5,660 research outputs found
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Pathophysiological roles of thrombospondin-4 in disease development
Thrombospondin-4 (TSP-4) belongs to the extracellular matrix glycoprotein family of thrombospondins (TSPs). The multidomain, pentameric structure of TSP-4 allows its interactions with numerous extracellular matrix components, proteins and signaling molecules that enable its modulation to various physiological and pathological processes. Characterization of TSP-4 expression under development and pathogenesis of disorders has yielded important insights into mechanisms underlying the unique role of TSP-4 in mediating various processes including cell-cell, cell-extracellular matrix interactions, cell migration, proliferation, tissue remodeling, angiogenesis, and synaptogenesis. Maladaptation of these processes in response to pathological insults and stress can accelerate the development of disorders including skeletal dysplasia, osteoporosis, degenerative joint disease, cardiovascular diseases, tumor progression/metastasis and neurological disorders. Overall, the diverse functions of TSP-4 suggest that it may be a potential marker or therapeutic target for prognosis, diagnosis, and treatment of various pathological conditions upon further investigations. This review article highlights recent findings on the role of TSP-4 in both physiological and pathological conditions with a focus on what sets it apart from other TSPs
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A Co-culture System for Studying Dorsal Spinal CordSynaptogenesis
Studying synapse formation, maintenance, and plasticity in adaptation to developmental and pathological changes is critical in our understanding of cellular mechanisms of biological processes and disease states. However, a major barrier in getting cell-type-specific detail information in these studies is the complexity of in vivo environment in high-density tissue or organs, such as spinal cord, that is packed with different types of cells, connecting tissues and structural components. In this chapter, we describe a co-culture system in which dorsal root ganglion sensory neurons and spinal cord neurons are cultured in separate compartments without culture medium diffusion between compartments, but allowing sensory neuron axons to outgrowth to adjacent chambers to establish synaptic connections with dendrites of spinal cord neurons. This provides an in vitro environment that mimics the in vivo synaptogenic environment between sensory neurons and spinal cord neurons and enables manipulation of specific neuronal populations and studying their detail contribution to synaptic formation, maintenance, and plastic changes
Calcium channel Ī±2Ī“1 proteins mediate trigeminal neuropathic pain states associated with aberrant excitatory synaptogenesis.
To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel Ī±2Ī“1 (CavĪ±2Ī“1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with CavĪ±2Ī“1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking CavĪ±2Ī“1 with gabapentin, a ligand for the CavĪ±2Ī“1 proteins, or CavĪ±2Ī“1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of CavĪ±2Ī“1 in orofacial pain processing. Importantly, increased CavĪ±2Ī“1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced CavĪ±2Ī“1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2
Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom
The goal of this research project was to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom. The approach consists of four steps: (1) developing analytical tools (models and computer programs); (2) conducting parameterization (what if?) studies; (3) predicting the global space station EMI environment; and (4) providing a basis for modification of EMI standards
Bone loss and aggravated autoimmune arthritis in HLA-DRĪ²1-bearing humanized mice following oral challenge with Porphyromonas gingivalis
BACKGROUND: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies. METHODS: To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production. RESULTS: Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice. CONCLUSIONS: Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The abilityĀ of P. gingivalis to induce disease expression in arthritis-resistant mice provides support for the idea that periodontal infection may be able to trigger autoimmunity if other disease-eliciting factors are already present
Table-like magnetocaloric effect in Gd56Ni15Al27Zr2 alloy and its field independence feature
In order to obtain ātable-likeā magnetocaloric effect (MCE), multiple-phase Gd56Ni15Al27Zr2 alloy was prepared by arc-melting followed by suck-casting method. Powder x-ray diffraction and calorimetric measurements reveal that the sample contains both glassy and crystalline phases. The fraction of the glassy phase is about 62%, estimated from the heat enthalpy of the crystallization. The crystalline phases, Gd2Al and GdNiAl further broadened the relatively wider magnetic entropy change (āĪSM) peak of the amorphous phase, which resulted in the table-like MCE over a maximum temperature range of 52.5āK to 77.5āK. The plateau feature of the MCE was found to be nearly independent of the applied magnetic field from 3āT to 5āT. The maximum āĪSMvalue of the MCE platforms is 6.0āJ/kg K under applied magnetic field change of 5āT. Below 3āT, the field independence of the table-like feature disappears. The relatively large constant values of āĪSM for the respective applied magnetic fields have promising applications in magnetic refrigeration using regenerative Ericsson cycle
MHV-Vertices for Gravity Amplitudes
We obtain a CSW-style formalism for calculating graviton scattering
amplitudes and prove its validity through the use of a special type of
BCFW-like parameter shift. The procedure is illustrated with explicit examples.Comment: 21 pages, minor typos corrected, proof added in section
An Activity Index for Raw Accelerometry Data and Its Comparison with Other Activity Metrics
Accelerometers have been widely deployed in public health studies in recent years. While they collect high-resolution acceleration signals (e.g., 10ā100 Hz), research has mainly focused on summarized metrics provided by accelerometers manufactures, such as the activity count (AC) by ActiGraph or Actical. Such measures do not have a publicly available formula, lack a straightforward interpretation, and can vary by software implementation or hardware type. To address these problems, we propose the physical activity index (AI), a new metric for summarizing raw tri-axial accelerometry data. We compared this metric with the AC and another recently proposed metric for raw data, Euclidean Norm Minus One (ENMO), against energy expenditure. The comparison was conducted using data from the Objective Physical Activity and Cardiovascular Health Study, in which 194 women 60ā91 years performed 9 lifestyle activities in the laboratory, wearing a tri-axial accelerometer (ActiGraph GT3X+) on the hip set to 30 Hz and an Oxycon portable calorimeter, to record both tri-axial acceleration time series (converted into AI, AC, and ENMO) and oxygen uptake during each activity (converted into metabolic equivalents (METs)) at the same time. Receiver operating characteristic analyses indicated that both AI and ENMO were more sensitive to moderate and vigorous physical activities than AC, while AI was more sensitive to sedentary and light activities than ENMO. AI had the highest coefficients of determination for METs (0.72) and was a better classifier of physical activity intensity than both AC (for all intensity levels) and ENMO (for sedentary and light intensity). The proposed AI provides a novel and transparent way to summarize densely sampled raw accelerometry data, and may serve as an alternative to AC. The AIās largely improved sensitivity on sedentary and light activities over AC and ENMO further demonstrate its advantage in studies with older adults
Impaired pain sensation in mice lacking prokineticin 2
Prokineticins (PKs), consisting of PK1 and PK2, are a pair of newly identified regulatory peptides. Two closely related G-protein coupled receptors, PKR1 and PKR2, mediate the signaling of PKs. PKs/PKRs participate in the regulation of diverse biological processes, ranging from development to adult physiology. A number of studies have indicated the involvement of PKs/PKRs in nociception. Here we show that PK2 is a sensitizer for nociception. Intraplantar injection of recombinant PK2 resulted in a strong and localized hyperalgesia with reduced thresholds to nociceptive stimuli. PK2 mobilizes calcium in dissociated dorsal root ganglion (DRG) neurons. Mice lacking the PK2 gene displayed strong reduction in nociception induced by thermal and chemical stimuli, including capsaicin. However, PK2 mutant mice showed no difference in inflammatory response to capsaicin. As the majority of PK2-responsive DRG neurons also expressed transient receptor potential vanilloid (TRPV1) and exhibited sensitivity to capsaicin, TRPV1 is likely a significant downstream molecule of PK2 signaling. Taken together, these results reveal that PK2 sensitize nociception without affecting inflammation
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