The Complex History of Trojan Asteroids

The Trojan asteroids provide a unique perspective on the history of Solar System. As a large population of small bodies, they record important gravitational interactions and dynamical evolution of the Solar System. In the past decade, significant advances have been made in understanding physical properties, and there has been a revolution in thinking about the origin of Trojans. The ice and organics generally presumed to be a significant part of Trojan compositions have yet to be detected directly, though low density of the binary system Patroclus (and possibly low density of the binary/moonlet system Hektor) is consistent with an interior ice component. By contrast, fine-grained silicates that appear to be similar to cometary silicates in composition have been detected, and a color bimodality may indicate distinct compositional groups among the Trojans. Whereas Trojans had traditionally been thought to have formed near 5 AU, a new paradigm has developed in which the Trojans formed in the proto-Kuiper Belt, and they were scattered inward and captured in the Trojan swarms as a result of resonant interactions of the giant planets. Whereas the orbital and population distributions of current Trojans are consistent with this origin scenario, there are significant differences between current physical properties of Trojans and those of Kuiper Belt objects. These differences may be indicative of surface modification due to the inward migration of objects that became the Trojans, but understanding of appropriate modification mechanisms is poor and would benefit from additional laboratory studies. Many open questions remain, and the future promises significant strides in our understanding of Trojans. The time is ripe for a spacecraft mission to the Trojans, to turn these objects into geologic worlds that can be studied in detail to unravel their complex history.Comment: Chapter for Asteroids IV book (UA Press), accepted for publication, 33 pages, 10 figure

Parallel Picoliter RT-PCR Assays Using Microfluidics

The development of microfluidic tools for high-throughput nucleic acid analysis has become a burgeoning area of research in the post-genome era. Here, we have developed a microfluidic chip to perform 72 parallel 450-pL RT-PCRs. We took advantage of Taqman hydrolysis probe chemistry to detect RNA templates as low as 34 copies. The device and method presented here may enable highly parallel single cell gene expression analysis

Hepatotoxicity Associated with the Use of Anti-TNF-α Agents

Medications to inhibit the actions of tumour necrosis factor alpha have revolutionized the treatment of several pro-inflammatory autoimmune conditions. Despite their many benefits, several serious side effects exist and adverse reactions do occur from these medications. While many of the medications' potential adverse effects were anticipated and recognized in clinical trials prior to drug approval, several more rare adverse reactions were recorded in the literature as the popularity, availability and distribution of these medications grew. Of these potential adverse reactions, liver injury, although uncommon, has been observed in some patients. As case reports accrued over time and ultimately case series developed, the link became better established between this family of medicines and various patterns of liver injury. Interestingly, it appears that the majority of cases exhibit an autoimmune hepatitis profile both in serological markers of autoimmune liver disease and in classic autoimmune features seen on hepatic histopathology. Despite the growing evidence of this relationship, the pathogenesis of this reaction remains incompletely understood, but it appears to depend on characteristics of the medications and the genetic composition of the patients; it is likely more complicated than a simple medication class effect. Because of this still incomplete understanding and the infrequency of the occurrence, treatments have also been limited, although it is clear that most patients improve with cessation of the offending agent and, in certain cases, glucocorticoid use. However, more needs to be done in the future to unveil the underlying mechanisms of this adverse reaction

Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro.

Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I. The application of mechanical strain increased vascular endothelial growth factor A secretion 2-4-fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac extracellular matrix. CPC proliferation was at least 25% higher on fibronectin than that on other matrices, especially for lower strain magnitudes. At 5% strain, connexin43 expression was highest on fibronectin. With increasing strain magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on collagen I and a naturally derived cardiac extracellular matrix. Cyclic mechanical strain induced the strongest CPC alignment when cultured on fibronectin or collagen I. This study demonstrates that culturing CPCs on fibronectin with 5% strain magnitude is optimal for their vascular endothelial growth factor A secretion, proliferation, connexin43 expression, and alignment

Dysregulated NK cell PLCγ2 signaling and activity in juvenile dermatomyositis

Juvenile dermatomyositis (JDM) is a debilitating pediatric autoimmune disease manifesting with characteristic rash and muscle weakness. To delineate signaling abnormalities in JDM, mass cytometry was performed with PBMCs from treatment-naive JDM patients and controls. NK cell percentages were lower while frequencies of naive B cells and naive CD4+ T cells were higher in JDM patients than in controls. These cell frequency differences were attenuated with cessation of active disease. A large number of signaling differences were identified in treatment-naive JDM patients compared with controls. Classification models incorporating feature selection demonstrated that differences in phospholipase Cγ2 (PLCγ2) phosphorylation comprised 10 of 12 features (i.e., phosphoprotein in a specific immune cell subset) distinguishing the 2 groups. Because NK cells represented 5 of these 12 features, further studies focused on the PLCγ2 pathway in NK cells, which is responsible for stimulating calcium flux and cytotoxic granule movement. No differences were detected in upstream signaling or total PLCγ2 protein levels. Hypophosphorylation of PLCγ2 and downstream mitogen-activated protein kinase-activated protein kinase 2 were partially attenuated with cessation of active disease. PLCγ2 hypophosphorylation in treatment-naive JDM patients resulted in decreased calcium flux. The identification of dysregulation of PLCγ2 phosphorylation and decreased calcium flux in NK cells provides potential mechanistic insight into JDM pathogenesis

Parallel Picoliter RT-PCR Assays Using Microfluidics

The development of microfluidic tools for high-throughput nucleic acid analysis has become a burgeoning area of research in the post-genome era. Here, we have developed a microfluidic chip to perform 72 parallel 450-pL RT-PCRs. We took advantage of Taqman hydrolysis probe chemistry to detect RNA templates as low as 34 copies. The device and method presented here may enable highly parallel single cell gene expression analysis

Microfluidic Single-Cell mRNA Isolation and Analysis

Single-cell gene expression analysis holds great promise for studying diverse biological systems, but methodology to process these precious samples in a reproducible, quantitative, and parallel fashion remains challenging. Here, we utilize microfluidics to isolate picogram and subpicogram mRNA templates, as well as to synthesize cDNA from these templates. We demonstrate single-cell mRNA isolation and cDNA synthesis, provide quantitative calibrations for each step in the process, and measure gene expression in individual cells. The techniques presented here form the foundation for highly parallel single-cell gene expression studies

Community Awareness and Utilization of School Based Health Centers in Burlington, Vermont

Most K-12 students will miss at least one day of school each year due to illness or injury; in 2010, six percent missed 11 days or more. School Based Health Clinics, SBHC, are provider-based health clinics located in schools, supplementing routine nursing care and complementing the role of a pediatrician while the child is in school. SBHCs aim to: • Reduce the amount of school that students miss • Provide quick and convenient care for a variety of routine and acute medical concerns Our objective was to: • Investigate community awareness and utilization of the SBHCs in the Burlington School District • Providing insight regarding how to increase engagement of students and parents with the SBHC’s and thereby reduce avoidable class absenteeism.https://scholarworks.uvm.edu/comphp_gallery/1274/thumbnail.jp