Direct inference of the distribution of fitness effects of spontaneous mutations from recombinant inbred Caenorhabditis elegans mutation accumulation lines.

The distribution of fitness effects of new mutations plays a central role in evolutionary biology. Estimates of the distribution of fitness effect from experimental mutation accumulation lines are compromised by the complete linkage disequilibrium between mutations in different lines. To reduce the linkage disequilibrium, we constructed 2 sets of recombinant inbred lines from a cross of 2 Caenorhabditis elegans mutation accumulation lines.

Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection.

Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival.

Design, Setting, And Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021.

Tracing the evolution of single-cell cancer 3D genomes: an atlas for cancer gene discovery.

Although three-dimensional (3D) genome structures are altered in cancer cells, little is known about how these changes evolve and diversify during cancer progression. Leveraging genome-wide chromatin tracing to visualize 3D genome folding directly in tissues, we generated 3D genome cancer atlases of murine lung and pancreatic adenocarcinoma. Our data reveal stereotypical, non-monotonic, and stage-specific alterations in 3D genome folding heterogeneity, compaction, and compartmentalization as cancers progress from normal to preinvasive and ultimately to invasive tumors, discovering a potential structural bottleneck in early tumor progression.

Characterization of GATA3 and Mammaglobin in breast tumors from African American Women.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin in breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes.

Characterization of GATA3 and Mammaglobin in breast tumors from African American women.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes.

Mutation, selection, and the prevalence of the Caenorhabditis elegans heat-sensitive mortal germline phenotype.

Caenorhabditis elegans strains with the heat-sensitive mortal germline phenotype become progressively sterile over the course of a few tens of generations when maintained at temperatures near the upper range of C. elegans' tolerance. Mortal germline is transgenerationally heritable, and proximately under epigenetic control.

Mutability of mononucleotide repeats, not oxidative stress, explains the discrepancy between laboratory-accumulated mutations and the natural allele-frequency spectrum in .

Important clues about natural selection can be gleaned from discrepancies between the properties of segregating genetic variants and of mutations accumulated experimentally under minimal selection, provided the mutational process is the same in the laboratory as in nature. The base-substitution spectrum differs between laboratory mutation accumulation (MA) experiments and the standing site-frequency spectrum, which has been argued to be in part owing to increased oxidative stress in the laboratory environment. Using genome sequence data from MA lines carrying a mutation (-) that increases the cellular titer of reactive oxygen species (ROS), leading to increased oxidative stress, we find the base-substitution spectrum is similar between -, its wild-type progenitor (N2), and another set of MA lines derived from a different wild strain (PB306).