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Volatile anesthetics have been used in modern medicine for over 160 years, but their sites and mechanisms of action remain unclear. While many effects of these agents are characterized, how these effects relate to the physiological state of anesthesia has not been elucidated. Volatile anesthetics affect all cells and tissues tested, including mammalian, plant, bacterial, and yeast cells. In yeast, these drugs arrest cell division in a manner that parallels their actions in mammals. To gain further insight into the cellular activities of these compounds, genes were isolated that, when overexpressed or deleted from the genome, alter the response of Saccharomyces cerevisiae (budding yeast) to the volatile anesthetic isoflurane. One of the genes we identified is UMP1, which encodes a chaperone required for maturation of the 20S proteasome complex in yeast. Overexpression of UMP1 renders yeast cells more resistant to the growth inhibitory effects of isoflurane, while deletion of the gene renders cells more sensitive than wild type cells. This suggests an important role for the proteasome in responding to volatile anesthetics in yeast, and may provide clues as to how these drugs exert their effects in more complex eukaryotes, including mammals.
Mangrove forests are among the world's most vulnerable subtropical and tropical habitats. With global losses already in excess of 50%, mangroves are being lost more rapidly than tropical rainforests. Those losses are critical to society because mangroves filter terrestrial contaminants, protecting coral reefs from eutrophication, sedimentation, and resulting degradation. Utila is a small island northeast of Honduras, well known for its diving opportunities. Anthropogenic development reduces the island's mangrove forests, threatening the health of surrounding coral reefs. We examined the effects of mangrove deforestation on coral reefs using shoreline mangrove density, near-shore nitrate levels, and algal coverage on adjacent reefs. These variables were measured offshore of both developed and undeveloped coasts. Mangrove density was significantly lower along the developed than the undeveloped coast (mean 0.27 stems/m2 vs. 3.01 stems/m2, respectively, p < 0.0001). Nitrate levels were significantly higher along the developed coast than along the undeveloped coast (mean 22.7 mg/L vs. 7.9 mg/L, respectively, p < 0.0001), as was algal cover (mean 48.1% vs. 32.4%, respectively, p < 0.0001). These results support arguments to reduce mangrove deforestation and encourage reforestation, which will protect not only mangroves and corals, but also avoid negative impacts to the local economy, which often is heavily reliant on dive tourism and fisheries.
Breast cancer currently has a relatively high survival rate, in part due to the prevalence of effective hormone therapies. However, one breast cancer subtype - triple negative breast cancer (TNBC) - has no targeted therapies available. Furthermore, even subtypes of breast cancer with effective therapies available see dramatic decreases in survival rate upon metastasis. IGFR is an upstream activator of the many different cellular growth and migration pathways, and previously studied inhibitors of IGF-1R have shown efficacy in breast cancer. In this study, we tested PQ401, an IGF-1R inhibitor, in MDA-MB-231 cells to determine the compound's effects on cell viability and migration potential. We determined that the EC50 of PQ401 in MDA-MB-231 cells was 1.95 µM, and that treating cells with 2.5 µM PQ401 significantly decreased cellular motility. This study demonstrates that PQ401 not only decreases cell viability, but also migration in a TNBC cell line.
Zebrafish is a common research model to study different physiological and genetic effects in humans. In the current research study, nutritional and environmental factors were altered to potentially create a sickle cell anemia model in zebrafish. The purpose of this study was to determine factors that affect hematopoiesis in order to better understand development and treatment of sickle cell anemia. The use of the zebrafish model for this project enabled the application of treatments by submersion. For each treatment ∼100 fertilized zebrafish eggs were placed in tank water containing the treatment. In addition to the control group, five supplements were included as treatments: iron, folic acid, vitamin B12, viper venom and the chelating agent deferoxamine mesylate. After 24 hours of development, 10 embryos from each treatment group were collected for gene expression analysis. After hatching, the zebrafish were raised for about 6 weeks to prepare blood smears to analyze the diameters and morphology of blood cells. Statistical analyses show there was a significant difference in the diameter of the folic acid and deferoxamine mesylate groups without significant alteration of growth of the fish. These data indicate the development of an anemia model in zebrafish is possible, and may provide evidence for the possibility of use of zebrafish for the development of treatment for anemia.
An amitochondriate parasite, Entamoeba histolytica, has a bifunctional ADHE enzyme (EhADH2) that contains separate acetaldehyde (ALDH) and alcohol (ADH) dehydrogenase activities. In a cluster of 25 bifunctional enzymes of single cell eukaryotes and bacteria, we present a phylogenetic analysis that suggests a lateral gene transfer event (prokaryotic ancestor to single-cell eukaryotic ancestor) and a complex structure that aligns with key homologs in the ADHE evolutionary history based on their similarity with bacterial alcohol dehydrogenases. We show that the ADHE in Entamoeba lineage diverged independently but shows significant similarities to the structure of ADHE in Fusobacterium, and a complex model that maps its ALDH and ADH domain well with bacteria such as Geobaccillus thermoglucosidasius. Our analyses likely support a lateral acquisition of an EhADH2-like ancestral gene from bacteria. Analysis using several evolutionary analyses software programs reveal that the enzyme structure is highly conserved, and maintains a similar function within a diverse set of pathogens, including Escherichia coli and Clostridium spp.
The Turkey Hill Oxbow, a small, locally significant forested/wetland area in central Columbia County, Pennsylvania, was surveyed for salamanders during 2015. A comparison of recent records was made to historic collections from this location within the herpetology collection housed at Bloomsburg University of Pennsylvania (BU). Nine salamander species, encompassing a total of 132 individuals, were found, revealing a slightly greater diversity represented by historic vouchers within the BU herpetology collection (eight species). The most common species were eastern red-backed salamanders (Plethodon cinereus) and Allegheny mountain dusky salamanders (Desmognathus ochrophaeus); the most uncommon were northern two-lined salamanders (Eurycea bislineata) and red salamanders (Pseudotriton ruber). Two species found in the recent survey (D. ochrophaeus and P. ruber) were not represented by historic vouchers in the BU collection. However, no spotted salamanders (Ambystoma maculatum) were found during this study, despite historic voucher records for this species from this locality.
Eastern Bluebirds (Sialia sialis) do not remove nest materials; therefore associated microorganisms remain in the cavity and can potentially colonize subsequent nestlings. The impact of nest reuse or removal on bacterial communities was examined during the 2012 breeding season in western Pennsylvania. Nest success, number of fledglings produced, and nestling body condition were assessed; bacterial communities were profiled via terminal restriction fragment length polymorphisms (T-RFLP) in which one fragment approximates one bacterial species. The composition of bacterial communities varied between treatments; in particular, reused nests had fewer terminal restriction fragments and a lower diversity index. In contrast, mean nest success, number of fledglings, and body condition did not differ by treatment. Seclusion of nest material in nest boxes may result in a bacterial community in reused nests that is less diverse due to less variable conditions in the nest box.