Showing papers by "Stony Brook University published in 1997"

Masculinity as homophobia: Fear, shame and silence in the construction of gender identity.

Abstract: In this article, I explore this social and historical construction of both hegemonic masculinity and alternate masculinities, with an eye toward offering a new theoretical model of American manhood. To accomplish this I first uncover some of the hidden gender meanings in classical statements of social and political philosophy, so that I can anchor the emergence of contemporary manhood in specific historical and social contexts. I then spell out the ways in which this version of masculinity emerged in the United States, by tracing both psychoanalytic developmental sequences and a historical trajectory in the development of marketplace relationships.

Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies.

Abstract: Choosing the best genetic strains of mice for developing a new knockout or transgenic mouse requires extensive knowledge of the endogenous traits of inbred strains. Background genes from the parental strains may interact with the mutated gene, in a manner which could severely compromise the interpretation of the mutant phenotype. The present overview summarizes the literature on a wide variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred strains of mice. Strain distributions are described for open field activity, learning and memory tasks, aggression, sexual and parental behaviors, acoustic startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine, cocaine, opiates, antipsychotics, and anxiolytics. Using the referenced information, molecular geneticists can choose optimal parental strains of mice, and perhaps develop new embryonic stem cell progenitors, for new knockouts and transgenics to investigate gene function, and to serve as animal models in the development of novel therapeutics for human genetic diseases.

Inducing features of random fields

Abstract: We present a technique for constructing random fields from a set of training samples. The learning paradigm builds increasingly complex fields by allowing potential functions, or features, that are supported by increasingly large subgraphs. Each feature has a weight that is trained by minimizing the Kullback-Leibler divergence between the model and the empirical distribution of the training data. A greedy algorithm determines how features are incrementally added to the field and an iterative scaling algorithm is used to estimate the optimal values of the weights. The random field models and techniques introduced in this paper differ from those common to much of the computer vision literature in that the underlying random fields are non-Markovian and have a large number of parameters that must be estimated. Relations to other learning approaches, including decision trees, are given. As a demonstration of the method, we describe its application to the problem of automatic word classification in natural language processing.

Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects.

Abstract: Cocaine blocks the reuptake of dopamine, a neurotransmitter involved in the control of movement, cognition, motivation and reward. This leads to an increase in extracellular dopamine; the reinforcing effect of cocaine is associated with elevated dopamine levels in the nucleus accumbens. But addiction to cocaine involves other effects, such as craving, loss of control and compulsive drug intake; the role of the dopamine system in these effects is less well-understood. We therefore used positron emission tomography (PET) to compare the responses of cocaine addicts and normal controls to intravenous methylphenidate, a drug that, like cocaine, causes an increase in synaptic dopamine. Addicts showed reduced dopamine release in the striatum, the brain region where the nucleus accumbens is located, and also had a reduced 'high' relative to controls. In contrast, addicts showed an increased response to methylphenidate in the thalamus (a region that conveys sensory input to the cortex). This thalamic response was associated with cocaine craving and was not seen in control subjects. Thus, our findings challenge the notion that addiction involves an enhanced striatal dopamine response to cocaine and/or an enhanced induction of euphoria. Moreover, they suggest a participation of thalamic dopamine pathways in cocaine addiction, a possibility that merits further investigation.

Perceived Threat and Authoritarianism

Abstract: There has been a long history of work on authoritarianism that has looked at the role of societal threat. Much of the empirical research in this tradition has relied on aggregate data to examine the relationship between societal threat and authoritarian attitudes and behaviors. Our analysis uses individual-level data and a range of perceived threat measures to better understand the dynamics of authoritarianism and threat. We also move beyond the hypothesis of a direct relationship between threat and authoritarianism, and hypothesize instead that the relationship involves interaction effects: societal threat activates authoritarian predispositions. As predicted, our analysis finds no evidence of a direct effect of societal threat but significant evidence of an interaction between authoritarian predispositions and perceived threat. We consider the implications of these results for our understanding of authoritarianism.

Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product

Abstract: THE oncogenic protein Vav1,2 harbours a complex array of structural motifs, including leucine-rich, Dbl-homology, pleckstrin-homology, zinc-finger, SH2 and SH3 domains. Upon stimulation by antigens or mitogens, Vav becomes phosphorylated on key tyrosine residues3–5 and associates with other signalling proteins, including the mitogen receptors3,4 Zap-70 (ref. 6), Vap-1 (ref. 5) and Slp-76 (ref. 7). Disruption of the vav locus by homologous recombination causes severe defects in signalling by primary antigen receptors, leading to abnormal lymphocyte proliferation and lymphopenia8,9. Despite the importance of Vav cell signalling, the function of this protein remains unknown. Here we show that tyrosine-phosphorylated Vav, but not the non-phosphorylated protein, catalyses GDP/GTP exchange on Rac-1, a protein implicated in cell proliferation and cytoskeletal organization10,11, causing this GTPase to switch from its inactive to its active state. Transfection experiments also show that phosphorylation of Vav on tyrosine residues leads to nucleotide exchange on Rac-1 in vivo and stimulates c-Jun kinase, a downstream element in the signalling pathway involving this GTPase. Our results have identified a function for Vav and define a mechanism in which engaged membrane receptors activate its signalling pathway.

The Experimental Generation of Interpersonal Closeness: A Procedure and Some Preliminary Findings

Abstract: A practical methodology is presented for creating closeness in an experimental context. Whether or not an individual is in a relationship, particular pairings of individuals in the relationship, and circumstances of relationship development become manipulated variables. Over a 45-min period subject pairs carry out self-disclosure and relationship-building tasks that gradually escalate in intensity. Study 1 found greater postinteraction closeness with these tasks versus comparable small-talk tasks. Studies 2 and 3 found no significant closeness effects, inspite of adequate power, for (a) whether pairs were matched for nondisagreement on important attitudes, (b) whether pairs were led to expect mutual liking, or (c) whether getting close was made an explicit goal. These studies also illustrated applications for addressing theoretical issues, yielding provocative tentative findings relating to attachment style and introversion/extraversion.

On the Origin of Sphingolipid/Cholesterol-Rich Detergent-Insoluble Cell Membranes: Physiological Concentrations of Cholesterol and Sphingolipid Induce Formation of a Detergent-Insoluble, Liquid-Ordered Lipid Phase in Model Membranes

Abstract: Detergent-insoluble membrane fragments that are rich in sphingolipid and cholesterol can be isolated from both cell lysates and model membranes. We have proposed that these arise from membranes that are in the liquid-ordered phase both in vivo and in vitro [Schroeder et al. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 12130−12134]. In order to detect formation of the liquid-ordered phase while avoiding possible detergent artifacts, we have now used fluorescence quenching to examine the phase behavior of mixtures of phosphatidylcholines, sphingolipids, and cholesterol. Phase separation was found in binary mixtures of either dipalmitoylphosphatidylcholine (DPPC) or sphingomyelin (SM) and a nitroxide-labeled phosphatidylcholine (12SLPC). A DPPC- or SM-enriched solidlike gel phase coexisted with a 12SLPC-enriched liquid-disordered fluid phase at 23 °C. As expected, phase separation was not seen at low concentrations of DPPC or SM. Instead, only a uniform fluid phase was present. Including 33 mol % cholesterol in ...

Relationship between subjective effects of cocaine and dopamine transporter occupancy

Abstract: Cocaine is believed to work by blocking the dopamine transporter (DAT) and thereby increasing the availability of free dopamine within the brain. Although this concept is central to current cocaine research and to treatment development, a direct relationship between DAT blockade and the subjective effects of cocaine has not been demonstrated in humans. We have used positron emission tomography to determine what level of DAT occupancy is required to produce a subjective 'high' in human volunteers who regularly abuse cocaine. We report here that intravenous cocaine at doses commonly abused by humans (0.3-0.6 mg kg(-1)) blocked between 60 and 77% of DAT sites in these subjects. The magnitude of the self-reported high was correlated with the degree of DAT occupancy, and at least 47% of the transporters had to be blocked for subjects to perceive cocaine's effects. Furthermore, the time course for the high paralleled that of cocaine concentration within the striatum, a brain region implicated in the control of motivation and reward. This is the first demonstration in humans that the doses used by cocaine abusers lead to significant blockade of DAT, and that this blockade is associated with the subjective effects of cocaine. Although these findings provide justification to target the DAT for medication development they suggest that for drugs to be effective in blocking cocaine's effects they would have to be given at doses that achieve almost complete DAT occupancy.

Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement

Abstract: The protein Hck is a member of the Src family of non-receptor tyrosine kinases which is preferentially expressed in haematopoietic cells of the myeloid and B-lymphoid lineages. Src kinases are inhibited by tyrosine-phosphorylation at a carboxy-terminal site. The SH2 domains of these enzymes play an essential role in this regulation by binding to the tyrosine-phosphorylated tail. The crystal structure of the downregulated form of Hck has been determined and reveals that the SH2 domain regulates enzymatic activity indirectly; intramolecular interactions between the SH3 and catalytic domains appear to stabilize an inactive form of the kinase. Here we compare the roles of the SH2 and SH3 domains in modulating the activity of Hck in an investigation of the C-terminally phosphorylated form of the enzyme. We show that addition of the HIV-1 Nef protein, which is a high-affinity ligand for the Hck SH3 domain, to either the downregulated or activated form of Hck causes a large increase in Hck catalytic activity. The intact SH3-binding motif in Nef is crucial for Hck activation. Our results indicate that binding of the Hck SH3 domain by Nef causes a more marked activation of the enzyme than does binding of the SH2 domain, suggesting a new mechanism for regulation of the activity of tyrosine kinases.

Sensory-processing sensitivity and its relation to introversion and emotionality.

Abstract: Over a series of 7 studies that used diverse samples and measures, this research identified a unidimensional core variable of high sensory-processing sensitivity and demonstrated its partial independence from social introversion and emotionality, variables with which it had been confused or subsumed in most previous theorizing by personality researchers. Additional findings were that there appear to be 2 distinct clusters of highly sensitive individuals (a smaller group with an unhappy childhood and related variables, and a larger group similar to nonhighly sensitive individuals except for their sensitivity) and that sensitivity moderates, at least for men, the relation of parental environment to reporting having had an unhappy childhood. This research also demonstrated adequate reliability and content, convergent, and discriminant validity for a 27-item Highly Sensitive Person Scale.

Resampling tests for meta-analysis of ecological data

Abstract: Meta-analysis is a statistical technique that allows one to combine the results from multiple studies to glean inferences on the overall importance of various phenomena. This method can prove to be more informative than common ''vote counting,'' in which the number of significant results is compared to the number with nonsignificant results to determine whether the phenomenon of interest is globally important. While the use of meta- analysis is widespread in medicine and the social sciences, only recently has it been applied to ecological questions. We compared the results of parametric confidence limits and ho- mogeneity statistics commonly obtained through meta-analysis to those obtained from re- sampling methods to ascertain the robustness of standard meta-analytic techniques. We found that confidence limits based on bootstrapping methods were wider than standard confidence limits, implying that resampling estimates are more conservative. In addition, we found that significance tests based on homogeneity statistics differed occasionally from results of randomization tests, implying that inferences based solely on chi-square signif- icance tests may lead to erroneous conclusions. We conclude that resampling methods should be incorporated in meta-analysis studies, to ensure proper evaluation of main effects in ecological studies.

Outward K+ Current Densities and Kv1.5 Expression Are Reduced in Chronic Human Atrial Fibrillation

Abstract: Chronic atrial fibrillation is associated with a shortening of the atrial action potential duration and atrial refractory period. To test the hypothesis that these changes are mediated by ...

Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons

Abstract: Membrane excitability in different tissues is due, in large part, to the selective expression of distinct genes encoding the voltage-dependent sodium channel. Although the predominant sodium channels in brain, skeletal muscle, and cardiac muscle have been identified, the major sodium channel types responsible for excitability within the peripheral nervous system have remained elusive. We now describe the deduced primary structure of a sodium channel, peripheral nerve type 1 (PN1), which is expressed at high levels throughout the peripheral nervous system and is targeted to nerve terminals of cultured dorsal root ganglion neurons. Studies using cultured PC12 cells indicate that both expression and targeting of PN1 is induced by treatment of the cells with nerve growth factor. The preferential localization suggests that the PN1 sodium channel plays a specific role in nerve excitability.

Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia

Abstract: Brain structural deviation is known to be present in chronic patients with schizophrenia when compared with normal age-matched individuals. While the assumption is that these differences are based on a neurodevelopmental disturbance, whether they are static or continue to change throughout the disease process remains unknown. The following report describes a prospective follow-up study of first episode cases of schizophrenic illness. Analyses of MRI evaluations on an approximate annual basis for a minimum of four years are presented on 50 patients and 20 controls. Computer-assisted image analysis measuring the volume of several brain regions, using the program ANALYZE (Mayo Clinic), was performed on all scans. Patients were compared with controls for the rate of change over time in size of structures. No differences were found for the volumes of the caudate nucleus, temporal lobes, or hippocampus; and no changes in the degree of cerebral laterality were detected. However, there was a significant difference in the rate of change in the overall volumes of left and right hemispheres (P < 0.0004 and 0.001, respectively), right cerebellum (P < 0.02) and area of the isthmus of the corpus callosum (P < 0.05). The left cerebral ventricle had significantly greater enlargement over time when measured on coronal slice sequences (P < 0.02), but was not detected by axial views. These findings suggest that a subtle active brain process may be continuing through the first few years of a schizophrenic illness causing greater than the normal adult cortical deterioration. Further studies using other methods of image analysis and over a longer period of time are needed to determine the course and nature of this biologic process.

Hyperexpression of mitogen-activated protein kinase in human breast cancer.

Abstract: Mitogen-activated protein (MAP) kinases act as transducers of extracellular signaling via tyrosine kinase-growth factor receptors and G-protein-linked receptors to elements regulating transcription. The activity, abundance, and localization of MAP kinase was investigated in normal and malignant neoplasia of the breast. In carcinoma of the breast, MAP kinase was heavily phosphorylated on tyrosyl residues and its activity elevated 5-10-fold over benign conditions, such as fibroadenoma and fibrocystic disease. By in situ reverse transcription-polymerase chain reaction, hyperexpression of MAP kinase mRNA can be localized to malignant, epithelial cells. Metastatic cells within involved lymph nodes of patients with breast cancer also display hyperexpression of MAP kinase. In spite of persistent activation via phosphorylation, MAP kinase expression is upregulated 5-20-fold and this hyperexpression may be a critical element to initiation as well as the metastatic potential of various forms of human breast cancer.

Cloning and characterization of a mammalian 8-oxoguanine DNA glycosylase

Abstract: Oxidative DNA damage is generated by reactive oxygen species. The mutagenic base, 8-oxoguanine, formed by this process, is removed from oxidatively damaged DNA by base excision repair. Genes coding for DNA repair enzymes that recognize 8-oxoguanine have been reported in bacteria and yeast. We have identified and characterized mouse and human cDNAs encoding homologs of the 8-oxoguanine DNA glycosylase (ogg1) gene of Saccharomyces cerevisiae. Escherichia coli doubly mutant for mutM and mutY have a mutator phenotype and are deficient in 8-oxoguanine repair. The recombinant mouse gene (mOgg1) suppresses the mutator phenotype of mutY/mutM E. coli. Extracts prepared from mutY/mutM E. coli expressing mOgg1 contain an activity that excises 8-oxoguanine from DNA and a β-lyase activity that nicks DNA 3′ to the lesion. The mouse ogg1 gene product acts efficiently on DNA duplexes in which 7,8-dihydroxy-8-oxo-2′-deoxyguanosine (8-oxodG) is paired with dC, acts weakly on duplexes in which 8-oxodG is paired with dT or dG, and is inactive against duplexes in which 8-oxodG is paired with dA. Mouse and human ogg1 genes contain a helix–hairpin–helix structural motif with conserved residues characteristic of a recently defined family of DNA glycosylases. Ogg1 mRNA is expressed in several mouse tissues; highest levels were detected in testes. Isolation of the mouse ogg1 gene makes it possible to modulate its expression in mice and to explore the involvement of oxidative DNA damage and associated repair processes in aging and cancer.

An Extracellular Proteolytic Cascade Promotes Neuronal Degeneration in the Mouse Hippocampus

Abstract: Mice lacking the serine protease tissue plasminogen activator (tPA) are resistant to excitotoxin-mediated hippocampal neuronal degeneration. We have used genetic and cellular analyses to study the role of tPA in neuronal cell death. Mice deficient for the zymogen plasminogen, a known substrate for tPA, are also resistant to excitotoxins, implicating an extracellular proteolytic cascade in degeneration. The two known components of this cascade, tPA and plasminogen, are both synthesized in the mouse hippocampus. tPA mRNA and protein are present in neurons and microglia, whereas plasminogen mRNA and protein are found exclusively in neurons. tPA-deficient mice exhibit attenuated microglial activation as a reaction to neuronal injury. In contrast, the microglial response of plasminogen-deficient mice was comparable to that of wild-type mice, suggesting a tPA-mediated, plasminogen-independent pathway for activation of microglia. Infusion of inhibitors of the extracellular tPA/plasmin proteolytic cascade into the hippocampus protects neurons against excitotoxic injury, suggesting a novel strategy for intervening in neuronal degeneration.

Ecological morphology of lacustrine threespine stickleback Gasterosteus aculeatus L. (Gasterosteidae) body shape

Abstract: Threespine sticklebacks, small fish with a circumglobal distribution in coastal marine and freshwater of the northern hemisphere, present a remarkable scope of variation in body and fin shape among populations. The repeated evolution of divergent body shapes in a radiation of stickleback from Cook Inlet, Alaska suggests that diversification has proceeded by extensive parallel selection. To explore this hypothesis, hydromechanical equations of fish propulsion and descriptions of stickleback foraging and anti-predator behaviours were used to develop a series of hypotheses that predicted the evolutionary effects of native predatory fishes (NPF) and relative littoral area (RLA) on body shape. Body shape was measured using Cartesian coordinates of anatomical landmarks transformed by the generalized resistant fit superimposition. In general, the results were consistent with the hypotheses that (1) RLA has a direct effect on selection for foraging behaviour and morphology, (2) RLA has an indirect effect on selection for morphology employed in predator evasion, (3) presence of NPF has a direct effect on selection for evasive morphology, and (4) presence of NPF has an indirect effect on selection for foraging behaviour and morphology. The magnitude of the divergence of body shapes present in the Cook Inlet system suggests that extreme phenotypes have evolved by opportunistic expansion into new habitat relatively free of interspecific competition.

Controlled diffusion models for optimal dividend pay-out

Abstract: The reserve r ( t ) of an insurance company at time t is assumed to be governed by the stochastic differential equation dr ( t ) = ( μ − a ( t )) d t + σ d w ( t ), where w is standard Brownian motion, μ , σ > 0 constants and a ( t ) the rate of dividend payment at time t (0 acts as absorbing barrier for r ( t )). The function a ( t ) is subject to dynamic allocation and the objective is to find the one which maximizes EJ x ( a (·)), where J x = ∫ 0 ∞ e − ct a ( t ) d t is the total (discounted) pay-out of dividend and x refers to r (0) = x . Two situations are considered: 1. (a) The dividend rate is restricted so that the function a ( t ) varies in [0, a 0 ] for some a 0 a 0 is smaller than some critical value, the optimal strategy is to always pay the maximal dividend rate a 0 . Otherwise, the optimal policy prescribes to pay nothing when the reserve is below some critical level m , and to pay maximal dividend rate a 0 when the reserve is above m . 2. (b) The dividend rate is unrestricted so that a ( t ) is allowed to vary in all of (0, ∞). Then the optimal strategy is of singular control type in the sense that it prescribes to pay out whatever amount exceeds some critical level m , but not pay out dividend when the reserve is below m .

Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells.

Abstract: Central to the pathogenesis of Salmonella typhimurium is its ability to engage the host cell in a two-way biochemical interaction. As a consequence of this interaction, a dedicated protein secretion system, termed type III, is activated in these bacteria and directs the translocation of signaling proteins into the host cell. Secretion of these proteins stimulates host cell signal transduction pathways that lead to a variety of cellular responses. An important feature of S. typhimurium pathogenesis is the induction of a profound inflammatory response in the intestinal epithelium. In this report, we show that S. typhimurium induces host cell signal transduction pathways that lead to the activation of the transcription factors NF-kappaB and AP-1, resulting in the production of proinflammatory cytokines such as IL-8. We also show that S. typhimurium infection of cultured intestinal epithelial cells results in the activation of the mitogen-activated protein (MAP) kinases ERK, JNK, and p38. Induction of these signaling pathways and the synthesis of IL-8 was strictly dependent on the function of the invasion-associated type III protein secretion system encoded by S. typhimurium. Pretreatment of cells with the highly specific p38 MAP kinase inhibitor SB 203580 prevented S. typhimurium-induced IL-8 production. These results indicate that the inflammatory response induced by S. typhimurium may be due to the specific stimulation of MAP kinase signaling pathways leading to nuclear responses.

The use of animal models to study the effects of aging on cognition

Abstract: This review addresses the importance of animal models for understanding the effects of normal aging on the brain and cognitive functions. First, studies of laboratory animals can help to distinguish between healthy aging and pathological conditions that may contribute to cognitive decline late in life. Second, research on individual differences in aging, a theme of interest in studies of elderly human beings, can be advanced by the experimental control afforded in the use of animal models. The review offers a neuropsychological framework to compare the effects of aging in human beings, monkeys, and rodents. We consider aging in relation to the role of the medial temporal lobe in memory, the information processing functions of the prefrontal cortex in the strategic use of memory, and the regulation of attention by distributed neural circuitry. We also provide an overview of the neurobiological effects of aging that may account for alterations in psychological functions.

A reference guide to drugs and dry mouth – 2nd edition

Abstract: Xerostomia (dry mouth) is an uncomfortable and potentially harmful oral symptom which is usually caused by a decrease in the secretion rate of saliva (salivary gland hypofunction, or SGH). It is more prevalent in the elderly population, primarily due to their increased use of drugs and their susceptibility to disease. Many drugs and drug classes have been linked to xerostomia; the xerogenic effect increases when many drugs are taken concurrently. This Reference Guide to Drugs and Dry Mouth is designed to allow the reader to rapidly identify those pharmacologic agents which have the capacity to induce xerostomia and SGH. Xerogenic drugs can be found in 42 drug categories and 56 sub-categories. A guide to the management of drug-induced SGH and xerostomia is also provided.

Multiple species of cpp32 and mch2 are the major active caspases present in apoptotic cells

Abstract: The activity of ICE-like proteases or caspases is essential for apoptosis. Multiple caspases participate in apoptosis in mammalian cells but how many caspases are involved and what is their relative contribution to cell death is poorly understood. To identify caspases activated in apoptotic cells, we developed an approach to simultaneously detect multiple active caspases. Using tumor cells as a model, we have found that CPP32 (caspase 3) and Mch2 (caspase 6) are the major active caspases in apoptotic cells, and are activated in response to distinct apoptosis-inducing stimuli and in all cell lines analyzed. Both CPP32 and Mch2 are present in apoptotic cells as multiple active species. In a given cell line these species remained the same irrespective of the apoptotic stimulus used. However, the species of CPP32 and Mch2 detected varied between cell lines, indicating differences in caspase processing. The strategy described here is widely applicable to identify active caspases involved in apoptosis.