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Quantitative definition of chemical synthetic pathway complexity of organic compounds

Baranwal et al. | Jun 19, 2023

Quantitative definition of chemical synthetic pathway complexity of organic compounds

Irrespective of the final application of a molecule, synthetic accessibility is the rate-determining step in discovering and developing novel entities. However, synthetic complexity is challenging to quantify as a single metric, since it is a composite of several measurable metrics, some of which include cost, safety, and availability. Moreover, defining a single synthetic accessibility metric for both natural products and non-natural products poses yet another challenge given the structural distinctions between these two classes of compounds. Here, we propose a model for synthetic accessibility of all chemical compounds, inspired by the Central Limit Theorem, and devise a novel synthetic accessibility metric assessing the overall feasibility of making chemical compounds that has been fitted to a Gaussian distribution.

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The role of xpa-1 and him-1 in UV protection of Caenorhabditis elegans

Tung et al. | Feb 25, 2022

The role of <em>xpa-1</em> and <em>him-1</em> in UV protection of <em>Caenorhabditis elegans</em>

Caenorhabditis elegans xpa-1 and him-1 are orthologs of human XPA and human SMC1A, respectively. Mutations in the XPA are correlated with Xeroderma pigmentosum, a condition that induces hypersensitivity to ultraviolet (UV) radiation. Alternatively, SMC1A mutations may lead to Cornelia de Lange Syndrome, a multi-organ disorder that makes patients more sensitive to UVinduced DNA damage. Both C. elegans genes have been found to be involved in protection against UV radiation, but their combined effects have not been tested when they are both knocked down. The authors hypothesized that because these genes are involved in separate pathways, the simultaneous knockdown of both of these genes using RNA interference (RNAi) in C. elegans will cause them to become more sensitive to UV radiation than either of them knocked down individually. UV protection was measured via the percent survival of C. elegans post 365 nm and 5.4x10-19 joules of UV radiation. The double xpa-1/him-1 RNAi knockdown showed a significantly reduced percent survival after 15 and 30 minutes of UV radiation relative to wild-type and xpa-1 and him-1 single knockdowns. These measurements were consistent with their hypothesis and demonstrated that xpa-1 and him-1 genes play distinct roles in resistance against UV stress in C. elegans. This result raises the possibility that the xpa-1/him-1 double knockdown could be useful as an animal model for studying the human disease Xeroderma pigmentosum and Cornelia de Lange Syndrome.

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Characterization of a UPEC DegS Mutant in vitro and in vivo

Bradley et al. | Mar 16, 2015

Characterization of a UPEC <em>DegS</em> Mutant <em>in vitro</em> and <em>in vivo</em>

DegS is an integral inner membrane protein in E. coli that helps break down misfolded proteins. When it is mutated, there is a large increase in the production of outer membrane vesicles (OMVs), which are thought to play a role in pathogenesis. This study used mutant strains of uropathogenic E. coli (UPEC) to characterize the role of DegS and OMVs on UPEC virulence.

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Pressure and temperature influence the efficacy of metal-organic frameworks for carbon capture and conversion

Lin et al. | May 07, 2023

Pressure and temperature influence the efficacy of metal-organic frameworks for carbon capture and conversion

Metal-organic frameworks (MOFs) are promising new nanomaterials for use in the fight against climate change that can efficiently capture and convert CO2 to other useful carbon products. This research used computational models to determine the reaction conditions under which MOFs can more efficiently capture and convert CO2. In a cost-efficient manner, this analysis tested the hypothesis that pressure and temperature affect the efficacy of carbon capture and conversion, and contribute to understanding the optimal conditions for MOF performance to improve the use of MOFs for controlling greenhouse CO2 emissions.

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Toxicity of aminomethylphosphonic acid via the Wnt signaling pathway as a novel mechanism

Zhuang et al. | Mar 08, 2023

Toxicity of aminomethylphosphonic acid via the Wnt signaling pathway as a novel mechanism
Image credit: Image credit: Dapur Melodi

The Wnt signaling pathway, known to coordinate important aspects of cellular homeostasis ranging from differentiation, proliferation, migration, and much more, is dysregulated in many human diseases. This study demonstrates that aminomethylphosphonic acid, which is the main metabolite found in the common herbicide Glyphosate, is toxic to planaria and capable of binding to canonical Wnt proteins.

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Sex differences in confidence and memory

Primack et al. | Oct 25, 2021

Sex differences in confidence and memory

In this work, the authors sought to provide an original experiment to investigate the conflict over whether males or females tend to exhibit greater accuracy or confidence in their memories. By using an online portal to obtain a convenience sample, the authors found that their results suggest that though males tend to be more confident regarding their memories, they may in fact remember fewer details. The authors suggest that these findings merit further research before making systematic changes regarding crime scene recall settings.

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