Proc Natl Acad Sci U S A
January 2025
Seeds are complex structures composed of three regions, embryo, endosperm, and seed coat, with each further divided into subregions that consist of tissues, cell layers, and cell types. Although the seed is well characterized anatomically, much less is known about the genetic circuitry that dictates its spatial complexity. To address this issue, we profiled mRNAs from anatomically distinct seed subregions at several developmental stages.
View Article and Find Full Text PDFObjective: To present a large U.S. clinical validation of a next-generation sequencing-based, noninvasive prenatal cell-free DNA test for fetal RHD.
View Article and Find Full Text PDFWe describe a rare case of capecitabine-induced palmar-plantar erythrodysesthesia (PPE), or hand-foot syndrome (HFS), involving the genitals, which resolved with tacrolimus therapy, in a patient with cT3dN3 stage IIIc moderately differentiated proximal rectal adenocarcinoma who was undergoing neoadjuvant chemotherapy. Given its severe impact on the quality of life, HFS often requires independent local anti-inflammatory treatment and subsequent dose delay and/or modification of the patient's chemotherapy. We believe that our findings in this report can aid clinicians in the early recognition and management of capecitabine-associated HFS resulting in balanitis, as prompt treatment may reduce morbidity and avoid prolonged interruption of chemotherapy in these patients.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
February 2024
Serendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and 14-day and 90-day oral (dietary) toxicity studies in rats. There was no indication of allergenicity for SBSP in the in silico analyses.
View Article and Find Full Text PDFIntroduction: Paraesophageal hernia repair (PEHR) is a safe and effective operation. Previous studies have described risk factors for poor peri-operative outcomes such as emergent operations or advanced patient age, and pre-operative frailty is a known risk factor in other major surgery. The goal of this retrospective cohort study was to determine if markers of frailty were predictive of poor peri-operative outcomes in elective paraesophageal hernia repair.
View Article and Find Full Text PDFRecurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after liver transplant (LT) is mediated by circulating tumour cells (CTCs) and exacerbated by the immunosuppressants required to prevent graft rejection. To circumvent the effects of immunosuppressants, we developed immunosuppressive drug-resistant armoured HBV-specific T-cell receptor-redirected T cells (IDRA HBV-TCR). However, their ability to eliminate HBV-HCC circulating in the whole blood has never been tested, and whether their lytic efficacy is compatible with the number of adoptively transferred T cells has never been measured.
View Article and Find Full Text PDFThe complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified to be pivotal regulators of genome structure and gene expression.
View Article and Find Full Text PDFBackground: Patients are often advised on smoking cessation prior to elective surgical interventions, but the impact of active smoking on paraesophageal hernia repair (PEHR) outcomes is unclear. The objective of this cohort study was to evaluate the impact of active smoking on short-term outcomes following PEHR.
Methods: Patients who underwent elective PEHR at an academic institution between 2011 and 2022 were retrospectively reviewed.
Objective: The purpose of this study was to describe the types of equestrian-related musculoskeletal injuries and their management.
Methods: We retrospectively reviewed the charts of 19 patients who presented with injuries from equestrian activities at a chiropractic practice from December 2000 to December 2020. Deidentified data were extracted from the charts and summarized.
Purpose: Fascial changes in hypermobile Ehlers-Danlos syndrome (hEDS), a heritable connective tissue disorder, can be used visualized with sonoelastography. The purpose of this study was to explore the inter-fascial gliding characteristics in hEDS.
Methods: In 9 subjects, the right iliotibial tract was examined with ultrasonography.
We sought to assess COVID-19 vaccination rates, as well as attitudes and beliefs towards the vaccine, of patients in a Spanish-speaking student-run free clinic in Columbus, Ohio. A cross-sectional study was performed. Surveys were distributed to all individuals over 18 years who presented to La Clínica Latina between July, 2022 and September, 2022.
View Article and Find Full Text PDFProtein-protein interactions (PPIs) have been extensively utilized in synthetic biology to construct artificial gene networks. However, synthetic regulation of gene expression by PPIs in has largely relied upon repressors, and existing PPI-controlled transcriptional activators have generally been employed with heterodimeric interactions. Here we report a highly modular, PPI-dependent transcriptional activator, cCadC, that was designed to be compatible with homomeric interactions.
View Article and Find Full Text PDFDespite the availability of Cas9 variants with varied protospacer-adjacent motif (PAM) compatibilities, some genomic loci-especially those with pyrimidine-rich PAM sequences-remain inaccessible by high-activity Cas9 proteins. Moreover, broadening PAM sequence compatibility through engineering can increase off-target activity. With directed evolution, we generated four Cas9 variants that together enable targeting of most pyrimidine-rich PAM sequences in the human genome.
View Article and Find Full Text PDFDirected evolution has been remarkably successful in identifying enzyme variants with new or improved properties, such as altered substrate scope or novel reactivity. Genetically encodable biosensors (GEBs), which convert the concentration of a small molecule ligand into an easily detectable output signal, have seen increasing application to enzyme directed evolution in the last decade. GEBs enable the use of high-throughput methods to assess enzyme activity of very large libraries, which can accelerate the search for variants with desirable activity.
View Article and Find Full Text PDFNeuronal injury during acute hypoxia, ischemia, and following reperfusion are partially attributable to oxidative damage caused by deleterious fluctuations of reactive oxygen species (ROS). In particular, mitochondrial superoxide (O•-) production is believed to upsurge during lowoxygen conditions and also following reperfusion, before being dismutated to HO and released into the cell. However, disruptions of redox homeostasis may be beneficially attenuated in the brain of hypoxia-tolerant species, such as the naked mole-rat (NMR, Heterocephalus glaber).
View Article and Find Full Text PDFWe examined the characteristics of pro-calcitonin (PCT) in hospitalized COVID-19 patients (cohort 1) and clinical outcomes of antibiotic use stratified by PCT in non-critically ill patients without bacterial co-infection (cohort 2). Retrospective reviews were performed in adult, hospitalized COVID-19 patients during March-May 2020. For cohort 1, we excluded hospital transfers, renal disease and extra-pulmonary infection without isolated pathogen(s).
View Article and Find Full Text PDFTherapeutic antibody development requires discovery of an antibody molecule with desired specificities and drug-like properties. For toxicological studies, a therapeutic antibody must bind the ortholog antigen with a similar affinity to the human target to enable relevant dosing regimens, and antibodies falling short of this affinity design goal may not progress as therapeutic leads. Herein, we report the novel use of mammalian recombination signal sequence (RSS)-directed recombination for complementarity-determining region-targeted protein engineering combined with mammalian display to close the species affinity gap of human interleukin (IL)-13 antibody 731.
View Article and Find Full Text PDFTremor Other Hyperkinet Mov (N Y)
January 2022
Am J Med Genet C Semin Med Genet
December 2021
There is a high prevalence of myofascial pain in people with hypermobile Ehlers-Danlos Syndrome (hEDS). The fascial origin of pain may correspond to changes in the extracellular matrix. The objective of this study was to investigate structural changes in fascia in hEDS.
View Article and Find Full Text PDFThe directed evolution of antibodies has yielded important research tools and human therapeutics. The dependence of many antibodies on disulfide bonds for stability has limited the application of continuous evolution technologies to antibodies and other disulfide-containing proteins. Here we describe periplasmic phage-assisted continuous evolution (pPACE), a system for continuous evolution of protein-protein interactions in the disulfide-compatible environment of the E.
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