Wnt4 and LAP2alpha as pacemakers of Thymic Epithelial Senescence

Age-associated thymic involution has considerable physiological impact by inhibiting de novo T-cell selection. This impaired T-cell production leads to weakened immune responses. Yet the molecular mechanisms of thymic stromal adipose involution are not clear. Age-related alterations also occur in the murine thymus providing an excellent model system. In the present work structural and molecular changes of the murine thymic stroma were investigated during aging. We show that thymic epithelial senescence correlates with significant destruction of epithelial network followed by adipose involution. We also show in purified thymic epithelial cells the age-related down-regulation of Wnt4 (and subsequently FoxN1), and the prominent increase in LAP2α expression. These senescence-related changes of gene expression are strikingly similar to those observed during mesenchymal to pre-adipocyte differentiation of fibroblast cells suggesting similar molecular background in epithelial cells. For molecular level proof-of-principle stable LAP2α and Wnt4-over-expressing thymic epithelial cell lines were established. LAP2α over-expression provoked a surge of PPARγ expression, a transcription factor expressed in pre-adipocytes. In contrast, additional Wnt4 decreased the mRNA level of ADRP, a target gene of PPARγ. Murine embryonic thymic lobes have also been transfected with LAP2α- or Wnt4-encoding lentiviral vectors. As expected LAP2α over-expression increased, while additional Wnt4 secretion suppressed PPARγ expression. Based on these pioneer experiments we propose that decreased Wnt activity and increased LAP2α expression provide the molecular basis during thymic senescence. We suggest that these molecular changes trigger thymic epithelial senescence accompanied by adipose involution. This process may either occur directly where epithelium can trans-differentiate into pre-adipocytes; or indirectly where first epithelial to mesenchymal transition (EMT) occurs followed by subsequent pre-adipocyte differentiation. The latter version fits better with literature data and is supported by the observed histological and molecular level changes

Surgical margins and survival after head and neck cancer surgery

BACKGROUND: Mixed results exist as to whether positive surgical margins impact survival. The aim of this study was to determine whether positive surgical margins are indeed associated with decreased survival in patients with primary head and neck cancer. METHODS: We conducted a retrospective cohort study of 261 cases diagnosed with cancer of the larynx or tongue between 1995 and 1999. Cases were followed through December 31, 2002. Survival curves by margin status were generated by Kaplan-Meier methods. Categorical data were evaluated with odds ratios (OR). RESULTS: All-cause mortality was markedly higher in cases with positive margins as compared with those with negative margins (54% versus 29%, P = 0.005). This pattern also appeared after adjusting for age and sex (OR = 2.97, 95% CI: 1.29 – 6.84). CONCLUSION: Our findings suggest that positive surgical margin status is associated with increased mortality. This association also generally persists after adjustment for tumor size, stage, and adjuvant therapy

The role of thrombospondins in wound healing, ischemia, and the foreign body reaction

Thrombospondin (TSP) 1 and TSP2 have been implicated in the regulation of several processes during tissue repair. Due to their matricellular nature, these proteins are thought to modulate cell-matrix interactions through a variety of mechanisms specific to the spatio-temporal context of their expression. Most notably, TSP1 and TSP2 appear to play distinct, non-overlapping roles in the healing of skin wounds. In contrast, both proteins have been implicated as regulators of ischemia-induced angiogenesis. Moreover, TSP2 has been shown to be a critical regulator of angiogenesis in the foreign body response (FBR). In this review, we discuss the role of TSPs in tissue repair and examine the mechanistic data regarding the ability of the thrombospondins to modulate cell-matrix interactions in this context

Palms and trees resist extreme drought in Amazon forests with shallow water tables

1. The intensity and frequency of severe droughts in the Amazon region has increase in recent decades. These extreme events are associated with changes in forest dynamics, biomass and floristic composition. However, most studies of drought response have focused on upland forests with deep water tables, which may be especially sensitive to drought. Palms, which tend to dominate the less well‐drained soils, have also been neglected. The relative neglect of shallow water tables and palms is a significant concern for our understanding of tropical drought impacts, especially as one third of Amazon forests grow on shallow water tables (<5m deep). 2. We evaluated the drought response of palms and trees in forests distributed over a 600 km transect in central‐southern Amazonia, where the landscape is dominated by shallow water table forests. We compared vegetation dynamics before and following the 2015–16 El Nino drought, the hottest and driest on record for the region (−214 mm of cumulative water deficit). 3. We observed no change in stand mortality rates and no biomass loss in response to drought in these forests. Instead, we observed an increase in recruitment rates, which doubled to 6.78% y‐1 ± 4.40 (mean ± SD) during 2015–16 for palms and increased by half for trees (to 2.92% y‐1 ± 1.21), compared to rates in the pre‐El‐Nino interval. Within these shallow water table forests, mortality and recruitment rates varied as a function of climatic drought intensity and water table depth for both palms and trees, with mortality being greatest in climatically and hydrologically wetter environments and recruitment greatest in drier environments. Across our transect there was a significant increase over time in tree biomass. 4. Synthesis: Our results indicate that forests growing over shallow water tables – relatively under‐studied vegetation that nonetheless occupies one‐third of Amazon forests ‐ are remarkably resistant to drought. These findings are consistent with the hypothesis that local hydrology and its interactions with climate strongly constrain forest drought effects, and has implications for climate change feedbacks. This work enhances our understanding of integrated drought effects on tropical forest dynamics and highlights the importance of incorporating neglected forest types into both the modeling of forest climate responses and into public decisions about priorities for conservation

Seasonal variations of EPG levels in gastro-intestinal parasitic infection in a southeast asian controlled locale:a statistical analysis

We present a data based statistical study on the effects of seasonal variations in the growth rates of the gastro-intestinal (GI) parasitic infection in livestock. The alluded growth rate is estimated through the variation in the number of eggs per gram (EPG) of faeces in animals. In accordance with earlier studies, our analysis too shows that rainfall is the dominant variable in determining EPG infection rates compared to other macro-parameters like temperature and humidity. Our statistical analysis clearly indicates an oscillatory dependence of EPG levels on rainfall fluctuations. Monsoon recorded the highest infection with a comparative increase of at least 2.5 times compared to the next most infected period (summer). A least square fit of the EPG versus rainfall data indicates an approach towards a super diffusive (i. e. root mean square displacement growing faster than the square root of the elapsed time as obtained for simple diffusion) infection growth pattern regime for low rainfall regimes (technically defined as zeroth level dependence) that gets remarkably augmented for large rainfall zones. Our analysis further indicates that for low fluctuations in temperature (true on the bulk data), EPG level saturates beyond a critical value of the rainfall, a threshold that is expected to indicate the onset of the nonlinear regime. The probability density functions (PDFs) of the EPG data show oscillatory behavior in the large rainfall regime (greater than 500 mm), the frequency of oscillation, once again, being determined by the ambient wetness (rainfall, and humidity). Data recorded over three pilot projects spanning three measures of rainfall and humidity bear testimony to the universality of this statistical argument. © 2013 Chattopadhyay and Bandyopadhyay