While urban disamenities and pollution sources have received considerable attention in environmental justice research, few studies have examined sociospatial inequities associated with the ...distribution of desirable land uses. In this paper we focus on addressing this limitation by investigating the environmental equity implications of street trees—an important publicly financed amenity that provides several direct and indirect benefits to urban residents. The specific objective was to determine if the spatial distribution of public right-of-way trees is equitable with respect to race and ethnicity, income, and housing tenure in the city of Tampa, Florida, USA. We seek to extend research on equity analysis of urban amenities through several methodological innovations, including: (a) accounting for the heterogeneity of urban land use; (b) utilizing high-resolution remote sensing techniques to quantify parcel-specific tree cover; and (c) using multivariate regression models that control for spatial dependence within the data. The results support the inequity hypothesis by indicating a significantly lower proportion of tree cover on public right-of-way in neighborhoods containing a higher proportion of African-Americans, low-income residents, and renters. These findings have important implications for local public investment and policy strategies.
How pseudouridylation (Ψ), the most common and evolutionarily conserved modification of rRNA, regulates ribosome activity is poorly understood. Medically, Ψ is important because the rRNA Ψ synthase, ...DKC1, is mutated in X-linked dyskeratosis congenita (X-DC) and Hoyeraal-Hreidarsson (HH) syndrome. Here, we characterize ribosomes isolated from a yeast strain in which Cbf5p, the yeast homolog of DKC1, is catalytically impaired through a D95A mutation (cbf5-D95A). Ribosomes from cbf5-D95A cells display decreased affinities for tRNA binding to the A and P sites as well as the cricket paralysis virus internal ribosome entry site (IRES), which interacts with both the P and the E sites of the ribosome. This biochemical impairment in ribosome activity manifests as decreased translational fidelity and IRES-dependent translational initiation, which are also evident in mouse and human cells deficient for DKC1 activity. These findings uncover specific roles for Ψ modification in ribosome-ligand interactions that are conserved in yeast, mouse, and humans.
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► rRNA pseudouridylation (Ψ) is important for eukaryotic translational fidelity ► rRNA Ψ fine-tunes ribosome affinity for highly structured RNA ligands ► rRNA Ψ is required for 48S preinitiation translation complex assembly on IRESes
The synthesis of nascent RNA is a discontinuous process in which phases of productive elongation by RNA polymerase are interrupted by frequent pauses. Transcriptional pausing was first observed ...decades ago, but was long considered to be a special feature of transcription at certain genes. This view was challenged when studies using genome-wide approaches revealed that RNA polymerase II pauses at promoter-proximal regions in large sets of genes in Drosophila and mammalian cells. High-resolution genomic methods uncovered that pausing is not restricted to promoters, but occurs globally throughout gene-body regions, implying the existence of key-rate limiting steps in nascent RNA synthesis downstream of transcription initiation. Here, we outline the experimental breakthroughs that led to the discovery of pervasive transcriptional pausing, discuss its emerging roles and regulation, and highlight the importance of pausing in human development and disease.
Sea-level rise is a consequence of climate change that can impact the ecological and physiological changes of coastal, ground-dwelling species. Sea-level rise has a potential to inundate birds, ...rodents, spiders, and insects that live on the ground in coastal areas. Yet, there is still much to be learned concerning the specifics of these impacts. The red imported fire ant Solenopsis invicta (Buren) excavates soil for its home and is capable of surviving flooding. Because of their ground-dwelling life history and rapid reproduction, fire ants make an ideal model for discovery and prediction of changes that may be due to sea-level rise. There are up to 500,000 individuals in a colony, and these invasive ants naturally have a painful sting. However, observations suggest that colonies of fire ants that dwell in tidally-influenced areas are more aggressive with more frequent stings and more venom injected per sting (behavioral and physiological changes) than those located inland. This may be an adaption to sea-level rise. Therefore, the objective of this study is to elucidate differences in inland and coastal defensiveness via micro-dissection and comparison of head width, head length, stinger length, and venom sac volume. But first because fire ants' ability to raft on brackish tidal water is unknown, it had to be determined if fire ants could indeed raft in brackish water and examine the behavior differences between those flooded with freshwater vs. saltwater.
To test the coastal-aggression hypothesis, inland colonies and coastal colonies, which experience relatively greater amounts of flooding, specifically regular tidal and windblown water and oscillations (i.e. El Nińo Southern Oscillation) from the Gulf of Mexico, were collected. To mimic sea-level rise, the colonies were flooded in salinities that correspond to both their collection site and conditions found in a variety of locales and situations (such as storm surge from a tropical storm). Individual ants were immediately taken from each colony for dissection before flooding, 1-hour into flooding, and 24-hours into flooding.
Fire ants use their venom to defend themselves and to communicate alarm or aggression. Dissections and measurement of heads, venom sacs, and stingers revealed both coastal and inland colonies experience an increase in venom sac volume after 24 hours; in fact coastal colonies increased their venom volume by 75% after 24 h of flooding Whether this venom sac enlargement is due to diffusion of water or venom sac production is unknown. These ground-dwelling ants exhibit physiological and behavioral adaptations to ongoing sea-level rise possibly indicating that they are responding to increased flooding. Fire ants will raft on high-salinity water; and sea-level rise may cause stings by flooded ants to be more severe because of increased venom volume.
During the co-translational assembly of protein complexes, a fully synthesized subunit engages with the nascent chain of a newly synthesized interaction partner. Such events are thought to contribute ...to productive assembly, but their exact physiological relevance remains underexplored. Here, we examine structural motifs contained in nucleoporins for their potential to facilitate co-translational assembly. We experimentally test candidate structural motifs and identify several previously unknown co-translational interactions. We demonstrate by selective ribosome profiling that domain invasion motifs of beta-propellers, coiled-coils, and short linear motifs may act as co-translational assembly domains. Such motifs are often contained in proteins that are members of multiple complexes (moonlighters) and engage with closely related paralogs. Surprisingly, moonlighters and paralogs assemble co-translationally in only some but not all of the relevant biogenesis pathways. Our results highlight the regulatory complexity of assembly pathways.
Various cellular quality control mechanisms support proteostasis. While, ribosome-associated chaperones prevent the misfolding of nascent chains during translation, importins were shown to prevent ...the aggregation of specific cargoes in a post-translational mechanism prior the import into the nucleoplasm. Here, we hypothesize that importins may already bind ribosome-associated cargo in a co-translational manner. We systematically measure the nascent chain association of all importins in Saccharomyces cerevisiae by selective ribosome profiling. We identify a subset of importins that bind to a wide range of nascent, often uncharacterized cargoes. This includes ribosomal proteins, chromatin remodelers and RNA binding proteins that are aggregation prone in the cytosol. We show that importins act consecutively with other ribosome-associated chaperones. Thus, the nuclear import system is directly intertwined with nascent chain folding and chaperoning.
Primary cardiac fibroblasts are notoriously difficult to maintain for extended periods of time in cell culture, due to the plasticity of their phenotype and sensitivity to mechanical input. In order ...to study cardiac fibroblast activation in vitro, we have developed cell culture conditions which promote the quiescent fibroblast phenotype in primary cells. Using elastic silicone substrata, both rat and mouse primary cardiac fibroblasts could be maintained in a quiescent state for more than 3 days after isolation and these cells showed low expression of myofibroblast markers, including fibronectin extracellular domain A, non-muscle myosin IIB, platelet-derived growth factor receptor-alpha and alpha-smooth muscle actin. Gene expression was also more fibroblast-like vs. that of myofibroblasts, as Tcf21 was significantly upregulated, while Fn1-EDA, Col1A1 and Col1A2 were markedly downregulated. Cell culture conditions (eg. serum, nutrient concentration) are critical for the control of temporal fibroblast proliferation. We propose that eliminating mechanical stimulus and limiting the nutrient content of cell culture media can extend the quiescent nature of primary cardiac fibroblasts for physiological analyses in vitro.
Effective management of protected sea turtle populations requires knowledge not only of mean values for demographic and life-history parameters, but also temporal and spatial trends, variability, and ...underlying causes. For endangered Kemp's ridley sea turtles (Lepidochelys kempii), the need for baseline information of this type has been emphasized during attempts to understand causes underlying the recent truncation in the recovery trajectory for nesting females. To provide insight into variability in age and size at sexual maturation (ASM and SSM) and long-term growth patterns likely to influence population trends, we conducted skeletochronological analysis of humerus bones from 333 Kemp's ridleys stranded throughout the Gulf of Mexico (GOM) from 1993 to 2010. Ranges of possible ASMs (6.8 to 21.8 yr) and SSMs (53.3 to 68.3 cm straightline carapace length (SCL)) estimated using the "rapprochement" skeletal growth mark associated with maturation were broad, supporting incorporation of a maturation schedule in Kemp's ridley population models. Mean ASMs estimated from rapprochement and by fitting logistic, generalized additive mixed, and von Bertalanffy growth models to age and growth data ranged from 11 to 13 yr; confidence intervals for the logistic model predicted maturation of 95% of the population between 11.9 and 14.8 yr. Early juvenile somatic growth rates in the GOM were greater than those previously reported for the Atlantic, indicating potential for differences in maturation trajectories between regions. Finally, long-term, significant decreases in somatic growth response were found for both juveniles and adults, which could influence recruitment to the reproductive population and observed nesting population trends.
Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve ...studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure, through minimally invasive biopsy of a small region of a single tumor. This assay takes into consideration physiologic effects that contribute to drug response by allowing drugs to interact with the living tumor in its native microenvironment. Because these effects are crucial to predicting drug response, we envision that these devices will help identify optimal drug therapy before systemic treatment is initiated and could improve drug response prediction beyond the biomarkers and in vitro and ex vivo studies used today. These devices may also be used in clinical drug development to safely gather efficacy data on new compounds before pharmacological optimization.
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