14 research outputs found

    Induction of Group IVC Phospholipase A2 in Allergic Asthma: Transcriptional Regulation by TNF-α in Bronchoepithelial Cells

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    Airway inflammation in allergen-induced asthma is associated with eicosanoid release. These bioactive lipids exhibit anti- and pro-inflammatory activities with relevance to pulmonary pathophysiology. We hypothesized that sensitization/challenge using an extract from the ubiquitous fungus, Aspergillus fumigatus (Af), in a mouse model of allergic asthma would result in altered phospholipase gene expression, thus modulating the downstream eicosanoid pathway. We observed the most significant induction in the group IVC phospholipase A2 (cPLA2Îł or PLA2G4C). Our results infer that Af extract can induce cPLA2Îł levels directly in eosinophils while induction in lung epithelial cells is most likely a consequence of TNF-α secretion by Af-activated macrophages. The mechanism of TNF-α-dependent induction of cPLA2Îł gene expression was elucidated through a combination of promoter deletions, ChIP and overexpression studies in human bronchoepithelial cells, leading to the identification of functionally relevant CRE, NF-ÎșB and E-box promoter elements. ChIP analysis demonstrated that RNA polymerase II, c-Jun/ATF-2, p65/p65 and USF1/USF2 complexes are recruited to the cPLA2Îł enhancer/promoter in response to TNF-α with overexpression and dominant negative studies implying a strong level of cooperation and interplay between these factors. Overall, our data link cytokine-mediated alterations in cPLA2Îł gene expression with allergic asthma and outline a complex regulatory mechanism

    Global urban environmental change drives adaptation in white clover

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    Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

    Control of potassium tantalate niobate thin film crystal phase and orientation by atomic layer deposition

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    Due to its appreciable electro-optical properties, potassium tantalate niobate (KTN) thin films of high quality are expected to enhance the functionality of integrated photonics optical modulators. Unfortunately, they are inherently hard to synthesize. Herein, the authors present atomic layer deposition (ALD) of oriented KTN for the first time. They study the variability in phase content with respect to potassium concentration across a variety of substrates. Films grown with a slight overstoichiometry in potassium show excellent crystal quality of a pure perovskite phase. Highly oriented films were obtained on substrates of a similar lattice constant to bulk potassium tantalate niobate. Nearly stoichiometric potassium contents yield films with similar quality, albeit with trace amounts of pyrochlore. Potassium deficient films consist of an overwhelming amount of pyrochlore. Phase control and orientation control are essential when considering device integration of optical modulators. The authors believe that ALD is an ideal technique to obtain KTN thin films with high growth control

    Biofunctionalization of Multiplexed Silicon Photonic Biosensors

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    Silicon photonic (SiP) sensors offer a promising platform for robust and low-cost decentralized diagnostics due to their high scalability, low limit of detection, and ability to integrate multiple sensors for multiplexed analyte detection. Their CMOS-compatible fabrication enables chip-scale miniaturization, high scalability, and low-cost mass production. Sensitive, specific detection with silicon photonic sensors is afforded through biofunctionalization of the sensor surface; consequently, this functionalization chemistry is inextricably linked to sensor performance. In this review, we first highlight the biofunctionalization needs for SiP biosensors, including sensitivity, specificity, cost, shelf-stability, and replicability and establish a set of performance criteria. We then benchmark biofunctionalization strategies for SiP biosensors against these criteria, organizing the review around three key aspects: bioreceptor selection, immobilization strategies, and patterning techniques. First, we evaluate bioreceptors, including antibodies, aptamers, nucleic acid probes, molecularly imprinted polymers, peptides, glycans, and lectins. We then compare adsorption, bioaffinity, and covalent chemistries for immobilizing bioreceptors on SiP surfaces. Finally, we compare biopatterning techniques for spatially controlling and multiplexing the biofunctionalization of SiP sensors, including microcontact printing, pin- and pipette-based spotting, microfluidic patterning in channels, inkjet printing, and microfluidic probes

    Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element

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    The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∌5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5â€Č ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains
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