Desiree Jones

PLCG2 C2 domain mutations co-occur with BTK and PLCG2 resistance mutations in chronic lymphocytic leukemia undergoing ibrutinib treatment

PLCG2 C2 domain mutations co-occur with BTK and PLCG2 resistance mutations in chronic lymphocytic leukemia undergoing ibrutinib treatment

Actin grips: Circular actin-rich cytoskeletal structures that mediate the wrapping of polymeric microfibers by endothelial cells

Interaction of endothelial-lineage cells with three-dimensional substrates was much less studied than that with flat culture surfaces. We investigated the in vitro attachment of both mature endothelial cells (ECs) and of less differentiated EC colony-forming cells to poly-e-capro-lactone (PCL) fibers with diameters in 5–20 μm range (‘scaffold microfibers’, SMFs). We found that notwithstanding the poor intrinsic adhesiveness to PCL, both cell types completely wrapped the SMFs after long-term cultivation, thus attaining a cylindrical morphology. In this system, both EC types grew vigorously for more than a week and became increasingly more differentiated, as shown by multiplexed gene expression. Three-dimensional reconstructions from multiphoton confocal microscopy images using custom software showed that the filamentous (F) actin bundles took a conspicuous ring-like organization around the SMFs. Unlike the classical F-actin-containing stress fibers, these rings were not associated with either focal adhesions or intermediate filaments. We also demonstrated that plasma membrane boundaries adjacent to these circular cytoskeletal structures were tightly yet dynamically apposed to the SMFs, for which reason we suggest to call them ‘actin grips’. In conclusion, we describe a particular form of F-actin assembly with relevance for cytoskeletal organization in response to biomaterials, for endothelial-specific cell behavior in vitro and in vivo, and for tissue engineering.

Robust detection and visualization of cytoskeletal structures in fibrillar scaffolds from 3-dimensional confocal image

Polymerized actin-based cytoskeletal structures provide the cells with shape, resilience and dynamics. A mechanistic understanding of actin-based structures is crucial for finding solutions to practical problems occurring in tissue engineering constructs that require the interaction of cells with materials. In this regard, the first step is to detect and quantify actin-based structures in 3D cellular ensembles. In this work, we propose visual-analytic tools to delineate specific structures involving F-actin in cells. Concave actin bundles (CABs) often occur in hybrid cell-seeded fibrillar scaffolds and seem to envelope the fibers, as a possible mechanism of stable attachment. There is much uncertainty that accompanies the detection and the identification of fibers. Our tools rely on well-known algorithms of image analysis. We first delineate fibers by employing an adaptive min-cut-max-flow algorithm. Then, from the extremities of the segmented fibers, a template matching and a fiber tracking algorithm is applied to more precisely characterize the fibers in the image. CABs that surround the scaffold fibers transversally are located by observing their radial distribution around the nearby templates in focus. Finally, we visually examine candidate templates that possibly contain CABs and further determine if candidate CABs are indeed legitimate. It can be unequivocally stated that in the absence of the proposed visual analytic tools, the detection of CABs is intractable tasks.

Most multiple myeloma patients have low testosterone

Sonya John, Nidhi Sharma, Douglas W. Sborov, Nita Williams, Desir ee Jones, Don M. Benson, Yvonne A. Efebera, Ashley E. Rosko, Jennifer Vincent and Craig C. Hofmeister College of Medicine, The Ohio State University, Columbus, OH, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; Division of Hematology & Hematologic Malignancies, Department of Internal Medicine, Huntsman Cancer Institute University of Utah, Salt Lake City, UT, USA

Use of a comprehensive frailty assessment to predict morbidity in patients with multiple myeloma undergoing transplant

Multiple myeloma (MM) is a disease of aging adults and autologous stem cell transplant (ASCT) is considered the standard of care. As the population ages a growing number of older adults will undergo ASCT and an objective approach to estimate physiologic reserve and transplant morbidity risk is warranted. Here, we evaluate assess p16INK4a (p16), a molecular aging biomarker, along with geriatric metrics to determine risk of transplant toxicity. METHODS We prospectively evaluated 100 MM patients for frailty before and after ASCT using a Geriatric Assessment (GA) and collected T-cells for analysis of p16 using a custom nanostring codeset. RESULTS Pre-transplant physical function was predicative of hospital length of stay (LOS). Each one-unit increase in physical function score, the average LOS decreased by 0.52 days (95% CI, -1.03-0.02); p = .04). Similarly, higher self-report of ADL/IADL (Human Activity Profile was associated with shorter LOS (0.65 less days (95% CI -1.15 to -0.15), p = .01). Patients with anxiety/depression (OR = 1.10 (95% CI 1.00-1.22), p = .056), lower handgrip strength (OR = 0.90 (95% CI 0.82-0.98), p = .02), falls (OR = 1.60 (95% CI 1.07-2.38), p = .02), or weight loss (OR = 5.65 (95% CI 1.17-25.24), p = .03) were more likely to be re-admitted. The estimated EFS at 1-year was 85% (95% CI, 75-91) with median follow-up of 15.7 months. Weight loss was a significant predictor of EFS (HR = 3.13 (95% CI 1.15-8.50), p = .03). Frailty assessment by self-reported fatigue minimally correlated with T-cell p16 expression (r = 0.28; p = .02). Age, Karnofsky Performance Status (KPS), or Hematopoietic cell transplantation-specific Co-Morbidity Index (HCT-CI) did not predict hospital LOS or readmissions. CONCLUSIONS Our data illustrate that a GA can identify individuals with MM who are at greater risk for morbidity following ASCT.