Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation.

The deposition of islet amyloid polypeptide (hIAPP) fibrils is a hallmark of ß-cell death in type II diabetes. In this study, we employ state-of-the-art MAS solid-state spectroscopy to investigate the previously elusive N-terminal region of hIAPP fibrils, uncovering both rigidity and heterogeneity. Comparative analysis between wild-type hIAPP and a disulfide-deficient variant (hIAPPC2S,C7S) unveils shared fibril core structures yet strikingly distinct dynamics in the N-terminus. Specifically, the variant fibrils exhibit extended ß-strand conformations, facilitating surface nucleation. Moreover, our findings illuminate the pivotal roles of specific residues in modulating secondary nucleation rates. These results deepen our understanding of hIAPP fibril assembly and provide critical insights into the molecular mechanisms underpinning type II diabetes, holding promise for future therapeutic strategies.

Unveiling the Dynamic Self-Assembly of a Recombinant Dragline-Silk-Mimicking Protein.

Despite the considerable interest in the recombinant production of synthetic spider silk fibers that possess mechanical properties similar to those of native spider silks, such as the cost-effectiveness, tunability, and scalability realization, is still lacking. To address this long-standing challenge, we have constructed an artificial spider silk gene using Golden Gate assembly for the recombinant bacterial production of dragline-mimicking silk, incorporating all the essential components: the N-terminal domain, a 33-residue-long major-ampullate-spidroin-inspired segment repeated 16 times, and the C-terminal domain (N16C). This designed silk-like protein was successfully expressed in Escherichia coli, purified, and cast into films from formic acid. We produced uniformly 13C-15N-labeled N16C films and employed solid-state magic-angle spinning nuclear magnetic resonance (NMR) for characterization. Thus, we could demonstrate that our bioengineered silk-like protein self-assembles into a film where, when hydrated, the solvent-exposed layer of the rigid, ß-nanocrystalline polyalanine core undergoes a transition to an α-helical structure, gaining mobility to the extent that it fully dissolves in water and transforms into a highly dynamic random coil. This hydration-induced behavior induces chain dynamics in the glycine-rich amorphous soft segments on the microsecond time scale, contributing to the elasticity of the solid material. Our findings not only reveal the presence of structurally and dynamically distinct segments within the film's superstructure but also highlight the complexity of the self-organization responsible for the exceptional mechanical properties observed in proteins that mimic dragline silk.

Surface-Catalyzed Secondary Nucleation Dominates the Generation of Toxic IAPP Aggregates.

The aggregation of the human islet amyloid polypeptide (IAPP) is associated with diabetes type II. A quantitative understanding of this connection at the molecular level requires that the aggregation mechanism of IAPP is resolved in terms of the underlying microscopic steps. Here we have systematically studied recombinant IAPP, with amidated C-terminus in oxidised form with a disulphide bond between residues 3 and 7, using thioflavin T fluorescence to monitor the formation of amyloid fibrils as a function of time and IAPP concentration. We used global kinetic analyses to connect the macroscopic measurements of aggregation to the microscopic mechanisms, and show that the generation of new aggregates is dominated by the secondary nucleation of monomers on the fibril surface. We then exposed insulinoma cells to aliquots extracted from different time points of the aggregation process, finding the highest toxicity at the midpoint of the reaction, when the secondary nucleation rate reaches its maximum. These results identify IAPP oligomers as the most cytotoxic species generated during IAPP aggregation, and suggest that compounds that target secondary nucleation of IAPP could be most effective as therapeutic candidates for diabetes type II.

Proliferation of Tau 304-380 Fragment Aggregates through Autocatalytic Secondary Nucleation.

The self-assembly of the protein tau into neurofibrillary tangles is one of the hallmarks of Alzheimer's disease and related tauopathies. Still, the molecular mechanism of tau aggregation is largely unknown. This problem may be addressed by systematically obtaining reproducible in vitro kinetics measurements under quiescent conditions in the absence of triggering substances. Here, we implement this strategy by developing protocols for obtaining an ultrapure tau fragment (residues 304-380 of tau441) and for performing spontaneous aggregation assays with reproducible kinetics under quiescent conditions. We are thus able to identify the mechanism of fibril formation of the tau 304-380 fragment at physiological pH using fluorescence spectroscopy and mass spectrometry. We find that primary nucleation is slow, and that secondary processes dominate the aggregation process once the initial aggregates are formed. Moreover, our results further show that secondary nucleation of monomers on fibril surfaces dominates over fragmentation of fibrils. Using separate isotopes in monomers and fibrils, through mass spectroscopy measurements, we verify the isotope composition of the intermediate oligomeric species, which reveals that these small aggregates are generated from monomer through secondary nucleation. Our results provide a framework for understanding the processes leading to tau aggregation in disease and for selecting possible tau forms as targets in the development of therapeutic interventions in Alzheimer's disease.

Expression, purification and characterisation of large quantities of recombinant human IAPP for mechanistic studies.

Malfunction and amyloid formation of the Islet Amyloid Polypeptide (IAPP) are factors contributing to Type 2 diabetes. Unravelling the mechanism of IAPP aggregate formation may forward our understanding of this process and its effect on pancreatic ß-islet cell. Such mechanistic studies require access to sequence homogeneous and highly pure IAPP. Here we present a new facile protocol for the production of pure recombinant human IAPP at relatively high yield. The protocol uses a His-tagged version of the Npro mutant EDDIE, which drives expression to inclusion bodies, from which the peptide is purified using sonication, refolding and auto-cleavage, removal of EDDIE using Ni-NTA chromatography and reverse-phase HPLC. The purified material is used at multiple concentrations in aggregation kinetics measurements monitored by thioflavin-T fluorescence. Global analysis of the data implies a double nucleation aggregation mechanism including both primary and secondary nucleation.

El derecho a la protección de datos personales, tecnologías digitales y pandemia por COVID-19 en Colombia / The right to personal data protection, digital technologies and the pandemic for COVID-19 in Colombia / El dret a la protecció de dades personals, tecnologies digitals I pandèmia per COVID-19 a Colòmbia

La pandemia COVID-19 ha generado impactos sociales y políticos adicionales a los estrictamente sanitarios, llevando de un aparte a que los países, en el contexto de los estados de emergencia decretados, limiten de manera temporal algunos derechos y libertades civiles, para preservar la vida y salud de los ciudadanos; y de otra parte, han acelerado la transformación digital con el desarrollo y uso de herramientas tecnológicas para complementar las medidas de salud pública. Diversos organismos internacionales han expresado su preocupación respecto a la vulneración del derecho a la protección de datos personales en este nuevo escenario, e incluso han propuesto lineamientos éticos a tener en cuenta. En este artículo se analizarán las medidas que han sido implementadas en Colombia con ocasión de la COVID-19, desde la perspectiva del marco jurídico del derecho a la protección de datos personales vigente, y como los principios y derechos que lo componen, pueden ser reinterpretados a la luz de estas nuevas recomendaciones éticas

COVID-19 pandemic has generated additional social and political impacts beyond those strictly related to health, leading countries to, within the context of declared states of emergency, temporarily limit some civil rights and liberties in order to preserve their citizen's life and health. On the other hand, it has accelerated the digital transformation with the development and use of technological tools to complement public health measures. Several international organizations have voiced their concern about the violation of the right to personal data protection in this new scenario and have even proposed ethical guidelines to be taken into account. This article will analyses the measures that have been implemented in Colombia during COVID-19 pandemic, from the actual perspective of the legal framework of the right to personal data protection, and how its principles and rights may be reinterpreted in the light of these new ethical recommendations

La pandèmia COVID-19 ha generat impactes socials I polítics addicionals als estrictament sanitaris, portant d'un a part al fet que els països, en el context dels estats d'emergència decretats, limitin de manera temporal alguns drets I llibertats civils, per preservar la vida I salut dels ciutadans; I d'una altra banda, accelerant la transformació digital amb el desenvolupament I l'ús d'eines tecnològiques per complementar les mesures de salut pública. Diversos organismes internacionals han expressat la seva preocupació pel que fa a la vulneració del dret a la protecció de dades personals en aquest nou escenari, I fins I tot han proposat directrius ètiques a tenir en compte. En aquest article s'analitzaran les mesures que han estat implementades a Colòmbia amb motiu de la COVID-19, des de la perspectiva del marc jurídic del dret a la protecció de dades personals vigent, I com els principis I drets que el componen, poden ser reinterpretats a la llum d'aquestes noves recomanacions ètiques

Small molecule induced toxic human-IAPP species characterized by NMR.

In this study, the effect of CurDAc, a water-soluble curcumin derivative, on the formation and stability of amyloid fibers is revealed. CurDAc interaction with amyloid is structurally selective, which is reflected in a strong interference with hIAPP aggregation while showing weaker interactions with human-calcitonin and amyloid-ß1-40 in comparison. Remarkably, CurDAc also exhibited potent fiber disaggregation for hIAPP generating a toxic oligomeric species.

Medicamentos biosimilares en Colombia: una revisión desde el consumo informado / Biosimilar Medicines in Colombia: An Approach from the Informed Consumption / Medicamentos biossimilares na Colômbia: uma revisão desde o consumo informado

Resumen Introducción: este artículo presenta un análisis sobre medicamentos biosimilares en Colombia con miras a establecer si existe un consumo informado respecto de estos fármacos, teniendo en cuenta la calidad y cantidad de información que circula en relación con su disponibilidad y acceso económico (precios). Desarrollo: el tipo de estudio es cualitativo con un diseño documental a partir de la revisión en bases de datos como Pubmed, Scopus, Scielo, Vlex y Redalyc, bases de información de registros sanitarios de agencias reguladoras de medicamentos (FDA, EMA e Invima) y el Sistema de Información de Vademecum Med Informática. Uno de los biosimilares autorizados en FDA y cuatro de la EMA se encuentran registrados en el Invima; sin embargo, son más los biosimilares no autorizados ni en FDA ni en EMA que se encuentran registrados en el Invima, los cuales aún no aparecen con esta clasificación de biosimilares ni en la agencia reguladora colombiana ni en ningún otro medio oficial o comercial. De los medicamentos biológicos de referencia de estos biosimilares, 12 tienen control de precios y 7 han sido autorizados al menos una vez vía judicial a los usuarios del sistema. Conclusiones: si bien, la reglamentación ha sido de gran avance en relación con el acceso a biosimilares y, en consecuencia, a sus biológicos pioneros, el sistema aún tiene barreras jurídicas, de información, disponibilidad y acceso que dificultan la protección y efectividad del derecho a la salud de la población en términos de un consumo informado de estos.

Abstract Introduction: This article presents an analysis of biosimilar drugs in Colombia, aiming at critically analyzing whether the consumption of biosimilar drugs in Colombia is fully informed or if it rather is characterized for its lack of information. Informed consumption in the sense of taking into account the quality and quantity of the information circulating in relation to the availability and affordability (prices) of biosimilar drugs. Development: This is a qualitative documentary analysis, based on the review of databases such as Pubmed, Scopus, Scielo, Vlex and Redalyc, and sanitary databases of drugs regulatory agencies (FDA, EMA and the Colombian Invima) and the Vademecum Med Informatica. One of the biosimilars authorized by FDA and four of those by EMA were also registered before by the Invima. However, the number of Invima authorized biosimilars is higher than that authorized by FDA and EMA. It is also important to highlight the fact that any biosimilar is not registered as such neither before the Invima nor before any other official or commercial source. Out of the biological reference products with biosimilars, twelve have regulated price and seven have been authorized at least once via court ruling. Conclusions: Although the regulations are progressive in relation to the access to biosimilars and, consequently, to their biological pioneers, the system still has legal, availability and information barriers that undermine the protection and effectiveness of the right to health.

Resumo Introdução: este artigo apresenta uma análise sobre medicamentos biossimilares na Colômbia com vista a estabelecer se existe um consumo informado respeito destes fármacos, tendo em conta a qualidade e quantidade de informação que circula em relação com a sua disponibilidade e acesso econômico (preços). Desenvolvimento: o tipo de estudo é qualitativo com um desenho documental a partir da revisão em bases de dados como Pubmed, Scopus, Scielo, Vlex e Redalyc, bases de informação de registros sanitários de agências reguladoras de medicamentos (FDA, EMA e Invima) e o Sistema de Informação de Vademecum Med Informática. Um dos biossimilares autorizados em FDA e 4 da EMA, se encontram registrados no Invima, no entanto são mais os biossimilares não autorizados nem na FDA nem na EMA que se encontram registrados no Invima, os quais ainda não aparecem com esta classificação de biossimilares nem na agência reguladora colombiana, nem em nenhum outro meio oficial ou comercial. Dos medicamentos biológicos de referência destes biossimilares, 12 têm controle de preços e 7 têm sido autorizados pelo menos uma vez via judicial aos usuários do sistema. Conclusões: se bem a regulamentação tem sido de grande avanço em relação com o acesso a biossimilares e, consequentemente, a seus biológicos pioneiros, o sistema ainda tem barreiras jurídicas, de informação, disponibilidade e acesso que dificultam a proteção e efetividade do direito à saúde da população em termos de um consumo informado dos mesmos.

Microsecond motions probed by near-rotary-resonance R1ρ15N MAS NMR experiments: the model case of protein overall-rocking in crystals.

Solid-state near-rotary-resonance measurements of the spin-lattice relaxation rate in the rotating frame (R1ρ) is a powerful NMR technique for studying molecular dynamics in the microsecond time scale. The small difference between the spin-lock (SL) and magic-angle-spinning (MAS) frequencies allows sampling very slow motions, at the same time it brings up some methodological challenges. In this work, several issues affecting correct measurements and analysis of 15N R1ρ data are considered in detail. Among them are signal amplitude as a function of the difference between SL and MAS frequencies, "dead time" in the initial part of the relaxation decay caused by transient spin-dynamic oscillations, measurements under HORROR condition and proper treatment of the multi-exponential relaxation decays. The multiple 15N R1ρ measurements at different SL fields and temperatures have been conducted in 1D mode (i.e. without site-specific resolution) for a set of four different microcrystalline protein samples (GB1, SH3, MPD-ubiquitin and cubic-PEG-ubiquitin) to study the overall protein rocking in a crystal. While the amplitude of this motion varies very significantly, its correlation time for all four sample is practically the same, 30-50 µs. The amplitude of the rocking motion correlates with the packing density of a protein crystal. It has been suggested that the rocking motion is not diffusive but likely a jump-like dynamic process.

hIAPP forms toxic oligomers in plasma.

In diabetes, hyperamylinemia contributes to cardiac dysfunction. The interplay between hIAPP, blood glucose and other plasma components is, however, not understood. We show that glucose and LDL interact with hIAPP, resulting in ß-sheet rich oligomers with increased ß-cell toxicity and hemolytic activity, providing mechanistic insights for a direct link between diabetes and cardiovascular diseases.

Osmolality predictive models of different polymers as tools in parenteral and ophthalmic formulation development.

During the development of parenteral dosage forms, different physicochemical studies are required to ensure stable, effective and safe formulations. The osmolality of this kind of dosage forms should bear a close similarity to the body fluids to prevent local irritation, pain or even more significant side effects like endothelial damage. The osmotic studies performed in Polyethylene glycol 400 (PEG 400), Polyethylene glycol 4000 (PEG 4000), Poloxamer 407 (P407), Sodium Hyaluronate (SH), Chondroitin Sulphate Sodium (CS), Cremophor RH 40 (CRE40) and Polyvinyl alcohol (PVA) aqueous solutions, showed that the theoretical determination of the osmolality based on their molecular weight as the only determinant factor did not agree with the values obtained by the measurement of colligative properties such as the freezing point depression. The data obtained from this study and its analysis, provided predictive equations that can be used as tools in the primary development to estimate formulation's osmolality at different concentrations; and its evolution over a period at the hypothetical worst-case scenario of storage temperature.

Physical Activity in Public Parks of High and Low Socioeconomic Status in Colombia Using Observational Methods.

BACKGROUND: Public parks are an important resource for the promotion of physical activity (PA). This is the first study in Colombia and the fourth in Latin America to describe the characteristics of park users and their levels of PA using objective measures. METHODS: A systematic observation assessed sex, age, and the level of PA of users of 10 parks in an intermediate-size city in Colombia, classified in low (5 parks) and high (5 parks) socioeconomic status (SES). A total of 10 daily observations were conducted, in 5 days of the week during 3 periods: morning, afternoon, and evening. RESULTS: In total, 16,671 observations were completed, recording 46,047 users. A higher number of users per park, per day, were recorded in high SES (1195) versus low SES (647). More men were observed in low-SES than high-SES parks (70.1% vs 54.2%), as well as more children were observed in low-SES than high-SES parks (30.1% vs 15.9%). Older adults in high-SES parks were more frequent (9.5% vs 5.2%). Moderate to vigorous PA was higher in low-SES parks (71.7% vs 63.2%). CONCLUSIONS: Low-SES parks need more green spaces, walk/bike trails, and areas for PA. All parks need new programs to increase the number of users and their PA level, considering sex, age group, and period of the week.

Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice.

The formation of amyloid fibrils by human islet amyloid polypeptide protein (hIAPP) has been implicated in pancreas dysfunction and diabetes. However, efficient treatment options to reduce amyloid fibrils in vivo are still lacking. Therefore, we tested the effect of epigallocatechin gallate (EGCG) on fibril formation in vitro and in vivo. To determine the binding of hIAPP and EGCG, in vitro interaction studies were performed. To inhibit amyloid plaque formation in vivo, homozygous (tg/tg), hemizygous (wt/tg), and control mice (wt/wt) were treated with EGCG. EGCG bound to hIAPP in vitro and induced formation of amorphous aggregates instead of amyloid fibrils. Amyloid fibrils were detected in the pancreatic islets of tg/tg mice, which was associated with disrupted islet structure and diabetes. Although pancreatic amyloid fibrils could be detected in wt/tg mice, these animals were non-diabetic. EGCG application decreased amyloid fibril intensity in wt/tg mice, however it was ineffective in tg/tg animals. Our data indicate that EGCG inhibits amyloid fibril formation in vitro and reduces fibril intensity in non-diabetic wt/tg mice. These results demonstrate a possible in vivo effectiveness of EGCG on amyloid formation and suggest an early therapeutical application.

Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate.

Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here, we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. ROSETTA and MD simulations resulted in a unique ß-strand structure distinct from the conventional amyloid ß-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated intermediate, suggesting a mechanism by which membrane-associated aggregation may be propagated. The ability of nanodiscs to trap amyloid intermediates as demonstrated could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation.

Individual and Environmental Correlates to Quality of Life in Park Users in Colombia.

Purpose: To explore individual and environmental correlates to quality of life (QoL) in park users in Colombia. Methods: A cross-sectional study with face-to-face interviews was conducted with 1392 park users from ten parks in Colombia. The survey included sociodemographic questions, health condition assessed with EuroQuol-5-Dimensions-5-Levels; in addition, questions about accessibility to the parks and perceptions about quality of infrastructure and green areas were asked. The Spanish version of the questionnaire EUROHIS-QOL-8 items was applied to assess QoL. Log-binomial regression models were applied for analyses. Results: Years of schooling, visits to the park with a companion, active use of the park, a maximum score for quality of trees and walking paths, and the perception of safety on the way to the park were positively associated with a better QoL (p < 0.05). Health conditions related to problems in the ability to perform activities of daily living and anxiety/depression showed negative associations. Conclusions: The present study contributes to the Latin American studies by providing information on how parks in an intermediate city may contribute to increased QoL of park users through safety in neighborhoods, social support, active use, and aesthetics, cleanliness, and care of green areas.

Limits of Resolution and Sensitivity of Proton Detected MAS Solid-State NMR Experiments at 111 kHz in Deuterated and Protonated Proteins.

MAS solid-state NMR is capable of determining structures of protonated solid proteins using proton-detected experiments. These experiments are performed at MAS rotation frequency of around 110 kHz, employing 0.5 mg of material. Here, we compare 1H, 13C correlation spectra obtained from protonated and deuterated microcrystalline proteins at MAS rotation frequency of 111 kHz, and show that the spectral quality obtained from deuterated samples is superior to those acquired using protonated samples in terms of resolution and sensitivity. In comparison to protonated samples, spectra obtained from deuterated samples yield a gain in resolution on the order of 3 and 2 in the proton and carbon dimensions, respectively. Additionally, the spectrum from the deuterated sample yields approximately 2-3 times more sensitivity compared to the spectrum of a protonated sample. This gain could be further increased by a factor of 2 by making use of stereospecific precursors for biosynthesis. Although the overall resolution and sensitivity of 1H, 13C correlation spectra obtained using protonated solid samples with rotation frequencies on the order of 110 kHz is high, the spectral quality is still poor when compared to the deuterated samples. We believe that experiments involving large protein complexes in which sensitivity is limiting will benefit from the application of deuteration schemes.

Quality of public urban parks for physical activity practice in Bucaramanga, Colombia / Qualidade dos parques públicos urbanos para a prática de atividades físicas em Bucaramanga, Colômbia

Abstract The characteristics of parks (availability, accessibility, conservation, quality, safety, etc.) are important predictors of their use for physical activity practices. The aim of this study was to verify the association among the socioeconomic level of neighborhoods, the characteristics and quality of urban public parks for physical activity in Bucaramanga, Colombia. Cross-sectional study, conducted in 2015, in which 10 parks with structures for physical activity were evaluated. The socioeconomic level of the district was evaluated based on the neighborhoods around the parks and classified in "low" and "high". The number of residents in the surrounding area of parks were evaluated with Geographic Information System (GIS), site characteristics and quality with the System for Observing Play and Recreation in Communities (SOPARC) and the Physical Activity Resource Assessment (PARA), respectively. The association was analyzed with Mann Whitney U test and Spearman correlation (rho) on STATA 14 and the significance level was maintained at 5%. A positive association was found between the socioeconomic level and the presence of walking paths (marginal, p=0.056), accessibility (rho=0.875; p=0.001) and general quality of parks (rho=0.657; p=0.039). The low socioeconomic level was associated with the presence of sports courts (p=0.032). These results can guide the actions of public managers for the modification of the built environment and structures of the parks for physical activity.

Resumo As características dos parques (disponibilidade, acessibilidade, conservação, qualidade, segurança, etc.) são importantes preditores da sua utilização para a prática de atividades físicas. O objetivo deste estudo foi verificar a associação entre o nível socioeconômico dos bairros com as características e a qualidade dos parques públicos urbanos para a prática de atividades físicas em Bucaramanga, Colômbia. Estudo transversal, realizado em 2015, no qual foram avaliados 10 parques com estruturas para atividades físicas. O nível socioeconômico da região foi avaliado com base nos bairros próximos aos parques e classificado em "baixo" e "alto". O número de residentes próximos foi avaliado com o Sistema de Informação Geográfica (SIG), as características do local e a qualidade foram avaliadas, respectivamente, com o System for Observing Play and Recreation in Communities (SOPARC) e o Physical Activity Resource Assessment (PARA). A associação foi analisada com o teste U de Mann Whitney e a correlação de Spearman (rho) no STATA 14 e o nível de significância mantido em 5%. Foi verificada associação positiva entre o nível socioeconômico e a presença de pistas de caminhada (marginal, p=0,056), acessibilidade (rho=0,875; p=0,001) e qualidade geral dos parques (rho=0,657; p=0,039). O baixo nível socioeconômico foi associado à presença de quadras para esportes (p=0,032). Esses resultados podem orientar as ações dos gestores públicos para a modificação do ambiente construído e estruturas dos parques para a atividade física.

Derechos humanos implicados en las investigaciones en recursos genéticos humanos en pueblos indígenas colombianos / No disponible

El artículo presenta un análisis de los derechos humanos implicados en el acceso a recursos genéticos humanos, atendiendo la perspectiva de derechos de los pueblos indígenas, a fin de plantear un diálogo intercultural que permita generar reflexiones respecto a realidades que son importantes para su supervivencia. Entendiendo que, si se pretende proponer estrategias de protección frente a las violaciones o amenazas de sus derechos humanos en relación con actividades de bioprospección humana, es necesario explorar el derecho alternativo, que no es otro que el derecho propio de los pueblos indígenas, para conectarlo con el sistema jurídico nacional e internacional

The article presents an analysis of human rights involved in access to human genetic resources, taking the perspective of the rights of indigenous peoples, to raise intercultural dialogue to generate reflections on realities that are important to their survival. Understanding that if we are to propose strategies for protection against violations or threats of human rights in relation to activities of human bioprospecting, it is necessary to explore alternative law, which is none other than the own right of indigenous peoples to connect with national and international legal system

The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes.

Type II diabetes (T2D) is characterized by diminished insulin production and resistance of cells to insulin. Among others, endoplasmic reticulum (ER) stress is a principal factor contributing to T2D and induces a shift towards a more reducing cellular environment. At the same time, peripheral insulin resistance triggers the over-production of regulatory hormones such as insulin and human islet amyloid polypeptide (hIAPP). We show that the differential aggregation of reduced and oxidized hIAPP assists to maintain the redox equilibrium by restoring redox equivalents. Aggregation thus induces redox balancing which can assist initially to counteract ER stress. Failure of the protein degradation machinery might finally result in ß-cell disruption and cell death. We further present a structural characterization of hIAPP in solution, demonstrating that the N-terminus of the oxidized peptide has a high propensity to form an α-helical structure which is lacking in the reduced state of hIAPP. In healthy cells, this residual structure prevents the conversion into amyloidogenic aggregates.

Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration.

The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25°C and 37°C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant.