Enhanced glutamate,IP3 and cAMP activity in the cerebral cortex of Unilateral 6-hydroxydopamine induced Parkinson's rats: Effect of 5-HT,GABA and bone marrow cell supplementation

Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in B_max (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B, mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's disease is of prominence.     

Detection of streptococcal mutants presumed to be defective in sugar catabolism

The tetrazolium method for detection of bacterial mutants defective in sugar catabolism was modified for use with streptococci. The critical factors were (i) the concentration of tetrazolium, which must be titrated to determine the optimum concentration for each species or even strain, and (ii) anaerobic incubation of tetrazolium-containing agar plates. When used with standard mutagenesis protocols, this method yielded lactose-negative mutants of nine streptococcal strains representing six species. A collection of lactose-negative mutants of streptococcus, sanguis Challis was characterized and contained phospho-beta-galactosidase, lactose phosphotransferase, and general phosphotransferase mutants.     

Variation in human fertility

Data on family size distribution and inheritance are presented. Variance in sibship size is in general greater than mean sibship size. The inherited component in the variation appears in general to be small, though not in a Scottish sample examined in more detail. Changes in family size distribution for social (or other) reasons are considered, together with some of their effects on the change in gene frequency in small populations.     

Castration Increases Cell Damage Induced by Porphyrins in the Harderian Gland of Male Syrian Hamster. Necrosis and Not Apoptosis Mediates the Subsequent Cell Death

It is known that the Harderian gland of male Syrian hamster synthesizes a much smaller amount of porphyrins than the gland of the female and that castration greatly increases this synthesis. We have studied in this experimental model the behavior of the different classes of secretory cells and their role in the synthesis of porphyrins, attempting to clarify the participation of these compounds in the cell damage leading to the formation of clear cells previously described in the gland of females. We have also investigated the mechanism underlying the death of these secretory cells after porphyrin accumulation (necrosis vs apoptosis). To achieve this, we have utilized the following techniques: (a) morphometrical; (b) ultrastructural; (c) biochemical (fluorescence spectrophotometry); and (d) molecular (DNA nick-end labeling in methacrylate sections and dot blot analysis). The glands from male hamsters (serving as control) present a very low rate of damaged cells that progressively rises after castration. This rise runs parallel to that of porphyrin synthesis, porphyrin deposits, and the decrease of Type II secretory cells. The damage and subsequent death of the secretory cells in the gland is produced by the deposit of porphyrins in the mitochondrial membrane. This porphyrin accumulation leads to a complete mitochondrial destruction that finally results in cell death and its secretion into the lumen. We finally conclude that this event is not a physiological cell death (apoptosis) but the consequence of the toxic accumulation of porphyrins (necrosis).     

Effects of different abiotic and biotic factors on spatial primary seed dispersal in the semachorous species Scrophularia canina

Seed dispersal is one of the most important steps in the plant life cycle. However, there is, generally, a lack of fieldworks focused on wind dispersal and especially on semachorous dispersal (seeds spread when the fruits are shaken by wind and other vectors, such as animals), including boleochorous dispersal. Therefore, we aimed to determine how different types of wind and animals affected seed dispersal under natural conditions in the widespread species Scrophularia canina. We evaluated the effects of wind gusts (simulating them using a leaf blower) and wild animals (using differently sized dogs) on seed dispersal in a population located in south-western Europe. We found that S. canina is a semachorous species, and its spatial seed dispersal was affected by wind gust speed and direction, plant structure and vector type. The results also revealed the presence of xerochasy, individual anisotropy with strong winds, and primary short-distance dispersal associated with successional processes independent of the vector. Additionally, there was a masking effect of plant structure on the seed shadow outline. It is essential to conduct fieldworks to reveal what actually happens in nature, taking into account the characteristics determining seed dispersal. In addition, in these works it is important to find out what factors affect seed distributions of anemochorous and semachorous species.     

Designed β-sheet-forming peptide 33mers with potent human bactericidal/permeability increasing protein-like bactericidal and endotoxin neutralizing activities

Novel peptide 33mers have been designed by incorporating β-conformation stabilizing residues from the β-sheet domains of α-chemokines and functionally important residues from the β-sheet domain of human neutrophil bactericidal protein (B/PI). B/PI is known for its ability to kill bacteria and to neutralize the action of bacterial endotoxin (lipopolysaccharide, LPS) which can induce septic shock leading to eventual death. Here, the goal was to make short linear peptides which demonstrate good β-sheet folding and maintain bioactivity as in native B/PI. A library of 24 peptide 33mers (βpep-1 to βpep-24) were synthesized with various amino acid substitutions. CD and NMR data acquired in aqueous solution indicate that βpep peptides form β-sheet structure to varying degrees and self-associate as dimers and tetramers like the α-chemokines. Bactericidal activity toward Gram-negative Pseudomonas aeruginosa was tested, and βpep-19 was found to be only about 5-fold less potent (62% kill at 1.2×10^?7 M) than native B/PI (80% kill at 2.9×10^?8 M). At LPS neutralization, βpep-2 and -23 were found to be most active (66–78% effective at 1.2×10^?6 M), being only about 50–100-fold less active than B/PI (50% at 1.5×10^?8 M). In terms of structure–activity relations, β-sheet structural stability correlates with the capacity to neutralize LPS, but not with bactericidal activity. Although a net positive charge is necessary for activity, it is not sufficient for optimal activity. Hydrophobic residues tend to influence activities indirectly by affecting structural stability. Furthermore, results show that sequentially and spatially related residues from the β-sheet domain of native B/PI can be designed into short linear peptides which show good β-sheet folding and retain much of the native activity. This research contributes to the development of solutions to the problem of multiple drug-resistant, opportunistic microorganisms like P. aeruginosa and of agents effective at neutralizing bacterial endotoxin.