Integrated genomics of chemotherapy resistant ovarian cancer: A role for extracellular matrix,TGFbeta and regulating microRNAs

Epithelial ovarian cancer is the sixth most common cancer in women worldwide and the most important cause of death from gynaecological cancers in the Western world.Our explorative pathway analysis on seven published gene-sets associated with platinum resistance in ovarian cancer reveals TP53 and transforming growth factor beta as key genes. Furthermore, the extracellular matrix was associated with chemotherapy resistance in ovarian cancer as well as endocrine resistance in breast cancer. Pathway analysis again revealed transforming growth factor beta as a key gene regulating extracellular matrix gene expression. A model is presented based on literature linking transforming growth factor beta, extracellular matrix, integrin signalling, epithelial to mesenchymal transition and regulating microRNAs with a (bivalent) role in chemotherapy response.     

Formulation of a medical food cocktail for Alzheimer's disease: beneficial effects on cognition and neuropathology in a mouse model of the disease

Background

Dietary supplements have been extensively studied for their beneficial effects on cognition and AD neuropathology. The current study examines the effect of a medical food cocktail consisting of the dietary supplements curcumin, piperine, epigallocatechin gallate, α-lipoic acid, N-acetylcysteine, B vitaminsvitamin C, and folate on cognitive functioning and the AD hallmark features and amyloid-beta (Aβ) in the Tg2576 mouse model of the disease.

Principal Findings

The study found that administering the medical food cocktail for 6 months improved cortical- and hippocampal- dependent learning in the transgenic mice, rendering their performance indistinguishable from non-transgenic controls. Coinciding with this improvement in learning and memory, we found that treatment resulted in decreased soluble Aβ, including Aβ oligomers, previously found to be linked to cognitive functioning.

Conclusion

In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD.     

Historic impact of watershed change and sedimentation to reefs along west-central Guam

Using coral growth parameters (extension, density, calcification rates, and luminescence) and geochemical measurements (barium to calcium rations; Ba/Ca) from coral cores collected in west-central Guam, we provide a historic perspective on sediment input to coral reefs adjacent to the Piti-Asan watershed. The months of August through December are dominated by increased coral Ba/Ca values, corresponding to the rainy season. With river water enriched in barium related to nearshore seawater, coral Ba/Ca ratios are presented as a proxy for input of fine-grained terrigenous sediment to the nearshore environment. The century-long Ba/Ca coral record indicates that the Asan fore reef is within the zone of impact from discharged sediments transported from the Piti-Asan watershed and has experienced increased terrestrial sedimentation since the 1940s. This abrupt shift in sedimentation occurred at the same time as both the sudden denudation of the landscape by military ordinance and the immediate subsequent development of the Asan area through the end of the war, from 1944 through 1945. In response to rapid input of sediment, as determined from coral Ba/Ca values, coral growth rates were reduced for almost two decades, while calcification rates recovered much more quickly. Furthermore, coral luminescence is decoupled from the Ba/Ca record, which is consistent with degradation of soil organic matter through disturbance by forest fires, suggesting a potential index of fire history and degradation of soil organic matter. These patterns were not seen in the cores from nearby reefs associated with watersheds that have not undergone the same degree of landscape denudation. Taken together, these records provide a valuable tool for understanding the compounding effects of land-use change on coral reef health.     

Longer Gestation among Children Born Full Term Influences Cognitive and Motor Development

Children born preterm show persisting impairments in cognitive functioning, school achievement, and brain development. Most research has focused on implications of birth prior to 37 gestational weeks; however, the fetal central nervous system continues to make fundamental changes throughout gestation. Longer gestation is associated with reduced morbidity and mortality even among infants born during the period clinically defined as full term (37–41 gestational weeks). The implications of shortened gestation among term infants for neurodevelopment are poorly understood. The present study prospectively evaluates 232 mothers and their full term infants (50.4% male infants) at three time points across the first postnatal year. We evaluate the association between gestational length and cognitive and motor development. Infants included in the study were full term (born between 37 and 41 weeks gestation). The present study uses the combination of Last Menstrual Period (LMP) and early ultrasound for accurate gestational dating. Hierarchical Linear Regression analyses revealed that longer gestational length is associated with higher scores on the Bayley scales of mental and motor development at 3, 6 and 12 months of age after considering socio-demographic, pregnancy, and infant-level covariates. Findings were identical using revised categories of early, term, and late term proposed by the Working Group for Defining Term Pregnancy. Our findings indicate that longer gestation, even among term infants, benefits both cognitive and motor development.     

Biogenic Mn-Oxides in Subseafloor Basalts

The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments.     

End of the chain? Rugosity and fine-scale bathymetry from existing underwater digital imagery using structure-from-motion (SfM) technology

The rugosity or complexity of the seafloor has been shown to be an important ecological parameter for fish, algae, and corals. Historically, rugosity has been measured either using simple and subjective manual methods such as ‘chain-and-tape’ or complicated and expensive geophysical methods. Here, we demonstrate the application of structure-from-motion (SfM) photogrammetry to generate high-resolution, three-dimensional bathymetric models of a fringing reef from existing underwater video collected to characterize the seafloor. SfM techniques are capable of achieving spatial resolution that can be orders of magnitude greater than large-scale lidar and sonar mapping of coral reef ecosystems. The resulting data provide finer-scale measurements of bathymetry and rugosity that are more applicable to ecological studies of coral reefs than provided by the more expensive and time-consuming geophysical methods. Utilizing SfM techniques for characterizing the benthic habitat proved to be more effective and quantitatively powerful than conventional methods and thus might portend the end of the ‘chain-and-tape’ method for measuring benthic complexity.