469 research outputs found

    Short- and long-term consequences of larval stage exposure to constantly and ephemerally elevated carbon dioxide for marine bivalve populations

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    While larval bivalves are highly sensitive to ocean acidification, the basis for this sensitivity and the longer-term implications of this sensitivity are unclear. Experiments were performed to assess the short-term (days) and long-term (months) consequences of larval stage exposure to varying CO2 concentrations for calcifying bivalves. Higher CO2 concentrations depressed both calcification rates assessed using 45Ca uptake and RNA : DNA ratios in Mercenaria mercenaria and Argopecten irradians larvae with RNA : DNA ratios being highly correlated with larval growth rates (r2>0.9). These findings suggested that high CO2 has a cascading negative physiological impact on bivalve larvae stemming in part from lower calcification rates. Exposure to elevated CO2 during the first four days of larval development significantly depressed A. irradians larval survival rates, while a 10-day exposure later in larval development did not, demonstrating the extreme CO2 sensitivity of bivalve larvae during first days of development. Short- (weeks) and long-term (10 month) experiments revealed that individuals surviving exposure to high CO2 during larval development grew faster when exposed to normal CO2 as juveniles compared to individuals reared under ambient CO2 as larvae. These increased growth rates could not, however, overcome size differences established during larval development, as size deficits of individuals exposed to even moderate levels of CO2 as larvae were evident even after 10 months of growth under normal CO2 concentrations. This "legacy effect" emphasizes the central role larval stage CO2 exposure can play in shaping the success of modern-day bivalve populations

    Harold M. Frost T J Musculoskel Neuron Interact 2001; 2(2):117-119 William F. Neuman Awardee 2001

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    Tribute to Harold M. Frost, honorary president of ISMNI, who received the William F. Neuman Award from the American Society of Bone and Mineral Research October 2001

    A RET-ER81-NRG1 Signaling Pathway Drives the Development of Pacinian Corpuscles

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    Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET(+) mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression. Interestingly, Er81 mutants have normal myelination but exhibit deficient interactions between axons and corpuscle-forming nonmyelinating Schwann cells. Finally, ablating Neuregulin-1 (Nrg1) in mechanosensory neurons results in no Pacinian corpuscles, and an Nrg1 isoform not required for communication with myelinating Schwann cells is specifically decreased in Er81-null somatosensory neurons. Collectively, our results suggest that a RET-ER81-NRG1 signaling pathway promotes axon communication with nonmyelinating Schwann cells, and that neurons use distinct mechanisms to interact with different types of Schwann cells.; Communication between neurons and Schwann cells is critical for development, normal function, and regeneration of the peripheral nervous system. Despite many studies about axonal communication with myelinating Schwann cells, mostly via a specific isoform of Neuregulin1, the molecular nature of axonal communication with nonmyelinating Schwann cells is poorly understood. Here, we described a RET-ER81-Neuregulin1 signaling pathway in neurons innervating Pacinian corpuscle somatosensory end organs, which is essential for communication between the innervating axon and the end organ nonmyelinating Schwann cells. We also showed that this signaling pathway uses isoforms of Neuregulin1 that are not involved in myelination, providing evidence that neurons use different isoforms of Neuregulin1 to interact with different types of Schwann cells

    Boson stars in massive dilatonic gravity

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    We study equilibrium configurations of boson stars in the framework of a class scalar-tensor theories of gravity with massive gravitational scalar (dilaton). In particular we investigate the influence of the mass of the dilaton on the boson star structure. We find that the masses of the boson stars in presence of dilaton are close to those in general relativity and they are sensitive to the ratio of the boson mass to the dilaton mass within a typical few percent. It turns out also that the boson star structure is mainly sensitive to the mass term of the dilaton potential rather to the exact form of the potential.Comment: 9 pages, latex, 9 figures, one figure dropped, new comments added, new references added, typos correcte

    Choral singing therapy following stroke or Parkinsons disease: An exploration of participants experiences

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    © 2015 Informa UK Ltd. Purpose: People with stroke or Parkinsons disease (PD) live with reduced mood, social participation and quality of life (QOL). Communication difficulties affect 90% of people with PD (dysarthria) and over 33% of people with stroke (aphasia). These consequences are disabling in many ways. However, as singing is typically still possible, its therapeutic use is of increasing interest. This article explores the experiences of and factors influencing participation in choral singing therapy (CST) by people with stroke or PD and their significant others. Method: Participants (eight people with stroke, six with PD) were recruited from a community music therapy choir running CST. Significant others (seven for stroke, two for PD) were also recruited. Supported communication methods were used as needed to undertake semi-structured interviews (total N = 23). Results: Thematic analysis indicated participants had many unmet needs associated with their condition, which motivated them to explore self-management options. CST participation was described as an enjoyable social activity, and participation was perceived as improving mood, language, breathing and voice. Conclusions: Choral singing was perceived by people with stroke and PD to help them self-manage some of the consequences of their condition, including social isolation, low mood and communication difficulties.Implications for RehabilitationChoral singing therapy (CST) is sought out by people with stroke and PD to help self-manage symptoms of their condition.Participation is perceived as an enjoyable activity which improves mood, voice and language symptoms.CST may enable access to specialist music therapy and speech language therapy protocols within community frameworks

    Structural and Functional Analysis of the Human Nuclear Xenobiotic Receptor PXR in Complex with RXRα

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    The human nuclear xenobiotic receptor PXR recognizes a range of potentially harmful drugs and endobiotic chemicals, but must complex with the nuclear receptor RXRα to control the expression of numerous drug metabolism genes. To date, the structural basis and functional consequences of this interaction have remained unclear. Here we present 2.8 Å resolution crystal structures of the heterodimeric complex formed between the ligand binding domains (LBDs) of human PXR and RXRα. These structures establish that PXR and RXRα form a heterotetramer unprecedented in the nuclear receptor family of ligand-regulated transcription factors. We further show that both PXR and RXRα bind to the transcriptional coregulator SRC-1 with higher affinity when they are part of the PXR-RXRα heterotetramer complex than they do when each LBD is examined alone. Furthermore, we purify the full-length forms of each receptor from recombinant bacterial expression systems, and characterize their interactions with a range of direct and everted repeat DNA elements. Taken together, these data advance our understanding of PXR, the master regulator of drug metabolism gene expression in humans, in its functional partnership with RXRα

    Electronically reconfigurable metal-on-silicon metamaterial

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    Reconfigurable metamaterial-based apertures can play a unique role in both imaging and in beam-forming applications, where current technology relies mostly on the fabrication and integration of large detector or antenna arrays. Here, we report the experimental demonstration of a voltage-controlled, silicon-based electromagnetic metamaterial operating in the W-band (75-110 GHz). In this composite semiconductor metamaterial, patterned gold metamaterial elements serve both to manage electromagnetic wave propagation while simultaneously acting as electrical Schottky contacts that control the local conductivity of the semiconductor substrate. The active device layers consist of a patterned metal on a 2-{\mu}m-thick n-doped silicon layer, adhesively bonded to a transparent Pyrex wafer. The transmittance of the composite metamaterial can be modulated over a given frequency band as a function of bias voltage. We demonstrate a quantitative understanding of the composite device through the application of numerical approaches that simultaneously treat the semiconductor junction physics as well as wave propagation.Comment: 28 double-spaced pages, 8 figure

    HLA-A2-Matched Peripheral Blood Mononuclear Cells From Type 1 Diabetic Patients, but Not Nondiabetic Donors, Transfer Insulitis to NOD-scid/ cnull/HLA-A2 Transgenic Mice Concurrent With the Expansion of Islet-Specific CD8+ T cells

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    OBJECTIVEType 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing β-cells. NOD mice provide a useful tool for understanding disease pathogenesis and progression. Although much has been learned from studies with NOD mice, increased understanding of human type 1 diabetes can be gained by evaluating the pathogenic potential of human diabetogenic effector cells in vivo. Therefore, our objective in this study was to develop a small-animal model using human effector cells to study type 1 diabetes.RESEARCH DESIGN AND METHODSWe adoptively transferred HLA-A2–matched peripheral blood mononuclear cells (PBMCs) from type 1 diabetic patients and nondiabetic control subjects into transgenic NOD-scid/γcnull/HLA-A*0201 (NOD-scid/γcnull/A2) mice. At various times after adoptive transfer, we determined the ability of these mice to support the survival and proliferation of the human lymphoid cells. Human lymphocytes were isolated and assessed from the blood, spleen, pancreatic lymph node and islets of NOD-scid/γcnull/A2 mice after transfer.RESULTSHuman T and B cells proliferate and survive for at least 6 weeks and were recovered from the blood, spleen, draining pancreatic lymph node, and most importantly, islets of NOD-scid/γcnull/A2 mice. Lymphocytes from type 1 diabetic patients preferentially infiltrate the islets of NOD-scid/γcnull/A2 mice. In contrast, PBMCs from nondiabetic HLA-A2–matched donors showed significantly less islet infiltration. Moreover, in mice that received PBMCs from type 1 diabetic patients, we identified epitope-specific CD8+ T cells among the islet infiltrates.CONCLUSIONSWe show that insulitis is transferred to NOD-scid/γcnull/A2 mice that received HLA-A2–matched PBMCs from type 1 diabetic patients. In addition, many of the infiltrating CD8+ T cells are epitope-specific and produce interferon-γ after in vitro peptide stimulation. This indicates that NOD-scid/γcnull/A2 mice transferred with HLA-A2–matched PBMCs from type 1 diabetic patients may serve as a useful tool for studying epitope-specific T-cell–mediated responses in patients with type 1 diabetes
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