Inhibition of Oncogenic and Activated Wild-Type ras–p21 Protein-Induced Oocyte Maturation by Peptides from the Guanine-Nucleotide Exchange Protein, SOS, Identified from Molecular Dynamics Calculations. Selective Inhibition of Oncogenic ras–p21

In the preceding paper we performed molecular dynamics calculations of the average structures of the SOS protein bound to wild-type and oncogenic ras–p21. Based on these calculations, we have identified four major domains of the SOS protein, consisting of residues 631–641, 676–691, 718–729, and 994–1004, which differ in structure between the two complexes. We have now microinjected synthetic peptides corresponding to each of these domains into Xenopus laevis oocytes either together with oncogenic (Val 12)-p21 or into oocytes subsequently incubated with insulin. We find that the first three peptides inhibit both oncogenic and wild-type p21-induced oocyte maturation, while the last peptide much more strongly inhibits oncogenic p21 protein-induced oocyte maturation. These results suggest that each identified SOS region is involved in ras–stimulated signal transduction and that the 994–1004 domain is involved uniquely with oncogenic ras–p21 signaling.     

The lingual (root analogue) and the labial (crown analogue) mouse incisor dentin promotes ameloblast differentiation

Previous studies have suggested that mouse molar ameloblast differentiation was triggered by the predentin-dentin. Knowing that enamel is absent on the lingual surface of the mouse incisor, the aim of this study was to compare in heterotopic tissue recombinations the behavior of mouse molar inner dental epithelium associated with lingual or labial mouse incisor dentin. It was shown that root-analogue and crown-analogue incisor dentin promotes ameloblast differentiation of competent molar inner dental epithelium.     

Why and how do Hebrew verbs change their form? A morpho-thematic account

This paper examines the criteria that are responsible for morphological variation in the verbal system of Modern Hebrew. The Hebrew verbal system consists of configurations called binyanim (and binyan in sg.): CaCaC, niCCaC, hiCCiC, CiCeC and hitCaCeC. The relation between Hebrew binyanim is manifested via valence changing operations (e.g. ni?ek ‘kiss’ and hitna?ek ‘kiss each other’). Some verbs demonstrate morphological variation with regard to their binyan. I define morphological variation as cases where two verbs occur in (at least) two different binyanim, but share the same (i) stem consonants (ii) thematic grid and (iii) denotation. For example, the verbs nirtav and hitratev are formed in niCCaC and hitCaCeC respectively; they are both intransitive verbs that denote ‘get wet’ and they share the stem consonants r-t-v. Morphological variation results from a change that takes place in the verbal system, where a verb takes another form. I analyze the factors that bring about the development of a new morphological form alongside the existing form, and are responsible for the choice of a specific binyan during that process. The main claim is that the addition of another binyan results from both morpho-phonological and thematic-syntactic factors. With respect to the former, the morphological mechanism changes the binyan of verbs in cases where their inflectional paradigm consists of prosodic or segmental alternation. With respect to the latter, verbs that are stored in the lexicon as thematically derived entries have a greater chance of undergoing binyan change than do basic entries. Verbs that are the output of syntactic operations do not undergo morphological change. In addition, verbs which are morphologically neutral with respect to transitivity change into a binyan that is marked as transitive or intransitive.     

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     

Tumor-Associated Antigen Peptides as Anti-Metastatic Vaccines

Cytotoxic T-lymphocytes (CTLs) kill abnormal cells. CTLs recognize major histocompatibility complex class I molecules in complex with peptides derived from relevant antigens. The identification of tumor associated antigen peptides enabled the design of anti-tumor and anti-metastatic vaccines in a murine lung carcinoma.     

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.