Elevation increases in moth assemblages over 42 years on a tropical mountain

Physiological research suggests that tropical insects are particularly sensitive to temperature, but information on their responses to climate change has been lacking—even though the majority of all terrestrial species are insects and their diversity is concentrated in the tropics. Here, we provide evidence that tropical insect species have already undertaken altitude increases, confirming the global reach of climate change impacts on biodiversity. In 2007, we repeated a historical altitudinal transect, originally carried out in 1965 on Mount Kinabalu in Borneo, sampling 6 moth assemblages between 1,885 and 3,675 m elevation. We estimate that the average altitudes of individuals of 102 montane moth species, in the family Geometridae, increased by a mean of 67 m over the 42 years. Our findings indicate that tropical species are likely to be as sensitive as temperate species to climate warming, and we urge ecologists to seek other historic tropical samples to carry out similar repeat surveys. These observed changes, in combination with the high diversity and thermal sensitivity of insects, suggest that large numbers of tropical insect species could be affected by climate warming. As the highest mountain in one of the most biodiverse regions of the world, Mount Kinabalu is a globally important refuge for terrestrial species that become restricted to high altitudes by climate warming.     

From the Cover: Algorithmic design of self-assembling structures

We study inverse statistical mechanics: how can one design a potential function so as to produce a specified ground state? In this article, we show that unexpectedly simple potential functions suffice for certain symmetrical configurations, and we apply techniques from coding and information theory to provide mathematical proof that the ground state has been achieved. These potential functions are required to be decreasing and convex, which rules out the use of potential wells. Furthermore, we give an algorithm for constructing a potential function with a desired ground state.     

Beverage intake improvement by high school students in Saskatchewan,Canada

Certain beverages contribute energy, protein, vitamins, and minerals. North American adolescents have shifted their beverage intake from predominantly milk to predominantly sugary beverages. Intake of these sugary beverages, in sufficient quantity, may increase the risk of bone fractures, may contribute to obesity, and may lead to tooth decay. This study evaluated the effectiveness of a school-nutrition education program (Fluids Used Effectively for Living) on nutrition knowledge, attitude, and self-reported behavior of grade 9 students in Saskatchewan, Canada. Two classes of grade 9 students, 1 (n = 33) in a high school in Saskatoon (n = 33) and 1 (n = 24) in a large high school in Prince Albert, Saskatchewan, received the peer educator intervention. Two other classes in the 2 cities (n = 24 and n = 24, respectively) were controls. Six sessions of Fluids Used Effectively for Living nutrition education were delivered by using 2 peer educator models (multiple and single), and the intervention was delivered in a 45-minute weekly class session over a 6-week period. After the intervention, students in these 2 peer educator classes decreased their sugary beverage intake significantly, which was sustained for 3 months. Students in the control self-taught class increased their juice intake at the end of the year. The significant decrease of juice and sugary beverage intakes in the single model peer educator class disappeared after Bonferroni correction. Carbonated sugary beverage intake of students in the control self-taught classes declined, but it was not sustainable at the 3-month follow-up. A peer educator school-based nutrition education approach can lead to a decrease in sugary beverage intake in high school children.     

Alteration of cellular and humoral immunity by mutant p53 protein and processed mutant peptide in head and neck cancer.

PURPOSE: To determine if serologic recognition of p53 mutations at the protein level depends upon the ability of mutant p53 to express new peptide epitopes that bind to human leukocyte antigen (HLA) class II molecules, we used anti-p53 antibody production as a marker for HLA class II-restricted T-cell involvement in head and neck cancer. EXPERIMENTAL DESIGN: An anti-p53 antibody response was correlated with specific p53 mutations and the patients' HLA class II alleles and haplotypes. HLA binding studies and in vitro stimulation (IVS) of peripheral blood mononuclear cells were done using a mutant versus wild-type HLA-DQ7-binding p53 peptide. RESULTS: Certain HLA-DQ and HLA-DR alleles were frequently present in p53 seropositive patients who produced serum anti-p53 antibodies. Selected mutated p53 peptides fit published allele-specific HLA class II binding motifs for the HLA-DQ7 or HLA-DR1 molecules. Moreover, a mutant p53 peptide bound with a 10-fold greater affinity than the wild-type p53 peptide to HLA-DQ7 molecules. IVS of CD4(+) T cells from seven healthy HLA-DQ7(+) donors using this mutant p53 peptide (p53(220C)) was associated with a partial T helper type 2 phenotype compared with IVS using the wild-type p53(210-223) peptide. CONCLUSIONS: Our results support the hypothesis that mutated p53 neoantigens can bind to specific HLA class II molecules, leading to a break in tolerance. This may lead to skewing of the CD4(+) T lymphocyte response toward a tumor-permissive T helper type 2 profile in head and neck cancer patients, as manifested by seropositivity for p53.     

The CYP1A2 genotype modifies the association between coffee consumption and breast cancer risk among BRCA1 mutation carriers.

We have recently reported that, among BRCA1 mutation carriers, the consumption of caffeinated coffee was associated with a significant reduction in breast cancer risk. Because the metabolism of caffeine is primarily by CYP1A2, we examined whether or not the CYP1A2 genotype modifies the association between a history of coffee consumption and the risk of breast cancer. A common A to C polymorphism in the CYP1A2 gene is associated with decreased enzyme inducibility and impaired caffeine metabolism. Information regarding coffee consumption habits and the CYP1A2 genotype was available for 411 BRCA1 mutation carriers (170 cases and 241 controls). We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) for breast cancer associated with the CYP1A2 genotype and a history of coffee consumption before age 35, adjusting for potential confounders. The CYP1A2 genotype did not affect breast cancer risk. Among women with at least one variant C allele (AC or CC), those who consumed coffee had a 64% reduction in breast cancer risk, compared with women who never consumed coffee (OR, 0.36; 95% CI, 0.18-0.73). A significant protective effect of coffee consumption was not observed among women with the CYP1A2 AA genotype (OR, 0.93; 95% CI, 0.49-1.77). Similar results were obtained when the analysis was restricted to caffeinated coffee. This study suggests that caffeine protects against breast cancer in women with a BRCA1 mutation and illustrates the importance of integrating individual genetic variability when assessing diet-disease associations.     

Effects of the administration of high-dose interleukin-2 on immunoregulatory cell subsets in patients with advanced melanoma and renal cell cancer.

PURPOSE: High-dose recombinant human interleukin-2 (IL-2) therapy is of clinical benefit in a subset of patients with advanced melanoma and renal cell cancer. Although IL-2 is well known as a T-cell growth factor, its potential in vivo effects on human immunoregulatory cell subsets are largely unexplored. EXPERIMENTAL DESIGN: Here, we studied the effects of high-dose IL-2 therapy on circulating dendritic cell subsets (DC), CD1d-reactive invariant natural killer T cells (iNKT), and CD4(+)CD25(+) regulatory-type T cells. RESULTS: The frequency of both circulating myeloid DC1 and plasmacytoid DC decreased during high-dose IL-2 treatment. Of these, only a significant fraction of myeloid DC expressed CD1d. Although the proportion of Th1-type CD4(-) iNKT increased, similarly to DC subsets, the total frequency of iNKT decreased during high-dose IL-2 treatment. In contrast, the frequency of CD4(+)CD25(+) T cells, including CD4(+)Foxp3(+) T cells, which have been reported to suppress antitumor immune responses, increased during high-dose IL-2 therapy. However, there was little, if any, change of expression of GITR, CD30, or CTLA-4 on CD4(+)CD25(+) T cells in response to IL-2. Functionally, patient CD25(+) T cells at their peak level (immediately after the first cycle of high-dose IL-2) were less suppressive than healthy donor CD25(+) T cells and mostly failed to Th2 polarize iNKT. CONCLUSIONS: Our data show that there are reciprocal quantitative and qualitative alterations of immunoregulatory cell subsets with opposing functions during treatment with high-dose IL-2, some of which may compromise the establishment of effective antitumor immune responses.     

A prospective analysis of long-term quality of life after permanent I-125 brachytherapy for localised prostate cancer.

BACKGROUND AND PURPOSE: To prospectively evaluate long-term urinary, bowel and sexual function after I-125 brachytherapy for localised prostate cancer using patient administered validated Quality of Life (QoL) instruments. MATERIALS AND METHODS: Between March 1995 and March 2004, 673 men underwent brachytherapy and recorded urinary symptoms prospectively using the International Prostate Symptom Score (IPSS). In addition, in a subgroup of 116 patients, the Expanded Prostate Cancer Index Composite (EPIC) was used to record QoL information on urinary, bowel and sexual function before treatment and at regular time intervals for at least two years. RESULTS: Initially, there was a sharp rise in urinary symptoms which was most marked within the first three months. Scores then resolved slowly and returned to within one or two units of pre-treatment level at one year. Subsequently, there was no significant deterioration in urinary symptoms up to nine years following brachytherapy. Few had significant bowel symptoms. Sexual function deteriorated initially and then improved but failed to return to pre-treatment levels by two years. Patients requiring neo-adjuvant hormones experienced significantly more dysfunction. CONCLUSIONS: After an initial period of mild to moderate urinary symptoms prostate brachytherapy is well tolerated with relatively little deterioration in long-term quality of life. Long-term reduction in sexual function may be seen particularly in those requiring hormones.     

Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis.

Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24h exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.