PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females

Background and aim

PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population.

Methodology

A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case–control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons.

Results

No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of T_rs2294008-G_rs2978974 haplotype with higher risk of GBC in females (FDR Pcorr = 0.021, OR = 1.6). In contrary, T_rs2294008-A _rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr = 0.013; OR = 0.25).

Conclusions

These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner.     

Contributions of water transfer energy to protein‐ligand association and dissociation barriers: Watermap analysis of a series of p38α MAP kinase inhibitors

In our previous work, we proposed that desolvation and resolvation of the binding sites of proteins can serve as the slowest steps during ligand association and dissociation, respectively, and tested this hypothesis on two protein‐ligand systems with known binding kinetics behavior. In the present work, we test this hypothesis on another kinetically‐determined protein‐ligand system—that of p38α and eight Type II BIRB 796 inhibitor analogs. The k_on values among the inhibitor analogs are narrowly distributed (10⁴ ≤ k_on ≤ 10⁵ M^?1 s^?1), suggesting a common rate‐determining step, whereas the k_off values are widely distributed (10^?1 ≤ k_off ≤ 10^?6 s^?1), suggesting a spectrum of rate‐determining steps. We calculated the solvation properties of the DFG‐out protein conformation using an explicit solvent molecular dynamics simulation and thermodynamic analysis method implemented in WaterMap to predict the enthalpic and entropic costs of water transfer to and from bulk solvent incurred upon association and dissociation of each inhibitor. The results suggest that the rate‐determining step for association consists of the transfer of a common set of enthalpically favorable solvating water molecules from the binding site to bulk solvent. The rate‐determining step for inhibitor dissociation consists of the transfer of water from bulk solvent to specific binding site positions that are unfavorably solvated in the apo protein, and evacuated during ligand association. Different sets of unfavorable solvation are evacuated by each ligand, and the observed dissociation barriers are qualitatively consistent with the calculated solvation free energies of those sets.     

Comparison of Complex DNA Mixtures with Generic Oligonucleotide Microchips

Abstract

The reproducibility of melting curves for repeated hybridizations of target DNA with generic oligonucleotide microchips is shown experimentally to depend on the character of matching between fragments of target DNA and immobilized oligonucleotides. The reproducibility of melting curves is higher for the perfect match duplexes and decreases as the number of mismatched pairs within duplexes increases. This effect was applied to the comparative analysis of complex DNA mixtures. We developed a scheme in which we can identify and discriminate between the probe oligonucleotides responsible for the distinctions between target DNA mixtures. A scheme is illustrated by comparing DNA mixtures corresponding to VD-J genes connected with populations of mRNAs CDR3 TCR Vb (T-cell receptor beta complementarity determining region 3) from the thymus and pancreas of NOD mice. Our results demonstrate that generic microchips can be applied efficiently to the analysis of DNA mixtures.     

OBSERVATIONS ON THE BREEDING OF THE WOOLLYNECKED STORK

Scott, J. A. 1975. Observations on the breeding of the Woollynecked Stork. Ostrich 46: 201–207.

Little is known about the breeding of the Woollynecked Stork Ciconia episcopus in Africa. This paper discusses breeding, adult and nestling behaviour, nests and sites. Seasonal movements are discussed briefly. Eight nests were studied during 1970 to 1974. At one nest incubation was established at 30 to 31 days and the fledging period 55 to 65 days. No feeding of the young was observed at any time, though one eight hour observation period was undertaken. Few mating displays were seen and none away from the nest.     

Seasonal Changes in Microhabitat Use and Niche Overlap between Akodon azarae and Calomys laucha (Rodentia,Muridae) in Agroecosystems of Central Argentina

We examined seasonal changes in microhabitat use by the murid rodents Akodon azarae and Calomys laucha in agroecosystems of the former pampa region of Argentina. In summer, trap data showed that both species had low densities and were almost equally distributed between the mature cropfields and their surrounding weedy borders. Analysis of vegetation at the trap sites revealed no selection for microhabitats at the borders, whereas in the cropfields both species shared preferences for covered microhabitats. In contrast, winter data revealed a sharp habitat segregation, being Calomys numerically dominant in post-harvest cropfields and Akodon more abundant in borders. Moreover, there were clear differences in microhabitat selection at the borders, A. azarae occupying the more covered microhabitats and C. laucha the less covered. Breadth and overlap of niches were calculated using principal component analysis, in order to recognize interspecific competition and its influence on community niche space. Available evidence indicates that the structure of this rodent community is strongly influenced by seasonal changes in habitat stucture and rodent abundance. The socially dominant A. azarae retains the best part of the available niche space, a fact becoming more evident under the harsh winter conditions.     

Defense against Pieris rapae in cabbage plants induced by Bemisia tabaci biotype B

Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) and Pieris rapae L. (Lepidoptera: Pieridae) are serious pests of vegetables, that can occur simultaneously on a single cabbage plant [Brassica oleracea var. capitata L. (Brassicaceae)]. We determined whether pre‐feeding or infestation by B. tabaci on cabbage could induce physiological and biochemical responses of the plant against P. rapae. Developmental time, length, and weight of immature P. rapae, and defense‐related plant compounds (SOD, superoxide dismutase; POD, peroxidase; CAT, catalase; APX, ascorbate peroxidase) were measured. Development of P. rapae larvae was 21% slower on B. tabaci‐pre‐infested plants than on plants without B. tabaci infestation. When feeding on B. tabaci‐pre‐infested plants, 22% of P. rapae larvae pupated as compared with 83% on B. tabaci‐free plants. Weights of P. rapae from first to fourth instars that fed on B. tabaci‐pre‐infested plants were also reduced, whereas those of fifth instars and pupae were not. Similarly, body length of P. rapae from first to fourth instars was affected by B. tabaci pre‐infestation, whereas that of the fifth instars was not. Peroxidase and APX activities of the B. tabaci‐pre‐infested plants increased more than SOD and CAT. Peroxidase and SOD activities of B. tabaci and P. rapae co‐infested plants increased as compared with those of P. rapae‐infested plants; however, CAT and APX activities were not different between B. tabaci‐ and P. rapae‐infested plants. These results showed that B. tabaci infestation had a negative effect on P. rapae when they occurred simultaneously on the same host plant. The implications of the induced plant changes on the herbivore are discussed.     

Natural genetic variation in male reproductive genes contributes to nontransitivity of sperm competitive ability in Drosophila melanogaster

Female Drosophila melanogaster frequently mate with multiple males, and the success of a given male depends not only on his genotype but also on the genotype of his competitor. Here, we assess how natural genetic variation affects male–male interactions for traits influencing pre‐ and postcopulatory sexual selection. Males from a set of 66 chromosome substitution lines were competed against each other in a ‘round‐robin’ design, and paternity was scored using bulk genotyping. We observed significant effects of the genotype of the first male to mate, the second male to mate and an interaction between the males for measures of male mating rate and sperm utilization. We also identified specific combinations of males who show nontransitive patterns of reproductive success and engage in ‘rock‐paper‐scissors’ games. We then tested for associations between 245 polymorphisms in 32 candidate male reproductive genes and male reproductive success. We identified eight polymorphisms in six reproductive genes that associate with male reproductive success independent of the competitor (experimentwise P < 0.05). We also identified four SNPs in four different genes where the relative reproductive success of the alternative alleles changes depending on the competing males' genetic background (experimentwise P < 0.05); two of these associations include premature stop codons. This may be the first study that identifies the genes contributing to nontransitivity among males and further highlights that ‘rock‐paper‐scissors’ games could be an important evolutionary force maintaining genetic variation in natural populations.     

Population genomic footprints of selection and associations with climate in natural populations of Arabidopsis halleri from the Alps

Natural genetic variation is essential for the adaptation of organisms to their local environment and to changing environmental conditions. Here, we examine genomewide patterns of nucleotide variation in natural populations of the outcrossing herb Arabidopsis halleri and associations with climatic variation among populations in the Alps. Using a pooled population sequencing (Pool‐Seq) approach, we discovered more than two million SNPs in five natural populations and identified highly differentiated genomic regions and SNPs using F_ST‐based analyses. We tested only the most strongly differentiated SNPs for associations with a nonredundant set of environmental factors using partial Mantel tests to identify topo‐climatic factors that may underlie the observed footprints of selection. Possible functions of genes showing signatures of selection were identified by Gene Ontology analysis. We found 175 genes to be highly associated with one or more of the five tested topo‐climatic factors. Of these, 23.4% had unknown functions. Genetic variation in four candidate genes was strongly associated with site water balance and solar radiation, and functional annotations were congruent with these environmental factors. Our results provide a genomewide perspective on the distribution of adaptive genetic variation in natural plant populations from a highly diverse and heterogeneous alpine environment.     

Learning and signal copying facilitate communication among bird species

Signals relevant to different sets of receivers in different contexts create a conflict for signal design. A classic example is vocal alarm signals, often used both during intraspecific and interspecific interactions. How can signals alert individuals from a variety of other species in some contexts, while also maintaining efficient communication among conspecifics? We studied heterospecific responses to avian alarm signals that drive the formation of anti-predator groups but are also used during intraspecific interactions. In three species-rich communities in the western Himalayas, alarm signals vary drastically across species. We show that, independently of differences in their calls, birds respond strongly to the alarm signals of other species with which they co-occur and much more weakly to those of species with which they do not co-occur. These results suggest that previous exposure and learning maintain heterospecific responses in the face of widespread signal divergence. At an area where only two species regularly interact, one species'' calls incorporate the call of the other. We demonstrate experimentally that signal copying allows strong responses even without previous exposure and suggest that such hybrid calls may be especially favoured when pairwise interactions between species are strong.