On the reported occurrence of a fusicoccin conjugate in maize cobs

The occurrence in immature maize cobs of a fusicoccin derivative, reported in 1980 by Russian workers, could not be confirmed. Extraction and fractionation procedures were identical to those used by the Soviet authors and the analysis of the fractions mainly relied on a very sensitive and specific radioimmunoassay. Possible reasons for these contradictory results are discussed.     

Furin-mediated cleavage of the feline foamy virus Env leader protein

The molecular biology of spuma or foamy retroviruses is different from that of the other members of the Retroviridae. Among the distinguishing features, the N-terminal domain of the foamy virus Env glycoprotein, the 16-kDa Env leader protein Elp, is a component of released, infectious virions and is required for particle budding. The transmembrane protein Elp specifically interacts with N-terminal Gag sequences during morphogenesis. In this study, we investigate the mechanism of Elp release from the Env precursor protein. By a combination of genetic, biochemical, and biophysical methods, we show that the feline foamy virus (FFV) Elp is released by a cellular furin-like protease, most likely furin itself, generating an Elp protein consisting of 127 amino acid residues. The cleavage site fully conforms to the rules for an optimal furin site. Proteolytic processing at the furin cleavage site is required for full infectivity of FFV. However, utilization of other furin proteases and/or cleavage at a suboptimal signal peptidase cleavage site can partially rescue virus viability. In addition, we show that FFV Elp carries an N-linked oligosaccharide that is not conserved among the known foamy viruses.     

Spectrum of chromosomal aberrations in peripheral lymphocytes of hospital workers occupationally exposed to low doses of ionizing radiation

Chromosome aberrations frequency was estimated in peripheral lymphocytes from hospital workers occupationally exposed to low levels of ionizing radiation and controls. Chromosome aberrations yield was analyzed by considering the effects of dose equivalent of ionizing radiation over time, and of confounding factors, such as age, gender and smoking status. Frequencies of aberrant cells and chromosome breaks were higher in exposed workers than in controls (P = 0.007, and P = 0.001, respectively). Seven dicentric aberrations were detected in the exposed group and only three in controls, but the mean frequencies were not significantly different. The dose equivalent to whole body of ionizing radiation (Hwb) did appear to influence the spectrum of chromosomal aberrations when the exposed workers were subdivided by a cut off at 50 mSv. The frequencies of chromosome breaks in both subgroups of workers were significantly higher than in controls (< or =50 mSv, P = 0.041; >50 mSv, P = 0.018). On the other hand, the frequency of chromatid breaks observed in workers with Hwb >50 mSv was significantly higher than in controls (P = 0.015) or workers with Hwb < or =50 mSv (P = 0.046). Regarding the influence of confounding factors on genetic damage, smoking status and female gender seem to influence the increase in chromosome aberration frequencies in the study population. Overall, these results suggested that chromosome breaks might provide a good marker for assessing genetic damage in populations exposed to low levels of ionizing radiation.     

Control of 4E-BP1 expression in mouse brown adipose tissue by the beta3-adrenoceptor

Knockout of the translation inhibitor 4E-BP1 induces an overexpression of uncoupling protein-1 (UCP1) [Nature Medicine 7 (2001) 1128]. A possible inverse control of UCP1 and 4E-BP1 expressions in mouse brown adipose tissue was investigated. Cold-exposure, which increases the expression of UCP1, decreased that of 4E-BP1 mRNA in wild type but not in beta1/beta2/beta3-adrenoceptor knockout mice. Administration of the beta3-adrenoceptor agonist CL 316246 decreased 4E-BP1 mRNA by 75% and protein by 41% after 6 and 48 h, respectively. Our data are the first report of a regulation by the beta3-adrenoceptor of 4E-BP1 expression. They support a role of the latter in adaptive thermogenesis.     

Amplification of Mdmx (or Mdm4) directly contributes to tumor formation by inhibiting p53 tumor suppressor activity

Human tumors are believed to harbor a disabled p53 tumor suppressor pathway, either through direct mutation of the p53 gene or through aberrant expression of proteins acting in the p53 pathway, such as p14(ARF) or Mdm2. A role for Mdmx (or Mdm4) as a key negative regulator of p53 function in vivo has been established. However, a direct contribution of Mdmx to tumor formation remains to be demonstrated. Here we show that retrovirus-mediated Mdmx overexpression allows primary mouse embryonic fibroblast immortalization and leads to neoplastic transformation in combination with HRas(V12). Furthermore, the human Mdmx ortholog, Hdmx, was found to be overexpressed in a significant percentage of various human tumors and amplified in 5% of primary breast tumors, all of which retained wild-type p53. Hdmx was also amplified and highly expressed in MCF-7, a breast cancer cell line harboring wild-type p53, and interfering RNA-mediated reduction of Hdmx markedly inhibited the growth potential of these cells in a p53-dependent manner. Together, these results make Hdmx a new putative drug target for cancer therapy.     

EMILIN-1 deficiency induces elastogenesis and vascular cell defects

EMILINs constitute a family of genes of the extracellular matrix with high structural similarity. Four genes have been identified so far in human and mouse. To gain insight into the function of this gene family, EMILIN-1 has been inactivated in the mouse by gene targeting. The homozygous animals were fertile and did not show obvious abnormalities. However, histological and ultrastructural examination revealed alterations of elastic fibers in aorta and skin. Formation of elastic fibers by mutant embryonic fibroblasts in culture was also abnormal. Additional alterations were observed in cell morphology and anchorage of endothelial and smooth muscle cells to elastic lamellae. Considering that EMILIN-1 is adhesive for cells and that the protein binds to elastin and fibulin-5, EMILIN-1 may regulate elastogenesis and vascular cell maintenance by stabilizing molecular interactions between elastic fiber components and by endowing elastic fibers with specific cell adhesion properties.     

A fast and accurate procedure to collect and analyze unfolding fluorescence signal: the case of dystroglycan domains

Monitoring the fluorescence signal upon unfolding often represents a very effective method to rapidly retrieve the first preliminary structural information on a protein domain. The relationship between intrinsic fluorescence signals and unfolding of proteins are discussed, including several practical considerations for properly setting fluorescence experiments and the phenomenological equations required to analyze the spectra. In particular, a fast and accurate method which allows to minimize the deleterious effect of photobleaching is provided. A number of unfolding reactions relative to immunoglobulins (IgG and IgM) and to the different domains of the adhesion molecule dystroglycan are presented. Special attention is dedicated to a alpha-dystroglycan immunoglobulin-like domain showing a "reverse" behavior of the fluorescence signal as a function of the denaturing agent concentration.     

Pharmacogenomics in colorectal carcinomas: future perspectives in personalized therapy

The recent introduction of new drugs such as capecitabine, irinotecan, and oxaliplatinum has greatly improved the clinical outcome of patients with advanced/metastatic colorectal cancer. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients; the different responses to a particular drug are due, in fact, not only to the specific clinico-pathological features of the patient or to environmental factors, but also to the ethnic origins and the particular individual's genetic profile. Genes which codify for the metabolism enzymes, receptor proteins, or protein targets of chemotherapy agents often present various genetic polymorphisms. The main aim of this review is to provide an overview of the known polymorphisms present in the genes which codify for factors (thymidylate synthase dihydropyrimidine dehydrogenase, uridine diphosphate (UDP)-glucuronosyl-transferase 1A1, enzymes implicated in DNA repair) involved in the action mechanisms of the drugs now utilized in chemotherapeutic treatment of colorectal carcinoma, such as fluoropyrimidines, irinotecan, and platinum agents.     

Synthesis and photochemotherapeutic activity of thiopyrano[2,3-e]indol-2-ones

A series of derivatives of the new ring system thiopyrano[2,3-e]indol-2-one was prepared with the aim of obtaining new photochemotherapeutic drugs. Biological screenings were performed on this new class of photoactivable drugs and a strong antiproliferative effect was observed upon irradiation with UVA light. The compound bearing a methyl substituent at the pyrrole nitrogen resulted as the most interesting showing IC50 in the nanomolar range.     

Individual recognition in ant queens

Personal relationships are the cornerstone of vertebrate societies, but insect societies are either too large for individual recognition, or their members were assumed to lack the necessary cognitive abilities . This paradigm has been challenged by the recent discovery that paper wasps recognize each other's unique facial color patterns . Individual recognition is advantageous when dominance hierarchies control the partitioning of work and reproduction . Here, we show that unrelated founding queens of the ant Pachycondyla villosa use chemical cues to recognize each other individually. Aggression was significantly lower in pairs of queens that had previously interacted than in pairs with similar social history but no experience with one another. Moreover, subordinates discriminated familiar and unfamiliar dominants in choice experiments in which physical contact, but not odor perception, was prevented and in tests with anaesthetized queens. The cuticular chemical profiles of queens were neither associated with dominance nor fertility and, therefore, do not represent status badges , and nestmate queens did not share a common odor. Personal recognition facilitates the maintenance of stable dominance hierarchies in these small societies. This suggests that the ability to discriminate between individual traits is selected for when it incurs net benefits for the resolution of conflict.