Predicting the Future: Parental Progeny Investment in Response to Environmental Stress Cues

Environmental stressors can severely limit the ability of an organism to reproduce as lifespan is decreased and resources are shifted away from reproduction to survival. Although this is often detrimental to the organism’s reproductive fitness, certain other reproductive stress responses may mitigate this effect by increasing the likelihood of progeny survival in the F1 and subsequent generations. Here we review three means by which these progeny may be conferred a competitive edge as a result of stress encountered in the parental generation: heritable epigenetic modifications to nucleotides and histones, simple maternal investments of cytosolic components, and the partially overlapping phenomenon of terminal investment, which can entail extreme parental investment strategies in either cytosolic components or gamete production. We examine instances of these categories and their ability to subsequently impact offspring fitness and reproduction. Ultimately, without impacting nucleotide sequence, these more labile alterations may shape development, evolution, ecology and even human health, necessitating further understanding and research into the specific mechanisms by which environmental stressors are sensed and elicit a corresponding response in the parental germline

HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia

Colorectal cancer (CRC) is often accompanied by formation of liver metastases (LM) and skeletal muscle wasting, i.e. cachexia. Despite affecting the majority of CRC patients, cachexia remains underserved, understudied and uncured. Animal models for the study of CRC-induced cachexia, in particular models containing LM, are sparse; therefore, we aimed to characterize two new models of CRC cachexia. Male NSG mice were injected subcutaneously (HCT116) or intrasplenically (mHCT116) with human HCT116 CRC tumor cells to disseminate LM, whereas experimental controls received saline (n=5-8/group). Tumor growth was accompanied by loss of skeletal muscle mass (HCT116: -20%; mHCT116: -31%; quadriceps muscle) and strength (HCT116: -20%; mHCT116: -27%), with worsened loss of skeletal muscle mass in mHCT116 compared with HCT116 (gastrocnemius: -19%; tibialis anterior: -22%; quadriceps: -21%). Molecular analyses revealed elevated protein ubiquitination in HCT116, whereas mHCT116 also displayed elevated Murf1 and atrogin-1 expression, along with reduced mitochondrial proteins PGC1α, OPA1, mitofusin 2 and cytochrome C. Further, elevated IL6 levels were found in the blood of mHCT116 hosts, which was associated with higher phosphorylation of STAT3 in skeletal muscle. To clarify whether STAT3 was a main player in muscle wasting in this model, HCT116 cells were co-cultured with C2C12 myotubes. Marked myotube atrophy (-53%) was observed, along with elevated phospho-STAT3 levels (+149%). Conversely, inhibition of STAT3 signaling by means of a JAK/STAT3 inhibitor was sufficient to rescue myotube atrophy induced by HCT116 cells (+55%). Overall, our results indicate that the formation of LM exacerbates cachectic phenotype and associated skeletal muscle molecular alterations in HCT116 tumor hosts

Techno-Economic and Fluid Dynamics Analysis for Growing Microalgae with the Intent of Producing Biofuel Using a System Model

Techno-economic and systems studies on microalgal growth scenarios to date are abbreviated and missing a number of important variables. By including these variables in a detailed model integrating biology, chemistry, engineering, and financial aspects, a more defined systems analysis is possible. Through optimizing the model productivity based on the resulting net profit, the system analysis results in a more accurate assessment of environmental and economic sustainability of specific algal growth scenarios. Photobioreactor algal growth scenario optimization in the system model has resulted in realistic engineering design requirements based on algal growth requirements and fluid dynamics analysis. Results show feasibility for photobioreactor growth scenarios to be economically sustainable when co-products are included, but definite technological advancements and productivity improvements must be made. The main factors inhibiting a cost effective photobioreactor growth scenario are culture density, temperature, and lighting distribution for solar illuminated photobioreactors, and lighting cost for artificially illuminated photobioreactors. Open pond algal growth scenarios do not show any prospect of economic or environmental sustainability with current technology due to the large amount of surface area required, inefficient water use, and low culture density. All algal growth scenarios are inferior to petro-diesel regarding energy inputs, carbon emissions, and environmental sustainability. No algal growth scenarios analyzed in this study meet the U.S. requirement of biofuel emitting at least 20% less carbon emissions than diesel from crude oil