Contrarian Majority Rule Model with External Oscillating Propaganda and Individual Inertias.

We study the Galam majority rule dynamics with contrarian behavior and an oscillating external propaganda in a population of agents that can adopt one of two possible opinions. In an iteration step, a random agent interacts with three other random agents and takes the majority opinion among the agents with probability p(t) (majority behavior) or the opposite opinion with probability 1-p(t) (contrarian behavior). The probability of following the majority rule p(t) varies with the temperature T and is coupled to a time-dependent oscillating field that mimics a mass media propaganda, in a way that agents are more likely to adopt the majority opinion when it is aligned with the sign of the field. We investigate the dynamics of this model on a complete graph and find various regimes as T is varied. A transition temperature Tc separates a bimodal oscillatory regime for TTc in which m oscillates around zero. These regimes are characterized by the distribution of residence times that exhibit a unique peak for a resonance temperature T*, where the response of the system is maximum. An insight into these results is given by a mean-field approach, which also shows that T* and Tc are closely related.

Filamentous Bacteria as Targets to Study Phagocytosis.

Filamentous targets are internalized via phagocytic cups that last for several minutes before closing to form a phagosome. This characteristic offers the possibility to study key events in phagocytosis with greater spatial and temporal resolution than is possible to achieve using spherical particles, for which the transition from a phagocytic cup to an enclosed phagosome occurs within a few seconds after particle attachment. In this chapter, we provide methodologies to prepare filamentous bacteria and describe how they can be used as targets to study different aspects of phagocytosis.

Microscopy-Based Tracking and Quantification Methods to Study Phagosome Resolution.

Phagosome resolution is a newly defined, terminal stage in the process of phagocytosis. During this phase, phagolysosomes are fragmented into smaller vesicles, which we called phagosome-derived vesicles (PDVs). PDVs gradually accumulate within macrophages, while the phagosomes diminish in size until the organelles are no longer detectable. Although PDVs share the same maturation markers as phagolysosomes, they are heterogeneous in size and very dynamic, which makes PDVs difficult to track. Thus, to analyze PDV populations in cells, we developed methods to differentiate PDVs from the phagosomes in which they were derived and further assess their characteristics. In this chapter, we describe two microscopy-based methods that can be used to quantify different aspects of phagosome resolution: volumetric analysis of phagosome shrinkage and PDV accumulation and co-occurrence analysis of various membrane markers with PDVs.

Contrarian Voter Model under the Influence of an Oscillating Propaganda: Consensus, Bimodal Behavior and Stochastic Resonance.

We study the contrarian voter model for opinion formation in a society under the influence of an external oscillating propaganda and stochastic noise. Each agent of the population can hold one of two possible opinions on a given issue­against or in favor­and interacts with its neighbors following either an imitation dynamics (voter behavior) or an anti-alignment dynamics (contrarian behavior): each agent adopts the opinion of a random neighbor with a time-dependent probability p(t), or takes the opposite opinion with probability 1−p(t). The imitation probability p(t) is controlled by the social temperature T, and varies in time according to a periodic field that mimics the influence of an external propaganda, so that a voter is more prone to adopt an opinion aligned with the field. We simulate the model in complete graph and in lattices, and find that the system exhibits a rich variety of behaviors as T is varied: opinion consensus for T=0, a bimodal behavior for TTc, and full disorder for T≫1. The transition temperature Tc vanishes with the population size N as Tc≃2/lnN in complete graph. In addition, the distribution of residence times tr in the bimodal phase decays approximately as tr−3/2. Within the oscillatory regime, we find a stochastic resonance-like phenomenon at a given temperature T*. Furthermore, mean-field analytical results show that the opinion oscillations reach a maximum amplitude at an intermediate temperature, and that exhibit a lag with respect to the field that decreases with T.

Aluminum hydroxide adjuvant diverts the uptake and trafficking of genetically detoxified pertussis toxin to lysosomes in macrophages.

Aluminum salts have been successfully utilized as adjuvants to enhance the immunogenicity of vaccine antigens since the 1930s. However, the cellular mechanisms behind the immune adjuvanticity effect of these materials in antigen-presenting cells are poorly understood. In this study, we investigated the uptake and trafficking of aluminum oxy-hydroxide (AlOOH), in RAW 264.7 murine and U-937 human macrophages-like cells. Furthermore, we determined the impact that the adsorption to AlOOH particulates has on the trafficking of a Bordetella pertussis vaccine candidate, the genetically detoxified pertussis toxin (gdPT). Our results indicate that macrophages internalize AlOOH by constitutive macropinocytosis assisted by the filopodial protrusions that capture the adjuvant particles. Moreover, we show that AlOOH has the capacity to nonspecifically adsorb IgG, engaging opsonic phagocytosis, which is a feature that may allow for more effective capture and uptake of adjuvant particles by antigen-presenting cells (APCs) at the site of vaccine administration. We found that AlOOH traffics to endolysosomal compartments that hold degradative properties. Importantly, while we show that gdPT escapes degradative endolysosomes and traffics toward the retrograde pathway, as reported for the wild-type pertussis toxin, the adsorption to AlOOH diverts gdPT to traffic to the adjuvant's lysosome-type compartments, which may be key for MHC-II-driven antigen presentation and activation of CD4+ T cell. Thus, our findings establish a direct link between antigen adsorption to AlOOH and the intracellular trafficking of antigens within antigen-presenting cells and bring to light a new potential mechanism for aluminum adjuvancy. Moreover, the in-vitro single-cell approach described herein provides a general framework and tools for understanding critical attributes of other vaccine formulations.

Phosphatidylinositol 3-Phosphate Mediates the Establishment of Infectious Bursal Disease Virus Replication Complexes in Association with Early Endosomes.

Infectious bursal disease virus (IBDV) is the archetypal member of the family Birnaviridae and the etiological agent of Gumboro disease, a highly contagious immunosuppressive infection of concern to the global poultry sector for its adverse health effects in chicks. Unlike most double-stranded RNA (dsRNA) viruses, which enclose their genomes within specialized cores throughout their viral replication cycle, birnaviruses organize their bisegmented dsRNA genome in ribonucleoprotein (RNP) structures. Recently, we demonstrated that IBDV exploits endosomal membranes for replication. The establishment of IBDV replication machinery on the cytosolic leaflet of endosomal compartments is mediated by the viral protein VP3 and its intrinsic ability to target endosomes. In this study, we identified the early endosomal phosphatidylinositol 3-phosphate [PtdIns(3)P] as a key host factor of VP3 association with endosomal membranes and consequent establishment of IBDV replication complexes in early endosomes. Indeed, our data reveal a crucial role for PtdIns(3)P in IBDV replication. Overall, our findings provide new insights into the replicative strategy of birnaviruses and strongly suggest that it resembles those of positive-strand RNA (+ssRNA) viruses, which replicate in association with host membranes. Furthermore, our findings support the role of birnaviruses as evolutionary intermediaries between +ssRNA and dsRNA viruses and, importantly, demonstrate a novel role for PtdIns(3)P in the replication of a dsRNA virus.IMPORTANCEInfectious bursal disease virus (IBDV) infects chicks and is the causative agent of Gumboro disease. During IBDV outbreaks in recent decades, the emergence of very virulent variants and the lack of effective prevention/treatment strategies to fight this disease have had devastating consequences for the poultry industry. IBDV belongs to the peculiar family Birnaviridae Unlike most dsRNA viruses, birnaviruses organize their genomes in ribonucleoprotein complexes and replicate in a core-independent manner. We recently demonstrated that IBDV exploits host cell endosomes as platforms for viral replication, a process that depends on the VP3 viral protein. In this study, we delved deeper into the molecular characterization of IBDV-endosome association and investigated the role of host cell phosphatidylinositide lipids in VP3 protein localization and IBDV infection. Together, our findings demonstrate that PtdIns(3)P serves as a scaffold for the association of VP3 to endosomes and reveal its essential role for IBDV replication.

Formulación de productos cosméticos con aceite de semillas de Cucurbita argyrosperma C. Huber / Formulation of cosmetic products from Cucurbita argyrosperma C. Huber seed oil

RESUMEN El presente trabajo tiene como objetivo aprovechar el aceite de las semillas de Cucurbita argyrosperma C. Huber (sin. Cucurbita mixta Pangalo), como fitoingrediente en la elaboración de productos cosméticos. El aceite empleado se obtuvo por extracción con soxhlet y se realizó su caracterización fisicoquímica. Se elaboraron emulgeles (O/W) variando el agente viscosante y emulgente. Las formulaciones logradas se valoraron mediante la evaluación de las propiedades organolépticas (color, olor, brillo), fisicoquímicas (pH, conductividad) y extensibilidad y fueron sometidas a estudios de estabilidad. Se obtuvieron productos tipo emulgel de color amarillento con ligero olor ceroso, con pH aceptable para la piel. Todas las formulaciones resultaron estables. Los resultados demostraron que las formulaciones propuestas permitieron incorporar el aceite de origen vegetal logrando un preparado cosmético de características y estabilidad aceptables.

SUMMARY The objective of this work is to take advantage of the oil of the seeds of Cucurbita argyrosperma C. Huber (sin. Cucurbita mixta Pangalo), as a phytoingredient in the elaboration of cosmetic products. The oil used was obtained by extraction with soxhlet and its physicochemical characterization was carried out. Emulgels (O/W) were prepared by varying the viscosifying and emulsifying agent. The formulations achieved were evaluated by evaluating the organoleptic properties (color, odor, brightness), physicochemical (pH, conductivity) and extensibility and were subjected to stability studies. Emulgel type products with yellowish color with slight waxy odor were obtained, with acceptable pH for the skin. All the formulations were stable. The results showed that the proposed formulations allowed incorporating the oil of vegetable origin achieving a cosmetic preparation of acceptable characteristics and stability.

Arsenic exposure of child populations in Northern Argentina.

Chronic exposure to inorganic arsenic (As) is associated with numerous adverse effects. Argentina is one of the countries affected by arsenicism; however, there are few studies that evaluate inorganic As exposure and its effects on child population. The aim of this study is to evaluate exposure to As through water and food in child populations living in the provinces of Santiago del Estero and Chaco (n = 101), and to determine the impact of this exposure analysing biomarkers of exposure (urine and hair As contents) and effect [8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG)]. The populations selected live in three areas with different levels of As in the drinking water (Santa Teresa de Carballo, 0.925 mg/L; Taco Pozo, 0.210 mg/L; Jumi Pozo, 0.016 mg/L). The As intakes through water and food are especially high in the areas with the greatest As exposure (Santa Teresa de Carballo, 1575 ±â€¯8 µg/day; Taco Pozo, 386 ±â€¯8 µg/day; Jumi Pozo, 39 ±â€¯1 µg/day). The total As contents in most of the samples of hair (0.11-13.11 mg/kg) and urine (31-4258 µg/g creatinine) are higher than the reference values (hair: 1 mg/kg; urine: 50 µg/g creatinine). The increase in the level of As exposure alters the profile of metabolites in urine, with a decrease of dimethylarsinic acid (10%) and an increase in the percentages of monomethylarsonic acid (4%) and inorganic As (6%). The results also show high values of 8-OHdG (3.7-37.8 µg/g creatinine), a oxidative DNA damage marker, in the two areas with greater As exposure.

Pseudobutyrivibrio xylanivorans adhesion to epithelial cells.

The ruminal bacteria Pseudobutyrivibrio xylanivorans strain 2 (P. xylanivorans 2), that mediates the digestion of plant fiber, is considered an attractive candidate for probiotics. Adherence to the epithelium of the digestive tract of the host is one of the major requirements for probiotics. In this study, we assessed the adhesion of P. xylanivorans 2 to SW480 cells and characterized this process utilizing multiple microscopy approaches. Our results indicate that a multiplicity of infection of 200 CFU/cell allows the highest bacteria to cell binding ratio, with a lower percentage of auto-agglutination events. The comparison of the adherence capacity subjected heat-shock treatment (100 °C, 1 min), which produces the denaturalization of proteins at the bacterial surface, as opposed untreated P. xylanivorans, suggested that this bacteria may attach to SW480 cells utilizing a proteinaceous structure. Confocal microscopy analyses indicate that P. xylanivorans 2 attachment induces the formation of F-actin-enriched areas on the surface of SW480 cells. Transmission electron microscopy (TEM) revealed the formation of a structure similar to a pedestal in the area of the epithelial cell surface, where the bacterium rests. Finally, a casual finding of TEM analysis of transverse and longitudinal thin-sections of P. xylanivorans 2, revealed irregular intra-cytoplasmic structures compatibles with the so-called bacterial microcompartments. This is the first ultrastructural description of bacterial microcompartments-like structures in the genus Pseudobutyrivibrio.

Infectious Bursal Disease Virus Hijacks Endosomal Membranes as the Scaffolding Structure for Viral Replication.

Birnaviruses are unconventional members of the group of double-stranded RNA (dsRNA) viruses that are characterized by the lack of a transcriptionally active inner core. Instead, the birnaviral particles organize their genome in ribonucleoprotein complexes (RNPs) composed by dsRNA segments, the dsRNA-binding VP3 protein, and the virally encoded RNA-dependent RNA polymerase (RdRp). This and other structural features suggest that birnaviruses may follow a completely different replication program from that followed by members of the Reoviridae family, supporting the hypothesis that birnaviruses are the evolutionary link between single-stranded positive RNA (+ssRNA) and dsRNA viruses. Here we demonstrate that infectious bursal disease virus (IBDV), a prototypical member of the Birnaviridae family, hijacks endosomal membranes of infected cells through the interaction of a viral protein, VP3, with the phospholipids on the cytosolic leaflet of these compartments for replication. Employing a mutagenesis approach, we demonstrated that VP3 domain PATCH 2 (P2) mediates the association of VP3 with the endosomal membranes. To determine the role of VP3 P2 in the context of the virus replication cycle, we used avian cells stably overexpressing VP3 P2 for IBDV infection. Importantly, the intra- and extracellular virus yields, as well as the intracellular levels of VP2 viral capsid protein, were significantly diminished in cells stably overexpressing VP3 P2. Together, our results indicate that the association of VP3 with endosomes has a relevant role in the IBDV replication cycle. This report provides direct experimental evidence for membranous compartments such as endosomes being required by a dsRNA virus for its replication. The results also support the previously proposed role of birnaviruses as an evolutionary link between +ssRNA and dsRNA viruses.IMPORTANCE Infectious bursal disease (IBD; also called Gumboro disease) is an acute, highly contagious immunosuppressive disease that affects young chickens and spreads worldwide. The etiological agent of IBD is infectious bursal disease virus (IBDV). This virus destroys the central immune organ (bursa of Fabricius), resulting in immunosuppression and reduced responses of chickens to vaccines, which increase their susceptibility to other pathogens. IBDV is a member of Birnaviridae family, which comprises unconventional members of dsRNA viruses, whose replication strategy has been scarcely studied. In this report we show that IBDV hijacks the endosomes of the infected cells for establishing viral replication complexes via the association of the ribonucleoprotein complex component VP3 with the phospholipids in the cytosolic leaflet of endosomal membranes. We show that this interaction is mediated by the VP3 PATCH 2 domain and demonstrate its relevant role in the context of viral infection.