A new monotypic genus and species from China, \u3cem\u3eLangxie feti\u3c/em\u3e gen. et sp. n. (Scorpiones: Buthidae)

A new monotypic genus, Langxie gen. n., is described from Xizang (Tibet), China. The new genus shares an important morphological character with Afrolychas Kovařík, 2019: absence of external accessory denticles (EADs) along the sixth row of median denticles (MDs) on the pedipalp movable finger. Langxie gen. n. is different from Afrolychas in the following aspects: loss of EAD near the proximally enlarged MD within each row (i. e., loss of all EAD on the movable finger; this also distinguishes the new genus from other related genera in the “(Ananteris + Isometrus)” clade (Štundlová et al., 2022)), subaculear tubercle armed with or without a secondary tubercle dorsally, immaculate color pattern, more slender appendages and metasoma, and less sexually dimorphic pectines. Langxie gen. n. further differs from another geographically close genus, Himalayotityobuthus Lourenço, 1997, by the presence of highly developed pectinal fulcra (vs. absent in Himalayotityobuthus), six rows of MDs on the pedipalp movable finger (vs. 7–8 in Himalayotityobuthus) and five pairs of lateral ocelli (vs. 3 in Himalayotityobuthus). The new species, Langxie feti sp. n., is small and slender, exhibiting no obvious sexual dimorphism in pedipalp and metasoma, but the sexes are visibly different in the relative size of median ocelli and coarseness of carapacial granulation. Lattice microstructures are prominently developed on its cuticle

Caracterización de la interacción de moléculas hidrotrópicas con drogas oncológicas como una estrategia de vehiculización de fármacos en medios acuosos.

Tesis (Grado Doctor en Ciencias Biológicas)--Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Lugar de Trabajo: CEPROCOR-Ministerio de Ciencia y Tecnología de la Provincia de Córdoba.--Facultad de Ciencia Exactas, Físicas y Naturales. Universidad Nacional de Córdoba. 2013 - 168 h. con Apéndices + CD. tabls.; ils.; grafs. Contiene Referencia Bibliográfica y Copia de Publicaciones Derivadas de la Tesis. Abstract en español e inglés.En este trabajo de investigación, se evaluó la capacidad que tienen los gangliósidos, moléculas hidrotrópicas que forman estructuras micelares de manera espontánea, para vehiculizar fármacos en medio acuoso. Se estudiaron en particular a los monosialogangliósidos, de los cuales el GM1 resultó ser el más apropiado para la encapsulación de fármacos oncológicos como Paclitaxel, Docetaxel y Doxorrubicina. Las estructuras micelares formadas resultaron ser muy estables en medio acuoso, de tamaño menor a 50 nm y con un radio hidrodinámico equivalente al de una proteína globular de 300 kDa, características con las que evitarían dos de los problemas fundamentales que tiene la administración endovenosa de fármacos: la rápida eliminación de circulación por el sistema retículo endotelial y la exclusión renal. Se determinó que el tipo de asociación que existe entre las micelas de GM1 y los fármacos es dominada principalmente por interacciones de tipo hidrofóbicas. Además se estudiaron las condiciones físico-químicas óptimas para la formación de los complejos y la estabilidad química y estructural de éstos en medios acuosos. Debido a que estos fármacos oncológicos se administran por vía endovenosa, se estudió la interacción de los complejos GM1-droga con componentes plasmáticos humanos. Se determinó que éstos: 1- No presentan un efecto lítico sobre los glóbulos rojos 2- No influyen en la actividad plaquetaria y 3- Interaccionan espontáneamente con la albúmina. Esto último resultó ser una cualidad beneficiosa debido a que se ha demostrado que en los tejidos tumorales se encuentra incrementada la secreción de una proteína fijadora de albúmina (SPARC) que permitiría la acumulación de los complejos en el sitio específico de acción, incrementando la eficiencia del fármaco antitumoral. Finalmente se evaluó el efecto citotóxico in-vitro de las formulaciones obtenidas sobre cultivos celulares, en donde se demostró que los principios activos estudiados son liberados desde las micelas al entrar en contacto con las células y que los mismos mantienen su efecto biológico, resultando éste muy similar al de las drogas libres. Los resultados obtenidos nos permitieron considerar a las micelas de GM1 como un modelo factible para la vehiculización de fármacos de distinta naturaleza polar

Selective binding of albumin to Gm1 ganglioside micelles containing paclitaxel

In our previous work we showed that taxanes (paclitaxel (Ptx) and docetaxel(Dtx)) can be spontaneously loaded into monosialoganglioside (GM1) nanomicelles, increasing their water solubility about 6,000 times, to render stable water soluble formulations that could be used as a novel strategy to deliver drugs in cancer. Here, we describe the hydrophobic interaction of Human Serum Albumin (HSA) with GM1 micelles loaded with Ptx, as a strategy that could improve tumour drug accumulation. This interaction is regulated by conditions such pH and temperature and generates ternary complexes GM1/Ptx/HSA with sizes around 19 to 24 nm and hydrodynamic radius equivalent to a globular protein of 140-180 kDa. These mixed micelles were stable in solution for at least 40 days and also upon freeze-thawing or lyophilization-solubilization cycles. The results of in vitro assays showed that the nano-structures developed are taken up by cell cultures with an antimitotic activity of Ptx on tumoral and nontumoral cell lines that was similar to that observed with the free drug in DMSO solution.Fil: Leonhard, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia En Productos y Procesos de Córdoba. Laboratorio de Biotecnología; ArgentinaFil: Alasino, Roxana Valeria. Centro de Excelencia En Productos y Procesos de Cordoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bianco, Ismael Dario. Universidad Nacional de La Rioja; Argentina. Centro de Excelencia En Productos y Procesos de Cordoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Beltramo, Dante Miguel. Centro de Excelencia En Productos y Procesos de Cordoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba; Argentin

LDL-conjugated to GM1 micelles incorporating anticancer drugs to improve tumor cell uptake

Objective(s): The role of lipoproteins (LDL) as active molecules with preferential tumor interaction, but limited drug delivery capacity, has been previously reported. On the other hand, in a previous report, we demonstrated the high capacity of monosialogangliosides (GM1) micelles as drug transporters. Materials and Methods: In this work, GM1 was loaded with high doses of oncologic drugs such Paclitaxel or Doxorubicin and binded to LDL lipoproteins to form GM1-drug-LDLwater soluble complex. Evidence suggests that both, hydrophobic and electrostatic forces, participate in the interaction, regulated by conditions such as pH, temperature and ionic strength. Results: Results of DLS and TEM show that GM1-LDL complexes are considerably larger than the sum of their individual compounds, with a high charge of electronegative surface (-55.9 mV). In addition, the cytotoxic effect on cell cultures is greater when drugs are contained in GM1-LDL complexes than when loaded in GM1 micelles. Conclusion: The results suggest the participation of active energy-dependent mechanism in the uptake of GM1-LDL drug, probably linked to the LDL receptor by the tumor cells. However, we could not confirm that the transport through LDL receptors is the only one that participates in the cellular uptake of the micelles.Fil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Alasino, Roxana Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Leonhard, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Polyamines in the Surface of Lipid Micelles Improve the Cellular Uptake of Antitumoral Agents

Purpose: The ability of spermidine to increase the selectivity of anticancer agents has been studied extensively. In this research we report the combination of this polyamine and GM1 ganglioside micelles and characterize their behavior for drug delivery.Methods: Dynamic light scattering and electron microscopy were used to characterize size and morphology of micelles. Zeta potential was determined using a Nano-zeta potential analyzer. Sizeexclusion chromatography was used to separate different populations. Cytotoxic effect of micelles was evaluated on Hep2 cell line.Results: Covalent conjugation of spermidine to gangliosides produces a clear reduction of the electronegative z potential of micelle surface. DLS analysis shows no significant differences between both micelles, while TEM image shows a smaller size of Spermidine-GM1.These modified micelles load hydrophilic or hydrophobic antitumor drugs and conjugation does not affect the stability of micelles/drug in solution. Spermidine-GM1/Doxo micelles show faster drug release into cells as compared with GM1/Doxo micelles; however, no evidence can be found for the participation of the polyamine transport system in the uptake of modified micelles.Conclusion: While Spermidine-GM1 and GM1 micelles show similar physical properties, spermidine modified micelles are most efficient to release drugs, making this an interesting alternative to consider for drug delivery.Fil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Alasino, Roxana Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leonhard, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Beltramo, Dante Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentin

Self-assembled micelles of monosialogangliosides as nanodelivery vehicles for taxanes

We demonstrate herein that taxanes (paclitaxel (Ptx) and docetaxel (Dtx)) can be spontaneously loaded into ganglioside nanomicelles. The efficiency of gangliosides to solubilize taxanes was highly dependent on their self-aggregating structure. Thus, GM3 that forms unilamellar vesicles was less efficient to solubilize taxanes than gangliosides that form micelles (i.e. GM1 and GM2). Sialic acid cyclization of GM1 by acid treatment led to an important reduction in its capacity to solubilize taxanes, as also did the replacement of the fatty acid of ceramide by a dicholoracetyl group. Water solubility of paclitaxel (Ptx) is less than 1 μg mL- 1 and increased up to 6.3 mg.mL- 1 upon its association with GM1 micelles. The incorporation of Ptx in GM1 reached an optimum at GM1/Ptx 20/1 molar ratio when performed at room temperature. An increase in the solubilization capacity of GM1 micelles was observed upon dehydration of their polar head group by pre-treatment at 55 °C. Loading of Ptx into the micelle induced a structural reorganization that led to an important protection of Ptx reducing its hydrolysis at alkaline pH. Diffusion of either GM1 or Ptx was restricted upon mixed-micelle formation indicating that they are kinetically more stable than pure ganglioside micelles. X-ray powder diffraction of lyophilized GM1 micelles with Ptx showed a change in their internal structure from a crystalline state to completely amorphous. Taxane-ganglioside mixed micelles were stable in solution for at least 4 months and also upon freeze-thawing or lyophilization-solubilization cycles. Upon mixing with human blood constituents, GM1/Ptx micelles did not induce hemolysis or platelet aggregation and were spontaneously covered with human serum albumin (HSA), which could aid in the delivery of micellar content to tumors. In vitro antimitotic activity of GM1/Ptx mixed micelles was qualitatively equivalent to that of free drug in DMSO solution. © 2012 Elsevier B.V. All rights reserved.Fil: Leonhard, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alasino, Roxana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Bianco, Ismael Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Universidad Nacional de La Rioja; ArgentinaFil: Garro, Ariel G.. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Heredia, Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Católica de Córdoba. Facultad de Ciencias Químicas; Argentin

Monosialoganglioside GM1 reduces toxicity of Ptx and increase anti-metastasic effect in a murine mammary cancer model

Having demonstrated the ability of monosialoganglioside GM1 micelles as oncology drug transporter, this work focuses on evaluating its application in an in vivo system, studying the toxicity and antitumoral effect of GM1-Ptx micellar formulation. The maximum tolerated dose (MTD) obtained after intravenous administration of GM1-Ptx in mice was 55 mg/kg and the 50% lethal dose (LD50) was 70 mg/kg. This value is higher than those described for the commercial formulations TAXOL and ABRAXANE, with LD50 of 30 and 45 mg/kg respectively. The antitumor activity, mortality and incidence of metastasis were studied on a murine model of mammary gland cancer. The GM1-Ptx formulation was administered i.v. at different doses for 9 weeks using empty GM1 micelles and saline as treatment controls. Once the treatments were completed, biochemical markers were quantified and histological tissue tests were performed. The most promising results were obtained with the treatment at a dose of 15 mg/kg/twice a week, condition in which a longer survival and significant reduction in the incidence of animals with metastasis, since only one 25% of the mice showed presence of pulmonary micro metastases.Fil: Leonhard, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alasino, Roxana Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Pasqualini, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Cremonezzi, David César. Universidad Nacional de Córdoba; ArgentinaFil: Garcia, Nestor Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Sistemas nanoparticulados de vehiculización de fármacos: transportador vs fármaco

La eficacia terapéutica de un fármaco está condicionada por muchos factores, dentro de los cuales la solubilidad y el acceso al sitio de acción juegan un rol primordial. Se estima que aproximadamente el 40% de los medicamentos que se encuentran actualmente en el mercado y cerca del90% de las moléculas en desarrollo presentan baja solubilidad en agua. Así, las propiedades de solubilidad de los compuestos continúa siendo uno de los mayores obstáculos en el desarrollo de sistemas de administración de fármacos.Fil: Alasino, Roxana Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Leonhard, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Spatio-temporal dynamics of oscillatory brain activity during the observation of actions and interactions between point-light agents

Predicting actions from non-verbal cues and using them to optimise one's response behaviour (i.e. interpersonal predictive coding) is essential in everyday social interactions. We aimed to investigate the neural correlates of different cognitive processes evolving over time during interpersonal predictive coding. Thirty-nine participants watched two agents depicted by moving point-light stimuli while an electroencephalogram (EEG) was recorded. One well-recognizable agent performed either a 'communicative' or an 'individual' action. The second agent either was blended into a cluster of noise dots (i.e. present) or was entirely replaced by noise dots (i.e. absent), which participants had to differentiate. EEG amplitude and coherence analyses for theta, alpha and beta frequency bands revealed a dynamic pattern unfolding over time: Watching communicative actions was associated with enhanced coupling within medial anterior regions involved in social and mentalising processes and with dorsolateral prefrontal activation indicating a higher deployment of cognitive resources. Trying to detect the agent in the cluster of noise dots without having seen communicative cues was related to enhanced coupling in posterior regions for social perception and visual processing. Observing an expected outcome was modulated by motor system activation. Finally, when the agent was detected correctly, activation in posterior areas for visual processing of socially relevant features was increased. Taken together, our results demonstrate that it is crucial to consider the temporal dynamics of social interactions and of their neural correlates to better understand interpersonal predictive coding. This could lead to optimised treatment approaches for individuals with problems in social interactions

Advancing human nutrition without degrading land resources through modeling cropping systems in the Ethiopian highlands

Food shortage in sub-Saharan Africa is generally considered a function of limited access to food, with little thought to nutritional quality. Analyzing household production of nutrients across farming systems could be valuable in guiding the improvement of those systems. An optimization model was employed to analyze the scenario of human nutrition and cropland allocation in enset (Enset ventricosum)/root crop-based and cereal-based systems of the Ethiopian Highlands. The type and amount of nutrients produced in each system were analyzed, and an optimization model was used to analyze which cropping strategies might improve the nutritional quality of the household using existing resources. Both production systems were in food deficit, in terms of quantity and quality of nutrients, except for iron. The energy supply of resource-poor households in the enset/root crop-based system was only 75% of the recommended daily dietary allowance (RDA) of the World Health Organization (WHO), whereas resource-rich farmers were able to meet their energy, protein, zinc, and thiamine demands. Extremely high deficiency was found in zinc, calcium, vitamin A, and vitamin C, which provided only 26.5%, 34%, 1.78%, and 12%, of the RDA, respectively. The RDA could be satisfied if the land area occupied by enset, kale, and beans were expanded by about 20%, 10%, and 40%, respectively, at the expense of maize and sweet potato. The cereal-based system also had critical nutrient deficits in calcium, vitamin A, and vitamin C, which provided 30%, 2.5%, and 2% of the RDA, respectively. In the cereal system, the RDA could be fully satisfied by reducing cropland allocated to barley by about 50% and expanding the land area occupied by faba beans, kale, and enset. A shift from the cereal/root crop-dominated system to a perennial-enset dominated system would decrease soil erosion by improving the crop factor by about 45%. This shift would also have a very strong positive impact on soil fertility management. However, any policy suggestions for change in cropland allocation should be done through negotiations with households, communities, and district stakeholders