Publications by authors named "M S Holdren"
Article Synopsis
- Polycyclic aromatic hydrocarbons (PAHs) are complex organic molecules with multiple interconnected aromatic rings, commonly found in space.
- Researchers discovered 1-cyanopyrene, a specific type of PAH derived from pyrene, in the dense cloud TMC-1 using the Green Bank Telescope.
- The findings imply that PAHs, particularly pyrene, play a significant role in contributing carbon to young planetary systems, suggesting they originate from cold molecular clouds.
Methods are lacking that can prepare deuterium-enriched building blocks, in the full range of deuterium substitution patterns at the isotopic purity levels demanded by pharmaceutical use. To that end, this work explores the regio- and stereoselective deuteration of tetrahydropyridine (THP), which is an attractive target for study due to the wide prevalence of piperidines in drugs. A series of d-d tetrahydropyridine isotopomers were synthesized by the stepwise treatment of a tungsten-complexed pyridinium salt with H/D and H/D.
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- The ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer Variant Curation Expert Panel (HBOP VCEP) created specific guidelines for interpreting variants in the ATM gene, modifying the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines.
- A pilot study testing 33 variants showed strong agreement between the VCEP classifications and existing ClinVar data, though some conflicting interpretations were clarified.
- Overall, the modified rules led to 85% of the variants being classified more definitively, significantly enhancing the reliability of genetic interpretations related to the ATM gene.
Article Synopsis
- The ENIGMA research consortium focuses on determining the clinical significance of variants in hereditary breast and ovarian cancer genes, specifically BRCA1 and BRCA2, and evolved from an external expert panel to an internal Variant Curation Expert Panel (VCEP) to enhance alignment with FDA recognized classification processes.
- The VCEP reviewed existing classification criteria and utilized statistical methods to assess evidence strength, testing new specifications on variants and updating documentation for better user clarity.
- Analysis led to refined classifications for variants—resolving uncertainties and maintaining confidence in others—while revealing gaps in both ENIGMA's research and ACMG/AMP criteria, ultimately improving the classification process for BRCA1 and BRCA2 variants.
Article Synopsis
- PMS2 is a critical gene for DNA-mismatch repair linked to Lynch syndrome and certain cancers, making it a key target in genetic testing.
- The presence of the similar pseudogene PMS2CL complicates the sequencing process, often requiring costly long-read strategies instead of traditional methods.
- The article introduces a new bioinformatics workflow that can streamline PMS2 testing, eliminating the need for these more complex and expensive approaches for most patients.