Interferons mediate terminal differentiation of human cortical thymic epithelial cells

In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-beta) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-beta induction. Finally, we demonstrated that recombinant IFN-alpha, IFN-beta, or IFN-gamma was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections.     

LPS-induced lung injury in neonatal rats: changes in gelatinase activities and consequences on lung growth

Postnatal lung growth disorders may involve imbalance between metalloproteinases and their inhibitors. Inflammatory cell 92-kDa gelatinase overactivity has been reported in adults with lung injury but has not been looked for in neonates. We compared gelatinase activity in neonatal and adult rats and evaluated postnatal lung growth after lipopolysaccharide (LPS)-induced lung injury. Significant intra-alveolar inflammatory cell recruitment occurred in adults and neonates; cell counts increased 16-fold in adults and 2.7-fold in neonates. Total 92-kDa gelatinase activity was increased in neonates and adults and was significantly correlated to inflammatory cell counts. For a given cell count, 92-kDa gelatinase increased more in neonates than in adults. Morphometric neonatal lung analysis showed that LPS-injured lungs had decreases in absolute values of lung volume (P < 0.03), alveolar surface (P < 0.004), and air space volume (P < 0.03). Doxycycline, a nonspecific metalloproteinase inhibitor, partly inhibited LPS-induced 92-kDa gelatinase overactivity but did not improve LPS-induced alveolar growth disorders. LPS-mediated lung injury in neonatal rats induced both gelatinase B overactivity and alveolar growth disorders, although no causal link between these two effects was demonstrated.     

Pathogenic Mycobacterium avium remodels the phagosome membrane in macrophages within days after infection

As part of their strategy for intracellular survival, mycobacteria prevent maturation of the phagosomes in which they reside inside macrophages. The molecular basis for this inhibition is only now beginning to emerge, by way of the molecular characterisation of the phagosome membrane when it encloses virulent mycobacteria. Our own work has shown that at 15 days after the phagocytic uptake of Mycobacterium avium by mouse bone marrow-derived macrophages, the phagosome membrane is depleted about 4-fold for cell surface-derived membrane glycoconjugates, labelled by exogalactosylation, in comparison to the membrane of early endosomes with which it continues to interact. Here we asked whether this depletion occurred at early or late stages after infection. We found that only about half of the depletion had occurred at about 5 hours after the beginning of phagocytic uptake, with the remainder becoming established thereafter, with a half-time of about 2.5 days. Phagosomes became depleted in relation to early endosomes with which they continued to exchange membrane constituents. Early endosomes themselves became gradually depleted by about 30% during the 15-day post-infection period. In contrast, late endosomes/lysosomes remained unchanged, with a concentration of surface-derived glycoconjugates between that of early endosomes and of phagosomes at day 15 post infection. In view of the slowness of the post-infection change of phagosome membrane composition, we proposed that this change did not play a role in preventing maturation immediately after phagosome formation, but rather correlated with the process of maintaining the phagosomes in an immature state.     

Genetics of schizophrenia and bipolar disorder: recent success of linkage studies with evidence of specific and shared susceptibility loci

Results claiming linkage on two chromosomes for schizophrenia (SZ) and bipolar affective disorder (BP) were prematurely published in Nature at the end of the '80s. This ended up into disappointment. The knowledge accumulated from the first generation of unsuccessful molecular genetics studies of SZ and BP provided a stronger basis for the following generation of linkage studies that are now yielding encouraging converging results. Hence, we report several genomics susceptibility loci for SZ and BP, some of them being probably shared by the two major psychiatric illnesses whereas others could be specific to each.     

Les Ostracodes et le Quaternaire d’Aigion (golfe de Corinthe, Grèce)

The Upper Pleistocene and the Holocene of Aigion have delivered an abundant microfauna with 35 ostracode species. The Pleistocene from Aigion borehole generally provides Ostracodes from oligohaline environment with Cyprideis torosa, Candona angulata and Tyrrhenocythere amnicola while, in the Holocene, marine infralittoral species dominate with Cytheridea neapolitana, Carinocythereis whitei, Loxoconcha ovulata and Cytherois frequens. The marine sedimentation occurred at depth from some meters to some tens of meters. In the Aghios Constantinos section, the lagoonal marls are characterised by Euxinocythere schuldtae and a dwarf species of Xestoleberis. Then, a drastic environmental change occurs around the Pleistocene-Holocene boundary and presumably affected the whole Corinth gulf.     

Neuroticism in the elderly. The utility of the shortened DPQ-scales

This article reports on the relation between aging and personal adjustment. Current personality scales are not developed for older persons. Scales contain items which are not valid for an aging population and contain too many items for administration in older populations. As part of the Longitudinal Aging Study Amsterdam (LASA) Neuroticism in older persons was measured with a shortened version of the Inadequacy (IN) and Social Inadequacy (SI) scales of the Dutch Personality Questionnaire (DPQ). The utility of these shortened scales was assessed based on internal consistency, inter-item correlations, test-retest reliability and factor analysis. The consistency of the personality dimension Neuroticism was assessed based on cohort-differences and a 6-year longitudinal comparison. The research-population contained 2118 respondents at baseline, aged between 55 and 85 years, 49% were male and they were not living in an institution. The shortened scales appeared to be reliable and valid instruments to measure Neuroticism in the elderly. The gaining of time due to the administration of the shortened scales enlarges the feasibility of the scales for measuring Neuroticism in older persons. Results showed no significant age-difference on the IN-scale, but revealed a significant difference on the SI-scale (p < .01). The 65+ elderly (65-74 and 75-85) have higher scores on Social Inadequacy than the youngest elderly (55-64). Longitudinal analyses showed an interaction between age at baseline and the stability and change of the level of Neuroticism. On both scales the youngest age-group showed a significant decline in mean level of Neuroticism (p < .01). The mean level of Social Inadequacy in the oldest age-group showed an increase during the 6-year follow-up period (p < .05). However, the differences were very small. Future research is needed to assess the effect of related variables on Neuroticism in older persons.     

Apathy syndrome: a clinical entity?

Apathy is defined as a disorder of motivation that expresses itself at an emotional, cognitive and behavioural level. Apathy can occur as a symptom and a syndrome. In the recent years diagnostic criteria and a number of scales for measuring apathy in elderly with psychiatric or neurological disorders have been introduced. Two scales are specifically developed to measure apathy, the Apathy Evaluation Scale (AES) from Marin and the Apathy Scale (AS) from Starkstein. Both scales have been translated into Dutch. The AS is more convenient. The AS in addition can be used when applying the criteria for the apathy syndrome which has been introduced in 2001 by Starkstein. In addition, the Neuropsychiatric Inventory (NPI) and the 'Gedragsobservatieschaal voor de Intramurale Psychogeniatrie' (GIP) (a scale in Dutch) have an apathy domain. Conceptual problems surrounding apathy have only partly been resolved. The criteria for the apathy syndrome can only be used for assessing the extent of the problem. Apathy and depression are strongly correlated. Studies show that apathy as a syndrome can occur without concomitant depression in the elderly, but regularly occurs besides a depressive disorder, in percentages varying between 9% and 53% of the population under study. Especially the varying validity of an apathy syndrome in relation to late life depression needs further clarification.     

Purification and characterization of YihA,an essential GTP-binding protein from Escherichia coli

YihA has previously been characterized as an essential gene of unknown function in both Escherichia coli and Bacillus subtilis. It is conserved in bacteria and represents an attractive target for the discovery of new antibiotics. YihA encodes a putative GTP-binding protein. We have cloned and overexpressed the gene encoding E. coli YihA and initiated biochemical studies as a first step towards understanding its biological function. We showed by circular dichroism that the purified protein has a secondary structure typical of most GTP-binding proteins. It binds guanine nucleotides specifically, as demonstrated by fluorescence resonance energy transfer between 2'-(or-3')-O-(N-methylanthraniloyl) nucleotides (mant-nucleotides) and the tryptophans of YihA. The K(d) values for GDP and GTP were determined by competition with 2'-(or-3')-O-(N-methylanthraniloyl) GDP to be 3 and 27 microM, respectively. Using mutants of YihA we show that nucleotide binding occurs at the putative GTP-binding domain predicted from the primary sequence.