201 research outputs found
Migración haitiana y derechos humanos: el acceso a la salud pública en la frontera en Brasil
Neste trabalho objetivamos problematizar o tema da desigualdade social expressa cotidianamente como uma desigualdade em saúde. De maneira mais precisa, a pesquisa se insere em uma região da América do Sul conhecida como tríplice fronteira latino-americana, local de intenso fluxo migratório. Lócus privilegiado para discutir as relações entre migrações e saúde. Neste contexto geográfico, pretendemos discutir a relação entre migração – especificamente, migração haitiana em contexto de região de fronteira no Brasil – e saúde pública. Para tanto, conduziremos a discussão na perspectiva de acesso à saúde como direito humano à todas as pessoas e dever do Estado. Faremos isso com um aporte teórico-metodológico das Ciências Sociais da Saúde, associado a um trabalho de campo que incluiu levantamento de dados quantitativos e qualitativos. A exposição destes dados, nos permite argumentar que o gozo dos direitos humanos é permitido a toda população fronteiriça, contudo estrangeiros residentes no Brasil, ainda que legalizados, não tem usufruto dos direitos na mesma proporção que os nacionais. Tal percurso analítico nos leva a conclusão, neste artigo, que os agentes da gestão, na região de fronteira, têm utilizado a estratégia de tensionamento da população local com os estrangeiros que utilizam o serviço público de saúde derivando numa desigualdade em saúde.This work seeks to problematize social inequality expressed daily as an inequality in health. More precisely, it is inserted in a region of South America known as the triple Latin American border, a place of intense migratory flow. A privileged locus for discussing relations between migration and health. In this geographic context, the objective is to discuss migration - more specifically, Haitian migration in the context of border region in Brazil - and public health. To do so, we will conduct a discussion in the perspective of access to health as a human right for all people and the duty of the State. Discounts of quantitative and qualitative data. And through the dissemination of data, we will argue that the enjoyment of human rights is allowed in the entire border population, yet non-legalized foreigners residing or domiciled in Brazil (even legalized), does not enjoy rights in the same proportion as nationals.En este trabajo tenemos como objectivo problematizar el tema de la desigualdad social expresa cotidianamente como una desigualdad en salud. De manera más precisa, la investigción se inserta en una región de Sudamérica conocida como triple frontera latino-americana, lugar de intenso flujo migratório. Lócus privilegiado para discutir las relaciones entre migraciones y salud. En este contexto geográfico, pretendemos discutir la relación entre migración – especificamente, migración haitiana en contexto de región de frontera en Brasil – y salud pública. Para tanto, guiaremos el debate en la perspectiva de acceso a la salud como derecho humano para todas las personas y deber del Estado. Para hacerlo, utilizaremos como aporte teórico- el método de las Ciencias Sociales de la Salud, asociado a un trabajo de campo que incluyó levantamiento de datos cuantitativos y cualitativos. La exposición de estes datos, nos permite argumentar que el goce de los derechos humanos es permitido a toda población de la frontera, sin embargo, extranjeros residentes en Brasil, aunque que legales, no tienen acceso a los derechos igual que los nacionales. Tal percurso analítico nos lleva a la conclusión, en este artículo, que los agentes de gestión, en la región de la frontera, vienen utilizando la estrategia de creación de conflictos entre la población local y los extranjeros que utilizan el servicio público de salud provocando una desigualdad en salud
Extended morphometric analysis of neuronal cells with Minkowski valuations
Minkowski valuations provide a systematic framework for quantifying different
aspects of morphology. In this paper we apply vector- and tensor-valued
Minkowski valuations to neuronal cells from the cat's retina in order to
describe their morphological structure in a comprehensive way. We introduce the
framework of Minkowski valuations, discuss their implementation for neuronal
cells and show how they can discriminate between cells of different types.Comment: 14 pages, 18 postscript figure
Hyperpolarization-Activated Current (Ih) in Ganglion-Cell Photoreceptors
Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and serve as the primary retinal drivers of non-image-forming visual functions such as circadian photoentrainment, the pupillary light reflex, and suppression of melatonin production in the pineal. Past electrophysiological studies of these cells have focused on their intrinsic photosensitivity and synaptic inputs. Much less is known about their voltage-gated channels and how these might shape their output to non-image-forming visual centers. Here, we show that rat ipRGCs retrolabeled from the suprachiasmatic nucleus (SCN) express a hyperpolarization-activated inwardly-rectifying current (Ih). This current is blocked by the known Ih blockers ZD7288 and extracellular cesium. As in other systems, including other retinal ganglion cells, Ih in ipRGCs is characterized by slow kinetics and a slightly greater permeability for K+ than for Na+. Unlike in other systems, however, Ih in ipRGCs apparently does not actively contribute to resting membrane potential. We also explore non-specific effects of the common Ih blocker ZD7288 on rebound depolarization and evoked spiking and discuss possible functional roles of Ih in non-image-forming vision. This study is the first to characterize Ih in a well-defined population of retinal ganglion cells, namely SCN-projecting ipRGCs
Constraint-Flow Nets: A Model for Building Constraints from Resource Dependencies
The major research in the resource management literature focuses primarily on two complementary sub-problems: (1) specification languages for formulating resource requests and (2) constraint problems modelling allocation and scheduling. Both directions assume the knowledge of the underlying platform architecture and the dependencies it induces on the usage of the various resources. In this paper, we bridge this gap by introducing constraint-flow nets (cfNets). A cfNet is defined by a set of resources and dependencies between them, each dependency having an associated constraint schema. The model is inspired by Petri nets, with resources corresponding to places and dependencies—to transitions. Given an architecture of dependent resources, an initial resource request is propagated through the dependencies. The generated constraints are then conjuncted into the global allocation constraint. We study the notion of conflicts in cfNets and prove that for conflict-free cfNets the global allocation constraint can be constructed unambiguously. Furthermore, we provide an SMT-based algorithm for conflict detection and discuss the use of priorities to dynamically resolve conflicts at run-time. Finally, we illustrate the use of cfNets on a case study inspired by the Kalray MPPA architecture
Mutations in or near the Transmembrane Domain Alter PMEL Amyloid Formation from Functional to Pathogenic
PMEL is a pigment cell-specific protein that forms physiological amyloid fibrils upon which melanins ultimately deposit in the lumen of the pigment organelle, the melanosome. Whereas hypomorphic PMEL mutations in several species result in a mild pigment dilution that is inherited in a recessive manner, PMEL alleles found in the Dominant white (DW) chicken and Silver horse (HoSi)—which bear mutations that alter the PMEL transmembrane domain (TMD) and that are thus outside the amyloid core—are associated with a striking loss of pigmentation that is inherited in a dominant fashion. Here we show that the DW and HoSi mutations alter PMEL TMD oligomerization and/or association with membranes, with consequent formation of aberrantly packed fibrils. The aberrant fibrils are associated with a loss of pigmentation in cultured melanocytes, suggesting that they inhibit melanin production and/or melanosome integrity. A secondary mutation in the Smoky chicken, which reverts the dominant DW phenotype, prevents the accumulation of PMEL in fibrillogenic compartments and thus averts DW–associated pigment loss; a secondary mutation found in the Dun chicken likely dampens a HoSi–like dominant mutation in a similar manner. We propose that the DW and HoSi mutations alter the normally benign amyloid to a pathogenic form that antagonizes melanosome function, and that the secondary mutations found in the Smoky and Dun chickens revert or dampen pathogenicity by functioning as null alleles, thus preventing the formation of aberrant fibrils. We speculate that PMEL mutations can model the conversion between physiological and pathological amyloid
N-Acetylcholinesterase-Induced Apoptosis in Alzheimer's Disease
Background: Alzheimer’s disease (AD) involves loss of cholinergic neurons and Tau protein hyper-phosphorylation. Here, we report that overexpression of an N-terminally extended ‘‘synaptic’ ’ acetylcholinesterase variant, N-AChE-S is causally involved in both these phenomena. Methodology and Principal Findings: In transfected primary brain cultures, N-AChE-S induced cell death, morphological impairments and caspase 3 activation. Rapid internalization of fluorescently labeled fasciculin-2 to N-AChE-S transfected cells indicated membranal localization. In cultured cell lines, N-AChE-S transfection activated the Tau kinase GSK3, induced Tau hyper-phosphorylation and caused apoptosis. N-AChE-S-induced cell death was suppressible by inhibiting GSK3 or caspases, by enforced overexpression of the anti-apoptotic Bcl2 proteins, or by AChE inhibition or silencing. Moreover, inherent N-AChE-S was upregulated by stressors inducing protein misfolding and calcium imbalances, both characteristic of AD; and in cortical tissues from AD patients, N-AChE-S overexpression coincides with Tau hyper-phosphorylation. Conclusions: Together, these findings attribute an apoptogenic role to N-AChE-S and outline a potential value to ACh
Derivation of Human Differential Photoreceptor-like Cells from the Iris by Defined Combinations of CRX, RX and NEUROD
Examples of direct differentiation by defined transcription factors have been provided for beta-cells, cardiomyocytes and neurons. In the human visual system, there are four kinds of photoreceptors in the retina. Neural retina and iris-pigmented epithelium (IPE) share a common developmental origin, leading us to test whether human iris cells could differentiate to retinal neurons. We here define the transcription factor combinations that can determine human photoreceptor cell fate. Expression of rhodopsin, blue opsin and green/red opsin in induced photoreceptor cells were dependent on combinations of transcription factors: A combination of CRX and NEUROD induced rhodopsin and blue opsin, but did not induce green opsin; a combination of CRX and RX induced blue opsin and green/red opsin, but did not induce rhodopsin. Phototransduction-related genes as well as opsin genes were up-regulated in those cells. Functional analysis; i.e. patch clamp recordings, clearly revealed that generated photoreceptor cells, induced by CRX, RX and NEUROD, responded to light. The response was an inward current instead of the typical outward current. These data suggest that photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. These findings contribute substantially to a major advance toward eventual cell-based therapy for retinal degenerative diseases
Bright green light treatment of depression for older adults [ISRCTN69400161]
BACKGROUND: Bright white light has been successfully used for the treatment of depression. There is interest in identifying which spectral colors of light are the most efficient in the treatment of depression. It is theorized that green light could decrease the intensity duration of exposure needed. Late Wake Treatment (LWT), sleep deprivation for the last half of one night, is associated with rapid mood improvement which has been sustained by light treatment. Because spectral responsiveness may differ by age, we examined whether green light would provide efficient antidepressant treatment in an elder age group. METHODS: We contrasted one hour of bright green light (1,200 Lux) and one hour of dim red light placebo (<10 Lux) in a randomized treatment trial with depressed elders. Participants were observed in their homes with mood scales, wrist actigraphy and light monitoring. On the day prior to beginning treatment, the participants self-administered LWT. RESULTS: The protocol was completed by 33 subjects who were 59 to 80 years old. Mood improved on average 23% for all subjects, but there were no significant statistical differences between treatment and placebo groups. There were negligible adverse reactions to the bright green light, which was well tolerated. CONCLUSION: Bright green light was not shown to have an antidepressant effect in the age group of this study, but a larger trial with brighter green light might be of value
Hormonally mediated effects of artificial light at night on behavior and fitness: linking endocrine mechanisms with function.
Alternation between day and night is a predictable environmental fluctuation that organisms use to time their activities. Since the invention of artificial lighting, this predictability has been disrupted and continues to change in a unidirectional fashion with increasing urbanization. As hormones mediate individual responses to changing environments, endocrine systems might be one of the first systems affected, as well as being the first line of defense to ameliorate any negative health impacts. In this Review, we first highlight how light can influence endocrine function in vertebrates. We then focus on four endocrine axes that might be affected by artificial light at night (ALAN): pineal, reproductive, adrenal and thyroid. Throughout, we highlight key findings, rather than performing an exhaustive review, in order to emphasize knowledge gaps that are hindering progress on proposing impactful and concrete plans to ameliorate the negative effects of ALAN. We discuss these findings with respect to impacts on human and animal health, with a focus on the consequences of anthropogenic modification of the night-time environment for non-human organisms. Lastly, we stress the need for the integration of field and lab experiments as well as the need for long-term integrative eco-physiological studies in the rapidly expanding field of light pollution
TSPO ligand residence time influences human glioblastoma multiforme cell death/life balance
Abstract
Ligands addressed to the mitochondrial Translocator Protein (TSPO) have been suggested as cell death/life and steroidogenesis modulators. Thus, TSPO ligands have been proposed as drug candidates in several diseases; nevertheless, a correlation between their binding affinity and in vitro efficacy has not been demonstrated yet, questioning the specificity of the observed effects. Since drug-target residence time is an emerging parameter able to influence drug pharmacological features, herein, the interaction between TSPO and irDE-MPIGA, a covalent TSPO ligand, was investigated in order to explore TSPO control on death/life processes in a standardized glioblastoma cell setting. After 90 min irDE-MPIGA cell treatment, 25 nM ligand concentration saturated irreversibly all TSPO binding sites; after 24 h, TSPO de-novo synthesis occurred and about 40 % TSPO binding sites resulted covalently bound to irDE-MPIGA. During cell culture treatments, several dynamic events were observed: (a) early apoptotic markers appeared, such as mitochondrial membrane potential collapse (at 3 h) and externalization of phosphatidylserine (at 6 h); (b) cell viability was reduced (at 6 h), without cell cycle arrest. After digitonin-permeabilized cell suspension treatment, a modulation of mitochondrial permeability transition pore was evidenced. Similar effects were elicited by the reversible TSPO ligand PIGA only when applied at micromolar dose. Interestingly, after 6 h, irDE-MPIGA cell exposure restored cell survival parameters. These results highlighted the ligand-target residence time and the cellular setting are crucial parameters that should be taken into account to understand the drug binding affinity and efficacy correlation and, above all, to translate efficiently cellular drug responses from bench to bedside
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