What is the best reference RNA? And other questions regarding the design and analysis of two-color microarray experiments

The reference design is a practical and popular choice for microarray studies using two-color platforms. In the reference design, the reference RNA uses half of all array resources, leading investigators to ask: What is the best reference RNA? We propose a novel method for evaluating reference RNAs and present the results of an experiment that was specially designed to evaluate three common choices of reference RNA. We found no compelling evidence in favor of any particular reference. In particular, a commercial reference showed no advantage in our data. Our experimental design also enabled a new way to test the effectiveness of pre-processing methods for two-color arrays. Our results favor using intensity normalization and foregoing background subtraction. Finally, we evaluate the sensitivity and specificity of data quality filters, and we propose a new filter that can be applied to any experimental design and does not rely on replicate hybridizations.     

Marine and freshwater regime changes impact a community of migratory Pacific salmonids in decline

Marine and freshwater ecosystems are increasingly at risk of large and cascading changes from multiple human activities (termed “regime shifts”), which can impact population productivity, resilience, and ecosystem structure. Pacific salmon exhibit persistent and large fluctuations in their population dynamics driven by combinations of intrinsic (e.g., density dependence) and extrinsic factors (e.g., ecosystem changes, species interactions). In recent years, many Pacific salmon have declined due to regime shifts but clear understanding of the processes driving these changes remains elusive. Here, we unpacked the role of density dependence, ecosystem trends, and stochasticity on productivity regimes for a community of five anadromous Pacific salmonids (Steelhead, Coho Salmon, Pink Salmon, Dolly Varden, and Coastal Cutthroat Trout) across a rich 40-year time-series. We used a Bayesian multivariate state-space model to examine whether productivity shifts had similarly occurred across the community and explored marine or freshwater changes associated with those shifts. Overall, we identified three productivity regimes: an early regime (1976–1990), a compensatory regime (1991–2009), and a declining regime (since 2010) where large declines were observed for Steelhead, Dolly Varden, and Cutthroat Trout, intermediate declines in Coho and no change in Pink Salmon. These regime changes were associated with multiple cumulative effects across the salmon life cycle. For example, increased seal densities and ocean competition were associated with lower adult marine survival in Steelhead. Watershed logging also intensified over the past 40 years and was associated with (all else equal) ≥97% declines in freshwater productivity for Steelhead, Cutthroat, and Coho. For Steelhead, marine and freshwater dynamics played approximately equal roles in explaining trends in total productivity. Collectively, these changing environments limited juvenile production and lowered future adult returns. These results reveal how changes in freshwater and marine environments can jointly shape population dynamics among ecological communities, like Pacific salmon, with cascading consequences to their resilience.     

Reproductive isolation and the maintenance of species boundaries in two serpentine endemic Jewelflowers

Speciation occurs when reproductive barriers substantially reduce gene flow between lineages. Understanding how specific barriers contribute to reproductive isolation offers insight into the initial forces driving divergence and the evolutionary and ecological processes responsible for maintaining diversity. Here, we quantified multiple pre‐ and post‐pollination isolating barriers in a pair of closely related California Jewelflowers (Streptanthus, Brassicaceae) living in an area of sympatry. S. breweri and S. hesperidis are restricted to similar serpentine habitats; however, populations are spatially isolated at fine‐scales and rarely co‐occur in intermixed stands. Several intrinsic postzygotic barriers were among the strongest we quantified, yet, postzygotic barriers currently contribute little to overall reproductive isolation due to the cumulative strength of earlier‐acting extrinsic barriers, including spatial isolation, and flowering time and pollinator differences. Data from multiple years suggest that pre‐pollination barriers may have different strengths depending on annual environmental conditions. Similarly, crossing data suggest that the strength of intrinsic isolation may vary among different population pairs. Estimates of total reproductive isolation in S. breweri and S. hesperidis are robust to uncertainty and variability in individual barrier strength estimates, demonstrating how multiple barriers can act redundantly to prevent gene flow between close relatives living in sympatry.     

Individuality in seaweeds and why we need to care

Documenting the causes and consequences of intraspecific variation forms the foundation of much of evolutionary ecology. In this Perspectives piece, we review the importance of individual variation in ecology and evolution, argue that contemporary phycology often overlooks this foundational biological unit, and highlight how this lack of attention has potentially constrained our understanding of seaweeds. We then provide some suggestions of promising but underrepresented approaches, for instance: conducting more studies and analyses at the level of the individual; designing studies to evaluate heritability and genetic regulation of traits; and measuring associations between individual variation in functional traits and ecological outcomes. We close by highlighting areas of phycological research (e.g., population biology, ecology, aquaculture, climate change management) that could benefit immediately from including a focus on individual variation. Algae, for their part, provide us with a powerful and diverse set of ecological and evolutionary traits to explore these topics. There is much to be discovered.     

Small Molecule Modifiers of In Vitro Manganese Transport Alter Toxicity In Vivo

Biological Trace Element Research - Manganese (Mn) is essential for several species and daily requirements are commonly met by an adequate diet. Mn overload may cause motor and psychiatric...     

Lipolytic Activity and the Utilization of Fatty Acids Associated with Bat Sebum by Pseudogymnoascus destructans

Mycopathologia - Pseudogymnoascus destructans is the causative agent of a fungal infection of bats known as white-nose syndrome (WNS). Since its discovery in 2006, it has been responsible for...     

Oxethazaine inhibits esophageal squamous cell carcinoma proliferation and metastasis by targeting aurora kinase A

Esophageal squamous cell carcinoma (ESCC), a malignant neoplasm with high incidence, is a severe global public health threat. The current modalities used for treating ESCC include surgery, chemotherapy, and radiotherapy. Although ESCC management and treatment strategies have improved over the last decade, the overall 5-year survival rate remains <20%. Therefore, the identification of novel therapeutic strategies that can increase ESCC patient survival rates is urgently needed. Oxethazaine, an amino-amide anesthetic agent, is mainly prescribed in combination with antacids to relieve esophagitis, dyspepsia, and other gastric disorders. In the present study, we found that oxethazaine inhibited the proliferation and migration of esophageal cancer cells. According to the results of in vitro screening and binding assays, oxethazaine binds directly to AURKA, suppresses AURKA activity, and inhibits the downstream effectors of AURKA. Notably, we found that oxethazaine suppressed tumor growth in three patient-derived esophageal xenograft mouse models and tumor metastasis in vivo. Our findings suggest that oxethazaine can inhibit ESCC proliferation and metastasis in vitro and in vivo by targeting AURKA.Subject terms: Cancer prevention, Cell growth