The regulation of nerve and blood vessel ingrowth in aneural and avascular intervertebral disc and articular cartilage

Introduction This review will discuss the regulatory mechanisms of both innervation and vascularisation within normally aneural and avascular tissues, and how they may become altered in degeneration enabling new nerve and blood vessel formation which is hypothesised to be a source of pain. Conclusion Normal intervertebral discs and articular cartilage are the largest aneural and avascular tissues in the human body yet during intervertebral disc degeneration and osteoarthritis these tissues become increasingly vascularised by small blood vessels and innervated by peptide containing sensory nerve fibres. The mechanism by which this process occurs remains largely unknown. Published data suggests that various factors present within the healthy tissues such as aggrecan, chondromodulin and semaphorins may act as repulsive barriers to neurite and endothelial cell invasion. During degeneration however, the synthesis of these molecules becomes disrupted, potentially leading to vascularisation and innervation of the tissue

Tree species-soils relationships in old-growth forests of the Oregon Coast Range

Tree species directly and indirectly affect soil nutrient cycles. I sought to characterize soils and foliage associated with four common canopy tree species (Douglas-fir, western hemlock, western redcedar, and bigleaf maple) in mixed-species old-growth forests of the Oregon Coast Range and to determine whether and how soils differ among the tree species. Sampling was replicated at eight forest sites to assess the generality of tree-species soils relationships across this region. Forest floor (Oe+Oa horizon) and mineral soils (0 to 10 cm and 10 to 20 cm depth) were analyzed for pools and concentrations of major elements (C, N, P, Ca, Mg, K, and H). Foliar nutrient concentrations, which reflect active nutrient cycling by the trees, were also determined for C, N, P, Ca, Mg, and K. Results were analyzed with respect to two complementary conceptual models of tree species-soils relationships. In a depth-based model, trees were inferred to influence soil properties if surface mineral soils (0 to 10 cm) differed beneath the canopies of tree species, but deeper mineral soils (10 to 20 cm) did not. Using a context-dependence model, I assessed whether species-based differences in each soil nutrient diverged, converged, or were constant as nutrient status increased across sites. Douglas-fir soils were characterized by greater mass of forest floor relative to other species and, at high-C and -N sites, large pools of C and N in mineral soils. Western hemlock soils and foliage were generally poor in bases, particularly Ca. Western redcedar soils and foliage were high in Ca and were low in P, and soil P was especially low at high-P sites. Bigleaf maple soils and foliage were rich in P and base cations, and soils had high available nitrate relative to other species at nitrate-rich sites. Overall, the depth-based model was best supported by data for pools of the weatherable elements P and Ca, while the context-dependence model was best supported by data for the atmospherically derived, biologically fixed elements C and N. This apparent dichotomy in patterns for soil pools of rock-derived vs. atmospherically-derived nutrients merits further investigation. Forest management or natural successional processes that foster stand dominance by a single tree species are likely to reduce soil nutrient heterogeneity relative to that of current old-growth forests, and in some cases, may reduce soil fertility

Choral Ensembles

Kennesaw State University School of Music presents Choral Ensembles: Women\u27s Chorus and Chamber Singers.https://digitalcommons.kennesaw.edu/musicprograms/1625/thumbnail.jp

Choral Ensembles: Choirs in 3-D

Kennesaw State University School of Music presents Choral Ensembles: Choirs in 3-Dhttps://digitalcommons.kennesaw.edu/musicprograms/1637/thumbnail.jp

The in vitro effects of chemokines on microglia: Implications for multiple sclerosis.

Microglia, the resident macrophages of the central nervous system (CNS), are the primary cell to respond to injury in the brain, both in inflammation e.g. in multiple sclerosis (MS), and in trauma. Microglia can be activated in vitro by proinflammatory cytokines such as IFNgamma and TNFalpha and respond by secretion of cytokines, chemokines, proteases, nitric oxide and superoxide radicals. As MS is a putative autoimmune disease of the CNS, chemokines (chemotactic cytokines), secreted by many cell types including T cells and macrophages in MS lesions, have been postulated as key players in the orchestration of the inflammatory response by recruitment and activation of inflammatory cells.As potential mediators of microglial cell recruitment to sites of injury, the ability of microglia to migrate in response to alpha and beta chemokines was assessed. All chemokines tested demonstrated the ability to induce migration and changes in the distribution of filamentous actin in adult rat microglia and a human microglial cell line, CHME3, in vitro. This study indicates that chemokines secreted by activated T cells in the CNS may attract microglia to areas of central nervous system inflammation where they could exert their well documented effects.Proteases are also found in close proximity to MS plaques in increased amounts as agents of myelin breakdown in MS. Matrix metalloproteinases (MMPs) are zinc-dependant enzymes, capable of degrading extracellular matrix proteins and are known to be produced by microglia. The control of MMP activity by plasmin, as well as the balance between MMP and levels of their natural inhibitors, TIMPs, may determine lytic or anti-lytic activity in MS. The in vitro control of MMPs 2 and 9, TIMPs 1 and 2 and urokinase type plasminogen activator (uPA) by microglia was examined in response to several chemokines using ELISA and zymography techniques. The chemokines tested were all found to significantly increase the secretion of MMPs and TIMPs by CHME3 cells after 24 hours stimulation. The chemokines, MCP1, MIP1beta and Fractalkine were also shown to increase MMP9 secretion by rat microglia with little or no effect on MMP2. Interestingly, MCP1, MIP1alpha/beta and RANTES significantly decreased the secretion of uPA by CHME3 cells which may indicate an increase in uPAR expression. These results suggest that chemokine mediated control of MMP activity in the breakdown of the blood brain barrier could allow further recruitment of immune cells into the CNS and also cause demyelination of axons by lysis of myelin basic protein.Since chemokines, as well as cytokines, are possible candidates for microglia activation, microglia were tested in their response to several chemokines by measurement of nitrite production, superoxide secretion and Fc receptor expression. The majority of the chemokines tested were able to increase superoxide and nitrite production as well as Fc receptor expression with the exception of the beta chemokine, RANTES, whereby only CHME3 cells produced a significant increase in superoxide production and Fc receptor expression above unstimulated levels suggesting a difference in chemokine receptor expression or a difference in the binding affinity and signal transduction in different cell types.The present study has led to a further understanding of the possible chemokine control of microglial migration, proteinase production and effector function in CNS diseases, as well as their well documented role in recruitment of lymphocytes. Targetting these chemokines in MS patients, with specific antibodies or use of synthetic inhibitors to block their receptors may lead to downregulation of the immune response and a decrease in the severity of the disease

Obama FY2017 Budget Proposal: Sustainable Energy, Buildings, Transportation and Climate

On February 9, 2016, President Obama released his $4.15 trillion fiscal year (FY) 2017 federal budget proposal, a 5 percent increase over 2016. In his final budget request, President Obama is calling for investment into clean energy research and development to double by 2021, from$6.4 billion (in 2016) to $12.8 billion. The budget seeks$7.7 billion for clean energy research at 12 federal agencies, with the Department of Energy receiving the bulk of the funding (80 percent). The extra funding would support the development of clean, renewable energies such as bioenergy, geothermal, hydrogen, solar, water, and wind, as well as clean-vehicle technologies and energy storage. The proposed 2017 budget increases the Department of Energy's (DOE) funding by 10 percent over 2016 estimated levels, raises the Environmental Protection Agency's (EPA) budget by 4.23 percent, and increases the Department of Transportation's (DOT) funding by 10.27 percent.This issue brief outlines the Obama administration's FY 2017 budget request for several clean energy programs within key agencies

Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration

Introduction : The degenerate intervertebral disc (IVD) becomes innervated by sensory nerve fibres, and vascularised by blood vessels. This study aimed to identify neurotrophins, neuropeptides and angiogenic factors within native IVD tissue and to further investigate whether pro-inflammatory cytokines are involved in the regulation of expression levels within nucleus pulposus (NP) cells, nerve and endothelial cells. Methods : Quantitative real-time PCR (qRT-PCR) was performed on 53 human IVDs from 52 individuals to investigate native gene expression of neurotrophic factors and their receptors, neuropeptides and angiogenic factors. The regulation of these factors by cytokines was investigated in NP cells in alginate culture, and nerve and endothelial cells in monolayer using RT-PCR and substance P (SP) protein expression in interleukin-1 (IL-1ß) stimulated NP cells. Results : Initial investigation on uncultured NP cells identified expression of all neurotrophins by native NP cells, whilst the nerve growth factor (NGF) receptor was only identified in severely degenerate and infiltrated discs, and brain derived neurotrophic factor (BDNF) receptor expressed by more degenerate discs. BDNF expression was significantly increased in infiltrated and degenerate samples. SP and vascular endothelial growth factor (VEGF) were higher in infiltrated samples. In vitro stimulation by IL-1ß induced NGF in NP cells. Neurotropin-3 was induced by tumour necrosis factor alpha in human dermal microvascular endothelial cells (HDMECs). SP gene and protein expression was increased in NP cells by IL-1ß. Calcitonin gene related peptide was increased in SH-SY5Y cells upon cytokine stimulation. VEGF was induced by IL-1ß and interleukin-6 in NP cells, whilst pleiotrophin was decreased by IL-1ß. VEGF and pleiotrophin were expressed by SH-SY5Y cells, and VEGF by HDMECs, but were not modulated by cytokines. Conclusions : The release of cytokines, in particular IL-1ß during IVD degeneration, induced significant increases in NGF and VEGF which could promote neuronal and vascular ingrowth. SP which is released into the matrix could potentially up regulate the production of matrix degrading enzymes and also sensitise nerves, resulting in nociceptive transmission and chronic low back pain. This suggests that IL-1ß is a key regulatory cytokine, involved in the up regulation of factors involved in innervation and vascularisation of tissues.</p

Gene expression profiling and expanded immunohistochemistry tests to guide selection of chemotherapy regimens in breast cancer management: a systematic review

OBJECTIVES: The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer. METHODS: A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016. RESULTS: Searches identified 7064 citations, of which 41 citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision-making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests. CONCLUSIONS: The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomised controlled trial data

Nerves are more abundant than blood vessels in the degenerate human intervertebral disc

Chronic low back pain (LBP) is the most common cause of disability worldwide. New ideas surrounding LBP are emerging that are based on interactions between mechanical, biological and chemical influences on the human IVD. The degenerate IVD is proposed to be innervated by sensory nerve fibres and vascularised by blood vessels, and it is speculated to contribute to pain sensation. However, the incidence of nerve and blood vessel ingrowth, as well as whether these features are always associated, is unknown. We investigated the presence of nerves and blood vessels in the nucleus pulposus (NP) of the IVD in a large population of human discs