Reduced dosage of genes encoding ribosomal protein S18 suppresses a mitochondrial initiation codon mutation in Saccharomyces cerevisiae

A yeast mitochondrial translation initiation codon mutation affecting the gene for cytochrome oxidase subunit III (COX3) was partially suppressed by a spontaneous nuclear mutation. The suppressor mutation also caused cold-sensitive fermentative growth on glucose medium. Suppression and cold sensitivity resulted from inactivation of the gene product of RPS18A, one of two unlinked genes that code the essential cytoplasmic small subunit ribosomal protein termed S18 in yeast. The two S18 genes differ only by 21 silent substitutions in their exons; both are interrupted by a single intron after the 15th codon. Yeast S18 is homologous to the human S11 (70% identical) and the Escherichia coli S17 (35% identical) ribosomal proteins. This highly conserved family of ribosomal proteins has been implicated in maintenance of translational accuracy and is essential for assembly of the small ribosomal subunit. Characterization of the original rps18a-1 missense mutant and rps18a delta and rps18b delta null mutants revealed that levels of suppression, cold sensitivity and paromomycin sensitivity all varied directly with a limitation of small ribosomal subunits. The rps18a-1 mutant was most affected, followed by rps18a delta then rps18b delta. Mitochondrial mutations that decreased COX3 expression without altering the initiation codon were not suppressed. This allele specificity implicates mitochondrial translation in the mechanism of suppression. We could not detect an epitope-tagged variant of S18 in mitochondria. Thus, it appears that suppression of the mitochondrial translation initiation defect is caused indirectly by reduced levels of cytoplasmic small ribosomal subunits, leading to changes in either cytoplasmic translational accuracy or the relative levels of cytoplasmic translation products.     

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells.     

Distributed Multirobot Exploration and Mapping

Efficient exploration of unknown environments is a fundamental problem in mobile robotics. We present an approach to distributed multirobot mapping and exploration. Our system enables teams of robots to efficiently explore environments from different, unknown locations. In order to ensure consistency when combining their data into shared maps, the robots actively seek to verify their relative locations. Using shared maps, they coordinate their exploration strategies to maximize the efficiency of exploration. This system was evaluated under extremely realistic real-world conditions. An outside evaluation team found the system to be highly efficient and robust. The maps generated by our approach are consistently more accurate than those generated by manually measuring the locations and extensions of rooms and objects.     

Hindshaker, a novel myelin mutant showing hypomyelination preferentially affecting the spinal cord

Animals with spontaneous mutations affecting myelin formation have provided useful information about the genetic and cellular mechanisms regulating normal and abnormal myelination. In this paper we describe a novel murine mutation termed hindshaker (hsh), which is inherited in an autosomal recessive manner. Affected mice are characterised by a variable tremor of the hind end which commences at about 2 weeks of age and largely disappears in animals older than 6 weeks. There is hypomyelination affecting predominantly the spinal cord, although the optic nerves and brain are involved to a much lesser degree. The defect of thinly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. The myelin structure appears normal and immunostains for the major proteins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are fewer mature cells. The hsh mutation appears to delay the maturation of oligodendrocytes, particularly in the spinal cord. Additionally, there is a considerable variation in phenotypic expression and in penetrance when the mutation is expressed on different genetic backgrounds, suggesting the hsh locus is subject to the influence of modifying gene(s). Identification of the hsh gene should identify a factor important in the development of oligodendrocytes, particularly those in the spinal cord.     

Activities of novel aryloxyalkylimidazolines on rat 5-HT2A and 5-HT2C receptors

One impact of socioeconomic progress on populations has been to reduce the number of cases due to diseases of undernutrition and microbial contamination of food, which affected mostly infants and young children, and to increase those due to diseases of excessive food consumption, which are affecting adults and a growing number of children. This article reviews the main dietary factors which have an influence on cardiovascular disease and cancer, and discusses the link between economic development and increased rates of chronic diseases. There is evidence that the noncommunicable diseases and their risk factors have risen rapidly in countries of the WHO Western Pacific Region. Data from 29 countries and areas in the region indicate that 70% of them show lifestyle diseases in three or more of the top five causes of death. While public health measures have been implemented by some countries to prevent and control nutrition-related chronic diseases, further action is needed.     

Electronic thermography for the assessment of acute temporomandibular joint pain

Electronic thermography (ET) has the potential to be a nonionizing, noninvasive, low-cost diagnostic alternative for evaluating temporomandibular joint (TMJ) disorders. This study was designed to evaluate the use of ET as a diagnostic aid in the assessment of patients with acute TMJ pain. Computer measurements made using facial thermography were able to distinguish normal patient populations from symptomatic patients with acute TMJ pain. Additional studies are needed before thermographic diagnosis of TMJ disorders will be clinically accepted.     

Fat and female fecundity: prospective study of effect of body fat distribution on conception rates

OBJECTIVES: To study the effect of body fat distribution in women of reproductive age on fecundity. DESIGN: Prospective cohort study of all women who had entered a donor insemination programme. SETTING: One fertility clinic serving a large part of the midwest of the Netherlands. SUBJECTS: Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES: Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment. RESULTS: A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity. CONCLUSIONS: Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.