HIV-1 Vpr Causes Synaptodendritic Damage in Neurons

HIV weakens the immune system by infecting and destroying T-cells, leaving the body vulnerable to infection and the development of AIDS. Conventional treatments for HIV, such as combined anti-rectroviral therapy (cART), fail to prevent the development of HIV-associated neurocognitive disorder (HAND). Neurological dysfunction has been directly related to the invasion of HIV in the central nervous system (CNS). HIV produces neurotoxic proteins, such as the Viral Protein R (Vpr), which contribute to HAND. Astrocytes are the most abundant cells in the brain and an important HIV target. We hypothesize that astrocytes expressing Vpr will cause neuronal damage in our co-culture system. Primary astrocytes were transfected with Vpr plasmid or control (pEGFP or mock) using electroporation. Astrocytes were then co-cultured with cortical neurons. At 48 and 72 hours we collected the primary astrocytes to confirm the Vpr expression via western blot analysis. We then measured structural damage in the neurons using immunofluorescence for cytoskeletal (MAP2, f-actin) and synaptic (synaptophysin) damage. Preliminary results showed strong staining of filamentous actin and MAP2 with weak detection of synaptophysin. The positive control for neurotoxicity (2.8µM acrylamide) showed substantial damage to the cellular structure. Results for Vpr expression are pending. After confirming that the immunofluorescence assays are working with our controls, we expect to detect any synaptodendritic damage in the neurons caused by Vpr in our upcoming experiments

FACTORES PREDISPONENTES EN LAS ALTERACIONES COGNITIVAS EN EL ADULTO MAYOR: REVISION DE LITERATURA

Introduction: The accelerated growth of the elderly population in the world and from which Colombia does not escape, shows how some people reach this stage of life with a decrease or loss of functional capacity; disability and other physical and mental disorders. Objective: to identify the predisposing factors for the presence of cognitive alterations in the elderly. Materials and methods: literature review, Scopus and Scielo databases were consulted, primary article without year limit, in full text, with Mesh terms (Cognitive impairment and elderly), selecting 20 with qualitative and quantitative designs, in English languages and Portuguese, the researchers independently consulted the Fulltext. Ethically, the referencing of the authors of the articles was carried out while maintaining intellectual property. Results: The analysis of the articles was carried out in two moments: the first was individually and independently, the second triangulating the information in pairs, within the research group. Analysis of each category and its descriptors was carried out, relating the terms by thematic axis, represented in 2 categories that allow describing and classifying the results obtained. The categories identified were: 1) Basic diseases and their relationship with cognitive impairment. 2) Socioeconomic factors, educational level and occupation. Conclusions: The main cognitive disorders of the elderly with mild cognitive impairment were identified, taking into account that it is one of the more frequent pathologies that affect their quality of life.Introducción: El crecimiento acelerado de la población mayor en el mundo y del que no escapa Colombia, muestra como algunas personas llegan a esta etapa de la vida con disminución o pérdida de la capacidad funcional; discapacidad y otros trastornos físicos y mentales. Objetivo:  identificar los factores predisponentes para la presencia de alteraciones cognitivas del adulto mayor. Materiales y métodos:  revisión de literatura , se consultaron las bases de datos Scopus y Scielo, articulo primarios sin límite de año, en texto completo,  con  términos Mesh (Cognitive impairment and elderly), seleccionando 20 con diseños cualitativos y cuantitativos, en idiomas inglés y portugués, los investigadores  consultaron independientemente  el Fulltext.. Éticamente se realizó la referenciación de los autores de los artículos manteniendo la propiedad intelectual. Resultados:  El análisis de los artículos se realizó en dos momentos: el primero fue de manera individual e independiente, el segundo triangulando la información en parejas, dentro del grupo de investigación. Se realizó análisis de cada categoría y sus descriptores relacionando los términos por eje temático, representados en 2 categorías que permiten describir y clasificar los resultados obtenidos. Las categorías identificadas fueron:1) Enfermedades de base y su relación con el deterioro cognitivo.2) Factores socioeconómicos, nivel educativo y ocupación conclusiones: Se identificaron las principales alteraciones cognitivas del adulto mayor con deterioro cognitivo leve teniendo en cuenta que es una de las patologías más frecuentes que afecta su calidad de vida. &nbsp

Stable endocytic structures navigate the complex pellicle of apicomplexan parasites

Apicomplexan parasites have immense impacts on humanity, but their basic cellular processes are often poorly understood. Where endocytosis occurs in these cells, how conserved this process is with other eukaryotes, and what the functions of endocytosis are across this phylum are major unanswered questions. Using the apicomplexan model Toxoplasma, we identified the molecular composition and behavior of unusual, fixed endocytic structures. Here, stable complexes of endocytic proteins differ markedly from the dynamic assembly/disassembly of these machineries in other eukaryotes. We identify that these endocytic structures correspond to the ‘micropore’ that has been observed throughout the Apicomplexa. Moreover, conserved molecular adaptation of this structure is seen in apicomplexans including the kelch-domain protein K13 that is central to malarial drug-resistance. We determine that a dominant function of endocytosis in Toxoplasma is plasma membrane homeostasis, rather than parasite nutrition, and that these specialized endocytic structures originated early in infrakingdom Alveolata likely in response to the complex cell pellicle that defines this medically and ecologically important ancient eukaryotic lineage

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

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Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

Does Research on Nature of Science and Social Justice Intersect? Exploring Theoretical and Practical Convergence for Science Education

Even though enhancement of students’ understanding of social justice is thought to contribute to good citizenship, contextualising social justice in science education remains challenging for teachers because social justice is not conventionally a common feature of science teaching and learning. A separate issue in science education concerns a vast body of work on nature of science (NOS) elated to understanding of and about science. Understanding NOS is thought to contribute to scientific literacy as well as citizenship. Although social justice and NOS literatures share similar themes such as citizenship goals, the precise intersection of these literatures remains relatively understudied. In this chapter, we present an argument about how contemporary conceptualizations of NOS as well as NOS instruction might be used to promote goals related to social justice. In so doing, we aim to contribute to NOS literature by drawing on theories of social justice grounded in political philosophy. We trace the potential overlap of social justice and NOS concepts and draw out example recommendations for curriculum statements and practical teaching as well as practical teaching and learning approaches. Overall, we advocate the promotion of educational goals related to social justice through NOS instruction

Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses