Resilience to the effects of social stress on vulnerability to developing drug addiction

We review the still scarce but growing literature on resilience to the effects of social stress on the rewarding properties of drugs of abuse. We define the concept of resilience and how it is applied to the field of drug addiction research. We also describe the internal and external protective factors associated with resilience, such as individual behavioral traits and social support. We then explain the physiological response to stress and how it is modulated by resilience factors. In the subsequent section, we describe the animal models commonly used in the study of resilience to social stress, and we focus on the effects of chronic social defeat (SD), a kind of stress induced by repeated experience of defeat in an agonistic encounter, on different animal behaviors (depression- and anxiety-like behavior, cognitive impairment and addiction-like symptoms). We then summarize the current knowledge on the neurobiological substrates of resilience derived from studies of resilience to the effects of chronic SD stress on depression- and anxiety-related behaviors in rodents. Finally, we focus on the limited studies carried out to explore resilience to the effects of SD stress on the rewarding properties of drugs of abuse, describing the current state of knowledge and suggesting future research directions

Resilience to the short- and long-term behavioral effects of intermittent repeated social defeat in adolescent male mice

Background Exposure to intermittent repeated social defeat (IRSD) increases the sensitivity of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. Some animals are resilient to this effect of IRSD, though research exploring this inconsistency in adolescent mice is scarce. Thus, our aim was to characterize the behavioral profile of mice exposed to IRSD during early adolescence and to explore a potential association with resilience to the short- and long-term effects of IRSD. Methods Thirty-six male C57BL/6 mice were exposed to IRSD during early adolescence (PND 27, 30, 33 and 36), while another 10 male mice did not undergo stress (controls). Defeated mice and controls then carried out the following battery of behavioral tests; the Elevated Plus Maze, Hole-Board and Social Interaction Test on PND 37, and the Tail Suspension and Splash tests on PND 38. Three weeks later, all the mice were submitted to the CPP paradigm with a low dose of cocaine (1.5 mg/kg). Results IRSD during early adolescence induced depressive-like behavior in the Social Interaction and Splash tests and increased the rewarding effects of cocaine. Mice with low levels of submissive behavior during episodes of defeat were resilient to the short- and long-term effects of IRSD. In addition, resilience to the short-term effects of IRSD on social interaction and grooming behavior predicted resilience to the long-term effects of IRSD on cocaine reward. Conclusion Our findings help to characterize the nature of resilience to the effects of social stress during adolescence

A network of filaments detected by Herschel in the Serpens core : a laboratory to test simulations of low-mass star formation

V.R. was partly supported by the DLR grant number 50 OR 1109 and by the Bayerische Gleichstellungsförderung (BGF). This research was partly supported by the Priority Programme 1573 “Physics of the Interstellar Medium” of the German Science Foundation (DFG), the DFG cluster of excellence “Origin and Structure of the Universe” and by the Italian Ministero dell’Istruzione, Università e Ricerca through the grant Progetti Premiali 2012 -iALMA (CUP C52I13000140001). C.E. is partly supported by Spanish Grants AYA 2011-26202 and AYA 2014-55840-P.Context. Filaments represent a key structure during the early stages of the star formation process. Simulations show that filamentary structures commonly formed before and during the formation of cores. Aims. The Serpens core is an ideal laboratory for testing the state of the art of simulations of turbulent giant molecular clouds. Methods. We used Herschel observations of the Serpens core to compute temperatureand column density maps of the region. We selected the early stages of are cent simulation of star-formation, before stellar feedback was initiated, with similar total mass and physical size as the Serpens core. We also derived temperature and column density maps from the simulations. The observed distribution of column densities of the filaments was analyzed, first including and then masking the cores. The same analysis was performed on the simulations as well. Results. A radial network of filaments was detected in the Serpens core. The analyzed simulation shows a striking morphological resemblance to the observed structures. The column density distribution of simulated filaments without cores shows only a log-normal distribution, while the observed filaments show a power-law tail. The power-law tail becomes evident in the simulation if the focus is only the column density distribution of the cores. In contrast, the observed cores show a flat distribution. Conclusions. Even though the simulated and observed filaments are subjectively similar-looking, we find that they behave in very different ways. The simulated filaments are turbulence-dominated regions; the observed filaments are instead self-gravitating structures that will probably fragment into cores.Publisher PDFPeer reviewe

Multidisciplinary approach to treatment with immune checkpoint inhibitors in patients with HIV, tuberculosis, or underlying autoimmune diseases

Autoimmune diseases; Checkpoint inhibition therapy; Human immunodeficiency virusEnfermedades autoinmunes; Terapia de inhibición de puntos de control; Virus de inmunodeficiencia humanaMalalties autoimmunes; Teràpia d'inhibició del punt de control; Virus de la immunodeficiència humanaWe reviewed the available information on the use of immune checkpoint inhibitors (ICIs) in populations with special conditions, namely, patients with HIV, tuberculosis, or underlying autoimmune disease. Available data show that treatment with ICIs is safe in patients with HIV; it is advisable, however, that these patients receive adequate antiretroviral therapy and have an undetectable viral load before ICIs are initiated. Tuberculosis reactivation has been reported with the use of ICIs, possibly due to immune dysregulation. Tuberculosis has also been associated with the use of immunosuppressors to treat immune-related adverse events (irAEs). Active tuberculosis must be ruled out in patients with symptoms or signs, and selected patients may benefit from screening for latent tuberculosis infection, although more data are required. Limited data exist regarding the safety of ICIs in patients with cancer and autoimmune disease. Data from observational studies suggest that up to 29% of patients with a preexisting autoimmune disease treated with an ICI present with an autoimmune disease flare, and 30% present with a de novo irAE of any type. The frequency of flares appears to differ according to the type of ICI received, with higher rates associated with PD-1/PD-L1 inhibitors. The most common autoimmune diseases for which patients reported flares with ICI therapy are rheumatoid arthritis, other inflammatory arthritis, and psoriasis. Most studies have reported flares or de novo irAEs associated with ICIs that were mild to moderate, with low rates of discontinuation and no deaths due to flares. Therefore, the use of ICIs in these patients is possible, but careful monitoring is required.ML-O's work is supported by the National Cancer Institute (#CA237619)

Best Practices and Methodologies for IT Project Portfolio Management

Abstract. In today's business environment, a key factor for decision making is the IT projects portfolio management (ITPPM). IT projects must be aligned with the objectives, goals and strategies, which is achieved through the appropriate application of a methodology for ITPPM. The experienced application of a methodology depends on the experience of the managers of ITPPM, considering that the application of methodologies generates best practices, it becomes necessary to study some of the more representative methodologies and obtain the best practices that allow novice administrators to initiate their portfolio management activities in information technology projects. In this article, three methodologies are studied, from which best practices are obtained, as results; a hierarchy of best practices is obtained so that project managers can be guided or introduced in their field

Análisis de la superficie de cultivo para la producción de bioplásticos

El presente trabajo establece el potencial de mercado de los Bioplásticos (BPL), en tres escenarios: Escenario CB (crecimiento bajo), Escenario CM (crecimiento medio) y Escenario CR (crecimiento rápido). El objetivo final es Obtener las superficies de cultivo necesarias para satisfacer la demanda de las empresas productoras de BPL, según los tres escenarios. Las regiones geográficas estudiadas son: La Unión Europea (UE-27), Estados Unidos (EE.UU) y la región de Asia-Pacífico, entendiéndose, que esta última región comprende la parte del Centro, Este y Sur de Asia, además de Australia y Nueva Zelanda. Son las principales zonas donde se encuentran las empresas productoras de los BPL estudiados. Más del 95% de los BPL son elaborados en estas regiones. Se han realizado tres proyecciones para los años 2010, 2015 y 2020

Environmental education in secondary schools in the region of Ribeirão Preto (SP, Brazil): how teachers' views of the environment determine their teaching and some reflections on chemistry teachers' higher education

During short courses, 95 secondary school teachers from 49 state schools and 421 students from the Ribeirão Preto region (in Sao Paulo state, Brazil, with a population of 530,000) were asked to fill in different questionnaires. The points raised in the teacher's questionnaire were used as a guide to establish a continuous dialogue during the short courses. Most of the schools claimed to have some kind of environmental education (EE). Based on the questionnaires and dialogues we analyzed how the teachers' perceptions on EE reflect on the views secondary students hold about their own responsibility for preserving the environment. The role of universities in the preparation of chemistry teachers capable of effectively approaching EE is also discussed

Bub3-Bub1 binding to Spc7/KNL1 toggles the spindle checkpoint switch by licensing the interaction of Bub1 with Mad1-Mad2

The spindle assembly checkpoint (SAC) ensures that sister chromatids do not separate until all chromosomes are attached to spindle microtubules and bi-oriented. Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), are recruited to unattached and/or tensionless kinetochores. SAC activation catalyzes the conversion of soluble Mad2 (O-Mad2) into a form (C-Mad2) that binds Cdc20, BubR1, and Bub3 to form the mitotic checkpoint complex (MCC), a potent inhibitor of the anaphase-promoting complex (APC/C). SAC silencing de-represses Cdc20-APC/C activity allowing poly-ubiquitination of Securin and Cyclin B, leading to the dissolution of sister chromatids and anaphase onset [1]. Understanding how microtubule interaction at kinetochores influences the timing of anaphase requires an understanding of how spindle checkpoint protein interaction with the kinetochore influences spindle checkpoint signaling. We, and others, recently showed that Mph1 (Mps1) phosphorylates multiple conserved MELT motifs in the Spc7 (Spc105/KNL1) protein to recruit Bub1, Bub3, and Mad3 (BubR1) to kinetochores [2-4]. In budding yeast, Mps1 phosphorylation of a central non-catalytic region of Bub1 promotes its association with the Mad1-Mad2 complex, although this association has not yet been detected in other organisms [5]. Here we report that multisite binding of Bub3 to the Spc7 MELT array toggles the spindle checkpoint switch by permitting Mph1 (Mps1)-dependent interaction of Bub1 with Mad1-Mad2

Immunosuppressive and angiogenic cytokine profile associated with Bartonella bacilliformis infection in post-outbreak and endemic areas of Carrion's disease in Peru

Analysis of immune responses in Bartonella bacilliformis carriers are needed to understand acquisition of immunity to Carrion's disease and may allow identifying biomarkers associated with bacterial infection and disease phases. Serum samples from 144 healthy subjects from 5 villages in the North of Peru collected in 2014 were analyzed. Four villages had a Carrion's disease outbreak in 2013, and the other is a traditionally endemic area. Thirty cytokines, chemokines and growth factors were determined in sera by fluorescent bead-based quantitative suspension array technology, and analyzed in relation to available data on bacteremia quantified by RT-PCR, and IgM and IgG levels measured by ELISA against B. bacilliformis lysates. The presence of bacteremia was associated with low concentrations of HGF (p = 0.005), IL-15 (p = 0.002), IL-6 (p = 0.05), IP-10 (p = 0.008), MIG (p = 0.03) and MIP-1alpha (p = 0.03). In multi-marker analysis, the same and further TH1-related and pro-inflammatory biomarkers were inversely associated with infection, whereas angiogenic chemokines and IL-10 were positively associated. Only EGF and eotaxin showed a moderate positive correlation with bacteremia. IgM seropositivity, which reflects a recent acute infection, was associated with lower levels of eotaxin (p = 0.05), IL-6 (p = 0.001), and VEGF (p = 0.03). Only GM-CSF and IL-10 concentrations were positively associated with higher levels of IgM (p = 0.01 and p = 0.007). Additionally, IgG seropositivity and levels were associated with high levels of angiogenic markers VEGF (p = 0.047) and eotaxin (p = 0.006), respectively. Our findings suggest that B. bacilliformis infection causes immunosuppression, led in part by overproduction of IL-10. This immunosuppression probably contributes to the chronicity of asymptomatic infections favoring B. bacilliformis persistence in the host, allowing the subsequent transmission to the vector. In addition, angiogenic markers associated with bacteremia and IgG levels may be related to the induction of endothelial cell proliferation in cutaneous lesions during chronic infections, being possible candidate biomarkers of asymptomatic infections

Chiral models in dilaton-Maxwell gravity

We study symmetry properties of the Einstein-Maxwell theory nonminimaly coupled to the dilaton field. We consider a static case with pure electric (magnetic) Maxwell field and show that the resulting system becomes a nonlinear sigma-model wich possesses a chiral representation. We construct the corresponding chiral matrix and establish a representation which is related to the pair of Ernst-like potentials. These potentials are used for separation of the symmetry group into the gauge and nongauge (charging) sectors. New variables, which linearize the action of charging symmetries, are also established; a solution generation technique based on the use of charging symmetries is formulated. This technique is used for generation of the elecricaly (magneticaly) charged dilatonic fields from the static General Relativity ones.Comment: 9 pages in LaTex; published in Gen. Rel. Grav. 32 (2000) pp 1389-139