p53 translational control: a new facet of p53 regulation and its implication for tumorigenesis and cancer therapeutics

While posttranslational regulation of p53 levels by its interaction with the ubiquitin ligase MDM2 is widely accepted, it has recently become clear that regulation of p53 translation also contributes to p53 induction following DNA damage. However, the mechanisms underlying the translational control of p53 are still poorly understood. In this review, we will focus on the translational regulation of p53 through the 5'- and 3'-untranslated regions of its mRNA. We will also discuss in detail the recent discovery of the p53 internal ribosome entry site (IRES), its role in p53 translation in response to DNA damage, and how it might lead to a better understanding of the process of oncogenesis and provide new avenues for cancer therapeutics.     

Impact of wet deposited nickel on the cation content of a mat-forming lichen Cladina stellaris

The impact of experimentally sprayed aqueous nickel solution on the concentrations of potassium, calcium, magnesium and nickel in three horizontal strata (top, 0-20 mm; middle, 20-40 mm; and base, 40-60 mm) of the cushion-forming lichen Cladina stellaris was investigated. The experimental nickel deposition range used corresponded with that from the pristine forests of the Finnish border to polluted industrial sites of Russian Kola Peninsula (0-1000 mg Ni(2+) m(-2) year(-1)). The lichen mat retained ca. 31-66% of the nickel deposited during two growing seasons and the relative retention efficiency was highest at the low deposition end. The concentrations of cations in lichen thalli were significantly reduced only after the highest nickel deposition. Furthermore, the separate horizontal strata responded differently to nickel exposure indicating that the cation exchange sites of the top stratum were not completely saturated by nickel even after the most severe treatment. However, nickel deposited in high doses caused considerable reduction in potassium concentration indicating damage to cell membranes. Episodically deposited high concentrations of nickel can probably affect membrane integrity before detectable changes in total concentrations of cations in the lichen thallus take place. Thus, ratios of total concentrations of cations in the lichen thallus are fairly insensitive to nickel deposition, which reduces the risk of compounding effects when the ratios are used to indicate long-term acid deposition in areas with multiple pollution problems such as Kola Peninsula.     

A case of deletion of the short arm of the chromosome 21 (21p-) (christchurch chromosome) discovered prenatally:clinical and cytogenetic data

Results of cytogenetic research of placental villi and amniotic fluid cells culture of the 22-weeks-old fetus with multiple congenital malformations (MCM) are presented. The absence of the short arm in one of the homologue of the chromosome 21 was revealed. Cytogenetic analysis of the fetus father's blood lymphocytes determined the similar chromosome. Further research of the father's karyotype made by FISH-method using specific DNA samples had discovered the absence of subtelomeric parts in the short arm of the chromosome 21 that might be considered as a deletion. It was suggested that the effect of position and interaction of genes could play a key role in appearing of MCM in the fetus in the case when the 21p-chromosome was transferred to it from the healthy parents.     

Structural features in the KshA terminal oxygenase protein that determine substrate preference of 3-ketosteroid 9α-hydroxylase enzymes

Rieske nonheme monooxygenase 3-ketosteroid 9α-hydroxylase (KSH) enzymes play a central role in bacterial steroid catabolism. KSH is a two-component iron-sulfur-containing enzyme, with KshA representing the terminal oxygenase component and KshB the reductase component. We previously reported that the KshA1 and KshA5 homologues of Rhodococcus rhodochrous DSM43269 have clearly different substrate preferences. KshA protein sequence alignments and three-dimensional crystal structure information for KshA(H37Rv) of Mycobacterium tuberculosis H37Rv served to identify a variable region of 58 amino acids organized in a β sheet that is part of the so-called helix-grip fold of the predicted KshA substrate binding pocket. Exchange of the β sheets between KshA1 and KshA5 resulted in active chimeric enzymes with substrate preferences clearly resembling those of the donor enzymes. Exchange of smaller parts of the KshA1 and KshA5 β-sheet regions revealed that a highly variable loop region located at the entrance of the active site strongly contributes to KSH substrate preference. This loop region may be subject to conformational changes, thereby affecting binding of different substrates in the active site. This study provides novel insights into KshA structure-function relationships and shows that KSH monooxygenase enzymes are amenable to protein engineering for the development of biocatalysts with improved substrate specificities.     

Homocysteine thiolactone is a positive effector of sigma(S) levels in Escherichia coli

sigma(S) is a regulator of the stationary phase response in Escherichia coli. Multi-copy suppressors were sought in a strain with decreased levels of sigma(S) and one such suppressor was found to encode HsrA, a putative efflux pump. Multi-copy expression of hsrA was shown to lead to accumulation of homocysteine, which is predicted to cause an increase in homocysteine thiolactone (HCTL) levels. A direct correlation between HCTL levels and sigma(S) accumulation was observed both in mutants and during normal cell growth, leading to the hypothesis that HCTL is a physiologically relevant positive effector of sigma(S) levels in vivo.     

Feeding habits of the squirrel Sciurus variegatoides (Rodentia: Sciuridae) in the Nicoya Peninsula, Costa Rica

Food items consumed by the squirrel Sciurus variegatoides atrirufus were determined in an agricultural setting in the Nicoya Peninsula (9 degrees 47' N, 84 degrees 56' W), Costa Rica, where two life zones (Premontane Moist Forest Basal Belt Transition, and Tropical Dry Forest) predominate. By analyzing the gut contents of 120 squirrels, from February 1987 through January 1988, it was determined that coconut (Cocos nucifera), indian almond (Terminalia catappa) and flamboyant (Delonix regia) were the most common dietary items. There were differences in food consumption according to age: adults preferred coconut, whereas young individuals preferred almond. This finding can be explained in terms of fruit characteristics, as well as tree architecture and accessibility for squirrels; almendro trees provide higher protection and a more accessible food resource, so that it was better used by young individuals.     

Tissue strain amplification at the osteocyte lacuna: a microstructural finite element analysis

A parametric finite element model of an osteocyte lacuna was developed to predict the microstructural response of the lacuna to imposed macroscopic strains. The model is composed of an osteocyte lacuna, a region of perilacunar tissue, canaliculi, and the surrounding bone tissue. A total of 45 different simulations were modeled with varying canalicular diameters, perilacunar tissue material moduli, and perilacunar tissue thicknesses. Maximum strain increased with a decrease in perilacunar tissue modulus and decreased with an increase in perilacunar tissue modulus, regardless of the thickness of the perilacunar region. An increase in the predicted maximum strain was observed with an increase in canalicular diameter from 0.362 to 0.421 microm. In response to the macroscopic application of strain, canalicular diameters increased 0.8% to over 1.0% depending on the perilacunar tissue modulus. Strain magnification factors of over 3 were predicted. However, varying the size of the perilacunar tissue region had no effect on the predicted perilacunar tissue strain. These results indicate that the application of average macroscopic strains similar to strain levels measured in vivo can result in significantly greater perilacunar tissue strains and canaliculi deformations. A decrease in the perilacunar tissue modulus amplifies the perilacunar tissue strain and canaliculi deformation while an increase in the local perilacunar tissue modulus attenuates this effect.     

A new tandem repeat in bovine fibrinogen Aalpha gene

In this study, we describe intraspecies variation in the alphaC connector region of the bovine fibrinogen Aalpha gene. Sequencing and genotyping of six bovine breeds revealed 7 to 10 tandem repeats in the alphaC connector region. In addition, we observed length differences between B. indicus and B. taurus, with the B. indicus having longer fibrinogen alphaC connectors (10-repeat alleles) than B. taurus (7- and 9-repeats). The difference in tandem repeats may be related to the function of blood coagulation system.