BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history

Background

In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia''s ethnic groups has not been well-characterised.

Methodology

Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (≤40 years) and no reported family history. Mutational analysis of BRCA1 and BRCA2 was conducted by full sequencing of all exons and intron-exon junctions.

Conclusions

Here, we report a total of 14 BRCA1 and 17 BRCA2 sequence alterations, of which eight are novel (3 BRCA1 and 5 BRCA2). One deleterious BRCA1 mutation and 2 deleterious BRCA2 mutations, all of which are novel mutations, were identified in 3 of 37 individuals. This represents a prevalence of 2.7% and 5.4% respectively, which is consistent with other studies in other Asian ethnic groups (4–9%).     

Effect of Dexamethasone on Rat Respiratory Pathways

It has been shown that a short-term application (10–15 min) of dexamethasone at a concentration of 1.0 µg/ml decreases the muscular contraction amplitude of the trachea and large bronchi to 76.2 ± 3.5% and increases the dilatational effect of histamine (1.0 µg/ml) to 47.4 ± 8.1% at stimulation of pre- and postganglionic nerve fibers. Atropine eliminates completely the effect of dexamethasone on the respiratory tract preparation at the stimulation of pre- and postganglionic nerve fibers. The ganglioblocker decreases the dilatational effect at a simultaneous application of atropine and dexamethasone from 47.4 ± 8.1 to 67.2 ± 5.3%. It is concluded that the dexamethasone effect is due to its action on tracheobronchial epithelial receptors and that this effect is mediated by intramural ganglionic neurons.     

Effect of Azospirillum inoculation on some growth parameters and n-content of wheat,sorghum and panicum

The potential of the nitrogen fixing bacteriumAzospirillum brasilense to enhance development and increase growth of several gramineae was investigated. In both sterilized and non-sterilized systems heading and flowering occurred earlier in the inoculated plants as compared to the noninoculated ones. Total shoot and root weights, total-N content, plant height and leaf length were significantly increased by inoculation.From the Department of Agricultural Botany.     

Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives

Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects.Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition.In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC₅₀ values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC₅₀:0.42?nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.     

Cost of reproduction and the evolution of deferred breeding in the western gull

Survival patterns in a population of western gulls (Larus occidentalis)of known age of first breeding, a, indicate a cost of reproductionrelated to the age of initial breeding. Among both sexes, birdsthat commenced breeding at the earliest ages (3 years in malesand 4 years in females) had higher annual mortality than thosethat deferred breeding one or more years. In addition, females(but not males) evidenced a cumulative cost of reproduction:holding age constant, females with more annual breeding attemptsdemonstrated poorer survival. These patterns of -specific survivalwere statistically significant after controlling for interannualvariation in food availability and are not explained simplyby variation in the intrinsic quality of individuals. To assessthe effects of these sex-specific costs on fitness, we combinedthe observed survival patterns with data on prebreeding survivorshipand -specific reproductive success to estimate rates of populationgrowth and lifetime reproductive success for different agesat first reproduction. Males showed a clearly defined fitnessoptimum at = 4 years, which coincided with the modal for malesin the population. Females showed no clear optimum, except thatbreeding at age 4 was suboptimal, hence females benefited fromdeferring breeding to ages 5-7 years. Observed age of firstbreeding also showed no clear mode for females, with slightpeaks at ages 5 and 7. As a result, in both sexes, the fitnesssurface for corresponded well with observed frequencies of. We suggest that stabilizing selection has acted to shape thephenotypic distribution of in males but, due to trade-offsbetween survival and early reproduction, stabilizing selectionis weak or absent in females     

Geographical distributions in tropical trees: can geographical range predict performance and habitat association in co‐occurring tree species?

Aim A major floristic and climatic transition from aseasonal to seasonal evergreen tropical forest (the Kangar–Pattani Line; KPL) exists in the Indo‐Sundaic region of Southeast Asia. Mechanisms constraining species distribution here are at present poorly understood, but it is hypothesized that species differ in their tolerances of abiotic factors, in particular water availability. Under this hypothesis, we anticipate differences in performance or habitat preferences, or both, of species differing in distribution with respect to the KPL. The aim of this study is to test whether geographical distributions can be used to explain variation in growth, mortality and habitat preferences in co‐occurring tree species differing in their distribution in relation to the KPL. Location Pasoh Forest Reserve, Negeri Sembilan, Malaysia; south of the KPL. Methods All tree species within a 50‐ha forest dynamics plot were classified as widespread or southern based upon their distributions in relation to the KPL and as habitat specialists or generalists based on spatial association with soil‐based habitat categories. Growth and mortality rates, variation in growth and mortality with respect to soil type, and levels of habitat association were quantified for species with different geographical distributions. Results Differences existed in species performance based upon geographical distributions. Specifically, widespread species had lower growth rates than did species restricted to the aseasonal forests. Mortality rates did not differ as a function of geographical distribution. The growth responses of species to soil habitats also diverged, such that differences in performance of widespread species among soil types were more conservative than those of species restricted in their distribution to the aseasonal forests. However, the proportion of species showing positive habitat associations did not differ significantly between widespread and southern species. Main conclusions Distribution‐based differences in species performance and response to soil type support the hypothesis that species tolerant of wider climatic variation perform less well in any given environment due to limitations on plasticity. These performance differences provide quantitative evidence of the role of climatic transitions in determining tree species distributions in relation to the Kangar–Pattani Line in the Indo‐Malay region. Such differences in performance have important implications for our understanding of biodiversity gradients and responses of Indo‐Sundaic forests to climate change.     

Synapsis and crossing over within a paracentric inversion in the grasshopper,Camnula pellucida

A male grasshopper, Camnula pellucida (Scudder), was found to be heterozygous for a paracentric inversion occupying approximately 10% of the length of one of the two longest chromosomes. Analysis of 297 cells in pachytene revealed inversion loops, suspected inversion loops, asynapsis, and straight pairing in 1.0, 2.7, 8.4, and 87.9% of the analyzable cells, respectively. The frequency of straight pairing (87.9%) indicated a high degree of non-homologous pairing. Analysis of 603 cells in anaphase I and II, and in telophase I and II for the presence of acentric fragments and dicentric chromatid bridges indicated that crossing over within the inversion region occured in about 8% of the cells. The difference between the frequency of the observed plus suspected inversion loops in pachytene and that of the dicentric chromatid bridges and acentric fragments in anaphase I or subsequent stages was not statistically significant. The correspondence between the presence of inversion loops and crossovers within the region of the inversion is thus similar to that observed by Maguire (1966) for a short paracentric inversion in maize. The reasons for this correspondence are considered.Supported by grants GB 1585 and GB 6745 from the National Science Foundation, Washington, D.C.