7 research outputs found

    Artificial intelligence for natural product drug discovery

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    Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to exciting developments in the computational drug design field, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature. We also discuss how to address key challenges in realizing the potential of these synergies, such as the need for high-quality datasets to train deep learning algorithms and appropriate strategies for algorithm validation

    Artificial intelligence for natural product drug discovery

    No full text
    Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to exciting developments in the computational drug design field, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature. We also discuss how to address key challenges in realizing the potential of these synergies, such as the need for high-quality datasets to train deep learning algorithms and appropriate strategies for algorithm validation. [Abstract copyright: © 2023. Springer Nature Limited.

    Ophthalmology in North America: Early Stories (1491-1801)

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    New World plants, such as tobacco, tomato, and chili, were held to have beneficial effects on the eyes. Indigenous healers rubbed or scraped the eyes or eyelids to treat inflammation, corneal opacities, and even eye irritation from smoke. European settlers used harsh treatments, such as bleeding and blistering, when the eyes were inflamed or had loss of vision with a normal appearance (gutta serena). In New Spain, surgery for corneal opacity was performed in 1601 and cataract couching in 1611. North American physicians knew of contralateral loss of vision after trauma or surgery (sympathetic ophthalmia), which they called “sympathy.” To date, the earliest identified cataract couching by a surgeon trained in the New World was performed in 1769 by John Bartlett of Rhode Island. The American Revolution negatively affected ophthalmology, as loyalist surgeons were expelled and others were consumed with wartime activities. After the war, cataract extraction was imported to America in earnest and academic development resumed. Charles F Bartlett, the son of John, performed cataract extraction but was also a “rapacious privateer.” In 1801, a doctor in the frontier territory of Kentucky observed anticholinergic poisoning by Datura stramonium (Jimsonweed) and suggested that this agent be applied topically to dilate the pupil before cataract extraction. John Warren at Harvard preferred couching in the 1790s, but, after his son returned from European training, recommended treating angle closure glaucoma by lens extraction. Other eye procedures described or advertised in America before the 19th century included enucleation, resection of conjunctival lesions or periocular tumors, treatment of lacrimal fistula, and fitting of prosthetic eyes

    New insights into the genetic etiology of Alzheimer’s disease and related dementias

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    Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    The Birds of Kentucky

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    New insights into the genetic etiology of Alzheimer’s disease and related dementias

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    Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
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