Ciberactivismo y tecnopolítica. Construcción de ciudadanías desde la socialización política, internet y las redesi / Cyberactivism and Technopolitics. Construction of Citizenships from Political Socialization, The Internet, and Networks

Resumen Internet y las redes sociales han generado conexiones distintas, posibilitan de sarrollos en diversas formas, construcciones de mundo y relaciones humanas. Las ciencias sociales aportan mecanismos de comprensión de realidades com plejas, la socialización y la subjetividad política contribuyen en la construcción de un carácter multicémico en dicha perspectiva. Las redes sociales en conver gencia de inmediatez, la información y la impresión emocional, posibilitan la tecnopolítica, así la política toma forma y se consolida como posibilidad de arti culación de ideas conduciendo al ciberactivismo; posibilitando acciones ciuda danas y ciudadanías emergentes que necesitan nuevas formas de comprensión desde las ciencias sociales.

Abstract The Internet and social networks have generated different connections, they enable developments in various forms, constructions of the world, and human relations. Social sciences provide mechanisms for understanding complex rea lities, socialization, and political subjectivity contribute to the construction of a multi-cultural character in this perspective. Social networks in convergence of immediacy, information and emotional impression, make Technopolitics possi ble. Thus, politics takes shape and consolidates as a possibility of articulation of ideas leading to Cyberactivism; by enabling citizen actions and by emerging citizenships that need new forms of understanding from the social sciences.

A novel vector for transgenesis in the rat CNS.

The larger brain of the rat enables a much greater repertoire of complex behaviors than mice, likely making rats preferential for investigating neurodegeneration. Because molecular tools for specific expression of transgenes in the rat brain are sparse, we chose Prnp encoding the prion protein (PrP) to develop a novel vector to drive transgene expression in the rat brain. We compared the rat Prnp sequence with mouse and Syrian hamster Prnp sequences, identifying conserved genetic elements and hypothesizing that these elements would be able to drive neuronal transgene expression. We investigated this by generating a vector termed RaPrnp that encompasses portions of the rat Prnp gene. Importantly, we replaced the rat Prnp open reading frame (ORF) with a cloning site for rapid and seamless In-Fusion cloning. To validate the in vivo neuronal specificity of the RaPrnp vector in rats, we generated stable RaPrnp-LacZ/enhanced green fluorescent protein (EGFP) transgenic (Tg) rat lines, which led to robust LacZ activity and high EGFP fluorescence in the central nervous system of embryos and adult animals. Next, we restored the rat Prnp ORF and generated multiple Tg(RaPrnp-PrP) lines, demonstrating that overexpression of Prnp accelerates the onset of scrapie. While the incubation time in wild-type (WT) rats was 175 ± 3 days post inoculation (dpi), one line, Tg2919, overexpressed RaPrPC at 4.4-fold and exhibited a reduced incubation time of 149 ± 2 dpi. The second line, Tg2922, overexpressed RaPrPC at 9.7-fold compared with WT animals and had an incubation time of 112 ± 0 dpi. Tg2922 rats inoculated with rat RML showed extensive vacuolation of the brainstem in contrast to WT and Tg2919 animals in which vacuolation was most prominent in the hippocampus and striatum as well as the motor and sensory cortices. It is possible that construction of Tg rats with modified phenotypes will prove more advantageous than mice for neurodegeneration studies.

Kinetics of Human Mutant Tau Prion Formation in the Brains of 2 Transgenic Mouse Lines.

Importance: Accumulation of the protein tau is a defining characteristic of several neurodegenerative diseases. Thorough assessment of transgenic (Tg) mouse lines that replicate this process is critical for establishing the models used for testing anti-tau therapeutics in vivo. Objective: To define a consistent mouse model of disease for use in future compound efficacy studies. Design, Setting, and Participants: In this time course study, cohorts of Tg and control mice were euthanized at defined intervals. Collected brains were bisected down the midline. One half was frozen and used to measure the tau prion content, while the other half was fixed for immunostaining with anti-tau antibodies. All mice were maintained at the Hunters Point Animal Facility at the University of California, San Francisco, and all experiments were performed at the Mission Bay Campus of the University of California, San Francisco. Study animals were PS19, homozygous and hemizygous Tg(MAPT*P301S), and B6/J mice. The study dates were August 9, 2010, to October 3, 2016. Main Outcomes and Measures: Tau prions were measured using a cell-based assay. Neuropathology was measured by determining the percentage area positive for immunostaining in defined brain regions. A separate cohort of mice was aged until each mouse developed neurological signs as determined by trained animal technicians to assess mortality. Results: A total of 1035 mice were used in this time course study. These included PS19 mice (51.2% [126 of 246] male and 48.8% [120 of 246] female), Tg(MAPT*P301S+/+) mice (52.3% [216 of 413] male, 43.8% [181 of 413] female, and 3.9% [16 of 413] undetermined), Tg(MAPT*P301S+/-) mice (51.8% [101 of 195] male and 48.2% [94 of 195] female), and B6/J mice (49.7% [90 of 181] male and 50.3% [91 of 181] female). While considerable interanimal variability in neuropathology, disease onset, and tau prion formation in the PS19 mice was observed, all 3 measures of disease were more uniform in the Tg(MAPT*P301S+/+) mice. Comparing tau prion formation in Tg(MAPT*P301S+/+) mice with B6/J controls, the 95% CIs for the 2 mouse lines diverged before age 5 weeks, and significant (P < .05) neuropathology in the hindbrain of 24-week-old mice was quantifiable. Conclusions and Relevance: The assessment of disease progression using 3 criteria showed that disease onset in PS19 mice is too variable to obtain reliable measurements for drug discovery research. However, the reproducibility of tau prion formation in young Tg(MAPT*P301S+/+) mice establishes a rapid assay for compound efficacy in vivo.

Immunosuppression alters disease severity in juvenile Batten disease mice.

Autoantibodies to brain proteins are present in Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease) patients and in the Cln3-/- mouse model of this disease, suggesting an autoimmune component to pathogenesis. Using genetic or pharmaceutical approaches to attenuate this immune response in Cln3-/- mice, we demonstrate decreased neuroinflammation, decreased deposition of immunoglobulin G in the brain and protection of vulnerable neuron populations. Moreover, immune suppression results in a significant improvement in motor performance providing for the first plausible therapeutic approach for juvenile Batten disease.

Concentraciones de metales en sedimientos y tejidos musculares de algunos peces de la laguna de castillero Venezuela / Metals concentration in sediments and muscular tissues of some fich from the castillero lagoon Venezuela

Con el propósito de detectar alteraciones en el productivo ecosistemade la Laguna de Castillero (Caicara del Orinoco, municipio Cedeño del estado Bolívar, Venezuela), se presentan resultados de mediciones granulométricas y de las concentraciones de los metales pesados: Fe, Mn, Zn, Pb y Co realizadas en junio 2001 sobre los sedimentos superficiales y del tejido muscular de varias especies autóctonas de peces (Plasgiosium squamossimos, Pigocentrus cariba, Pheudoplastyloma fascia-tum, e Hypostomus spp realizadas en junio 2001. Utilizando técnica de espectrofotometría de absorción atómica con llama de aire acetileno, se determinó que, las concentraciones de metales más altas están representadas por manganeso, zinc y plomo. En la parte más interna de la laguna, el tipo de sedimento predominante es el lodo, constituyendo entre 30 por ciento y un 65 por ciento del material colectado por estación. Se encuentra, que esos niveles decrecen hacia la boca de la laguna, producto de la interacción de las corrientes de flujo/reflujo que lavan el sedimento y que se refleja en la mayor presencia de arena fina. El análisis estadístico de ANOVA muestra diferencias significativas entre las concentraciones de los metales en las estaciones, tipificadas por la presencia de promedios discrepantes. Los niveles promedios para los sedimentos superficiales de la zona son los siguientes: Fe (3365,44 ± 261,61), Mn (132,17 ± 25,46), Zn (253,04 ±86,48), Pb (17,02 ± 2,21) y Co (4,65 ± 0,76) µg/g. Similarmente, en el tejido muscular de los peces se cuantificaron las siguientes concentraciones: Fe entre (31,26 ± 0,06) y (68,36 ± 0,05);Mn entre (2,02 ± 0,05) y (4,16 ±0,03); Zn entre (19,09 ± 0,01) y (28,89 ± 0,01); Pb entre (0,38 ± 0,01) y (0,47 ± 0,03) µg/g. El análisis refleja una notable asociación entre los altos valores de concentraciones de metales y el tipo de sedimento, con un gradiente creciente hacia el sedimento tipo lodo. Se encuentran valores elevados en la concentración de Pb y Zn...

To detected alterations in the productive ecosystem of the Castillero Lagoon (Caicara of the Orinoco, Cedeño Municipality, Bolivar State, Venezuela), results are presented for granulometric measurements and heavy metals concentrations: Fe, Mn, Zn, Pb and Co made in June 2001 on superface sediments and of the muscular tissue of several native species of fish (Plasgiosium squamossimos, Pigocentrus cariba, Pheudoplastyloma fasciatum, and Hypostomus spp. By using atomic absorption spectrophotometry with an air-acetylene flame, it was determined that the highest concentrations of metals are represented by manganese, zinc and lead. It was determined that the highest concentrations of metals are represented by manganese, zinc and lead. In the most internal part in the lagoon the type of predominant sediments is the mud, constituting among 30% and 65% of the material collected by station. Is that those levels fall toward the mouth of the lagoon, product of the interaction of the flow / reflux currents that washes the sediment and that is reflected in the biggest presence of fine sand. The statistical analysis of ANOVA shows significant differences among the concentrations of the metals in the stations, tipificated for the presence of different averages. The averages levels for the superficial sediments of the area are the following ones: Fe (3365.44 ± 261.61), Mn (132.17 ± 25.46), Zn (253.04 ± 86.48), Pb (17.02 ± 2.21) y Co (4.65 ± 0.76) µg/g. In similarly way, in the muscular tissue of the fish the following concentrations were quantified: Fe between (31.26 ± 0.06) and (68.36 ± 0.05); Mn between (2.02 ± 0.05) and (4.16 ± 0.03); Zn between (19.09 ± 0.01) and (28.89 ± 0.01); Pb between (0.38 ± 0.01) and (0.47 ± 0.03) µg/g. The analysis reflects a remarkable association between the high securities of concentrations of metals and the sediments type, with a growing gradient toward the sediments type mud. These are alarming values in concentration of Pb and Zn...

Cuantificación de las concentraciones de metales pesados en tejidos de peces y crustáceos de la Laguna de Unare estado Anzoátegui Venezuela / Quantification of the concentrations of heavy metals in tissues of fich and crustaceans of the Unare Lagoon Anzoategui state Venezuela

Se analizó por Espectrofotometría de Absorcion Atomica de llama el contenido de Fe, Mn, Cu, Cr, Ni, Zn, Cd y Pb en tejidos musculares de peces y crustáceos de la laguna de Unare, estado Anzoátegui, Venezuela. Adicionalmente, se determinaron los niveles en el material en suspension del agua y en el sedimento para detectar posibles impactos en el ecosistema. En el agua, las concentraciones medias de metales fueron bajos (0,104-0,53 µmol/L Fe; 0,004-0,06 µmol/L Mn; 0,002-0,028 µmol/L Zn; 0,004-0,012 µmol/L Cr; no detectado-0,011 µmol/LNi y no detectado- 0,001 µmol/L Cd). En el sedimento se evidencia intervención antropogénica con valores medios que decrecen Mn (516,37)>Zn (127,49)>Ni (52,41)>Cr (51,69)>Cu (41,13)>Pb (29)>Cd (1,51 µg/g) y que superan los niveles establecidos para sedimentos no contaminados. En los tejidos de los organismos se detectó la presencia de metales tóxicos como el plomo y cadmio que superan los 0,16 y 0,04 µg/g, res-pectivamente, al igual que el zinc que alcanza niveles elevados que sobrepasan 17 µg/g en la mayoría de las especies. Las pruebas estadísticas de ANOVA (P<0,05) indican discrepancias en las concentraciones metales en los tejidos por los diferentes géneros y especies, al igual que en los valores de los individuos de la misma especie (Cathorops spixii) que habitan dentro y fuera de la laguna. Los niveles son mayores en los habitantes del interior de la laguna evidenciando fenómenos de bioacumulación. La investigación confirman un progresivo deterioro ambiental de la laguna y de las especies ícticas de este ecosistema que son comercializadas por las poblaciones aledañas a la laguna, las cuales sustentan su economía de su explotación pesquera.

The content of Fe, Mn, Cu, Cr, Ni, Zn, Cd and Pb in muscle tissues of fish and crustaceans from the Unare lagoon (Laguna de Unare) in the state of Anzoátegui, Venezuela, was analyzed by flame Atomic Absorption Spectrometry. The levels of these metals present in suspended material of the water and in sediments were also determined in order to detect possible impact on the ecosystem. The mean concentrations in the water were low (0.104-0.53 µmol/L Fe; 0.004-0.06 µmol/L Mn; 0.002-0.028 µmol/L Zn; 0.004-0.012 µmol/L Cr; undetectable-0.011 µmol/L Ni and undectable-0.001 µmol/L Cd). In the sediments, evidence was found of anthropogenic intervention with mean values in decreasing order of Mn (516.37) > Zn (127.49) > Ni (52.41) > Cr (51.69) > Cu (41.13) > Pb (29) > Cd (1.51 µg/g), all of which are greater than established levels for uncontaminated sediments. Toxic metals were detected in the examined organisms, such as lead and cadmium with levels above 0.16 and 0.04 µg/g, respectively, and zinc with levels greater than 17 µg/g in the majority of the species. ANOVA statistical tests (P < 0.05) show discrepancies in the concentrations or the metals in the tissues of the different genera and species, as well as in the values for individuals of the same species (Cathorops spixii) which live inside and outside of the lagoon. The levels are higher in those which live within the lagoon, which indicates bioaccumulation processes. This study confirms that the lagoon and its biota have suffered a progressive and important deterioration inasmuch as the neighboring population relies on the commercialization of the fish and crustaceans for their economic stability.

Identification of alpha-fetoprotein as an autoantigen in juvenile Batten disease.

Humoral autoimmunity against glutamic acid decarboxylase has been described in juvenile Batten disease patients and in the Cln3(-/-) mouse model. To obtain a more comprehensive understanding of the repertoire of antigens targeted, we examined the reactivity of Cln3(-/-) mouse sera to brain proteins from fetal, postnatal and adult rats. Among the candidate antigens identified was alpha-fetoprotein (AFP), a protein that has altered expression in several nervous system disorders and hepatic malignancies. Moreover, AFP levels were upregulated in the brains and livers of postnatal day 14 Cln3(-/-) animals. Sera from 31 juvenile Batten disease patients revealed the presence of anti-AFP autoantibodies in juvenile Batten disease male patients (12/13) and female patients (8/18). While these findings provide more evidence that autoimmunity is an active component of juvenile Batten disease, the gender-apparent difference evidenced by patients with regard anti-AFP antibodies may underlie variation in progression and clinical manifestations in this disorder.

Immune system irregularities in lysosomal storage disorders.

Lysosomal storage disorders (LSDs) are genetically inherited diseases characterized by the accumulation of disease-specific biological materials such as proteolipids or metabolic intermediates within the lysosome. The lysosomal compartment's central importance to normal cellular function can be appreciated by examining the various pathologies that arise in LSDs. These disorders are invariably fatal, and many display profound neurological impairment that begins in childhood. However, recent studies have revealed that several LSDs also have irregularities in the function of the immune system. Gaucher disease, mucopolysaccharidosis VII, and alpha-mannosidosis are examples of a subset of LSD patients that are predisposed towards immune suppression. In contrast, GM2 gangliosidosis, globoid cell leukodystrophy, Niemann-Pick disease type C1 and juvenile neuronal ceroid lipofuscinosis are LSDs that are predisposed towards immune system hyperactivity. Antigen presentation and processing by dedicated antigen presenting cells (APCs), secretion of pore-forming perforins by cytotoxic-T lymphocytes, and release of pro-inflammatory mediators by mast cells are among the many crucial immune system functions in which the lysosome plays a central role. Although the relationship between the modification of the lysosomal compartment in LSDs and modulation of the immune system remains unknown, there is emerging evidence for early neuroimmune responses in a variety of LSDs. In this review we bridge biochemical studies on the lysosomal compartment's role in the immune system with clinical data on immune system irregularities in a subset of LSDs.

The role of osteoactivin-derived peptides in osteoblast differentiation.

BACKGROUND: In our previous studies, we found that osteoactivin (OA) plays an important role in the regulation of osteoblast differentiation in vitro. Our studies also suggested that the region of OA protein that contains an RGD motif might play a vital role in the function of OA in osteoblast differentiation. In this study, we examined the functional role of OA-derived peptide containing the RGD motif (OA-D) in osteoblast differentiation. MATERIAL/METHODS: For this purpose, we designed another peptide, termed OA-E, that has sequence similar to OA-D but with glutamic acid (E) instead of aspartic acid (D). The effect of OA-E peptide on osteoblast differentiation was examined. Interestingly, OA-E peptide induced osteoblast differentiation in a manner similar to OA-D peptide. These data suggested that the effect of OA-derived peptides is RGD independent and it could be dependent on other features in the amino acid sequence of these peptides. RESULTS: OA-D peptide treatment markedly induced osteoblast differentiation markers in vitro compared to cultures treated with negative control peptide (NCP). Interestingly, OA-E peptide induced osteoblast differentiation in a manner similar to OA-D peptide. These data suggested that the effect of OA-derived peptides is RGD independent and it could be dependent on other features in the amino acid sequence of these peptides. Since phosphorylation of amino acid residues in proteins and peptides plays a major role in biological systems, the phosphorylation pattern of amino acid sequences of OA-derived peptides and OA protein family members were examined using bioinformatic analysis tools. We found that OA-derived peptides and OA protein family members have serine residue, close to c-terminus and might be phosphorylated with casein kinase II. Casein kinase II is known to phosphorylate many osteoblast-related proteins that regulate osteoblast development and differentiation such as osteopontin and vitronectin. CONCLUSIONS: Collectively, these data showed that both OA-D and OA-E peptides significantly induced osteoblast differentiation in vitro and that effect is RGD independent.

Amelioration of inflammation, angiogenesis and CTGF expression in an arthritis model by a TSP1-derived peptide treatment.

OBJECTIVE: To evaluate the effect of a thrombospondin 1 (TSP1)-derived peptide on inflammation and angiogenesis in an animal model of erosive arthritis and to assess the relationship between TSP1 and connective tissue growth factor (CTGF) in the pathophysiology of rheumatoid arthritis. METHODS: Erosive arthritis in Lewis rats was induced by peptidoglycan-polysaccharide (PG-PS). Animals were divided into four groups: (1) negative control and groups receiving, (2) no treatment, (3) treatment with a TSP1-derived peptide, and (4) treatment with a scrambled peptide. Samples obtained from ankle joint, spleen and liver were studied using histology, histomorphometry, immunohistochemistry and RT-PCR. RESULTS: Histological data indicated that the TSP1-derived peptide treatment decreased neovascularization, leukocyte infiltration and thickening of the synovial lining of the joint, and reduced granuloma formation in the spleen and liver when compared to control groups. Higher concentrations of CTGF and TSP1 proteins were observed in the affected areas of animals which did not receive TSP1-derived peptide treatment. Also, immunofluorescence and RT-PCR analyses showed an increase in CTGF protein expression and regulation, respectively, in the tissues of untreated animals when compared to the TSP1-derived peptide treated animals. By immunofluorescence, TSP1 expression was decreased in the TSP1-derived peptide treated animals. Moreover, macrophage/monocyte-specific staining revealed a decrease in cell infiltration in the articular tissue of the TSP1-derived peptide treated animals. CONCLUSION: Both inflammation and angiogenesis were decreased after TSP1-derived peptide treatment indicating a potential pathway by which TSP1 interaction with neutrophils induces CTGF in RA affected tissues.

Maternal antibrain antibodies in autism.

Autism is a neurodevelopmental disorder of prenatal onset that is behaviorally defined. There is increasing evidence for systemic and neuroimmune mechanisms in children with autism. Although genetic factors are important, atypical prenatal maternal immune responses may also be linked to the pathogenesis of autism. We tested serum reactivity in 11 mothers and their autistic children, maternal controls, and several groups of control children, to prenatal, postnatal, and adult rat brain proteins, by immunoblotting. Similar patterns of reactivity to prenatal (gestational day 18), but not postnatal (day 8) or adult rat brain proteins were identified in autistic children, their mothers, and children with other neurodevelopmental disorders, and differed from mothers of normal children, normal siblings of children with autism and normal child controls. Specific patterns of antibody reactivity were present in sera from the autism mothers, from 2 to 18 years after the birth of their affected children and were unrelated to birth order. Immunoblotting using specific antigens for myelin basic protein (MBP) and glial acidic fibrillary protein (GFAP) suggests that these proteins were not targets of the maternal antibodies. The identification of specific serum antibodies in mothers of children with autism that recognize prenatally expressed brain antigens suggests that these autoantibodies could cross the placenta and alter fetal brain development.

A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating connective tissue growth factor.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with leukocyte adhesion to and extravasation through vascular endothelium into synovial tissue. Recent evidence indicates that the thrombospondin 1 gene is up-regulated in patients with RA. We have identified a region within the TSP-1 type 3 repeats that inhibits human neutrophil elastase (HNE) and binds to human neutrophils. The present study was undertaken to investigate the therapeutic benefit of this TSP-1-derived peptide sequence and its effect on connective tissue growth factor (CTGF), a protein involved in fibrotic disorders and in neovascularization, which is a hallmark of RA. METHODS: CTGF gene and protein expression, as well as protein levels of CTGF in the synovium, after treatment with the TSP-1-derived peptide were studied in the peptidoglycan-polysaccharide animal model of erosive arthritis. RESULTS: Peptide treatment prevented joint infiltration and inflammation and was associated with reduced circulating antigen levels of HNE and TSP-1. Additionally, CTGF was up-regulated in this experimental model of RA. Treatment with the TSP-1-derived peptide was associated with down-regulation of the message and protein levels of CTGF. Immunofluorescence studies showed that the mean area fraction of CTGF immunoreactivity in the peptide-treated group of animals was significantly less than that in the untreated group. CONCLUSION: These results document a role for TSP-1 in regulating CTGF gene and protein expression in synovial tissue, suggesting a link with the disease course in this model of RA. This TSP-1-derived synthetic peptide may represent an important template for drug development in RA and other inflammatory conditions associated with neutrophil activation.

Modulation of inflammation by kininogen deficiency in a rat model of inflammatory arthritis.

OBJECTIVE: To compare inflammatory peripheral arthritis in wild-type and high molecular weight kininogen (HK)-deficient rats, both on the genetically susceptible Lewis background. METHODS: By backcrossing Brown-Norway HK-deficient rats with Lewis rats for 6 generations, 2 new strains were produced, wild-type F6 and HK-deficient F6, each with a 98.5% Lewis genome. Inflammatory arthritis was induced by intraperitoneal injection of peptidoglycan-polysaccharide (PG-PS), and the clinical, histopathologic, and biochemical responses were compared in both strains. RESULTS: Eighteen days after PG-PS injection, rats with normal concentrations of HK showed weight loss and marked increase in hind ankle diameter with severe synovial inflammation and cartilage abnormalities. In contrast, HK-deficient rats showed no weight loss (P < 0.05), no increase in hind ankle diameter (P < 0.05), and an absence of inflammatory changes (P < 0.05), as measured by the histologic and morphometric Mankin grading system for synovial and cartilage injury. CONCLUSION: Plasma HK is a key mediator of acute and chronic inflammatory arthritis in genetically susceptible Lewis rats.