Altered gray matter morphometry and resting-state functional and structural connectivity in social anxiety disorder

In social anxiety disorder (SAD), impairments in limbic/paralimbic structures are associated with emotional dysregulation and inhibition of the medial prefrontal cortex (MPFq. Little is known, however, about alterations in limbic and frontal regions associated with the integrated morphometric, functional, and structural architecture of SAD. Whether altered gray matter volume is associated with altered functional and structural connectivity in SAD. Three techniques were used with 18 SAD patients and 18 healthy controls: voxel-based morphometry; resting-state functional connectivity analysis; and diffusion tensor imaging tractography. SAD patients exhibited significantly decreased gray matter volumes in the right posterior inferior temporal gyrus (ITG) and right parahippocampal/hippocampal gyrus (PHG/HIP). Gray matter volumes in these two regions negatively correlated with the fear factor of the Liebowitz Social Anxiety Scale. In addition, we found increased functional connectivity in SAD patients between the right posterior ITG and the left inferior occipital gyrus, and between the right PHF/HIP and left middle temporal gyms. SAD patients had increased right MPFC volume, along with enhanced structural connectivity in the genu of the corpus callosum. Reduced limbic/paralimbic volume, together with increased resting-state functional connectivity, suggests the existence of a compensatory mechanism in SAD. Increased MPFC volume, consonant with enhanced structural connectivity, suggests a long-time overgeneralization of structural connectivity and a role of this area in the mediation of clinical severity. Overall, our results may provide a valuable basis for future studies combining morphometric, functional and anatomical data in the search for a comprehensive understanding of the neural circuitry underlying SAD. (C) 2011 Elsevier B.V. All rights reserved.

Slight activation of nuclear factor kappa-B is associated with increased hepatic stellate cell apoptosis in human schistosomal fibrosis

To investigate the relationship between NF-kappa B activation and hepatic stellate cell (HSC) apoptosis in hepatosplenic schistosomiasis, hepatic biopsies from patients with Schistosoma mansoni-induced periportal fibrosis, hepatitis C virus-induced cirrhosis, and normal liver were submitted to alpha-smooth muscle actin (alpha-SMA) and NF-kappa B p65 immunohistochemistry, as well as to NF-kappa B Southwestern histochemistry and TUNEL assay. The numbers of alpha-SMA-positive cells and NF-kappa B- and NF-kappa B p65-positive HSC nuclei were reduced in schistosomal fibrosis relative to liver cirrhosis. In addition, increased HSC NF-kappa B p65 and TUNEL labeling was observed in schistosomiasis when compared to cirrhosis. These results suggest a possible relationship between the slight activation of the NF-kappa B complex and the increase of apoptotic HSC number in schistosome-induced fibrosis, taking place to a reduced HSC number in schistosomiasis in relation to liver cirrhosis. Therefore, the NF-kappa B pathway may constitute an important down-regulatory mechanism in the pathogenesis of human schistosomiasis mansoni, although further studies are needed to refine the understanding of this process. (C) 2009 Elsevier B.V. All rights reserved.

Mice with genetic deletion of the heparin-binding growth factor midkine exhibit early preclinical features of Parkinson`s disease

There is considerable evidence showing that the neurodegenerative processes that lead to sporadic Parkinson`s disease (PD) begin many years before the appearance of the characteristic motor symptoms and that impairments in olfactory, cognitive and motor functions are associated with time-dependent disruption of dopaminergic neurotransmission in different brain areas. Midkine is a 13-kDa retinoic acid-induced heparin-binding growth factor involved in many biological processes in the central nervous system such as cell migration, neurogenesis and tissue repair. The abnormal midkine expression may be associated with neurochemical dysfunction in the dopaminergic system and cognitive impairments in rodents. Here, we employed adult midkine knockout mice (Mdk(-/-)) to further investigate the relevance of midkine in dopaminergic neurotransmission and in olfactory, cognitive and motor functions. Mdk(/-) mice displayed pronounced impairments in their olfactory discrimination ability and short-term social recognition memory with no gross motor alterations. Moreover, the genetic deletion of midkine decreased the expression of the enzyme tyrosine hydroxylase in the substantia nigra reducing partially the levels of dopamine and its metabolites in the olfactory bulb and striatum of mice. These findings indicate that the genetic deletion of midkine causes a partial loss of dopaminergic neurons and depletion of dopamine, resulting in olfactory and memory deficits with no major motor impairments. Therefore, Mdk(-/-) mice may represent a promising animal model for the study of the early stages of PD and for testing new therapeutic strategies to restore sensorial and cognitive processes in PD.

Diversity and commonality in national identities: an exploratory analysis of cross-national patterns

Issues of boundary maintenance are implicit in all studies of national identity. By definition, national communities consist of those who are included but surrounded (literally or metaphorically) by those who are excluded. Most extant research on national identity explores criteria for national membership largely in terms of official or public definitions described, for example, in citizenship and immigration laws or in texts of popular culture. We know much less about how ordinary people in various nations reason about these issues. An analysis of cross-national (N = 23) survey data from the 1995 International Social Science Program reveals a core pattern in most of the countries studied. Respondents were asked how important various criteria were in being 'truly' a member of a particular nation. Exploratory factor analysis shows that these items cluster in terms of two underlying dimensions. Ascriptive/objectivist criteria relating to birth, religion and residence can be distinguished from civic/voluntarist criteria relating to subjective feelings of membership and belief in core institutions. In most nations the ascriptive/objectivist dimension of national identity was more prominent than the subjective civic/voluntarist dimension. Taken overall, these findings suggest an unanticipated homogeneity in the ways that citizens around the world think about national identity. To the extent that these dimensions also mirror the well-known distinction between ethnic and civic national identification, they suggest that the former remains robust despite globalization, mass migration and cultural pluralism. Throughout the world official definitions of national identification have tended to shift towards a civic model. Yet citizens remain remarkably traditional in outlook. A task for future research is to investigate the macrosociological forces that produce both commonality and difference in the core patterns we have identified.

Assessing alternative models of individualism and collectivism: A confirmatory factor analysis

Six alternative structural models of individualism-collectivism are reviewed and empirically compared in a confirmatory factor analysis of questionnaire data from an Australian student sample (N=340). Central to the debate about the structure of this broad social attitude are the issues of (I) polarity (are individualism and collectivism bipolar opposites, or orthogonal factors?) and (2) dimensionality (are individualism and collectivism themselves higher-order constructs subsuming several more specific factors and, if so, what are they?). The data from this Australian sample support a model that represents individualism and collectivism as a higher-order bipolar factor hierarchically subsuming several bipolar reference-group-specific individualisms and collectivisms. Copyright (C) 2001 John Wiley & Sons, Ltd.

Insulin-like growth factor 2 cDNA cloning and ontogeny of gene expression in the liver of the marsupial brushtail possum (Trichosurus vulpecula)

The cDNA sequence for insulin-like growth factor 2 (IGF-2) was determined from the liver of the marsupial brushtail possum (Trichosurus vulpecula) using reverse transcription followed by polymerase chain reaction (RT-PCR) with gene-specific primers. The 359 bp of possum sequence encompassed the mature peptide, 27 bp of the signal peptide, and 125 bp of the E-peptide. Alignment of the deduced amino acid sequence with those from other species indicated that the mature peptide was 71 amino acids in length, 4 amino acids longer than most other mammals. At both the nucleotide and amino acid levels there was a high degree of sequence identity with IGF-2 from other mammalian and nonmammalian species. Amino acid identity ranged from 94.4% with a variant form of human IGF-2 to 80.3% with zebrafinch IGF-2. Northern analysis revealed that radiolabeled possum IGF-2, cDNA hybridized to multiple transcripts in the liver of both adult possums and 150-day-old pouch young and that the overall level of expression was greater in pouch young. Semiquantitative RT-PCR with total RNA from liver samples of pouch young aged 12 to 150 days postpartum and adults confirmed that IGF-2 gene expression was two to three times more abundant in pouch young than in adults but there was no significant change in the level of expression during pouch life. Unlike other mammalian species, in which there is a decline in levels of liver IGF-2 gene expression around the time of birth, levels in the marsupial brushtail possum remain elevated for at least 150 days after birth. This suggests that the decline in liver IGF-2 expression in marsupials and eutherians occurs at a similar stage of development and may reflect a role for this growth factor during the postnatal growth and development of the marsupial, (C) 2001 Academic Press.

A comparison between three and five factor models of Pakistani personality data

The Eysenck Personality Questionnaire-Revised (EPQ-R), the Eysenck Personality Profiler Short Version (EPP-S), and the Big Five Inventory (BFI-V4a) were administered to 135 postgraduate students of business in Pakistan. Whilst Extraversion and Neuroticism scales from the three questionnaires were highly correlated, it was found that Agreeableness was most highly correlated with Psychoticism in the EPQ-R and Conscientiousness was most highly correlated with Psychoticism in the EPP-S. Principal component analyses with varimax rotation were carried out. The analyses generally suggested that the five factor model rather than the three-factor model was more robust and better for interpretation of all the higher order scales of the EPQ-R, EPP-S, and BFI-V4a in the Pakistani data. Results show that the superiority of the five factor solution results from the inclusion of a broader variety of personality scales in the input data, whereas Eysenck's three factor solution seems to be best when a less complete but possibly more important set of variables are input. (C) 2001 Elsevier Science Ltd. All rights reserved.

Individual and societal bases of national identity - A comparative multi-level analysis

In a previous study (Jones and Smith, 1999) we established that much the same core pattern of national identity characterizes many developed countries. Using the national identity module from the 1995 International Social Survey Programme, we identified two dimensions of national identity: an ascriptive dimension resembling the concept of ethnic identity described in the historical and theoretical literature, and a voluntarist dimension closer to the notion of civic identity. Some writers view these dimensions in terms of a historical sequence but we find that both constructs coexist in the minds of individual respondents in the nations we examine (we exclude Bulgaria and the Philippines from the present but not the earlier analysis). The dataset used for the multilevel analyses reported here consists of 28 589 respondents in the remaining 21 countries included in the national identity database for the 1995 round of surveys. The macrosociological literature on national identity does not offer well-defined predictions about what precise patterns of national identification we might expect to find among the masses of the developed countries. There are, however, recurring themes from which one can construct plausible hypotheses about how countries might differ according to their level of development, broadly conceived. Thus, we hypothesize that forces such as post-industrialism and globalization tend to favour the more open voluntaristic form of national identity over the more restrictive ascribed form. We develop different multi-level models in order to evaluate specific hypotheses pertaining to such issues, by simultaneously relating individual and societal characteristics to the relative strength of individual commitment to these different types of national identity.

Identity and security in Korea

The summit meeting between the two Korean heads of state, which took place in Pyongyang in June 2000, constitutes a major turning point in the peninsula's history. As the effects of the meeting are gradually unfolding, a period of detente no longer seems impossible. But major difficulties remain unsolved and Korea will continue to be one of the world's most volatile areas. The task of this essay is to identify and analyse some of the entrenched political patterns that will challenge policy-makers in the years ahead. To do so it is necessary to portray the conflict in Korea not only in conventional ideological and geopolitical terms, but also, and primarily, as a question of identity. From such a vantage-point two components are essential in the search for a more peaceful peninsula. Substantial progress has recently been made in the first realm, the need to approach security problems, no matter how volatile they seem. in a cooperative and dialogical, rather than merely a coercive manner. The second less accepted but perhaps more important factor, revolves around the necessity to recognize that dialogue has its limits, that the party on the other side of the DMZ cannot always be accommodated or subsumed into compromise. Needed is an ethics of difference: a willingness to accept that the other's sense of identity and politics may be inherently incompatible with one's own.

Phylogenetic analysis of evolutionary relationships of the planctomycete division of the domain bacteria based on amino acid sequences of elongation factor Tu

Sequences from the tuf gene coding for the elongation factor EF-Tu were amplified and sequenced from the genomic DNA of Pirellula marina and Isosphaera pallida, two species of bacteria within the order Planctomycetales. A near-complete (1140-bp) sequence was obtained from Pi. marina and a partial (759-bp) sequence was obtained for I. pallida. Alignment of the deduced Pi. marina EF-Tu amino acid sequence against reference sequences demonstrated the presence of a unique Il-amino acid sequence motif not present in any other division of the domain Bacteria. Pi. marina shared the highest percentage amino acid sequence identity with I. pallida but showed only a low percentage identity with other members of the domain Bacteria. This is consistent with the concept of the planctomycetes as a unique division of the Bacteria. Neither primary sequence comparison of EF-Tu nor phylogenetic analysis supports any close relationship between planctomycetes and the chlamydiae, which has previously been postulated on the basis of 16S rRNA. Phylogenetic analysis of aligned EF-Tu amino acid sequences performed using distance, maximum-parsimony, and maximum likelihood approaches yielded contradictory results with respect to the position of planctomycetes relative to other bacteria, It is hypothesized that long-branch attraction effects due to unequal evolutionary rates and mutational saturation effects may account for some of the contradictions.

Social structure in migrating humpback whales (Megaptera novaeangliae)

Although largely solitary, humpback whales exhibit a number of behaviours where individuals co-operate with one another, for example during bubble net feeding. Such cases could be due to reciprocal altruism brought on by exceptional circumstances, for example the presence of abundant shoaling fish. An alternative explanation is that these behaviours have evolved through kin selection. With little restriction to either communication or movement, diffuse groups of relatives could maintain some form of social organization without the need to travel in tight-nit units. To try to distinguish between these hypotheses, we took advantage of the fact that migrating humpback whales often swim together in small groups. If kin selection is important in humpback whale biology, these groups should be enriched for relatives. Consequently, we analysed biopsy samples from 57 groups of humpback whales migrating off Eastern Australia in 1992. A total of 142 whales were screened for eight microsatellite markers. Mitochondrial DNA sequences (371 bp) were also used to verify and assist kinship identification. Our data add support to the notion that mothers travel with their offspring for the first year of the calf's life. However, beyond the presence of mother-calf/yearling pairs, no obvious relatedness pattern was found among whales sampled either in the same pod or on the same day. Levels of relatedness did not vary between migratory phases (towards or away from the breeding ground), nor between the two sexes considered either overall or in the north or south migrations separately. These findings suggest that, if any social organization does exist, it is formed transiently when needed rather than being a constant feature of the population, and hence is more likely based on reciprocal altruism than kin selection.

The development and psychometric properties of a measure of social and adaptive functioning for children and adolescents

Developed, piloted, and examined the psychometric properties of the Child and Adolescent Social and Adaptive Functioning Scale (CASAFS), a self-report measure designed to examine the social functioning of young people in the areas of school performance, peer relationships, family relationships, and home duties/self-care. The findings of confirmatory and exploratory factor analysis support a 4-factor solution consistent with the hypothesized domains. Fit indexes suggested that the 4-correlated factor model represented a satisfactory solution for the data, with the covariation between factors being satisfactorily explained by a single, higher order factor reflecting social and adaptive functioning in general. The internal consistency and 12-month test-retest reliability of the total scale was acceptable. A significant, negative correlation was found between the CASAFS and a measure of depressive symptoms, showing that high levels of social functioning are associated with low levels of depression. Significant differences in CASAFS total and subscale scores were found between clinically depressed adolescents and a matched sample of nonclinical controls. Adolescents who reported elevated but subclinical levels of depression also reported lower levels of social functioning in comparison to nonclinical controls.

Which aspects of socio-economic status are related to health in mid-aged and older women?

A population-based study was conducted to validate gender- and age-specific indexes of socio-economic status (SES) and to investigate the associations between these indexes and a range of health outcomes in 2 age cohorts of women. Data from 11,637 women aged 45 to 50 and 9,5 10 women aged 70 to 75 were analyzed. Confirmatory factor analysis produced four domains of SES among the mid-aged cohort (employment, family unit, education, and migration) and four domains among the older cohort (family unit, income, education, and migration). Overall, the results supported the factor structures derived from another population-based study (Australian Bureau of Statistics, 1995), reinforcing the argument that SES domains differ across age groups. In general, the findings also supported the hypotheses that women with low SES would have poorer health outcomes than higher SES women, and that the magnitude of these effects would differ according to the specific SES domain and by age group, with fewer and smaller differences observed among older women. The main exception was that in the older cohort, the education domain was significantly associated with specific health conditions. Results suggest that relations between SES and health are highly complex and vary by age, SES domain, and the health outcome under study.

Purification and characterisation of functional early pregnancy factor expressed in Sf9 insect cells and in Escherichia coli

Early pregnancy factor (EPF) is a secreted protein with growth regulatory and immunomodulatory properties. It is an extracellular form of the mitochondrial matrix protein chaperonin 10 (Cpn10), a molecular chaperone. An understanding of the mechanism of action of EPF and an exploration of therapeutic potential has been limited by availability of purified material. The present study was undertaken to develop a simple high-yielding procedure for preparation of material for structure/function studies, which could be scaled up for therapeutic application. Human EPF was expressed in Sf9 insect cells by baculovirus infection and in Escherichia coli using a heat inducible vector. A modified molecule with an additional N-terminal alanine was also expressed in E coli. The soluble protein was purified from cell lysates via anion exchange (negative-binding mode), cation exchange, and hydrophobic interaction chromatography, yielding similar to42 and 36 mg EPF from 300 ml bacterial and I L Sf9 cultures, respectively. The preparations were highly purified ( greater than or equal to99% purity on SDS-PAGE for the bacterial products and greater than or equal to97% for that of insect cells) and had the expected mass and heptameric structure under native conditions, as determined by mass spectrometry and gel permeation chromatography, respectively. All recombinant preparations exhibited activity in the EPF bioassay, the rosette inhibition test, with similar potency both to each other and to the native molecule. In two in vivo assays of immuno suppressive activity, the delayed-type hypersensitivity reaction and experimental autoimmune encephalomyelitis, the insect cell and modified bacterial products, both with N-terminal additions (acetylation or amino acid), exhibited similar levels of suppressive activity, but the bacterial product with no N-terminal modification had no effect in either assay. Studies by others have shown that N-terminal addition is not necessary for Cpn10 activity. By defining techniques for facile production of molecules with and without immunosuppressive properties, the present studies make it possible to explore mechanisms underlying the distinction between EPF and Cpn10 activity. (C) 2003 Elsevier Inc. All rights reserved.

Early pregnancy factor treatment suppresses the inflammatory response and adhesion molecule expression in the spinal cord of SJL/J mice with experimental autoimmune encephalomyelitis and the delayed-type hypersensitivity reaction to trinitrochlorobenzene in normal BALB/c mice

Early pregnancy factor (EPF) is a secreted protein, present in serum during early pregnancy and essential for maintaining viability of the embryo. It is a homologue of chaperonin 10 (Cpn10) but, unlike Cpn10, it has an extracellular role. EPF has immunosuppressive and growth regulatory properties. Previously we have reported the preparation of recombinant EPF (rEPF) and shown that treatment with rEPF will suppress clinical signs of MBP-EAE in Lewis rats and PLP-EAE in SJL/J mice. In the present study, these findings have been extended to investigate possible mechanisms involved in the action of EPF. Following treatment of mice with rEPF from the day of inoculation, there were fewer infiltrating CD3+ and CD4+ cells in the parenchyma of the spinal cord during the onset of disease and after the initial episode, compared with mice treated with vehicle. Expression of the integrins LFA-1, VLA-4 and Mac-1 and of members of the immunoglobulin superfamily of adhesion molecules ICAM-1 and VCAM-1 was suppressed in the central nervous system (CNS) following rEPF treatment. The expression of PECAM-1 was not affected. To determine if rEPF suppressed T cell activation in the periphery, the delayed-type hypersensitivity (DTH) reaction of normal BALB/c mice to trinitrochlorobenzene (TNCB) following treatment with rEPF was studied. The results showed that treatment with rEPF suppressed the DTH reaction, demonstrating the ability of EPF to downregulate the cell-mediated immune response. These results indicate that suppression of immunological mechanisms by rEPF plays a major role in the reduction of clinical signs of disease in experimental autoimmune encephalomyelitis (EAE). (C) 2003 Elsevier Science B.V. All rights reserved.