The Effect of Vaccination Coverage and Climate on Japanese Encephalitis in Sarawak,Malaysia

Background

Japanese encephalitis (JE) is the leading cause of viral encephalitis across Asia with approximately 70,000 cases a year and 10,000 to 15,000 deaths. Because JE incidence varies widely over time, partly due to inter-annual climate variability effects on mosquito vector abundance, it becomes more complex to assess the effects of a vaccination programme since more or less climatically favourable years could also contribute to a change in incidence post-vaccination. Therefore, the objective of this study was to quantify vaccination effect on confirmed Japanese encephalitis (JE) cases in Sarawak, Malaysia after controlling for climate variability to better understand temporal dynamics of JE virus transmission and control.

Methodology/principal findings

Monthly data on serologically confirmed JE cases were acquired from Sibu Hospital in Sarawak from 1997 to 2006. JE vaccine coverage (non-vaccine years vs. vaccine years) and meteorological predictor variables, including temperature, rainfall and the Southern Oscillation index (SOI) were tested for their association with JE cases using Poisson time series analysis and controlling for seasonality and long-term trend. Over the 10-years surveillance period, 133 confirmed JE cases were identified. There was an estimated 61% reduction in JE risk after the introduction of vaccination, when no account is taken of the effects of climate. This reduction is only approximately 45% when the effects of inter-annual variability in climate are controlled for in the model. The Poisson model indicated that rainfall (lag 1-month), minimum temperature (lag 6-months) and SOI (lag 6-months) were positively associated with JE cases.

Conclusions/significance

This study provides the first improved estimate of JE reduction through vaccination by taking account of climate inter-annual variability. Our analysis confirms that vaccination has substantially reduced JE risk in Sarawak but this benefit may be overestimated if climate effects are ignored.     

Element content and expression of genes of interest in guard cells are connected to spatiotemporal variations in stomatal conductance

Element content and expression of genes of interest on single cell types, such as stomata, provide valuable insights into their specific physiology, improving our understanding of leaf gas exchange regulation. We investigated how far differences in stomatal conductance (g_s) can be ascribed to changes in guard cells functioning in amphistomateous leaves. g_s was measured during the day on both leaf sides, on well-watered and drought-stressed trees (two Populus euramericana Moench and two Populus nigra L. genotypes). In parallel, guard cells were dissected for element content and gene expressions analyses. Both were strongly arranged according to genotype, and drought had the lowest impact overall. Normalizing the data by genotype highlighted a structure on the basis of leaf sides and time of day both for element content and gene expression. Guard cells magnesium, phosphorus, and chlorine were the most abundant on the abaxial side in the morning, where g_s was at the highest. In contrast, genes encoding H⁺-ATPase and aquaporins were usually more abundant in the afternoon, whereas genes encoding Ca²⁺-vacuolar antiporters, K⁺ channels, and ABA-related genes were in general more abundant on the adaxial side. Our work highlights the unique physiology of each leaf side and their analogous rhythmicity through the day.     

Intragroup Behavioral Changes Following Intergroup Conflict in Mountain Gorillas (Gorilla beringei beringei)

International Journal of Primatology - Group-living animals face a number of threats from extragroup conspecifics: from individuals seeking mating opportunities to rival groups attempting to access...     

Can long range mechanical interaction between drugs and membrane proteins define the notion of molecular promiscuity? Application to P-glycoprotein-mediated multidrug resistance (MDR)

Background

Failure of treatment in over 90% of patients with metastatic cancer is due to acquired MDR. P-glycoprotein (Pgp) remains the archetypal drug membrane transporter expressed in many MDR cancer cells. Albeit the ATPase activity of Pgp is triggered by the presence of drug in the membrane, it is commonly assumed that when two drug molecules meet the same Pgp the protein cannot handle them efficiently due to steric effects and as a result the ATPase activity drops. However it is also possible that drug accumulating in the lipid-phase may affect the membrane in such a way that it imposes the mechanical closure of transporters by opposing the force mediated by ATP consumption. In this context, long range interactions between drug and membrane proteins could exist.

Methods

Recent data concerning Pgp structure have allowed us to formalize this hypothesis and we present a physico-mathematical model that is not based on predictive QSAR or other empirical methods applied to experimental data.

Results

Long range mechanical interactions between Pgp and drugs are predicted to occur at an external concentration of drug ~ 10–100 μM as previously determined experimentally at which concentration ~ 50% of transporters should be rendered inactive.

Conclusion

Distance interaction(s) between Pgp and drugs exist explaining an ill-defined effect concerning the ability of any drug to inhibit Pgp once a threshold concentration in the membrane has been reached.

General significance

Potential application of the theory in the field of pharmacology concentrating on the notion of molecular promiscuity and toxicity in drug discovery prediction is discussed.     

Inhibition of DNA damage repair by artificial activation of PARP with siDNA

One of the major early steps of repair is the recruitment of repair proteins at the damage site, and this is coordinated by a cascade of modifications controlled by phosphatidylinositol 3-kinase-related kinases and/or poly (ADP-ribose) polymerase (PARP). We used short interfering DNA molecules mimicking double-strand breaks (called Dbait) or single-strand breaks (called Pbait) to promote DNA-dependent protein kinase (DNA-PK) and PARP activation. Dbait bound and induced both PARP and DNA-PK activities, whereas Pbait acts only on PARP. Therefore, comparative study of the two molecules allows analysis of the respective roles of the two signaling pathways: both recruit proteins involved in single-strand break repair (PARP, XRCC1 and PCNA) and prevent their recruitment at chromosomal damage. Dbait, but not Pbait, also inhibits recruitment of proteins involved in double-strand break repair (53BP1, NBS1, RAD51 and DNA-PK). By these ways, Pbait and Dbait disorganize DNA repair, thereby sensitizing cells to various treatments. Single-strand breaks repair inhibition depends on direct trapping of the main proteins on both molecules. Double-strand breaks repair inhibition may be indirect, resulting from the phosphorylation of double-strand breaks repair proteins and chromatin targets by activated DNA-PK. The DNA repair inhibition by both molecules is confirmed by their synthetic lethality with BRCA mutations.     

The effects of surgically implanted acoustic transmitters on laboratory growth, survival and tag retention in hatchery yearling Chinook salmon

Telemetry has proven an effective means for studying the movement of fishes, however, biases associated with tagged animals requires careful scrutiny if accurate conclusions are to be made from field studies. The objective of this study was to evaluate growth, survival, and tag retention in hatchery yearling Chinook salmon (Oncorhynchus tshawytscha) juveniles with intracoelomic surgically implanted acoustic transmitters representing 2.6 to 5.6% of body weight. The first trial consisted of three treatments; passive integrated transponder (PIT) tag-only (25 fish), acoustic-tag+PIT-tag (25 fish), and sham-surgery+PIT-tag (25 fish). There were no significant differences in relative growth rate (% change in weight day^?1) among treatments over the 221 day trial. Survival in the acoustic-tag treatment (80%) was not significantly different from the PIT-tag-only and sham treatments (92 and 88% respectively). The second trial consisted of three treatments; PIT-tag-only (22 fish), acoustic-tag+PIT-tag with absorbable sutures (12 fish) and acoustic-tag+PIT-tag with non-absorbable sutures (12 fish). There were no significant differences in relative growth rate among treatments over the 160 day trial. Survival in the second trial was 100%. Fish with absorbable sutures healed sooner and with less inflammation compared to fish with non-absorbable sutures. Tag retention was 100% in both trials. The results of this study suggest that acoustic transmitters of less than 5.6% body weight can be effectively used in 1-year old Chinook salmon.     

Fruiting and flushing phenology in Asian tropical and temperate forests: implications for primate ecology

In order to understand the ecological adaptations of primates to survive in temperate forests, we need to know the general patterns of plant phenology in temperate and tropical forests. Comparative analyses have been employed to investigate general trends in the seasonality and abundance of fruit and young leaves in tropical and temperate forests. Previous studies have shown that (1) fruit fall biomass in temperate forest is lower than in tropical forest, (2) non-fleshy species, in particular acorns, comprise the majority of the fruit biomass in temperate forest, (3) the duration of the fruiting season is shorter in temperate forest, and (4) the fruiting peak occurs in autumn in most temperate forests. Through our comparative analyses of the fruiting and flushing phenology between Asian temperate and tropical forests, we revealed that (1) fruiting is more annually periodic (the pattern in one year is similar to that seen in the next year) in temperate forest in terms of the number of fruiting species or trees, (2) there is no consistent difference in interannual variations in fruiting between temperate and tropical forests, although some oak-dominated temperate forests exhibit extremely large interannual variations in fruiting, (3) the timing of the flushing peak is predictable (in spring and early summer), and (4) the duration of the flushing season is shorter. The flushing season in temperate forests (17–28 % of that in tropical forests) was quite limited, even compared to the fruiting season (68 %). These results imply that temperate primates need to survive a long period of scarcity of young leaves and fruits, but the timing is predictable. Therefore, a dependence on low-quality foods, such as mature leaves, buds, bark, and lichens, would be indispensable for temperate primates. Due to the high predictability of the timing of fruiting and flushing in temperate forests, fat accumulation during the fruit-abundant period and fat metabolization during the subsequent fruit-scarce period can be an effective strategy to survive the lean period (winter).     

The Upper Palaeolithic site of Kalavan 1 (Armenia): An Epigravettian settlement in the Lesser Caucasus

The open-air site of Kalavan 1 is located in the Aregunyats mountain chain (at 1640 m above sea level) on the northern bank of Lake Sevan. It is the first Upper Palaeolithic site excavated in Armenia. Led by an Armenian-French team, several excavations (2005–2009) have revealed a well preserved palaeosoil, dated to around 14,000 BP (years before present), containing fauna, lithic artefacts, as well as several hearths and activity areas that structure the settlement. The initial studies enable placement of the site in its environment and justify palaeoethnological analysis of the Epigravettian human groups of the Lesser Caucasus.