Rescue in vitro maturation using ovarian support cells of human oocytes from conventional stimulation cycles yields oocytes with improved nuclear maturation and transcriptomic resemblance to in vivo matured oocytes.

Purpose: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM).

Methods: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h.

Allelic variation in class I HLA determines CD8 T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2.

Effective presentation of antigens by human leukocyte antigen (HLA) class I molecules to CD8 T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multiomic technology to generate a unified ex vivo characterization of the CD8 T cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across four major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCRα/β sequence diversity, and the utilization of pre-existing SARS-CoV-2-reactive memory T cell pools.

Reproducible Novel Transcriptional Differences Between Psoriatic Lesional and Non-Lesional Skin Show Increased Inflammation and Metabolism.

Background: Psoriasis is a common but complex chronic inflammatory skin Disease. Array-based studies can help identify therapeutic targets.

Objective: To reproducibly assess single-gene transcriptional changes in psoriatic skin.

Redirector: designing cell factories by reconstructing the metabolic objective.

Advances in computational metabolic optimization are required to realize the full potential of new in vivo metabolic engineering technologies by bridging the gap between computational design and strain development. We present Redirector, a new Flux Balance Analysis-based framework for identifying engineering targets to optimize metabolite production in complex pathways. Previous optimization frameworks have modeled metabolic alterations as directly controlling fluxes by setting particular flux bounds.

Potentiation of dietary restriction-induced lifespan extension by polyphenols.

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension.

Large-scale identification of genetic design strategies using local search.

In the past decade, computational methods have been shown to be well suited to unraveling the complex web of metabolic reactions in biological systems. Methods based on flux-balance analysis (FBA) and bi-level optimization have been used to great effect in aiding metabolic engineering. These methods predict the result of genetic manipulations and allow for the best set of manipulations to be found computationally.

Validation of genomics-based prognostic tests in malignant pleural mesothelioma.

Purpose: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm with limited pretreatment prognostication strategies. In this report, we examine the accuracy of a previously proposed prognostic test in an independent cohort of MPM patients. This test uses simple ratios of gene expression levels to provide a novel prognostication scheme.

Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.

Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n = 40), normal lung specimens (n = 4), normal pleura specimens (n = 5), and MPM and SV40-immortalized mesothelial cell lines (n = 5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma that correlated loosely with tumor histology.