Childhood absence epilepsy and febrile seizures: A family with a GABAA receptor mutation

Although several genes for idiopathic epilepsies from families with simple Mendelian inheritance have been found, genes for the common idiopathic generalized epilepsies, where inheritance is complex, presently are elusive. We studied a large family with epilepsy where the two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS), which offered a special opportunity to identify epilepsy genes. A total of 35 family members had seizures over four generations. The phenotypes comprised typical CAE (eight individuals); FS alone (15), febrile seizures plus (FS+) (three); myoclonic astatic epilepsy (two); generalized epilepsy with tonic-clonic seizures alone (one); partial epilepsy (one); and unclassified epilepsy despite evaluation (two). In three remaining individuals, no information was available. FS were inherited in an autosomal dominant fashion with 75% penetrance. The inheritance of CAE in this family was not simple Mendelian, but suggestive of complex inheritance with the involvement of at least two genes. A GABA(A) receptor gamma2 subunit gene mutation on chromosome 5 segregated with FS, FS+ and CAE, and also occurred in individuals with the other phenotypes. The clinical and molecular data suggest that the GABA(A) receptor subunit mutation alone can account for the FS phenotype. An interaction of this gene with another gene or genes is required for the CAE phenotype in this family. Linkage analysis for a putative second gene contributing to the CAE phenotype suggested possible loci on chromosomes 10, 13, 14 and 15. Examination of these loci in other absence pedigrees is warranted.

Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the beta-subunit of the GM-CSF receptor

Several reports have suggested an interaction between the erythropoietin receptor (EpoR) and the shared signaling subunit (hbeta(c)) of the human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors, although the functional consequences of this interaction are unclear. We previously showed that in vivo expression of constitutively active extracellular (EC) mutants of hbeta(c) induces erythrocytosis and Epo independence of erythroid colony-forming units (CFU-E). This occurs despite an apparent requirement of these mutants for the GM-CSF receptor alpha-subunit (GMRalpha), which is not expressed in CFU-E. Here, we show that coexpression of hbeta(c) EC mutants and EpoR in BaF-B03 cells, which lack GMRalpha, results in factor-independent proliferation and JAK2 activation. Mutant receptors that cannot activate JAK2 fail to produce a functional interaction. As there is no detectable phosphorylation of hbeta(c). on intracellular tyrosine residues, EpoR displays constitutive tyrosine phosphorylation. These observations suggest that JAK2 activation mediates cross-talk between EC mutants of hbeta(c) and EpoR. The implications of these data are discussed as are our findings that activated hbeta(c) mutants can functionally interact with certain other cytokine receptors.

Stereotypic explanatory bias: Implicit stereotyping as a predictor of discrimination

Two experiments examined whether a measure of implicit stereotyping based on the tendency to explain Black stereotype-incongruent events more often than Black stereotype-congruent events (Stereotypic Explanatory Bias or SEB) is predictive of behavior toward a partner in an interracial interaction. In Experiment I SEB predicted White males' choice to ask stereotypic questions of a Black female (but not a White male or White female) in an interview. In Experiment 2 the type of explanation (internal or external attribution) made for stereotype-inconsistency was examined. Results showed that White participants who made internal attributions for Black stereotype-incongruent behavior were rated more positively and those who made external attributions were rated more negatively by a Black male confederate. These results point to the potential of implicit stereotyping as an important predictor of behavior in an interracial interaction. (C) 2002 Elsevier Science (USA). All rights reserved.

John Waldridge, The Leaven of the Ancients: Suhrawardi and the Heritage of the Greeks, SUNY Series in Islam (Albany: State University of New York Press, 1999). Pp. 323

In the Leaven of the Ancients, John Walbridge studies the appropriation of non–Peripatetic philosophical ideas by an anti–Aristotelian Islamic philosopher, Shihab al-Din al-Suhrawardi (d. 1191). He proposes a comprehensive explanation of the origin of Suhrawardi's philosophical system, a revival of the “wisdom of the Ancients” and its philosophical affiliations “grounded” in Greek philosophy (p. xiii). Walbridge attempts to uncover the reasons for Suhrawardi's rejection of the prevailing neo–Aristotelian synthesis in Islamic philosophy, Suhrawardi's knowledge and understanding of non–Aristotelian Greek philosophy, the ancient philosophers Suhrawardi was attempting to follow, the relationship between Suhrawardi's specific philosophical teachings (logic, ontology, physics, and metaphysics), and his understanding of non–Aristotelian ancient philosophy and the relationship between Suhrawardi's system and the major Greek philosophers, schools, and traditions—in particular the Presocratics, Plato, and the Stoics (p. 8). Copyright © 2003 Cambridge University Press

A qualitative study of Australian GPs' attitudes and practices in the diagnosis and management of attention-deficit/hyperactivity disorder (ADHD)

Background. The importance of general practice involvement in the care of attention-deficit/hyperactivity disorder (ADHD) is increasing due to the rising numbers of patients who present with the disorder. It has been suggested by consensus bodies that GPs should be identifying and referring patients at the severe end of the ADHD spectrum and managing those with less severe symptoms. However, GPs' views of their role in ADHD care are unknown. Objective. Our aim was to explore the attitudes and practices of Australian GPs towards the diagnosis and management of ADHD. Methods. We conducted a series of focus groups to explore GPs' beliefs regarding the causes of ADHD, their perceived role in ADHD diagnosis and management and their views on the role of behaviour therapies and pharmacotherapies in ADHD management. The subjects were 28 GPs in six focus groups. Results. GPs in this study did not want to be the primary providers of care for patients with ADHD. Participants indicated a preference to refer the patient to medical specialists for diagnosis and treatment of ADHD, and expressed low levels of interest in becoming highly involved in ADHD care. Concerns about overdiagnosis and misdiagnosis of the disorder, diagnostic complexity, time constraints, insufficient education and training about the disorder, and concerns regarding misuse and diversion of stimulant medications were the reasons cited for their lack of willingness. Conclusions. The Australian GPs in this study identify a role for themselves in ADHD care which is largely supportive in nature, and involves close liaison with specialist services.

Comparative surface accessibility of a pore-lining threonine residue (T6') in the glycine and GABA(A) receptors

The substituted cysteine accessibility method was used to probe the surface exposure of a pore-lining threonine residue (T6’) common to both the glycine receptor (GlyR) and GABAA receptor (GABAAR) chloride channels. This residue lies close to the channel activation gate, the ionic selectivity filter and the main pore blocker binding site. Recent studies have suggested that the GlyRs and GABAARs have divergent open state pore structures at the 6’ position. When both the human a1T6’C homomeric GlyR and the rat a1T6’Cb1T6’C heteromeric GABAAR were expressed in HEK293 cells, their 6’ residue surface accessibilities differed significantly in the closed state. However, when a soluble cysteine-modifying compound was applied in the presence of saturating agonist concentrations, both receptors were locked into the open state. This action was not induced by oxidising agents in either receptor. These results provide evidence for a conserved pore opening mechanism in anion-selective members of the ligand-gated ion channel family. The results also indicate that the GABAAR pore structure at the 6’ level may vary between different expression systems.

Interaction of RTD-1, a cyclic antimicrobial defensin from Rhesus macaque leukocytes, and its open chain analogue with membrane mimics

In contrast to other mammalian defensins, rhesus theta defensin-1 (RTD-1) is composed of just 18 amino acids with the backbone cyclized through peptide bonds. Antibacterial activities of both the native cyclic peptide and a linear form were examined, showing that the cyclic form was 3-fold more active than the open chain analogue, oRTD-1, although both peptides adopt very similar structures in water. It was suggested that the additional charges at the termini of oRTD-1 are the cause for its lower antimicrobial activity. Therefore, we studied the interaction of both peptides with membrane mimics composed of zwitterionic (PC) and negatively charged (PG) phospholipids, major lipid components of erythrocyte and bacterial cell membranes, respectively. Microcalorimetry showed that RTD-1 and oRTD-1 did not affect the phase behavior of PC liposomes, while in PG liposomes both peptides induced new phase transitions above the chain melting transition of the lipid. The shape and fraction differed between both peptides, depending also on their concentration, which will be discussed in terms of their antimicrobial activity.

The amygdaloid complex: Anatomy and physiology

A converging body of literature over the last 50 years has implicated the amygdala in assigning emotional significance or value to sensory information. In particular, the amygdala has been shown to be an essential component of the circuitry underlying fear-related responses. Disorders in the processing of fear-related information are likely to be the underlying cause of some anxiety disorders in humans such as posttraumatic stress. The amygdaloid complex is a group of more than 10 nuclei that are located in the midtemporal lobe. These nuclei can be distinguished both on cytoarchitectonic and connectional grounds. Anatomical tract tracing studies have shown that these nuclei have extensive intranuclear and internuclear connections. The afferent and efferent connections of the amygdala have also been mapped in detail, showing that the amygdaloid complex has extensive connections with cortical and subcortical regions. Analysis of fear conditioning in rats has suggested that long-term synaptic plasticity of inputs to the amygdala underlies the acquisition and perhaps storage of the fear memory. In agreement with this proposal, synaptic plasticity has been demonstrated at synapses in the amygdala in both in vitro and in vivo studies. In this review, we examine the anatomical and physiological substrates proposed to underlie amygdala function.

The coincidences of time travel

In this paper I consider two objections raised by Nick Smith (1997) to an argument against the probability of time travel given by Paul Horwich (1995, 1987). Horwich argues that time travel leads to inexplicable and improbable coincidences. I argue that one of Smith's objections fails, but that another is correct. I also consider an instructive way to defend Horwich's argument against the second of Smith's objections, but show that it too fails. I conclude that unless there is something faulty in the conception of explanation implicit in Horwich's argument, time travel presents us with nothing that is inexplicable.

Women victims of assault: Age differences in victim-aggressor relationship and location

This article presents the findings from a secondary analysis of the 1991 Queensland Crime Victim Survey. Although now more than 10 years old, this survey still has validity as it remains the largest of its kind conducted in Queensland, and it is a rich source of information about the experiences of victims of violence. The study investigated how the experiences of younger female assault victims differ from older female victims in terms of their relationship with their aggressor and the assault location. The following factors were examined: whether or not the assault occurred (a) at the hands of a partner or former partner, (b) in a private dwelling, (c) in a public place, and (d) in a leisure venue away from home. Results pointed to important differences between younger and older women in terms of their experiences of violence. Teenage women reported significantly more assaults in public places compared with older women, and were less likely to be assaulted in their own dwelling. Also, trends in the data suggested that compared to older women, teenage women were more likely to be assaulted in leisure venues away from home, and were less likely to be assaulted by partners or former partners. Considering that young women are at a much higher risk than older women of being assaulted, consideration of these age differences may be helpful in the design of violence prevention strategies. In particular, more attention should be paid to the public place prevention of violence against young women.

Potential triggers for akinete differentiation in an Australian strain of the cyanobacterium Cylindrospermopsis raciborskii (AWT 205/1)

Understanding the triggers for some cyanobacteria of the Nostocales and Stigonematales orders to produce specialised reproductive cells termed akinetes, is very important to gain further insights into their ecology. By improving our understanding of their life cycle, appropriate management options may be devised to control the formation of these cells, and therefore the potential bloom inoculum which they are thought to provide, may be reduced. This study investigated the effect of chemical (phosphorus limitation), and environmental variables (temperature shock) on akinete differentiation in the freshwater cyanobacterium Cylindrospermopsis raciborskii (AWT 205/1). From the preliminary results, it is suggested that the availability of phosphorus and changes in temperature were a necessary requirement for the formation of akinetes in this particular strain of C. raciborskii. In the four phosphorus treatments investigated (0, 3, 38 and 75 mug l(-1) P), only the two higher treatments produced akinetes (approximately 220 ml(-1)). When the first akinetes were observed in the 38 and 75 mug l(-1) P treatments, filterable reactive phosphorus (FRP) concentrations in the medium were approximately 22 and 52 mug l(-1) P, respectively, indicating that there was no phosphorus limitation. In the temperature shock experiment, akinetes were observed in the 15 and 20degreesC treatments. However, akinetes were degraded (pale yellow colour, limited swelling and shrivelled edges) and in much lower concentrations, which was thought to be a result of the daily temperature shock. We suggest that the formation of akinetes in C. raciborskii (AWT 205/1) can be triggered by an initial temperature shock and that phosphorus is a necessary requirement to allow further growth and full development of akinetes.

Attenuation of perceptual asymmetries in patients with early-onset schizophrenia: Evidence in favour of reduced hemispheric differentiation in schizophrenia?

Lateral biases in visual perception have been demonstrated in normal individuals and in patients with unilateral brain lesions. It has been suggested that the absence of structural and functional asymmetries in schizophrenia could be due to a failure in lateralisation that may be most pronounced in those patients whose illness onset is at an early age. Here we examined lateral biases in patients with schizophrenia of an early onset (N = 21) and a late onset.(N = 19), and their respective age-matched control groups, using the greyscales task, a sensitive measure of asymmetries in visual processing. The stimuli consisted of two rectangles, one above the other, shaded in opposite directions and matched overall for darkness. Participants judged which of the two rectangles looked darker overall. Previous studies using this task in healthy participants have reported a reliable bias, such that the rectangle with the darker end on the left is selected preferentially. Whereas the late-onset patients in this study exhibited a perceptual bias of similar direction and magnitude to that of controls, this was not the case for the early-onset patients, who exhibited significantly less bias than their control group. The reduced perceptual bias seen in the early-onset group, but not the late-onset group, suggests an attenuation of right hemisphere mechanisms dedicated to processing vistiospatial information. The attenuated perceptual asymmetry in the early-onset group only may be consistent with the view that (i) an earlier illness onset reflects a greater loss of hemispheric differentiation and (ii) reduced functional asymmetries in the early-onset group are a manifestation of a failure to allocate functions to one or the other hemisphere.

Millennial and orbital variations of El Nino/Southern Oscillation and high-latitude climate in the last glacial period

The El Nino/Southern Oscillation (ENSO) phenomenon is believed to have operated continuously over the last glacial interglacial cycle(1). ENSO variability has been suggested to be linked to millennial-scale oscillations in North Atlantic climate during that time(2,3), but the proposals disagree on whether increased frequency of El Nino events, the warm phase of ENSO, was linked to North Atlantic warm or cold periods. Here we present a high-resolution record of surface moisture, based on the degree of peat humification and the ratio of sedges to grass, from northern Queensland, Australia, covering the past 45,000 yr. We observe millennial-scale dry periods, indicating periods of frequent El Nino events ( summer precipitation declines in El Nino years in northeastern Australia). We find that these dry periods are correlated to the Dansgaard - Oeschger events - millennial-scale warm events in the North Atlantic climate record - although no direct atmospheric connection from the North Atlantic to our site can be invoked. Additionally, we find climatic cycles at a semiprecessional timescale (, 11,900 yr). We suggest that climate variations in the tropical Pacific Ocean on millennial as well as orbital timescales, which determined precipitation in northeastern Australia, also exerted an influence on North Atlantic climate through atmospheric and oceanic teleconnections.

IB Theory and the Entry of MNCs in Brazil from 1850 to 2007

This paper analyses the applicability of the main enterprise internationalization theories to the entry of the multinational corporations into Brazil, throughout five phases of Brazilian economy, from 1850 to nowadays. It seeks to verify the explanation power of each theory over the FDI flows in Brazil. It concludes that there is a contingency relation between the theories and the phases of the economy, and. it shows such relationship in a table. In addition, it concludes that the most powerful theory along the researched period was Dunning`s eclectic paradigm, mainly due to the Localization considerations. Theoretical propositions are put forward as a contribution to future research.

Non-linear pathways of corporate environmental management: a survey of ISO 14001-certified companies in Brazil

A study was conducted to verify whether the theory on the evolution of corporate environmental management (CEM) is applicable to organizations located in Brazil. Some of the most important proposals pertaining to the evolution of CEM were evaluated in a systematic fashion and integrated into a typical theoretical framework containing three evolutionary stages: reactive, preventive and proactive. The validity of this framework was tested by surveying 94 companies located in Brazil with ISO 14001 certification. Results indicated that the evolution of CEM tends to occur in a manner that is counter to what has generally been described in the literature. Two evolutionary stages were identified: 1) synergy for eco-efficiency and 2) environmental legislation view, which combine variables that were initially categorized into different theoretical CEM stages. These data, obtained from a direct study of Brazilian companies, suggest that the evolution of environmental management in organizations tends to occur in a non-linear fashion, requiring a re-analysis of traditional perceptions of CEM development, as suggested by Kolk and Mauser (2002). (C) 2010 Elsevier Ltd. All rights reserved.