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The present research is an examination of 245 responses to three death notice posts published on Facebook. The respondents, all friends of whom published the posts, had no other choice in acting upon the news given the gathering restrictions created by COVID-19 (April 2020-November 2021). First, I examine the personal deixis (e.g., to whom the message is oriented towards) through the close examination of pronouns in the expressions of condolences. Results reveal that to maintain the social relationships, the respondents preferred to orient their message of condolence towards the bereaved or the family followed by orienting the condolence towards both the bereaved and the deceased. In Spanish, orienting the message toward the self (i.e., I am sorry) is the least preferred response. Behavioral cultural expectations also suggests that to demonstrate empathy, Colombian Spanish speakers tend to offer condolences in the form of routine formulas—focused on religious sayings, or expressions that reveal signs of affection. In managing the respect component, the respondents tend to praise God for mercy and strength for the bereaved/family and prayed for the deceased’s soul. In addition, it was noted that the responses included emojis (18.8%) which were used to upgrade and strengthen the force of the expressions of condolence. Although, the results cannot be generalized to the entire Colombian population, this study serves as the base to understand how Spanish speakers respond to condolences, a topic scarcely investigated.

We have developed a single process for producing two key COVID-19 vaccine antigens: SARS-CoV-2 receptor binding domain (RBD) monomer and dimer. These antigens are featured in various COVID-19 vaccine formats, including SOBERANA 01 and the licensed SOBERANA 02, and SOBERANA Plus. Our approach involves expressing RBD (319-541)-His6 in Chinese hamster ovary (CHO)-K1 cells, generating and characterizing oligoclones, and selecting the best RBD-producing clones. Critical parameters such as copper supplementation in the culture medium and cell viability influenced the yield of RBD dimer. The purification of RBD involved standard immobilized metal ion affinity chromatography (IMAC), ion exchange chromatography, and size exclusion chromatography. Our findings suggest that copper can improve IMAC performance. Efficient RBD production was achieved using small-scale bioreactor cell culture (2 L). The two RBD forms - monomeric and dimeric RBD - were also produced on a large scale (500 L). This study represents the first large-scale application of perfusion culture for the production of RBD antigens. We conducted a thorough analysis of the purified RBD antigens, which encompassed primary structure, protein integrity, N-glycosylation, size, purity, secondary and tertiary structures, isoform composition, hydrophobicity, and long-term stability. Additionally, we investigated RBD-ACE2 interactions, in vitro ACE2 recognition of RBD, and the immunogenicity of RBD antigens in mice. We have determined that both the monomeric and dimeric RBD antigens possess the necessary quality attributes for vaccine production. By enabling the customizable production of both RBD forms, this unified manufacturing process provides the required flexibility to adapt rapidly to the ever-changing demands of emerging SARS-CoV-2 variants and different COVID-19 vaccine platforms.

La urgente necesidad de desarrollar y producir vacunas seguras y efectivas para garantizar la reducción de la propagación del coronavirus de tipo 2 causante del síndrome respiratorio agudo severo, hizo que el Centro de Inmunología Molecular y el Instituto Finlay de Vacunas, desarrollaran dos vacunas y un candidato vacunal contra la COVID-19, que tienen como componente la molécula del dominio de unión al receptor (aa 319-541) del virus. Para establecer el proceso productivo, se realizaron experimentos en los posibles pasos del proceso de purificación de la molécula del dominio de unión al receptor (aa 319-541), con vistas a su posterior transferencia tecnológica a escala industrial. Dicha molécula está fusionada con una etiqueta de hexahistidina en su extremo C-terminal y presenta nueve residuos de cisteína en su secuencia que forman cuatro enlaces disulfuros intramoleculares, quedando una cisteína libre que permite obtener dos moléculas: dimérica y monomérica, antígenos que forman parte de las vacunas SOBERANA®02 y SOBERANA®Plus y el candidato vacunal SOBERANA 01. Se determinaron las mejores condiciones de adsorción de las matrices cromatográficas de afinidad por quelatos metálicos, intercambio catiónico y exclusión molecular. Se evaluó el desempeño del proceso a escala piloto y se caracterizó la molécula de acuerdo a sus propiedades físico-químicas y biológicas. Los resultados obtenidos mostraron un 60,02 ± 5,15% de recuperación total de la proteína de interés, con más del 98% de pureza en ambas moléculas, una eficiente remoción de contaminantes y una antigenicidad mayor del 90% referido al monómero control del dominio de unión al receptor con 99% de pureza, lo que demuestra que el proceso establecido es eficiente en la obtención de un producto con la calidad requerida.

Abstract Interleukin-2 (IL-2) engineered versions, with biased immunological functions, have emerged from yeast display and rational design. Here we reshaped the human IL-2 interface with the IL-2 receptor beta chain through the screening of phage-displayed libraries. Multiple beta super-binders were obtained, having increased receptor binding ability and improved developability profiles. Selected variants exhibit an accumulation of negatively charged residues at the interface, which provides a better electrostatic complementarity to the beta chain, and faster association kinetics. These findings point to mechanistic differences with the already reported superkines, characterized by a conformational switch due to the rearrangement of the hydrophobic core. The molecular bases of the favourable developability profile were tracked to a single residue: L92. Recombinant Fc-fusion proteins including our variants are superior to those based on H9 superkine in terms of expression levels in mammalian cells, aggregation resistance, stability, in vivo enhancement of immune effector responses, and anti-tumour effect.

D-galactose has been widely used as an inducer of cellular senescence and pathophysiological processes related to aging because it induces oxidative stress. On the other hand, the consumption of antioxidants such as curcumin can be an effective strategy to prevent phenotypes related to the enhanced production of reactive oxygen species (ROS), such as aging and senescence. This study aimed to evaluate the potential protective effect of curcumin on senescence and oxidative stress and endoplasmic reticulum stress induced by D-galactose treatment in Lilly Laboratories Culture-Porcine Kidney 1 (LLC-PK1) and human kidney 2 (HK-2) proximal tubule cell lines from pig and human, respectively. For senescence induction, cells were treated with 300 mM D-galactose for 120 h and, to evaluate the protective effect of the antioxidant, cells were treated with 5 µM curcumin for 24 h and subsequently treated with curcumin + D-galactose for 120 h. In LLC-PK1 cells, curcumin treatment decreased by 20% the number of cells positive for senescence-associated (SA)-β-D-galactosidase staining and by 25% the expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and increased by 40% lamin B1 expression. In HK-2 cells, curcumin treatment increased by 60% the expression of proliferating cell nuclear antigen (PCNA, 50% Klotho levels, and 175% catalase activity. In both cell lines, this antioxidant decreased the production of ROS (20% decrease for LLC-PK1 and 10 to 20% for HK-2). These data suggest that curcumin treatment has a moderate protective effect on D-galactose-induced senescence in LLC-PK1 and HK-2 cells.

IntroductionThe anti-CD20 antibody rituximab (RTX) has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. An approach to increase the clinical effectiveness of anti-tumor therapy is the use of antibody-cytokine fusion proteins (immunocytokines (ICKs)) to deliver at the tumor site the antibody effector functions and cytokines that trigger anti-tumor activities. In particular, IL-2-based ICKs have shown significant results in preclinical studies but not in clinical trials due to the toxicity profile associated to high doses IL-2 and the undesired expansion of Tregs.MethodsTo improve the efficacy of RTX therapy, we fused a murine (mIgG2a) or a human (hIgG1) version of RTX to a mutated IL-2 (no-alpha mutein), which has a disrupted affinity for the high affinity IL-2 receptor (IL-2R) to prevent the stimulation of Tregs and reduce the binding to endothelial cells expressing CD25, the α chain of high affinity IL-2R. Characterization of anti-CD20-IL2no-alpha ICKs was performed by SDS-PAGE, Western-blotting and SEC-HPLC and also by several functional in vitro techniques like T-cell proliferation assays, apoptosis, CDC and ADCC assays. The in vivo activity was assessed by using murine tumor cells expressing huCD20 in C57/Bl6 mice.ResultsBoth ICKs exhibited similar in vitro specific activity of their IL2no-alpha mutein moieties and kept CD20-binding capacity. Anti-CD20-IL2no-alpha (hIgG1) retained antibody effector functions as complement-dependent cytotoxicity and enhanced direct apoptosis, NK cell activation and antibody-dependent cellular cytotoxicity relative to RTX. In addition, both ICKs demonstrated a higher antitumor efficacy than parental molecules or their combination in an EL4-huCD20 tumor model in immunocompetent mice. Anti-CD20-IL2no-alpha (hIgG1) strongly expanded NK and CD8+ T cells but not Tregs in tumor-bearing mice.DiscussionThese findings suggest that anti-CD20-IL2no-alpha could represent an alternative treatment for B cell lymphoma patients, mainly those refractory to RTX therapy.

To better guide dengue prevention and control efforts, the use of routinely collected data to develop risk maps is proposed. For this purpose, dengue experts identified indicators representative of entomological, epidemiological and demographic risks, hereafter called components, by using surveillance data aggregated at the level of Consejos Populares (CPs) in two municipalities of Cuba (Santiago de Cuba and Cienfuegos) in the period of 2010–2015. Two vulnerability models (one with equally weighted components and one with data-derived weights using Principal Component Analysis), and three incidence-based risk models were built to construct risk maps. The correlation between the two vulnerability models was high (tau > 0.89). The single-component and multicomponent incidence-based models were also highly correlated (tau ≥ 0.9). However, the agreement between the vulnerability- and the incidence-based risk maps was below 0.6 in the setting with a prolonged history of dengue transmission. This may suggest that an incidence-based approach does not fully reflect the complexity of vulnerability for future transmission. The small difference between single- and multicomponent incidence maps indicates that in a setting with a narrow availability of data, simpler models can be used. Nevertheless, the generalized linear mixed multicomponent model provides information of covariate-adjusted and spatially smoothed relative risks of disease transmission, which can be important for the prospective evaluation of an intervention strategy. In conclusion, caution is needed when interpreting risk maps, as the results vary depending on the importance given to the components involved in disease transmission. The multicomponent vulnerability mapping needs to be prospectively validated based on an intervention trial targeting high-risk areas.

Urinary tract infections (UTIs) are the most common infectious diseases worldwide. These infections are common in all people; however, they are more prevalent in women than in men. The main microorganism that causes 80–90% of UTIs is Escherichia coli. However, other bacteria such as Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae cause UTIs, and antibiotics are required to treat them. However, UTI treatment can be complicated by antibiotic resistance and biofilm formation. Therefore, medicinal plants, such as spices generally added to foods, can be a therapeutic alternative due to the variety of phytochemicals such as polyphenols, saponins, alkaloids, and terpenes present in their extracts that exert antimicrobial activity. Essential oils extracted from spices have been used to demonstrate their antimicrobial efficacy against strains of pathogens isolated from UTI patients and their synergistic effect with antibiotics. This article summarizes relevant findings on the antimicrobial activity of cinnamon, clove, cumin, oregano, pepper, and rosemary, spices popularly used in Mexico against the uropathogens responsible for UTIs.

Endoplasmic reticulum (ER) stress is induced by intrinsic and extrinsic factors and, in consequence, activates the unfolded protein response (UPR); which in an acute phase restores cellular homeostasis, whereas in a chronic phase promotes apoptosis. ER stress has been detected in a broad range of kidney diseases and the different degrees of ER stress and UPR stimulation could activate antioxidant and immune responses, autophagy, cell maintenance, inflammation, apoptosis and fibrosis. Understanding the regulation of ER stress and the UPR signaling pathways will allow to develop treatments that favor cellular functions in order to reduce the progression of diseases. The regulation of ER stress is carried out with natural or pharmacological compounds. The pharmacological inhibitors of ER stress commonly used are 4-phenylbutyric acid (4-PBA), tauroursodeoxycholic acid (TUDCA) and salubrinal, whereas pharmacological inducers of ER stress generally used are thapsigargin and tunicamycin. In addition, natural compounds such as polyphenols are able to induce and inhibit ER stress, and their effects are dose-dependent. In this review, we summarize notable findings on strategies of the induction of ER stress, as well as its inhibition, in the context of kidney diseases. Furthermore, these two methods of regulating ER stress are discussed.

Trypanosoma rangeli es un hemoparásito no patógeno, frecuente en humanos y otros mamíferos. La forma epimastigota de T. rangeli expresan una enzima con actividad de sialidasa (SA), la cual es diferente a la trans-sialidasa encontrada en T. cruzi. Se han descrito dos subpoblaciones de T. rangeli, una con actividad de sialidasa (SA+) y otra sin actividad (SA-). El objetivo de este estudio fue analizar y comparar la secuencia del gen de la SA de T. rangeli en aislados SA+ y SA-. Para este fin, se analizaron 2 aislados, uno SA+ de T. rangeli, y otro SA-. La actividad de la Sialidasa fue medida utilizando la técnica MU-NANA. El RNA total y mRNA de cada aislado fueron extraídos, posteriormente los genes SA fueron clonados con pGEM-T Easy y secuenciados con 3130 Genetic Analyzer Sanger. La secuencia SA de los aislados analizados poseen 99% de identidad con un gen precursor de sialidasa anteriormente reportado, pero a la vez presentó diferencias en 4 posiciones de los aminoácidos.

Para la realización de este estudio se entrenó un panel constituido por seis personas, las cuales evaluaron los atributos: color blanco, textura granulosa al tacto, suave al tacto, olor a cuajo, salado, grumoso en boca, suave en boca y aroma a suero. También se contó con dos grupos de 400 consumidores, donde un grupo evaluó características sensoriales y el segundo grupo evaluó la apreciación global. Los resultados del ANOVA de tres factores mostraron que el panel entrenado fue discriminante en todos los atributos, mientras que el ANOVA de dos factores reveló que los paneles de consumidores fueron discriminantes en seis atributos; el ACP reveló similitudes entre ambos paneles para el posicionamiento de los quesos en el espacio sensorial. El MEP reveló que los consumidores del municipio de Asunción Ixtaltepec y de San Pedro Comitancillo pudieron identificar y preferir el queso que se elabora en su municipio, caso contrario a los consumidores pertenecientes a Santo Domingo Ingenio y Juchitán de Zaragoza. Los resultados del MEP generados con los datos descriptivos evaluados por el panel entrenado y el panel de consumidores fueron complementarios; esto quedó demostrado por el R2 ya que en algunos casos, la explicación de la preferencia de alguna clase no pudo ser determinada mediante el MEP con los datos del panel entrenado. Por tal motivo, el vocabulario que se genere a través de un panel entrenado también puede ser evaluado mediante paneles de consumidores para la generación del MEP, el cual es una alternativa rápida para la determinación de la preferencia basado en un lenguaje completamente de consumidores. Abstract For this study, a panel of six judges was trained to evaluate attributes in cheese as white color, granular texture to the touch, soft to the touch, smell of rennet, salty, lumpy in the mouth, soft on the palate and aroma to serum. There were also included two groups of 400 consumers; where a group evaluated the sensory characteristics and the second group evaluated the overall assessment. Three-way ANOVA results showed that the trained panel discriminated all attributes, while the two-way ANOVA revealed that the group of consumers discriminated six attributes. Principal components analysis revealed similarities between both panels to the positioning of the cheeses in the sensory space. The EPM revealed that consumers from the municipalities of Asuncion Ixtaltepec and San Pedro Comitancillo were able to identify and prefer the cheese made in their municipality; contrary to this, consumers from Santo Domingo Ingenio y Juchitan de Zaragoza were not able to identify or prefer their own. The EPM results generated with the descriptive data evaluated by the trained panel and consumer groups were complementary, and this was demonstrated by the R2 since in some cases the explanation of the preference of some kind, could not be determinated by EPM with the trained panel data. For this reason, the vocabulary that is generated by a trained panel can be also evaluated by a consumer panel to generate the EPM, which is a fast alternative for the determination of preference based on a language entirely of consumers. Keywords: Sensory profiles, consumers, trained judges, external preference map.

Este artigo almeja lançar luz sobre a relação entre a trajetória intelectual da psicóloga russa Helena Antipoff, a formação da Sociedade Pestalozzi do Brasil e os primeiros cursos de teatro de bonecos do país, que tiveram início em 1946. Objetiva-se desenvolver a ideia de que tais cursos possuíam forte ligação com a psicologia da educação e os conceitos da moderna pedagogia vinculada à Escola Nova. Tais cursos tinham como propósito a “missão” de levar “teatrinhos de bonecos” a todas as regiões onde houvessem crianças que necessitassem de recreação para a sua “formação saudável”. Palavras-chave: Helena Antipoff. Sociedade Pestalozzi do Brasil. Escola Nova. Teatro de Bonecos. Psicologia educacional.

Isoliquiritigenin (IsoLQ) is a flavonoid with antioxidant properties and inducer of endoplasmic reticulum (ER) stress. In vitro and in vivo studies show that ER stress-mediated hormesis is cytoprotective; therefore, natural antioxidants and ER stress inducers have been used to prevent renal injury. Oxidative stress and ER stress are some of the mechanisms of damage involved in cisplatin (CP)-induced nephrotoxicity. This study aims to explore whether IsoLQ pretreatment induces ER stress and produces hormesis to protect against CP-induced nephrotoxicity in Lilly Laboratories Cell-Porcine Kidney 1 (LLC-PK1) cells. During the first stage of this study, both IsoLQ protective concentration and pretreatment time against CP-induced toxicity were determined by cell viability. At the second stage, the effect of IsoLQ pretreatment on cell viability, ER stress, and oxidative stress were evaluated. IsoLQ pretreatment in CP-treated cells induces expression of glucose-related proteins 78 and 94 kDa (GRP78 and GRP94, respectively), attenuates CP-induced cell death, decreases reactive oxygen species (ROS) production, and prevents the decrease in glutathione/glutathione disulfide (GSH/GSSG) ratio, free thiols levels, and glutathione reductase (GR) activity. These data suggest that IsoLQ pretreatment has a moderately protective effect on CP-induced toxicity in LLC-PK1 cells, through ER stress-mediated hormesis, as well as by the antioxidant properties of IsoLQ.

A raíz del conflicto socioambiental de Bagua en 2009 —causado por la ofensiva policial contra los indígenas awajus y wampis que defendían la mantenencia del régimen de derechos colectivos y garantías territoriales— el Perú se convirtió forzosamente en el primer país latinoamericano en promulgar la ley de Consulta Previa (2011). Esto parecía aperturar una vía institucionalizada de la tensa y desigual relación entre el Estado y los pueblos indígenas. No obstante, en 2015 el pueblo wampis apuesta por un camino político divergente al declarar públicamente la articulación del Gobierno Territorial Autónomo de la Nación wampis. Este artículo busca explicar la construcción de esta estrategia de defensa territorial, desde un análisis de la interacción dialéctica entre la estructura de oportunidad política que abre el conflicto de Bagua para el ejercicio del derecho al autogobierno; y la reformulación creativa desde la agencia política wampis, que logra retar la política dentro de los marcos del Estado-nación.

BACKGROUND:Aedes control interventions are considered the cornerstone of dengue control programmes, but there is scarce evidence on their effect on disease. We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-domiciliary residual insecticide (deltamethrin) treatment (RIT) and long lasting insecticide treated curtains (ITC). METHODOLOGY/PRINCIPAL FINDINGS:Sixty three clusters (around 250 households each) were randomly allocated to two intervention (RIT and ITC) and one control arm. Routine Aedes control activities (entomological surveillance, source reduction, selective adulticiding, health education) were applied in the whole study area. The outcome measures were clinical dengue case incidence and immature Aedes infestation. Effectiveness of tools was evaluated using a generalized linear regression model with a negative binomial link function. Despite significant reduction in Aedes indices (Rate Ratio (RR) 0.54 (95%CI 0.32-0.89) in the first month after RIT, the effect faded out over time and dengue incidence was not reduced. Overall, in this setting there was no protective effect of RIT or ITC over routine in the 17months intervention period, with for house index RR of 1.16 (95%CI 0.96-1.40) and 1.25 (95%CI 1.03-1.50) and for dengue incidence RR of 1.43 (95%CI 1.08-1.90) and 0.96 (95%CI 0.72-1.28) respectively. The monthly dengue incidence rate (IR) at cluster level was best explained by epidemic periods (Incidence Rate Ratio (IRR) 5.50 (95%CI 4.14-7.31)), the IR in bordering houseblocks (IRR 1.03 (95%CI 1.02-1.04)) and the IR pre-intervention (IRR 1.02 (95%CI 1.00-1.04)). CONCLUSIONS:Adding RIT to an intensive routine Aedes control programme has a transient effect on the already moderate low entomological infestation levels, while ITC did not have any effect. For both interventions, we didn't evidence impact on disease incidence. Further studies are needed to evaluate impact in settings with high Aedes infestation and arbovirus case load.

We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer’s disease (AD). Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aβ42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aβ42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aβ peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aβ lowering effect in vivo might be related to its lower in vitro potency toward Aβ aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio.

Reaction of 1,3-diphenylisobenzofuran (DPIBF) with 2-(iodoethynyl)(phenyl)-iodonium triflate at room temperature gave the expected Diels-Alder adduct, but using an excess of DFIBF (2 equiv.) and performing the reaction at 55 °C or heating at this temperature during the concentration stage, the initial orange solution or product mixture became dark brown and the products 1,2-phenylene-1,2-bis(phenylmethanone) and 2-(3-iodo-1,4-diphenylnaphthyl)(phenyl)iodonium triflate were obtained, which suggests an oxygen transfer between DPIBF and the initial adduct.

The educational system treats ethics and value formation, develops the ideological and political work by reinforcing values as an entire and general culture of the students. The development of the value laboriosity in the Technical Professional Education at Los Palacios’ town is one of the most important objectives in the political and social aspects. The teacher ́s example is the main concern. It is developed through a system of teaching activities based on the contents of the subject Bases of the Agropecuarian Production II.

7a-(Methoxycarbonyl)-N-methyl-1,3a,5,6,7,7a-hexahydro-4H-1,4,6-(epiethane[1,1,2]triyl)indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The overall yield of the new synthetic sequence is comparable to the previous one. Two advantages of the new procedure are: (a) no benzyl ester was formed and (b) a stereoisomeric mixture of syn- and anti-alcohols at the beginning of the synthetic sequence could be separated and the rest of the synthesis could be carried out with the main syn-stereoisomer instead of the corresponding stereoisomeric mixture as it was the case in the previous process. Additionally, several functional 2,8-ethanonoradamantane derivatives have been prepared.