Oxidation of Thiols to Disulfides using an Environmentally “Green” Organocatalyst and New Mechanistic Insights

The selective oxidation of thiols to disulfides is an area of great importance in the areas of materials and medicinal chemistry research. The production of polymers, rubber, pharmaceuticals, and the folding of proteins in biological systems all rely on the formation of disulfide bonds. Herein, we introduce a stoichiometric and electrocatalytic method for the oxidation of various pharmaceutically and biologically relevant thiols into their respective disulfides in more environmentally benign solvents such as water and alcohol solvents. The scope of the transformation was evaluated and a detailed mechanistic study involving control experiments, experimental kinetic studies, and computational investigations led to new insights into how the oxidation takes place via an unusual anionic process

The McDonald Accelerating Stars Survey (MASS):Discovery of a Long-Period Substellar Companion Orbiting the Old Solar Analog HD 47127

Brown dwarfs with well-determined ages, luminosities, and masses provide rare but valuable tests of low-temperature atmospheric and evolutionary models. We present the discovery and dynamical mass measurement of a substellar companion to HD 47127, an old ($\approx$7-10 Gyr) G5 main sequence star with a mass similar to the Sun. Radial velocities of the host star with the Harlan J. Smith Telescope uncovered a low-amplitude acceleration of 1.93 $\pm$ 0.08 m s$^{-1}$ yr$^{-1}$ based on 20 years of monitoring. We subsequently recovered a faint ($\Delta H$=13.14 $\pm$ 0.15 mag) co-moving companion at 1.95$''$ (52 AU) with follow-up Keck/NIRC2 adaptive optics imaging. The radial acceleration of HD 47127 together with its tangential acceleration from Hipparcos and Gaia EDR3 astrometry provide a direct measurement of the three-dimensional acceleration vector of the host star, enabling a dynamical mass constraint for HD 47127 B (67.5-177 $M_\mathrm{Jup}$ at 95% confidence) despite the small fractional orbital coverage of the observations. The absolute $H$-band magnitude of HD 47127 B is fainter than the benchmark T dwarfs HD 19467 B and Gl 229 B but brighter than Gl 758 B and HD 4113 C, suggesting a late-T spectral type. Altogether the mass limits for HD 47127 B from its dynamical mass and the substellar boundary imply a range of 67-78 $M_\mathrm{Jup}$ assuming it is single, although a preference for high masses of $\approx$100 $M_\mathrm{Jup}$ from dynamical constraints hints at the possibility that HD 47127 B could itself be a binary pair of brown dwarfs or that another massive companion resides closer in. Regardless, HD 47127 B will be an excellent target for more refined orbital and atmospheric characterization in the future.Comment: Accepted to ApJ Letter

Tribute to Professor Doug Rendleman

A tribute to Professor Doug Rendleman, who served on the faculty of the Washington and Lee University School of Law from 1988 to 2020. Rendleman became Professor of Law, Emeritus in 2020

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Quantifying annual spatial consistency in chick-rearing seabirds to inform important site identification

Animal tracking has afforded insights into patterns of space use in numerous species and thereby informed area-based conservation planning. A crucial consideration when estimating spatial distributions from tracking data is whether the sample of tracked animals is representative of the wider population. However, it may also be important to track animals in multiple years to capture changes in distribution in response to varying environmental conditions. Using GPS-tracking data from 23 seabird species, we assessed the importance of multi-year sampling for identifying important sites for conservation during the chick-rearing period, when seabirds are most spatially constrained. We found a high degree of spatial overlap among distributions from different years in most species. Multi-year sampling often captured a significantly higher portion of reference distributions (based on all data for a population) than sampling in a single year. However, we estimated that data from a single year would on average miss only 5 % less of the full distribution of a population compared to equal-sized samples collected across three years (min: −0.3 %, max: 17.7 %, n = 23). Our results suggest a key consideration for identifying important sites from tracking data is whether enough individuals were tracked to provide a representative estimate of the population distribution during the sampling period, rather than that tracking necessarily take place in multiple years. By providing an unprecedented multi-species perspective on annual spatial consistency, this work has relevance for the application of tracking data to informing the conservation of seabirds.Fundação para a Ciência e Tecnologia - FCT; ARNETinfo:eu-repo/semantics/publishedVersio

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies