A teoria da escolha pública e as reformas do Estado: uma crítica habermasiana

Neste artigo é apresentada uma análise crítica da teoria da Escolha Pública sob a ótica da teoria social de Jürgen Habermas. Essa análise se justifica pelos pontos de convergência entre as duas teorias, ainda que a partir de perspectivas opostas. Enquanto a teoria da Escolha Pública concebe a política como uma relação de troca entre Estado e eleitores, a teoria crítica habermasiana considera que é justamente esse aspecto da polí- tica de massas que deve ser superado pela ação comunicativa de cidadãos participantes. Procura-se demonstrar ao longo do texto que o impasse teórico da Escolha Pública – de um lado, como postula o “Teorema da Possibilidade Geral” de Kenneth Arrow, a impossibilidade de uma função-utilidade coletiva e de outro, a ambição normativa de fornecer parâmetros de eficiência para o fornecimento de bens públicos – reside, fundamentalmente, no pressuposto do individualismo metodológic

Evaluating the potential risks and benefits of infant rotavirus vaccination in England.

Rotarix(®), a vaccine for the prevention of gastroenteritis in young children, was introduced in England in July 2013. At around this time, an elevated risk of intussusception (a cause of bowel obstruction) was reported among infants vaccinated in Australia and the USA. A risk-benefit analysis compared potential vaccine-related risks (additional intussusception admissions and deaths) with estimated vaccine benefits (prevented rotavirus general practitioner visits, emergency visits, admissions and deaths) in the 2012 birth cohort. Detailed data from England included the incidence of intussusception events aged <2 years by week of age, the coverage of vaccination aged <2 years by week of age, and the incidence of rotavirus gastroenteritis (RVGE) events aged <5 years by week of age. Recent estimates of vaccine-related risk from Australia were applied during the 1-21 day period after the first and second dose of vaccination. Rotarix(®) is estimated to cause one additional intussusception admission in every 18,551 vaccinated English infants (5th and 95th percentiles, 6728-93,952), equivalent to 35 (7-98) additional intussusception admissions each year. The vaccine is estimated to prevent three rotavirus deaths, 13,000 rotavirus admissions, 27,000 rotavirus emergency visits and 74,000 rotavirus GP consultations in children aged <5 years, and lead to annual savings of over £11 million, each year. We estimate 375 (136-1900) fewer RVGE admissions for every additional intussusception admission, and 88 (18-852) fewer RVGE deaths for every additional intussusception death. The estimated benefits of Rotarix(®) vaccination would greatly exceed the potential risk in England

The exocyst is required for trypanosome invasion and the repair of mechanical plasma membrane wounds

The process of host cell invasion by Trypanosoma cruzi shares mechanistic elements with plasma membrane injury and repair. Both processes require Ca2+-triggered exocytosis of lysosomes, exocytosis of acid sphingomyelinase and formation of ceramide-enriched endocytic compartments. T. cruzi invades at peripheral sites, suggesting a need for spatial regulation of membrane traffic. Here, we show that Exo70 and Sec8 (also known as EXOC7 and EXOC4, respectively), components of the exocyst complex, accumulate in nascent T. cruzi vacuoles and at sites of mechanical wounding. Exo70 or Sec8 depletion inhibits T. cruzi invasion and Ca2+-dependent resealing of mechanical wounds, but does not affect the repair of smaller lesions caused by pore-forming toxins. Thus, T. cruzi invasion and mechanical lesion repair share a unique requirement for the exocyst, consistent with a dependence on targetedmembrane delivery.The process of host cell invasion by Trypanosoma cruzi shares mechanistic elements with plasma membrane injury and repair. Both processes require Ca2+-triggered exocytosis of lysosomes, exocytosis of acid sphingomyelinase and formation of ceramide-enriche12812732sem informaçãosem informaçãoWe thank Dr D. Toomre (Yale University) for the VSVG construct, Dr W. Guo (University of Pennsylvania) for antibodies and A. Beaven and K. Class (University of Maryland) for assistance with confocal microscopy and flow cytometry, respectivel

Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis

Ca2+ influx through plasma membrane lesions triggers a rapid repair process that was previously shown to require the exocytosis of lysosomal organelles (Reddy, A., E. Caler, and N. Andrews. 2001. Cell. 106:157–169). However, how exocytosis leads to membrane resealing has remained obscure, particularly for stable lesions caused by pore-forming proteins. In this study, we show that Ca2+-dependent resealing after permeabilization with the bacterial toxin streptolysin O (SLO) requires endocytosis via a novel pathway that removes SLO-containing pores from the plasma membrane. We also find that endocytosis is similarly required to repair lesions formed in mechanically wounded cells. Inhibition of lesion endocytosis (by sterol depletion) inhibits repair, whereas enhancement of endocytosis through disruption of the actin cytoskeleton facilitates resealing. Thus, endocytosis promotes wound resealing by removing lesions from the plasma membrane. These findings provide an important new insight into how cells protect themselves not only from mechanical injury but also from microbial toxins and pore-forming proteins produced by the immune system

Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair

Lysosomal enzyme acid sphingomyelinase is released extracellularly when cells are wounded, converting sphingomyelin to ceramide and inducing endosome formation to internalize membrane lesions

Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease

OBJECTIVE: Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt-Jakob disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3 which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real-time quaking induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD. METHODS: An exploratory study was undertaken which analysed 108 CSF samples from patients with neuropathologically confirmed sCJD or from control patients. Of the 108 CSF samples 56 were from sCJD patients (30 female, 26 male, aged 31–84 years; 62.3 ± 13.5 years) and 52 were from control patients (26 female, 26 male, aged 43–84 years; 67.8 ± 10.4 years). A confirmatory group of 118 patients were subsequently examined which consisted of 67 cases of neuropathologically confirmed sCJD (33 female, 34 male, aged 39–82 years; 67.5 ± 9.0 years) and 51 control cases (26 female, 25 male, aged 36–87 years; 63.5 ± 11.6 years). RESULTS: The exploratory study showed that RT-QuIC analysis had a sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These results were confirmed in the confirmatory study which showed that CSF RT-QuIC analysis had a sensitivity and specificity of 87% and 100% respectively. INTERPRETATION: This study shows that CSF RT-QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests

Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion

Trypanosoma cruzi takes advantage of a sphingomyelinase-dependent plasma membrane repair pathway to gain access to host cells

Kynurenine 3-Monooxygenase Inhibition in Blood Ameliorates Neurodegeneration

SummaryMetabolites in the kynurenine pathway, generated by tryptophan degradation, are thought to play an important role in neurodegenerative disorders, including Alzheimer's and Huntington's diseases. In these disorders, glutamate receptor-mediated excitotoxicity and free radical formation have been correlated with decreased levels of the neuroprotective metabolite kynurenic acid. Here, we describe the synthesis and characterization of JM6, a small-molecule prodrug inhibitor of kynurenine 3-monooxygenase (KMO). Chronic oral administration of JM6 inhibits KMO in the blood, increasing kynurenic acid levels and reducing extracellular glutamate in the brain. In a transgenic mouse model of Alzheimer's disease, JM6 prevents spatial memory deficits, anxiety-related behavior, and synaptic loss. JM6 also extends life span, prevents synaptic loss, and decreases microglial activation in a mouse model of Huntington's disease. These findings support a critical link between tryptophan metabolism in the blood and neurodegeneration, and they provide a foundation for treatment of neurodegenerative diseases