Efferocytosis of viable versus heat-inactivated MSC induces human monocytes to distinct immunosuppressive phenotypes.

Background: Immunomodulation by mesenchymal stromal cells (MSCs) can occur through trophic factor mechanisms, however, intravenously infused MSCs are rapidly cleared from the body yet a potent immunotherapeutic response is still observed. Recent work suggests that monocytes contribute to the clearance of MSCs via efferocytosis, the body's natural mechanism for clearing dead and dying cells in a non-inflammatory manner. This begs the questions of how variations in MSC quality affect monocyte phenotype and if viable MSCs are even needed to elicit an immunosuppressive response.

Native adiponectin plays a role in the adipocyte-mediated conversion of fibroblasts to myofibroblasts.

Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a three-dimensional human adipocyte spheroid system that has an adipokine profile similar to adipose tissues.

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl.

Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.

Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells.

Mesenchymal stromal cells (MSCs) are administered locally to treat sites of inflammation. Local delivery is known to cause MSCs to aggregate into "spheroids," which alters gene expression and phenotype. While adherent MSCs are highly efficient in their inhibition of T cells, whether or not this property is altered upon MSC aggregation has not been thoroughly determined.

Nature vs. Nurture: Defining the Effects of Mesenchymal Stromal Cell Isolation and Culture Conditions on Resiliency to Palmitate Challenge.

As MSC products move from early development to clinical translation, culture conditions shift from xeno- to xeno-free systems. However, the impact of isolation and culture-expansion methods on the long-term resiliency of MSCs within challenging transplant environments is not fully understood. Recent work in our lab has shown that palmitate, a saturated fatty acid elevated in the serum of patients with obesity, causes MSCs to convert from an immunosuppressive to an immunostimulatory state at moderate to high physiological levels.

Large-Scale Analysis of 48 DNA and 48 RNA Tetranucleotides Studied by 1 μs Explicit-Solvent Molecular Dynamics Simulations.

An understanding of how the conformational behavior of single-stranded DNAs and RNAs depend on sequence is likely to be important for attempts to rationalize the thermodynamics of nucleic acid folding. In an attempt to further our understanding of such sequence dependences, we report here the results of 192 (1 μs) explicit-solvent molecular dynamics (MD) simulations of 48 DNA and 48 RNA tetranucleotide sequences performed using recently reported modifications to the AMBER force field. Each tetranucleotide was simulated starting from two different conformations, a fully natively stacked and a completely unstacked conformation, and populations of the various possible base stacking arrangements were analyzed.

Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-NMR Force Field.

Understanding the intrinsic conformational preferences of amino acids and the extent to which they are modulated by neighboring residues is a key issue for developing predictive models of protein folding and stability. Here we present the results of 441 independent explicit-solvent MD simulations of all possible two-residue peptides that contain the 20 standard amino acids with histidine modeled in both its neutral and protonated states. (3)J(HNHα) coupling constants and δ(Hα) chemical shifts calculated from the MD simulations correlate quite well with recently published experimental measurements for a corresponding set of two-residue peptides.

Blunt force impact to the head using a teeball bat: systematic comparison of physical and finite element modeling.

Blunt head trauma secondary to violent actions with various weapons is frequently a cause of injury in forensic casework; differing striking tools have varying degrees of injury capacity. The systematic approach used to examine a 19-year-old student who was beaten with a wooden teeball bat will be described. The assailant stopped beating the student when the teeball bat broke into two pieces.

Reverse engineering--rapid prototyping of the skull in forensic trauma analysis.

Rapid prototyping (RP) comprises a variety of automated manufacturing techniques such as selective laser sintering (SLS), stereolithography, and three-dimensional printing (3DP), which use virtual 3D data sets to fabricate solid forms in a layer-by-layer technique. Despite a growing demand for (virtual) reconstruction models in daily forensic casework, maceration of the skull is frequently assigned to ensure haptic evidence presentation in the courtroom. Owing to the progress in the field of forensic radiology, 3D data sets of relevant cases are usually available to the forensic expert.