S-antigen and rod-opsin immunoreactions in midline brain neoplasms of transgenic mice: Similarities to pineal cell tumors and certain medulloblastomas in man.

Transgenic mice expressing the large T-antigen of the simian virus 40 (SV 40) under the control of 1) the enhancer of Moloney murine sarcoma virus (MSV) and 2) the SV 40 promoter develop undifferentiated neuroectodermal tumors located in the midline of the dorsal brain surface, abnormalities in lens fiber differentiation and retinal dysplasia. In this study the brain neoplasms of six adult animals and the brain of one 11-day old mouse were examined by conventional histology and immunocytochemical demonstration of S-antigen, rod-opsin, neuron-specific enolase, neurofilaments (160 and 200 kDa) and glial fibrillary acidic protein. According to histologic criteria the neoplasms were characterized as "primitive" neuroectodermal tumors composed mainly of small cells with scanty and ill-defined cytoplasm. Neoplastic cells displaying immunoreactive S-antigen were found in five brain tumors; three of these tumors also contained a limited number of rod-opsin immunoreactive neoplastic cells. Some tumor cells had neurite-like processes containing immunoreactive neurofilament (200 kDa). No pathologic lesions were found in the brain of the 11-day old animal. Tumors in transgenic mice may resemble pineal cell tumors and a special subtype of medulloblastoma in man. These neoplasms contain S-antigen immunoreactive and also rod-opsin immunoreactive tumors cells in certain cases. The findings suggest that transgenic mice expressing the large T-antigen of SV 40 may become a valuable animal model for analysing the origin, histogenesis and development of primitive neuroectodermal tumors with photoreceptor-like features (pineal cell tumors and certain medulloblastomas)

A Jurisprudential Analysis of Government Intervention and Prenatal Drug Abuse

This article takes a different approach in considering the problem of prenatal drug abuse. After briefly discussing government intervention and constitutional issues, this article will consider the concept of duty and correlative rights. This discussion of duty and correlative rights suggests that the government can take measures to curb prenatal drug use without recognizing fetal rights. The article concludes with a discussion of the utility of criminal legislation as compared to public health legislation that treats drug addiction as a disease requiring treatment. As formulated, the proposal for public health legislation is not based on any concept of fetal rights. Instead, it is based on the recognition of societal interests, as well as the woman’s needs

Protest Cycles and Political Process: American Peace Movements in the Nuclear Age

Since the dawn of the nuclear age small groups of activists have consistently protested both the content of United States national security policy, and the process by which it is made. Only occasionally, however, has concern about nuclear weapons spread beyond these relatively marginal groups, generated substantial public support, and reached mainstream political institutions. In this paper, I use histories of peace protest and analyses of the inside of these social movements and theoretical work on protest cycles to explain cycles of movement engagement and quiescence in terms of their relation to external political context, or the "structure of political opportunity." I begin with a brief review of the relevant literature on the origins of movements, noting parallels in the study of interest groups. Building on recent literature on political opportunity structure, I suggest a theoretical framework for understanding the lifecycle of a social movement that emphasizes the interaction between activist choices and political context, proposing a six-stage process through which challenging movements develop. Using this theoretical framework I examine the four cases of relatively broad antinuclear weapons mobilization in postwar America. I conclude with a discussion of movement cycles and their relation to political alignment, public policy, and institutional politics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68552/2/10.1177_106591299304600302.pd

The Rad51 paralogs facilitate a novel DNA strand specific damage tolerance pathway

Accurate DNA replication is essential for genomic stability and cancer prevention. Homologous recombination is important for high-fidelity DNA damage tolerance during replication. How the homologous recombination machinery is recruited to replication intermediates is unknown. Here, we provide evidence that a Rad51 paralog-containing complex, the budding yeast Shu complex, directly recognizes and enables tolerance of predominantly lagging strand abasic sites. We show that the Shu complex becomes chromatin associated when cells accumulate abasic sites during S phase. We also demonstrate that purified recombinant Shu complex recognizes an abasic analog on a double-flap substrate, which prevents AP endo-nuclease activity and endonuclease-induced double-strand break formation. Shu complex DNA binding mutants are sensitive to methyl methanesulfonate, are not chromatin enriched, and exhibit increased mutation rates. We propose a role for the Shu complex in recognizing abasic sites at replication intermediates, where it recruits the homologous recombination machinery to mediate strand specific damage tolerance

Effects of morphine, nalorphine and naloxone on neocortical release of acetylcholine in the rat

The effects of morphine (10 mg/kg), nalorphine (1 and 10 mg/kg), and naloxone (1 mg/kg) were studied on the neocortical release of acetylcholine (ACh) in midpontine pretrigeminal transected rats. Morphine and, to a lesser extent, nalorphine decreased ACh release. Naloxone was ineffective alone but antagonized the action of morphine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46384/1/213_2004_Article_BF00422643.pd

Abnormal Intracellular Accumulation and Extracellular Aβ Deposition in Idiopathic and Dup15q11.2-q13 Autism Spectrum Disorders

<div><h3>Background</h3><p>It has been shown that amyloid ß (Aβ), a product of proteolytic cleavage of the amyloid β precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.</p> <h3>Methodology/Principal Findings</h3><p>In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Aβ load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 of 12 examined regions (p<0.0001 for all comparisons; Kruskall-Wallis test). In eight regions, intraneuronal Aβ load differed significantly between idiopathic autism and control groups (p<0.0001). The intraneuronal Aβ was mainly N-terminally truncated. Increased intraneuronal accumulation of Aβ_17–40/42 in children and adults suggests a life-long enhancement of APP processing with α-secretase in autistic subjects. Aβ accumulation in neuronal endosomes, autophagic vacuoles, Lamp1-positive lysosomes and lipofuscin, as revealed by confocal microscopy, indicates that products of enhanced α-secretase processing accumulate in organelles involved in proteolysis and storage of metabolic remnants. Diffuse plaques containing Aβ_1–40/42 detected in three subjects with ASD, 39 to 52 years of age, suggest that there is an age-associated risk of alterations of APP processing with an intraneuronal accumulation of a short form of Aβ and an extracellular deposition of full-length Aβ in nonfibrillar plaques.</p> <h3>Conclusions/Significance</h3><p>The higher prevalence of excessive Aβ accumulation in neurons in individuals with early onset of intractable seizures, and with a high risk of sudden unexpected death in epilepsy in autistic subjects with dup(15) compared to subjects with idiopathic ASD, supports the concept of mechanistic and functional links between autism, epilepsy and alterations of APP processing leading to neuronal and astrocytic Aβ accumulation and diffuse plaque formation.</p> </div

Validar a guerra: a construção do regime de Expertise estratégica

This article is intended to contribute to the interpretative analysis of war. For that purpose, it investigates how some apparatuses located in strategic thinking help to make modern war a social practice considered both technically feasible and, at the same time, legitimate for soldiers. In so doing, it makes use of two different but closely related theoretical fields, pragmatic sociology (finding inspiration in the work of scholars such as Luc Boltanski, Nicolas Dodier and Francis Chateauraynaud), and the sociology of scientific knowledge (based mostly on the work of Bruno Latour). On the one hand, the sociology of scientific knowledge has developed a productive questioning of the construction of scientific facts that is particularly relevant to the present research. On the other hand, pragmatic sociology generates a compatible framework able to describe collective actions. The combination of both approaches allows the description of the formation of a strategic expertise regime that supports the technical legitimacy of the use of military force. Together, the sociology of scientific knowledge and pragmatic sociology bring a particularly relevant perspective to research pertaining to war.info:eu-repo/semantics/publishe

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches