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Biology subjects

Hughes, N.

Publications and source records attributed to Hughes, N..

6 recordsLinked to original sources

Infrared imaging supports warming effects of anthocyanin pigments in flowers of diverse plant taxa

Flower color has primarily been studied in the context of pollinator attraction, although effects on thermal energy balance are also important, especially in the context of global climate change. We used infrared imaging to compare petal temperatures of white versus pigmented cultivars of ten angiosperm taxa under controlled environmental conditions. Excised sets of flowers (n= 6 sets per species) exhibiting white, light, and/or dark anthocyanin (red to purple) coloration were mounted perpendicularly to the sun at mid-day, under clear sky, low wind (<1 m s-1) conditions. Sunlight was filtered through either UV-transparent or UV-opaque film, and petal temperatures were measured using an infrared camera after one minute equilibration. In all species, pigmented flowers were significantly warmer than lighter-colored conspecifics. Mean differences averaged +5.3{degrees}C for darker-colored versus white morphs, +2.9{degrees}C for lighter-colored versus white. Most warming was associated with visible wavelengths, but additional warming under UV-inclusion was also observed in some species. In situ observations of intact landscape plants under low-wind, high-light conditions corroborated experimental results, with differences exceeding 10{degrees}C observed in some taxa. Temperature differences >7{degrees}C were also recorded for purple versus white sections of the same flower in multicolored Viola and Petunia cultivars. Follow-up experiments using dark-pink and white varieties of Impatiens x hybrida corroborated well-known effects of sunlight intensity and wind speed on floral temperatures, helping to explain inconsistent reports in the literature. Our results clearly demonstrate that anthocyanin pigments can have significant and dramatic impacts on floral temperatures, which could be an important factor driving evolution of flower color. In the context of climate change, floral pigments could amplify the effects of rising global temperatures, negatively impacting plant reproduction and crop yields, especially on the warmer end of species ranges. Changes in flower color could also potentially induce shifts in pollinator communities, which could have community-scale effects.

ecology↗

CXCL-CXCR2 signaling drives cancer-endothelium interactions in SCLC metastatic seeding

Small cell lung cancer (SCLC) is a highly metastatic malignancy with tropism to the liver, yet the signals that enable organ-specific metastatic colonization remain largely undefined. During metastasis, disseminated cancer cells first encounter endothelial cells (ECs) at the vascular-tissue interface, positioning cancer-endothelium crosstalk as a key determinant of metastatic success. Defining the signaling pathways underlying this reciprocal communication may uncover actionable vulnerabilities for preventing and treating this lethal disease. Here, we uncover an EC-derived CXCL chemokine program that activates cancer-intrinsic CXCR2-RAC1 signaling as a critical mediator of SCLC liver metastasis. By integrating in vitro and in vivo models, we show that SCLC cells induce robust CXCL chemokine expression from liver ECs, which in turn enhances SCLC migration and reinforces cancer cell-EC interactions. We applied highly quantitative metastatic colony barcode sequencing coupled with individual gene inactivation to demonstrate that CXCR2 is essential for SCLC migration and liver metastatic seeding. Mechanistically, CXCL-CXCR2 signaling activates RAC1-dependent F-actin assembling to drive SCLC motility during CXCL-induced metastatic seeding. Pharmacologic inhibition of CXCR2 or RAC1 suppresses SCLC migration and prevents SCLC liver metastasis. Together, our research defined a chemokine-driven signaling circuit that governs cancer-endothelium communication during the metastatic cascade and nominate the CXCL-CXCR2-RAC1 axis as a promising therapeutic vulnerability for preventing and treating metastatic SCLC.

cancer biology↗

Positive selection on hotspot and reinforcing regulatory alleles contributed to hexaploid bread wheat improvement.

BackgroundGenetic variation of regulatory alleles plays a key role in evolution and breeding. In polyploids, regulatory differences may preferentially affect genes on homoeologous chromosomes or sub-genomes. Selection in plant breeding may act upon total transcript dosage across homoeologous genes and on alleles that have strong effects on the transcriptome. ResultsTo investigate these questions, we identified regulatory polymorphisms between an old and a recent hexaploid bread wheat cultivar (Triticum aestivum, 2n=6x=42, AABBDD). The recent cultivar was the product of decades of selection for grain yield and quality. Regulatory allele polymorphisms preferentially affected genes on homoeologous chromosomes but rarely affected genes on specific sub-genomes. The chromosomal distributions of regulatory alleles indicated that past selection had acted upon them, and the effect of selection differed between alleles targeting environmental response genes and genes involved in other processes. Modern cultivar alleles that affected many genes transcripts corresponded to known selection targets and improved field crop performance. Modern cultivar alleles also had significant effects on homoeologous genes, and these alleles also improved crop performance. ConclusionsPolyploid breeding across many species has been and will continue to be the key factor in plant improvement. By enhancing the favorability of strong regulatory alleles and by expanding the range of gene transcript abundances, genome duplications enable breeding progress.

genomics↗

Contributions of mirror-image hair cell orientation to mouse otolith organ and zebrafish neuromast function

Otolith organs in the inner ear and neuromasts in the fish lateral-line harbor two populations of hair cells oriented to detect stimuli in opposing directions. The underlying mechanism is highly conserved: the transcription factor EMX2 is regionally expressed in just one hair cell population and acts through the receptor GPR156 to reverse cell orientation relative to the other population. In mouse and zebrafish, loss of Emx2 results in sensory organs that harbor only one hair cell orientation and are not innervated properly. In zebrafish, Emx2 also confers hair cells with reduced mechanosensory properties. Here, we leverage mouse and zebrafish models lacking GPR156 to determine how detecting stimuli of opposing directions serves vestibular function, and whether GPR156 has other roles besides orienting hair cells. We find that otolith organs in Gpr156 mouse mutants have normal zonal organization and normal type I-II hair cell distribution and mechano-electrical transduction properties. In contrast, gpr156 zebrafish mutants lack the smaller mechanically-evoked signals that characterize Emx2-positive hair cells. Loss of GPR156 does not affect orientation-selectivity of afferents in mouse utricle or zebrafish neuromasts. Consistent with normal otolith organ anatomy and afferent selectivity, Gpr156 mutant mice do not show overt vestibular dysfunction. Instead, performance on two tests that engage otolith organs is significantly altered - swimming and off-vertical-axis rotation. We conclude that GPR156 relays hair cell orientation and transduction information downstream of EMX2, but not selectivity for direction-specific afferents. These results clarify how molecular mechanisms that confer bi-directionality to sensory organs contribute to function, from single hair cell physiology to animal behavior.

neuroscience↗

A 2.8A structure of zoliflodacin in a DNA-cleavage complex with Staphylococcus aureus DNA gyrase

Since 2000 some thirteen quinolones/fluoroquinolones have been developed and come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA-cleavage complexes with DNA gyrase and topo IV, the two bacterial type IIA topoisomerases. The dual targeting of gyrase and topo IV helps decrease the likelihood of resistance developing. Here we report a 2.8 [A] X-ray crystal structure which shows that zoliflodacin, a spiropyrimidinetrione antibiotic, binds in the same DNA-cleavage site(s) as quinolones sterically blocking DNA religation. The structure shows that zoliflodacin interacts with highly conserved residues on GyrB (and does not use the quinolone water-metal ion bridge to GyrA) suggesting it may be more difficult for bacteria to develop target mediated resistance. We found that zoliflodacin had an MIC of 4 {micro}g/mL against Acinetobacter baumannii, an improvement of 4-fold over its progenitor QPT-1. The current phase III clinical trial of zoliflodacin for gonorrhea is due to be read out in 2023. Zoliflodacin, together with the unrelated novel bacterial topoisomerase inhibitor gepotidacin, are likely to become the first entirely novel chemical entities approved against Gram-negative bacteria in the 21st century. Zoliflodacin may also become the progenitor of a new safer class of antibacterial drugs against other problematic Gram-negative bacteria.

biophysics↗

Colletotrichum higginsianum effectors exhibit cell to cell hypermobility in plant tissues and modulate intercellular connectivity amongst a variety of cellular processes

Multicellular organisms exchange information and resources between cells to co-ordinate growth and responses. In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. Some plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion. However, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To begin to investigate this and identify which effectors are cell-to-cell mobile, we performed a live imaging-based screen and identified 15 cell-to-cell mobile effectors of the fungal pathogen Colletotrichum higginsianum. Of these, 6 are "hypermobile", showing cell-to-cell mobility greater than expected for a protein of its size. We further identified 3 effectors that can indirectly modify plasmodesmal aperture. Transcriptional profiling of plants expressing hypermobile effectors implicate them in a variety of processes including senescence, glucosinolate production, cell wall integrity, growth and iron metabolism. However, not all effectors had an independent effect on virulence. This suggests a wide range of benefits to infection gained by the mobility of C. higginsianum effectors that likely interact in a complex way during infection.

plant biology↗