Promoter hypermethylation using 24-gene array in early head and neck cancer: Better outcome in oral than in oropharyngeal cancer

Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis and a potential target for personalized cancer treatment. In head and neck cancer, little is known about the role of promoter hypermethylation in survival. Using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) we investigated the role of promoter hypermethylation of 24 well-described genes (some of which are classic TSGs), which are frequently methylated in different cancer types, in 166 HPV-negative early oral squamous cell carcinomas (OSCC), and 51 HPV-negative early oropharyngeal squamous cell carcinomas (OPSCC) in relation to clinicopathological features and survival. Early OSCC showed frequent promoter hypermethylation in RARB (31% of cases), CHFR (20%), CDH13 (13%), DAPK1 (12%), and APC (10%). More hypermethylation (≥ 2 genes) independently correlated with improved disease specific survival (hazard ratio 0.17, P = 0.014) in early OSCC and could therefore be used as prognostic biomarker. Early OPSCCs showed more hypermethylation of CDH13 (58%), TP73 (14%), and total hypermethylated genes. Hypermethylation of two or more genes has a significantly different effect on survival in OPSCC compared with OSCC, with a trend toward worse instead of better survival. This could have a biological explanation, which deserves further investigation and could possibly lead to more stratified treatment in the future.     

Relative accuracy of spatial predictive models for lynx Lynx canadensis derived using logistic regression-AIC,multiple criteria evaluation and Bayesian approaches

We compared probability surfaces derived using one set of environmental variables in three Geographic Information Systems (GIS) -based approaches: logistic regression and Akaike's Information Criterion (AIC),Multiple Criteria Evaluation (MCE),and Bayesian Analysis (specifically Dempster-Shafer theory). We used lynx Lynx canadensis as our focal species,and developed our environment relationship model using track data collected in Banff National Park,Alberta,Canada,during winters from 1997 to 2000. The accuracy of the three spatial models were compared using a contingency table method. We determined the percentage of cases in which both presence and absence points were correctly classified (overall accuracy),the failure to predict a species where it occurred (omission error) and the prediction of presence where there was absence (commission error). Our overall accuracy showed the logistic regression approach was the most accurate (74.51% ). The multiple criteria evaluation was intermediate (39.22%),while the Dempster-Shafer (D-S) theory model was the poorest (29.90%). However,omission and commission error tell us a different story: logistic regression had the lowest commission error,while D-S theory produced the lowest omission error. Our results provide evidence that habitat modellers should evaluate all three error measures when ascribing confidence in their model. We suggest that for our study area at least,the logistic regression model is optimal. However,where sample size is small or the species is very rare,it may also be useful to explore and/or use a more ecologically cautious modelling approach (e.g. Dempster-Shafer) that would over-predict,protect more sites,and thereby minimize the risk of missing critical habitat in conservation plans.     

Bryophytes in perennially moist forests of Papua New Guinea: ecological orientation and predictions of disturbance effects

Water relations of bryophytes must be understood along at least four dimensions: hydration/dehydration frequency; hydration duration; dehydration duration; degree of water loss. All these are biomass-dependent functions such that large colonies of bryophytes may maintain hydration longer than smaller colonies. The spread of a bryophyte colony allows lateral movement of capillary water; contiguous clones will thus allow lateral conduction of that water. In contrast, separated tufts or cushions may store water but will contribute very little to its transfer over the surface of the phorophyte.
Many of the tropical rainforests of New Guinea have a larger mass of epiphytic bryophytes than any temperate forest. The primary effect of disturbance in these forests is a reduction in bryomass, presumably due to desiccation because of increased insolation and wind movement. The reduction of bryomass will decrease water and mineral retention in the bryophyte clones; and the reduction in the size of those clones will reduce their contiguity and thus interfere with bryophyte-mediatcd water and mineral transfer. Disturbance may alter bryophyte species frequency but, under present agricultural and forestry practices in New Guinea, I have seen no evidence of significant loss of bryophyte species.     

Heat Shock Responses of Closely Related Species of Tropical and Desert Fish

Over the past twelve years, we have studied heat shock proteinsin two tropical species, a half dozen desert species and a numberof hemiclones of viviparous fishes in the genus Poeciliopsis.Heat shock protein (Hsp) isoform patterns were determined usinghigh resolution two-dimensional polyacrylamide gels. Two familiesof Hsps were studied in detail, the nucleocytoplasmic 70 kilodaltonHsp70 family and the 30 kilodalton Hsp30 family related to -crystallin.The temperature dependence of Hsp accumulation was investigatedusing both intact fish and cultured cells. When the thresholdtemperatures were mapped onto thermal preference profiles, itwas apparent that the Hsp70 threshold (33°C) was closelylinked to the most frequently selected temperatures and theHsp30 threshold (37°C) was closely linked to high temperaturesthat fish rarely selected, indicating that fish deploy thesetwo molecular chaperones differently. One tropical species P.gracilis is a genetic reservoir for most of the Hsp70 isoformsof the desert species. Acquired resistance to 41°C was stronglycorrelated with Hsp70 abundance for gracilis that containedHsp70 isoform 3 whereas fish lacking this isoform showed similarlevels of acquired thermotolerance which did not correlate withHsp70 abundance, suggesting multiple, compensating mechanismsof acquired resistance. Isoform 3 was degraded in cultured cellsfrom a desert species during several hours of recovery at normaltemperature following heat shock whereas two other Hsp70 isoformswere stable. The implications of this property of isoform 3are discussed.     

The oxygen delivery response to acute hypoxia during incremental knee extension exercise differs in active and trained males

Background

It is well known that hypoxic exercise in healthy individuals increases limb blood flow, leg oxygen extraction and limb vascular conductance during knee extension exercise. However, the effect of hypoxia on cardiac output, and total vascular conductance is less clear. Furthermore, the oxygen delivery response to hypoxic exercise in well trained individuals is not well known. Therefore our aim was to determine the cardiac output (Doppler echocardiography), vascular conductance, limb blood flow (Doppler echocardiography) and muscle oxygenation response during hypoxic knee extension in normally active and endurance-trained males.

Methods

Ten normally active and nine endurance-trained males (VO_2max = 46.1 and 65.5 mL/kg/min, respectively) performed 2 leg knee extension at 25, 50, 75 and 100% of their maximum intensity in both normoxic and hypoxic conditions (FIO₂ = 15%; randomized order). Results were analyzed with a 2-way mixed model ANOVA (group × intensity).

Results

The main finding was that in normally active individuals hypoxic sub-maximal exercise (25 – 75% of maximum intensity) brought about a 3 fold increase in limb blood flow but decreased stroke volume compared to normoxia. In the trained group there were no significant changes in stroke volume, cardiac output and limb blood flow at sub-maximal intensities (compared to normoxia). During maximal intensity hypoxic exercise limb blood flow increased approximately 300 mL/min compared to maximal intensity normoxic exercise.

Conclusion

Cardiorespiratory fitness likely influences the oxygen delivery response to hypoxic exercise both at a systemic and limb level. The increase in limb blood flow during maximal exercise in hypoxia (both active and trained individuals) suggests a hypoxic stimulus that is not present in normoxic conditions.