The Human IGF1R IRES likely operates through a Shine–Dalgarno‐like interaction with the G961 loop (E‐site) of the 18S rRNA and is kinetically modulated by a naturally polymorphic polyU loop

IGF1R is a proto‐oncogene with potent mitogenic and antiapoptotic activities, and its expression must be tightly regulated to maintain normal cellular and tissue homeostasis. We previously demonstrated that translation of the human IGF1R mRNA is controlled by an internal ribosome entry site (IRES), and delimited the core functional IRES to a 90‐nucleotide segment of the 5′‐untranslated region positioned immediately upstream of the initiation codon. Here we have analyzed the sequence elements that contribute to the function of the core IRES. The Stem2/Loop2 sequence of the IRES exhibits near‐perfect Watson–Crick complementarity to the G961 loop (helix 23b) of the 18S rRNA, which is positioned within the E‐site on the platform of the 40S ribosomal subunit. Mutations that disrupt this complementarity have a negative impact on regulatory protein binding and dramatically decrease IRES activity, suggesting that the IGF1R IRES may recruit the 40S ribosome by a eukaryotic equivalent of the Shine–Dalgarno (mRNA–rRNA base‐pairing) interaction. The homopolymeric Loop3 sequence of the IRES modulates accessibility and limits the rate of translation initiation mediated through the IRES. Two functionally distinct allelic forms of the Loop3 poly(U)‐tract are prevalent in the human population, and it is conceivable that germ‐line or somatic variations in this sequence could predispose individuals to development of malignancy, or provide a selectable growth advantage for tumor cells. J. Cell. Biochem. 110: 531–544, 2010. © 2010 Wiley‐Liss, Inc.     

Effect of the activation of macrophages on the course of regeneration of rat liver following partial hepatectomy

Stimulation of the Kupffer cells with E. coli endotoxin (the purified lipopolysaccharide) or with prodigiosan (a polysaccharide from Serratia marcescens) 24 h before partial hepatectomy (resection of 65-70% of the liver) stimulated and intensified the onset of liver regenerative activity (evaluated from changes in liver DNA synthesis, the H5 labelling index and the mitotic activity of the hepatocytes). Liver DNA synthesis increased together with the dose of endotoxin (i.v., from 25 to 1000 micrograms/kg body weight). If E. coli endotoxin was injected during or 3 h after partial hepatectomy, partial inhibition of liver DNA synthesis was observed. In mice stimulated with zymosan (a polysaccharide isolated from yeast), administered 5 days before performing partial hepatectomy, proliferation of the hepatocytes (evaluated from changes in the 3H labelling index and in the mitotic activity of the hepatocytes) was evaluated. The results confirm that proliferation is correlated to the state of reactivity of the Kupffer cells.     

The osmotic magnetometer: a new model for magnetite-based magnetoreceptors in animals

Homing pigeons and migratory birds are well known examples for animals that use the geomagnetic field for their orientation. Yet, neither the underlying receptor mechanism nor the magnetoreceptor itself is known. Recently, an innervated structure containing clusters of magnetite nanocrystals was identified in the upper beak skin of the homing pigeon. Here we show theoretically that such a cluster has a magnetic-field-dependent shape, even in fields as weak as the Earth's magnetic field; by converting magnetic stimuli into mechanical strain, the clusters can be assumed as primary units of magnetoperception in homing pigeons. Since the orientation of the strain ellipsoid indicates the direction of the external magnetic field, a cluster of magnetite nanocrystals also has the potential to serve as the basis of the so-called inclination compass of migratory birds. It is quantitatively demonstrated that the magnetic-field-induced shape change of a cluster can be amplified as well as counterbalanced by means of osmotic pressure regulation, which offers an elegant possibility to determine the magnetic field strength just by measuring changes in concentration. Received: 18 May 1998 / Revised version: 11 February 1999 / Accepted: 11 February 1999     

Biosynthesis of indole-3-acetic acid in Azospirillum brasilense. Insights from quantum chemistry.

Quantum chemical methods AM1 and PM3 and chromatographic methods were used to qualitatively characterize pathways of bacterial production of indole-3-acetic acid (IAA). The standard free energy changes (delta G(o)'sum) for the synthesis of tryptophan (Trp) from chorismic acid via anthranilic acid and indole were calculated, as were those for several possible pathways for the synthesis of IAA from Trp, namely via indole-3-acetamide (IAM), indole-3-pyruvic acid (IPyA), and indole-3-acetonitrile (IAN). The delta G(o)'sum for Trp synthesis from chorismic acid was -402 (-434) kJ.mol-1 (values in parentheses were calculated by PM3). The delta G(o)'sum for IAA synthesis from Trp were -565 (-548) kJ.mol-1 for the IAN pathway, -481 (-506) kJ.mol-1 for the IAM pathway, and -289 (-306) kJ.mol-1 for the IPyA pathway. By HPLC analysis, the possibility was assessed that indole, anthranilic acid, and Trp might be utilized as precursors for IAA synthesis by Azospirillum brasilense strain Sp 245. The results indicate that there is a high motive force for Trp synthesis from chorismic acid and for IAA synthesis from Trp, and make it unlikely that anthranilic acid and indole act as the precursors to IAA in a Trp-independent pathway.     

Oligonucleotide-binding proteins of Drosophila: tissue specificity]

A reaction of native Drosophila proteins with an alkylating oligonucleotide derivative bearing 4-[(N-2-chlorethyl-N-methyl)amino]benzylamine at the 5' terminal phosphate has been investigated. It was found, that the reagent alkylates a few proteins (90, 50, 44, 39, 32 kDa). The modification was organ specific. The labeled 39 kDa protein is present in the ovaries only, while the modified 32 kDa protein is found only in the bulbus.     

Spatial perception of stimuli during unilateral exclusion of the temporal portion of the neocortex by cold]

Behavioral reaction of twelve cats were studied in conditions of inactivation by cold of the temporal area (AI, AII, Ep and partly I-T) of one hemisphere. A typical vestibular ataxy was observed: deflection of the cats when walking, circular movements in the direction of the inactivated temporal area. Orienting reactions both to acoustic and photic stimuli persisted, but their spatial localization was completely lost. In every case the animals exhibited a clear orienting reaction towards the inactivated hemisphere, regardless of the localization of the source of signal. Reactions ot pain and olfactory stimulations likewise proceded in one direction. such a one-sided perception of sounds in the case of inactivation by cold of the temporal neocortex of one hemispheres is apparently due to the functional elimination of contralateral auditory structures. Disturbance of adequate spatial perception of photic, pain and olfactory stimuli under similar conditions results from a sharp drop in the tone predominantly of the ipsilateral hemisphere.