686 research outputs found
\u3cem\u3eChlamydomonas\u3c/em\u3e mutants display reversible deficiencies in flagellar beating and axonemal assembly
Axonemal complexes in flagella are largely prepackaged in the cell body. As such, one mutation often results in the absence of the co-assembled components and permanent motility deficiencies. For example, a Chlamydomonas mutant defective in RSP4 in the radial spoke (RS), which is critical for bend propagation, has paralyzed flagella that also lack the paralogue RSP6 and three additional RS proteins. Intriguingly, recent studies showed that several mutant strains contain a mixed population of swimmers and paralyzed cells despite their identical genetic background. Here we report a cause underlying these variations. Two new mutants lacking RSP6 swim processively and other components appear normally assembled in early log phase indicating that, unlike RSP4, this paralogue is dispensable. However, swimmers cannot maintain the typical helical trajectory and reactivated cell models tend to spin. Interestingly the motile fraction and the spokehead content dwindle during stationary phase. These results suggest that (1) intact RS is critical for maintaining the rhythm of oscillatory beating and thus the helical trajectory; (2) assembly of the axonemal complex with subtle defects is less efficient and the inefficiency is accentuated in compromised conditions, leading to reversible dyskinesia. Consistently, several organisms only possess one RSP4/6 gene. Gene duplication in Chlamydomonas enhances RS assembly to maintain optimal motility in various environments
Modeling Land and Hold Short Operations: Balancing Safety and Arrival Rate
Many airports conduct simultaneous operations on intersecting runways to increase the rate of takeoffs and landings. This requires landing aircraft to hold short of the intersecting runway, which incurs a safety risk of runway incursions in the process. A Monte Carlo simulation was conducted to analyze the traffic load at maximum operational capacity at Charlotte-Douglas International Airport in order to analyze the fleet types and the rate of those landing aircraft unable to stop short of the intersecting runway. The researchers used the actual and four alternative compositions of the subject airline’s aircraft arrivals, interspersed among other airport traffic, to assess how such changes affect the rate of runway incursions, the rate of operations at the airport, and the mean number of passengers the subject airline can land per hour. The simulation revealed that runway length up to the hold short point was the biggest determinant of aircraft being unable to hold short. The total airport rate of operations decreased when heavy wake turbulence category aircraft were introduced. Despite heavy wake turbulence category aircraft carrying more passengers individually, the decreased operations rate also led to fewer passengers per hour that the subject airline could carry
Dimeric heat shock protein 40 binds radial spokes for generating coupled power strokes and recovery strokes of 9 + 2 flagella
T-shape radial spokes regulate flagellar beating. However, the precise function and molecular mechanism of these spokes remain unclear. Interestingly, Chlamydomonas reinhardtii flagella lacking a dimeric heat shock protein (HSP) 40 at the spokehead–spokestalk juncture appear normal in length and composition but twitch actively while cells jiggle without procession, resembling a central pair (CP) mutant. HSP40− cells begin swimming upon electroporation with recombinant HSP40. Surprisingly, the rescue doesn't require the signature DnaJ domain. Furthermore, the His-Pro-Asp tripeptide that is essential for stimulating HSP70 adenosine triphosphatase diverges in candidate orthologues, including human DnaJB13. Video microscopy reveals hesitance in bend initiation and propagation as well as irregular stalling and stroke switching despite fairly normal waveform. The in vivo evidence suggests that the evolutionarily conserved HSP40 specifically transforms multiple spoke proteins into stable conformation capable of mechanically coupling the CP with dynein motors. This enables 9 + 2 cilia and flagella to bend and switch to generate alternate power strokes and recovery strokes
A temporal framework of large wildfire suppression in practice, a qualitative descriptive study
Suppression activities on large wildfires are complicated. Existing suppression literature does not take into account this complexity which leaves existing suppression models and measures of resource productivity incomplete. A qualitative descriptive analysis was performed on the suppression activities described in operational documents of 10 large wildfires in Victoria, Australia. A five-stage classification system summarises suppression in the everyday terms ofwildfire management. Suppression can be heterogeneous across different sectors with different stages occurring across sectors on the same day. The stages and the underlying 20 suppression tasks identified provide a fundamental description of how suppression resources are being used on largewildfires. We estimate that at least 57% of resource use on our sample of 10 large wildfires falls outside of current suppression modelling and productivity research
Differential physiological responses to environmental change promote woody shrub expansion
Direct and indirect effects of warming are increasingly modifying the carbon-rich vegetation and soils of the Arctic tundra, with important implications for the terrestrial carbon cycle. Understanding the biological and environmental influences on the pr
Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies
Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations
Loss of N-WASP drives early progression in an Apc model of intestinal tumourigenesis
N‐WASP (WASL) is a widely expressed cytoskeletal signalling and scaffold protein also implicated in regulation of Wnt signalling and homeostatic maintenance of skin epithelial architecture. N‐WASP mediates invasion of cancer cells in vitro and its depletion reduces invasion and metastatic dissemination of breast cancer. Given this role in cancer invasion and universal expression in the gastrointestinal tract, we explored a role for N‐WASP in the initiation and progression of colorectal cancer. While deletion of N‐wasp is not detectably harmful in the murine intestinal tract, numbers of Paneth cells increased, indicating potential changes in the stem cell niche and migration up the crypt‐villus axis was enhanced. Loss of N‐wasp promoted adenoma formation in an adenomatous polyposis coli (Apc) deletion model of intestinal tumourigenesis. Thus, we establish a tumour suppressive role of N‐WASP in early intestinal carcinogenesis despite its later pro‐invasive role in other cancers. Our study highlights that while the actin cytoskeletal machinery promotes invasion of cancer cells, it also maintains normal epithelial tissue function and thus may have tumour suppressive roles in pre‐neoplastic tissues
Orally administered oxygen nanobubbles enhance tumor response to sonodynamic therapy
Suspensions of oxygen-filled bubbles are under active investigation as potential means of relieving tissue hypoxia. Intravenous administration of large quantities of bubbles is, however, undesirable. Previous work by the authors has demonstrated that tumor oxygen levels can be increased following oral administration of phospholipid stabilized oxygen nanobubbles. The aim of this study was to determine whether this would enhance the efficacy of sonodynamic therapy (SDT), which is known to be inhibited in hypoxic tissue. Experiments were conducted in a murine model of pancreatic cancer. Animals were treated with SDT (intratumoural injection of 1 mM Rose Bengal followed by exposure to 1 MHz ultrasound, 0.1 kHz pulse repetition frequency, 30% duty cycle, 3.5 W cm−2 for 3.5 minutes) either with or without a prior gavage of oxygen bubbles. A statistically significant reduction in the rate of tumor growth was observed in the groups receiving oxygen nanobubbles either 5 or 20 minutes before SDT. Separate measurements of tumor oxygen using a fiber optic probe and expression of hypoxia inducible factor (HIF)1α following tumor excision, confirmed the change in tumor oxygen levels. These findings offer a potentially promising new approach to relieving tissue hypoxia in order to facilitate cancer therapy
Phylogenetic evidence from freshwater crayfishes that cave adaptation is not an evolutionary dead-end.
Caves are perceived as isolated, extreme habitats with a uniquely specialized biota, which long ago led to the idea that caves are evolutionary dead-ends. This implies that cave-adapted taxa may be doomed for extinction before they can diversify or transition to a more stable state. However, this hypothesis has not been explicitly tested in a phylogenetic framework with multiple independently evolved cave-dwelling groups. Here, we use the freshwater crayfish, a group with dozens of cave-dwelling species in multiple lineages, as a system to test this hypothesis. We consider historical patterns of lineage diversification and habitat transition as well as current patterns of geographic range size. We find that while cave-dwelling lineages have small relative range sizes and rarely transition back to the surface, they exhibit remarkably similar diversification patterns to those of other habitat types and appear to be able to maintain a diversity of lineages through time. This suggests that cave adaptation is not a dead-end for freshwater crayfish, which has positive implications for our understanding of biodiversity and conservation in cave habitats
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