The edge-reinforced branching random walk on the triangle and generalised balls and bins with positive feedback

Edge-reinforced random walks are processes with reinforcement, on which the effect of branching has not been investigated. Our discrete time model starts with a particle, which branches at a constant rate, at the vertex of a triangle initialised with edge crossing numbers. The offspring particles, independently of each other, traverse the incident edges at random, with probabilities proportional to the edge crossing numbers, correspondingly updated at each traversal. Then the process repeats. We show the convergence of the proportions of edge crossings to a random variable using dynamical systems techniques, and prove that two events have positive probability: when none of the edges is crossed negligibly, and when exactly one is. We show that all edges are crossed infinitely many times and conjecture that no two edges can be negligibly crossed. This conjecture stems from connections between this model and balls and bins, where balls are added to bins at random, following certain rules. There is positive feedback when the probability of incoming balls choosing a bin with m balls is proportional to a power of m, bigger than 1; no feedback when the power is 1. In a time-dependent version, the number of balls added at discrete times varies, yielding different regimes of growth. Generalising results known for two bins to any number of bins, we investigate the proportion of balls in each bin, depending on feedback and regime of growth. We focus on the events of monopoly (eventually one of the bins will receive all incoming balls) and dominance (one of the bins gets all but a negligible number of balls). When there is no feedback, neither monopoly nor dominance occur. When feedback is introduced, several regimes are identified, at which dominance and monopoly occur. While at certain regimes monopoly does not occur, we conjecture dominance to always occur

Immunopathogenesis of Hepatic Brucellosis

The hepatic immune system can induce rapid and controlled responses to pathogenic microorganisms and tumor cells. Accordingly, most of the microorganisms that reach the liver through the blood are eliminated. However, some of them, including Brucella spp., take advantage of the immunotolerant capacity of the liver to persist in the host. Brucella has a predilection for surviving in the reticuloendothelial system, with the liver being the largest organ of this system in the human body. Therefore, its involvement in brucellosis is practically invariable. In patients with active brucellosis, the liver is commonly affected, and the most frequent clinical manifestation is hepatosplenomegaly. The molecular mechanisms implicated in liver damage have been recently elucidated. It has been demonstrated how Brucella interacts with hepatocytes inducing its death by apoptosis. The inflammatory microenvironment and the direct effect of Brucella on hepatic stellate cells (HSC) induce their activation and turn these cells from its quiescent form to their fibrogenic phenotype. This HSC activation induced by Brucella infection relies on the presence of a functional type IV secretion system and the effector protein BPE005 through a mechanism involved in the activation of the autophagic pathway. Finally, the molecular mechanisms of liver brucellosis observed so far are shedding light on how the interaction of Brucella with liver cells may play an important role in the discovery of new targets to control the infection. In this review, we report the current understanding of the interaction between liver structural cells and immune system cells during Brucella infection.Fil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

Prophet Inequalities: Separating Random Order from Order Selection

Prophet inequalities are a central object of study in optimal stopping theory. A gambler is sent values online, sampled from an instance of independent distributions, in an adversarial, random or selected order, depending on the model. When observing each value, the gambler either accepts it as a reward or irrevocably rejects it and proceeds to observe the next value. The goal of the gambler, who cannot see the future, is maximising the expected value of the reward while competing against the expectation of a prophet (the offline maximum). In other words, one seeks to maximise the gambler-to-prophet ratio of the expectations. The model, in which the gambler selects the arrival order first, and then observes the values, is known as Order Selection. Recently it has been shown that in this model a ratio of $0.7251$ can be attained for any instance. If the gambler chooses the arrival order (uniformly) at random, we obtain the Random Order model. The worst case ratio over all possible instances has been extensively studied for at least $40$ years. Still, it is not known if carefully choosing the order, or simply taking it at random, benefits the gambler. We prove that, in the Random Order model, no algorithm can achieve a ratio larger than $0.7235$, thus showing for the first time that there is a real benefit in choosing the order.Comment: 36 pages, 2 figure

Estudio anatómico y dimensional del disco del complejo articular témporomandibular durante el desarrollo prenatal humano. Correlación histológica

Estudio Anatómico y Dimensional del Disco del Complejo Articular Témporomandibular durante el Desarrollo Prenatal Humano, Correlación HistológicaEl complejo articular témporomandibular (CATM) permite el movimiento de la mandíbula para una de las funciones vitales del ser humano, como es la lactancia. Su alteración, involucro desde deficiencias nutritivas, neurológicas, sensoriales, inmunológicas hasta efectivas. También afecta el normal desarrollo buco - máxilo - facial, por tanto es necesario la detección precoz de las disfunciones que alteren o impidan la adecuada alimentación en el recién nacido. Entre los factores por los cuales el neonato no podría prenderse al pezón materno o biberón, se señalan las alteraciones anátomofuncionales articulares. El conocimiento anatómico del CATM durante el desarrollo prenatal, respaldaría significativamente la valoración clínica de la fisiopatogenia en las disfunciones articulares. El propósito de este trabajo fue realizar el estudio estructural (macro y microscópico) y morfométrico del disco articular con la finalidad de establecer un patrón normal en la etapa embrionaria.Mediante un analizador de imágenes, se registró la longitud sagital, el espesor de las bandas anterior, media y posterior del disco (D), en cortes sagitales oblicuos del CATM de fetos humanos de 16, 18 y 20 semanas de Oda intrauterina (SVI).la longitud promedio del disco fue de 1,98mm, 2,69mm y 2,90mm a las 16, 18 y 20 SVI respectivamente. También los espesores de las bandas anterior, intermedia y posterior mostraron diferencias significativas. Los resultados proporcionan datos anatómicos e histológicos normales del D entre las 16 y 20 SVI. Referencia que puede servir de base para ulteriores investigaciones del CATM humano, generando un patrón de referencia que puede ser transferido al área de la salud y/o enseñanza

Endocrine modulation of Brucella abortus-infected osteocytes function and osteoclastogenesis via modulation of RANKL/OPG

Osteoarticular brucellosis is the most frequent complication of active disease. A large amount of cells in bone are osteocytes. Since bone remodeling process is regulated by hormones we sought to study the effect of cortisol and DHEA in Brucella abortus-infected osteocytes. Cortisol treatment inhibited the expression of IL-6, TNF-α, MMP-2 and RANKL in B. abortus-infected osteocytes. DHEA could reverse the inhibitory effect of cortisol on MMP-2 production. B. abortus infection inhibited connexin 43 (Cx43) expression in osteocytes. This expression was increased when cortisol was incorporated during the infection and DHEA treatment partially reversed the effect of cortisol. Osteocytes-infected with B. abortus induced osteoclast's differentiation. Yet, the presence of cortisol, but not DHEA, during osteocyte infection inhibited osteoclastogenesis. Glucocorticoid receptor (GR) is implicated in the signaling of cortisol. Infection with B. abortus was able to increase GRα/β ratio. Levels of intracellular cortisol are not only dependent on GR expression but also a result of the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (11β-HSD)-1 (cortisone to cortisol conversion), 11β-HSD2 (cortisol to cortisone conversion). B. abortus infection increased 11β-HSD 1/2 ratio and cortisone mimicked the effect of cortisol. Our results indicated that cortisol and DHEA could modulate osteocyte responses during B. abortus infection.Fil: Pesce Viglietti, Ayelén Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

Adrenal Steroids Modulate Fibroblast-Like Synoviocytes Response During B. abortus Infection

Brucella abortus stimulates an inflammatory immune response that stimulates theendocrine system, inducing the secretion of dehydroepiandrosterone (DHEA) andcortisol. In humans, the active disease is generally present as osteoarticular brucellosis.In previous studies we showed that B. abortus infection of synoviocytes creates aproinflammatory microenvironment. We proposed to determine the role of cortisoland DHEA on synoviocytes and infiltrating monocytes during B. abortus infection.Cortisol inhibited IL-6, IL-8, MCP-1, and MMP-2 secretion induced by B. abortusinfection in synovial fibroblast. Cortisol-mediated MMP-2 inhibition during B. abortusinfection was reversed by IL-6. DHEA inhibited B. abortus-induced RANKL up-regulationin synovial fibroblast through estrogen receptor (ER). B. abortus infection did notmodulate glucocorticoid receptor (GR) expression. Cell responses to cortisol alsodepended on its intracellular bioavailability, according to the activity of the isoenzymes11b-hydroxysteroid dehydrogenase (HSD) type-1 and 11b-HSD2 (which are involvedin cortisone-cortisol interconversion). B. abortus infection did not modify 11b-HSD1expression and GRa/b ratio in the presence or absence of adrenal steroids. Supernatantsfrom B. abortus-infected monocytes induced 11b-HSD1 in synovial cells. Administrationof cortisone was capable of inhibiting the secretion of RANKL by synoviocytes mimickingcortisol?s effect. These results go along with previous observations that highlighted theability of synovial tissue to secrete active steroids, making it an intracrine tissue. This isthe first study that contributes to the knowledge of the consequence of adrenal steroidson synoviocytes in the context of a bacterial infection.Fil: Gentilini, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

Human Infection with M- Strain of Brucella canis

The less mucoid strain of Brucella canis or M- strain is used for the serologic diagnosis of canine brucellosis. While this strain is avirulent in dogs, we report the case of clinical brucellosis that developed in a laboratory worker a few days after handling live M- cells for antigen production

Editorial: Advances in Liver Inflammation and Fibrosis due to Infectious Diseases

Liver inflammation is a common trigger of hepatic disease, and it is considered the main driver of tissue damage (1). Although the liver is able to regenerate, chronic liver inflammation leads to tissue damage with concomitant fibrosis, frequently leading to cirrhosis, and carcinogenesis (2). The etiology of chronic liver inflammation may be infectious or not. Several microorganisms including bacteria, parasites, fungi, and virus could be involved...Fil: Oliveira, Sergio C.. Universidade Federal de Minas Gerais; BrasilFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Splitter, Gary. University of Wisconsin; Estados Unido

Brucella abortus Infection Modulates 3T3-L1 Adipocyte Inflammatory Response and Inhibits Adipogenesis

Brucellosis is a prevalent global zoonotic infection but has far more impact in developing countries. The adipocytes are the most abundant cell type of adipose tissue and their secreted factors play an important role in several aspects of the innate and adaptive immune response. Here, we demonstrated the ability of Brucella abortus to infect and replicate in both adipocytes and its precursor cells (pre-adipocytes) derived from 3T3-L1 cell line. Additionally, infection of pre-adipocytes also inhibited adipogenesis in a mechanism independent of bacterial viability and dependent on lipidated outer membrane protein (L-Omp19). B. abortus infection was able to modulate the secretion of IL-6 and the matrix metalloproteases (MMPs) -2 and-9 in pre-adipocytes and adipocytes, and also modulated de transcription of adiponectin, leptin, and resistin in differentiated adipocytes. B. abortus-infected macrophages also modulate adipocyte differentiation involving a TNF-α dependent mechanism, thus suggesting a plausible interplay between B. abortus, adipocytes, and macrophages. In conclusion, B. abortus is able to alter adipogenesis process in adipocytes and its precursors directly after their infection, or merely their exposure to the B. abortus lipoproteins, and indirectly through soluble factors released by B. abortus-infected macrophages.Fil: Pesce Viglietti, Ayelén Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Quarleri, Jorge Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin