Autonomic responses of autistic children to people and objects

Several recent lines of inquiry have pointed to the amygdala as a potential lesion site in autism. Because one function of the amygdala may be to produce autonomic arousal at the sight of a significant face, we compared the responses of autistic children to their mothers' face and to a plain paper cup. Unlike normals, the autistic children as a whole did not show a larger response to the person than to the cup. We also monitored sympathetic activity in autistic children as they engaged in a wide range of everyday behaviours. The children tended to use self-stimulation activities in order to calm hyper-responsive activity of the sympathetic ('fight or flight') branch of the autonomic nervous system. A small percentage of our autistic subjects had hyporesponsive sympathetic activity, with essentially no electrodermal responses except to self-injurious behaviour. We sketch a hypothesis about autism according to which autistic children use overt behaviour in order to control a malfunctioning autonomic nervous system and suggest that they have learned to avoid using certain processing areas in the temporal lobes.     

Resolution of (RS)-proglumide using lipase from Candida cylindraceae

Proglumide is used in the treatment of neuropathic pain. It acts by inhibiting peptide cholecystokinin (CCK). Neural injury produces an elevation in plasma CCK. Proglumide has been also shown to augment the analgesic effect of sustained release morphine in neuropathic pain. Currently proglumide is administered as a racemic mixture. In the present study, an attempt is made to separate the racemic mixture of the drug using lipase obtained from Candida cylindracea by stereoselective esterification. Enzymatic stereoselective esterification was carried out in organic solvents. The resolution was studied using a chromatographic column with a chiral support and mass spectrometry. The reaction conditions for stereoselective esterification including amount of substrate, amount of enzyme, alcohol, solvent and temperature were optimised during the present investigation. Butanol and hexanol were found to be suitable for formation of S and R esters, respectively. Hexane was the best solvent for esterification and the optimum temperature was found to be 30 degreesC.     

Structural insights into the membrane-anchoring mechanism of a cholesterol-dependent cytolysin

Perfringolysin O (PFO), a cytolytic toxin secreted by pathogenic Clostridium perfringens, forms large pores in cholesterol-containing membranes. Domain 4 (D4) of the protein interacts first with the membrane and is responsible for cholesterol recognition. By using several independent fluorescence techniques, we have determined the topography of D4 in the membrane-inserted oligomeric form of the toxin. Only the short hydrophobic loops at the tip of the D4 beta-sandwich are exposed to the bilayer interior, whereas the remainder of D4 projects from the membrane surface and is surrounded by water, making little or no contact with adjacent protein monomers in the oligomer. Thus, a limited interaction of D4 with the bilayer core seems to be sufficient to accomplish cholesterol recognition and initial binding of PFO to the membrane. Furthermore, D4 serves as the fulcrum around which extensive structural changes occur during the formation and insertion of the large transmembrane beta-barrel into the bilayer.     

Mitochondria,nitric oxide,and cardiovascular dysfunction

Cardiovascular diseases encompass a wide spectrum of abnormalities with diverse etiologies. The molecular mechanisms underlying these disorders include a variety of responses such as changes in nitric oxide- (NO) dependent cell signaling and increased apoptosis. An interesting aspect that has received little or no attention is the role mitochondria may play in the vascular changes that occur in both atherosclerosis and hypertension. With the changing perspective of the organelle from simply a role in metabolism to a contributor to signal transduction pathways, the role of mitochondria in cells with relatively low energy demands such as the endothelium has become important to understand. In this context, the definition of the NO-cytochrome c oxidase signaling pathway and the influence this has on cytochrome c release is particularly important in understanding apoptotic mechanisms involving the mitochondrion. This review examines the role of compromised mitochondrial function in a variety of vascular pathologies and the modulation of these effects by NO. The interaction of NO with the various mitochondrial respiratory complexes and the role NO plays in modulating mitochondrial-mediated apoptosis in these systems will be discussed.     

Apoptosis in yeasts

Although yeasts lack some elements of the complex apoptotic machinery of metazoan cells, recent studies show that many features of apoptosis, including a caspase-like activity, can be induced in these organisms by DNA damage and other apoptotic triggers. These remarkable findings provide a compelling argument for increased efforts to bring the powerful genetic approaches available to yeast researchers more directly to bear on questions related to apoptosis and its induction or inhibition by drugs. Yeasts may provide a particularly useful model for understanding connections between DNA damage, cell cycle regulation and apoptosis. Here we summarize these recent findings and explore their implications, particularly for the development of more effective therapeutic strategies for treating cancer.     

Crypt architecture of tonsilla lingualis in the monkey,Macaca fascicularis

Summary Crypts of the lingual tonsil were investigated in 10 male and female Macaca fascicularis by use of correlated light and scanning-electron microscopy. Counting of crypt openings provided an estimate of the total number of respective crypto-lymphatic units, which were found to range from 20 to 39. Crypt openings appeared in three distinct morphological varieties, i.e. circular, oval or slit-like. Tonsillar units existed individually or were arranged in a rosary fashion below a slit-like mucosal fold serving as a common exit. Although the crypt epithelium was generally non-keratinized, individual cells showing a surface pattern similar to that of the keratinized cells could be encountered. The crypt epithelium was frequently fragmented and showed heavy mononuclear cell infiltration and surface discontinuities, with lymphoid cells coming in contact with luminal contents. The crypt lumen either appeared as a simple epithelial invagination or existed as a complex, cavernous pouch with many blind-ending diverticula. The lumen contained a mixture of exfoliated epithelial cells, leucocytes and bacteria. The secretory ducts of the posterior lingual glands opened occasionally at various levels into the crypt lumina or independently to the exterior.     

The Mycobacterial MsDps2 Protein Is a Nucleoid-Forming DNA Binding Protein Regulated by Sigma Factors σA and σB

The Dps (DNA-binding protein from starved cells) proteins from Mycobacterium smegmatis MsDps1 and MsDps2 are both DNA-binding proteins with some differences. While MsDps1 has two oligomeric states, with one of them responsible for DNA binding, MsDps2 has only one DNA-binding oligomeric state. Both the proteins however, show iron-binding activity. The MsDps1 protein has been shown previously to be induced under conditions of starvation and osmotic stress and is regulated by the extra cellular sigma factors σ^H and σ^F. We show here, that the second Dps homologue in M. smegmatis, namely MsDps2, is purified in a DNA-bound form and exhibits nucleoid-like structures under the atomic force microscope. It appears that the N-terminal sequence of Dps2 plays a role in nucleoid formation. MsDps2, unlike MsDps1, does not show elevated expression in nutritionally starved or stationary phase conditions; rather its promoter is recognized by RNA polymerase containing σ^A or σ^B, under in vitro conditions. We propose that due to the nucleoid-condensing ability, the expression of MsDps2 is tightly regulated inside the cells.     

The renal Na+/Ca2+ exchange system is located exclusively in the distal tubule.

The movement of Ca2+ across the basolateral plasma membrane was determined in purified preparations of this membrane isolated from rabbit proximal and distal convoluted tubules. The ATP-dependent Ca2+ uptake was present in basolateral membranes from both these tubular segments, but the activity was higher in the distal tubules. A very active Na+/Ca2+ exchange system was also demonstrated in the distal-tubular membranes, but in proximal-tubular membranes this exchange system was not demonstrable. The presence of Na+ outside the vesicles gradually inhibited the ATP-dependent Ca2+ uptake in the distal-tubular-membrane preparations, but remained without effect in those from the proximal tubules. The activity of the Na+/Ca2+ exchange system in the distal-tubular membranes was a function of the imposed Na+ gradient. These results suggest that the major differences in the characteristics of Ca2+ transport in the proximal and in the distal tubules are due to the high activity of a Na+/Ca2+ exchange system in the distal tubule and its virtual absence in the proximal tubule.