Objectives: Home-based hematopoietic stem cell transplantation (HCT) is a novel approach that has the potential to improve outcomes, however, the impact of transplant location on the gut microbiome remains uncharacterized. We hypothesized that patients randomized to undergo home HCT would have higher gut taxonomic diversity and lower antimicrobial resistance (AMR) gene abundance compared to those undergoing standard hospital HCT.
Methods: We identified 28 patients enrolled in Phase II randomized trials of home (n=16) v.
We present replication-aware single-molecule accessibility mapping (RASAM), a method to nondestructively measure replication status and protein-DNA interactions on chromatin genome-wide. Using RASAM, we uncover a genome-wide state of single-molecule "hyperaccessibility" post-replication that resolves over several hours. Combining RASAM with cellular models for rapid protein degradation, we demonstrate that histone chaperone CAF-1 reduces nascent chromatin accessibility by filling single-molecular "gaps" and generating closely spaced dinucleosomes on replicated DNA.
View Article and Find Full Text PDFThe centromeric histone H3 variant CENP-A is overexpressed in many cancers. The mislocalization of CENP-A to noncentromeric regions contributes to chromosomal instability (CIN), a hallmark of cancer. However, pathways that promote or prevent CENP-A mislocalization remain poorly defined.
View Article and Find Full Text PDFIntroduction: Patients with metastatic NSCLC (mNSCLC) treated with immune checkpoint inhibitors in clinical practice may often not meet the strict inclusion criteria of clinical trials. Our aim was to assess the trial eligibility of patients with mNSCLC treated with pembrolizumab monotherapy in real-world and to compare the outcome of "trial-ineligible" and "potentially trial-eligible" patients.
Methods: Data from the prospective, clinical research platform CRISP were used to compare patient characteristics, treatment, and outcome of patients with programmed cell death-ligand 1 tumor proportion score greater than or equal to 50% tumors treated with pembrolizumab monotherapy who are deemed either "potentially trial-eligible" or "trial-ineligible" according to inclusion and exclusion criteria of the registrational studies (KEYNOTE-024 and -042).
Long-term perturbation of chromatin assembly during DNA replication has profound effects on epigenome maintenance and cell fate. The early mechanistic origin of these defects is unknown. Here, we combine acute degradation of Chromatin Assembly Factor 1 (CAF-1), a key player in chromatin assembly, with single-cell genomics, quantitative proteomics, and live-microscopy to uncover these initiating mechanisms in human cells.
View Article and Find Full Text PDFCurr Opin Genet Dev
April 2024
Sustaining cell identity and function across cell division is germane to human development, healthspan, and cancer avoidance. This relies significantly on propagation of chromatin organization between cell generations, as chromatin presents a barrier to cell fate and cell state conversions. Inheritance of chromatin states across the many cell divisions required for development and tissue homeostasis represents a major challenge, especially because chromatin is disrupted to allow passage of the DNA replication fork to synthesize the two daughter strands.
View Article and Find Full Text PDFIntroduction: Military transport can induce whole-body vibrations, and combat almost always involves high impact between lower extremities and the ground. Therefore, robust splinting technology is necessary for lower extremity fractures in these settings. Our team compared a novel one-step spray-on foam splint (FastCast) to the current military standard structured aluminum malleable (SAM) splint.
View Article and Find Full Text PDFBackground: Gastrointestinal eosinophilic sclerosing fibroplasia (GESF) in cats presents as mass(es) associated with the gastrointestinal tract, mesentery, and abdominal lymph nodes.
Hypothesis/objectives: To report the clinicopathological findings, treatment, and outcome of cats with GESF.
Animals: Sixty client-owned cats diagnosed with GESF.
Neurologic foot contractures pose a challenging situation for orthopaedic surgeons. These deformities are long-standing problems for patients with acute brain injuries, ultimately affecting their quality of life. We report our experience with using arthroscopic assisted, minimally invasive contracture tenotomies paired with a tibio-talo-calcaneal arthrodesis to achieve improved alignment and functional reconstruction of spastic equinovarus foot deformities.
View Article and Find Full Text PDFThe gene in is an orthologue of the gene in and the odd-skipped related genes in mammals. The mammalian genes have been shown to be expressed in a variety of tissues and cancers. It was previously reported that ODD-2 is expressed in the intestine and shows some expression outside of the intestine in the tail region.
View Article and Find Full Text PDFModified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. How this may sustain the epigenome and cell identity remains unknown. Here we show that transmission of histone-based information during DNA replication maintains epigenome fidelity and embryonic stem cell plasticity.
View Article and Find Full Text PDFObjective: To assess whether gonioscopy performed on Samoyed puppies (6-14 weeks of age) is a reliable predictor of their gonioscopy results as adults (>11 months of age).
Procedure: A retrospective medical record search was performed to identify Samoyed dogs that had undergone gonioscopy as a puppy (6-14 weeks of age). A second prospective gonioscopy examination was performed as an adult (>11 months of age) and the results were compared.
Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks.
View Article and Find Full Text PDFContext: Achilles tendon (AT) injuries are common in female runners and military personnel where increased AT loading may be a contributing factor. Few studies have examined AT stress during running with added mass. The purpose was to examine the stress, strain, and force placed on the AT, kinematics and temporospatial variable in running with different amounts of added mass.
View Article and Find Full Text PDFIntroduction: Cervical spine immobilization in a low-resource environment is difficult secondary to limited equipment, prolonged transportation, and secondary complications. A structural aluminum malleable (SAM) splint is commonly utilized because of its availability and multipurpose intention. A one-step spray-on foam immobilization technique (Fast Cast) has been shown to be effective in lower-extremity splinting.
View Article and Find Full Text PDFDuring every cell cycle, both the genome and the associated chromatin must be accurately replicated. Chromatin Assembly Factor-1 (CAF-1) is a key regulator of chromatin replication, but how CAF-1 functions in relation to the DNA replication machinery is unknown. Here, we reveal that this crosstalk differs between the leading and lagging strand at replication forks.
View Article and Find Full Text PDFOperons are transcriptional modules that allow bacteria to adapt to environmental changes by coordinately expressing the relevant set of genes. In humans, biological pathways and their regulation are more complex. If and how human cells coordinate the expression of entire biological processes is unclear.
View Article and Find Full Text PDFMethods Mol Biol
February 2023
Open or accessible chromatin typifies euchromatic regions and helps define cell type-specific transcription programs. DNA replication massively disorders chromatin composition and structure, and how accessible regions are affected by and recover from this disruption has been unclear. Here, we present repli-ATAC-seq, a protocol to profile accessible chromatin genome-wide on replicated DNA starting from 100,000 cells.
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