mejorar la calidad del aprendizaje en el área.Eje: Tecnología informática aplicada en educación.Red de Universidades con Carreras en Informátic

La mediazione pedagogica della famiglia a favore dell’infanzia con impianto cocleare durante la pandemia

Since 2007, the Center of Attention for Communication, Hearing and Language (CCAL-UCA), a dependency of the Department of Education Sciences of the Central American University José Simón Cañas – UCA (El Salvador), has provided speech therapy to children with cochlear implants due to hearing disability. From March 2020, all therapeutic and educational processes faced the need of modifying from a face-to-face modality to a distance approach due to the global COVID-19 pandemic. The new strategy consisted of planning an intervention proposal which could be implemented with the pedagogical mediation of families, taking into account that the majority of cochlear implant users are groups with limited economic resources, who live in vulnerableareas at social risk. The qualitative research, through three case-study, analyzes how the pedagogical mediation of families of children with cochlear implants has been effective in the therapeutic care offered by CCAL-UCA. The results underline the importance of building a model of therapeutic care with pedagogical mediation according to the diversity of emergency circumstances; to carry out the evaluation of the activities taking into account both the family context and the childhood; to train families in language development strategies and to strengthen theresearch process in these same directions

Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

Production and nutrimental quality of cowpea pods, Vigna unguiculata (L.) Walp, as function of topological arrangement and fertilization type

El frijol chino (FC) se utiliza en alimentación humana y se cultiva en espaldera viva de maíz, pero, son escasos los estudios sobre arreglos topológicos adecuados. En este sistema, la biofertilización (BIO) y fertilización foliar (FF) podrían complementar la nutrición. En Huitzuco, Guerrero, México, durante el periodo lluvioso se sembró FC tipo guía en espaldera de maíz a 80 (D8) y 160 cm (D16) de distancia entre hileras (D), con y sin BIO (B y SB) y con y sin FF (F y SF), para determinar los efectos de D, BIO y FF sobre el rendimiento y calidad nutrimental de vainas. La emergencia del FC se presentó a los 6 días después de la siembra (dds), la floración a los 58 dds, el primer corte de vaina a los 70 dds y el último a los 110 dds. El mayor rendimiento de vaina se logró con D8-B-F (851 g m-2), seguido por D8-SB-F (758 g m-2) y D16-B-F (657 g m-2), con los que se generó la más alta concentración de minerales (6,5%) y proteínas (28,1%), y la menor de carbohidratos solubles y fibras. El mayor rendimiento y calidad nutricional de vaina verde se obtuvo con D8-B-F.Cowpea (FC) is usedin human feeding, and is cultivated on maize living trellis; however, few studies about suitable topological arrangements are available. Plant nutrition in this system could be completed by biofertilization (BIO) and foliar fertilization (FF). In Huitzuco, Guerrero. Mexico, during the rainy season FC guide type was sowing on trellis maize at 80(D8) and 160 cm (D16) of distance between rows (D), with and without BIO (B and SB), and with and without FF(F and SF), in order to determine the effect of D, BIO and FF on yield and nutritional quality of pods. Emergency of FC occurred at 6 days after sowing (dds); flowering at 58 dds; the first pod cut at 70 dds and the last at 110 dds. The higher pod yield was achieved with D8-B-F (851 g m-2), followed by D8-SB-F (758 g m-2) and D16-B-F (657 g m-2). This last treatment also generated the highest concentration of minerals (6.5%) and proteins (28.1%), but less carbohydrates and fiber. The highest yield and quality of green pod was obtained with D8-B-F.Fil: Apáez Barrios, Patricio. Universidad Michoacana de San Nicolás de HidalgoFil: Escalante Estrada, José Alberto Salvador. Colegio de Postgraduados. Campus Montecillo (México)Fil: Sosa Montes, Eliseo. Universidad Autónoma Chapingo (México)Fil: Apáez Barrios, Maricela. Colegio de Postgraduados. Campus Montecillo (México)Fil: Rodríguez González, María Teresa. Colegio de Postgraduados. Campus Montecillo (México)Fil: Raya Montaño, Yurixhi Atenea. Universidad Michoacana de San Nicolás de Hidalg