Differential response of T cells to an immunogen,a mitogen and a chemical carcinogen in a mouse model system

In this study, we examined the relative immune response of T‐lymphocytes and its intracellular cholesterol homeostasis, in a mouse model system, after treatment with immunogen, mitogen, and carcinogen. We studied the T‐lymphocyte percentage, their LDL‐receptor expression, along with the levels of serum interleukins (IL‐2, IFNγ, IL‐4, and IL‐10) and intracellular cholesterol concentration (cytoplasmic and nuclear). The mitogen was found to be a better stimulator of T‐cell marker expressions than the immunogen; though the immunogen was more effective on immunogenic response as was marked from interleukin levels. The chemical carcinogen benzo‐α‐pyrene at low concentration acted potentially like a mitogen but a reduced immune response was apparent at a carcinogenic dose. The findings in our study focus on the effect of carcinogenic dose of benzo‐α‐pyrene (BaP) on T‐cell immunity. Benzo‐α‐pyrene causes immunosuppression through restriction of the T‐cell population by targeting intracellular cholesterol.     

A novel form of vitamin B-12 and its derivatives

A new isomeric form of cobalamins is reported. The conversion of cobalamin to cobalamin′ (the new form) is achieved by substituting the benzimidazole base by a less bulky group like H₂O of CN^? and modest thermal treatment. The back conversion of adenosylcobalamin′ to the corresponding regular form occurs in the ‘base-off’ form at room temperature. It seems that the corrin ring becomes quite flexible in the ‘base-off’ form and the freer axial movement of the cobalt atom flips the corrin ring into a different conformation. The change in conformation is borne out by subtle changes in the proton magnetic resonances on the corrin ring and the base, and very marked variation in the emission Mössbauer spectra. The latter is indicative of appreciable changes in the spatial conformation in the immediate vicinity of the central metal atom.The ultraviolet-visible and infrared spectra of a cobalamin′ are indistinguishable from those of its corresponding regular form.The new conformational isomeric species is present as an impurity in all commercially available cobalamins (including pharmaceutical preparations). It raises the question whether the cobalamins′ constitute the real biologically active anti-anemic factor in humans     

Selective Chromatid Segregation Mechanism Invoked For the Human Congenital Mirror Hand Movement Disorder Development by RAD51 Mutations: A Hypothesis

The vertebrate body plan externally is largely symmetrical across the midline but internal organs develop asymmetrically. The biological basis of asymmetric organ development has been investigated extensively for years, although the proposed mechanisms remain controversial. By comparison, the biological origin of external organs symmetry has not been extensively investigated. Bimanual hand control is one such external organs symmetry allowing independent motor control movements of both hands to a person. This gap in our knowledge is illustrated by the recent reports of heterozygous rad51 mutations causing mysterious symptoms of congenital mirror hand movement disorder (MM) in humans with 50% penetrance by an unknown mechanism. The analysis of mutations that vary symmetry or asymmetry could be exploited to decipher the mechanisms of laterality development. Here I present a hypothesis for explaining 50% penetrance of the rad51 mutation. The MM''s origin is explained with the Somatic Strand-specific Imprinting and selective sister chromatid Segregation (SSIS) hypothesis proposed originally as the mechanism of asymmetric cell division to promote visceral organs body plan laterality development in vertebrates. By hypothesis, random sister chromatid segregation in mitosis occurs for a specific chromosome due to rad51/RAD51 constitution causing MM disorder development in 50% of subjects.     

Stabilization of Thermolysin Induced by a Decrease in the PH and Dielectric Constant of the Reaction Medium Resulting from a Temperature Increase in Z-Phe-Phe-OMe Synthesis

Thermolysin was stabilized by increasing the reaction temperature from 90°C to 110°C during peptide synthesis of N-(benzyloxycarbonyl)-_L-phenylalanyl-_L-phenylalanine methyl ester (Z-Phe-Phe-OMe). The stabilization energy was acquired from the drop in both pH and dielectric constant due to the temperature increase. The acquired stabilization energy was as high as ca. 42 kJ/mol (corresponding to 20°C). This acquired stabilization energy did not result from a single event such as a change in electrical charges. It was evaluated as the overall stabilization energy at and around the active site area of the enzyme using an electrostatic potential equation.     

Inhibition of Oncogenic and Activated Wild-Type ras-p21 Protein-Induced Oocyte Maturation by Peptides from the ras-Binding Domain of the raf-p74 Protein, Identified from Molecular Dynamics Calculations

In the preceding paper we found from molecular dynamics calculations that the structure of the ras-binding domain (RBD) of raf changes predominantly in three regions depending upon whether it binds to ras-p21 protein or to its inhibitor protein, rap-1A. These three regions of the RBD involve residues from the protein–protein interaction interface, e.g., between residues 60 and 72, residues 97–110, and 111–121. Since the rap-1A–RBD complex is inactive, these three regions are implicated in ras-p21-induced activation of raf. We have therefore co-microinjected peptides corresponding to these three regions, 62–76, 97–110, and 111–121, into oocytes with oncogenic p21 and microinjected them into oocytes incubated in in insulin, which activates normal p2l. All three peptides, but not a control peptide, strongly inhibit both oncogenic p21- and insulin-induced oocyte maturation. These findings corroborate our conclusions from the theoretical results that these three regions constitute raf effector domains. Since the 97–110 peptide is the strongest inhibitor of oncogenic p21, while the 111–121 peptide is the strongest inhibitor of insulin-induced oocyte maturation, the possibility exists that oncogenic and activated normal p21 proteins interact differently with the RBD of raf.