Acid-sensing ion channel 3 decreases phosphorylation of extracellular signal-regulated kinases and induces synoviocyte cell death by increasing intracellular calcium.

IntroductionAcid-sensing ion channel 3 (ASIC3) is expressed in synoviocytes, activated by decreases in pH, and reduces inflammation in animal models of inflammatory arthritis. The purpose of the current study was to characterize potential mechanisms underlying the control of inflammation by ASIC3 in fibroblast-like synoviocytes (FLS).MethodsExperiments were performed in cultured FLS from wild-type (WT) and ASIC3-/- mice, ASIC1-/- mice, and people with rheumatoid arthritis. We assessed the effects of acidic pH with and without interleukin-1β on FLS and the role of ASICs in modulating intracellular calcium [Ca(2+)](i), mitogen activated kinase (MAP kinase) expression, and cell death. [Ca(2+)](i) was assessed by fluorescent calcium imaging, MAP kinases were measured by Western Blots; ASIC, cytokine and protease mRNA expression were measured by quantitative PCR and cell death was measured with a LIVE/DEAD assay.ResultsAcidic pH increased [Ca(2+)](i) and decreased p-ERK expression in WT FLS; these effects were significantly smaller in ASIC3-/- FLS and were prevented by blockade of [Ca(2+)]i. Blockade of protein phosphatase 2A (PP2A) prevented the pH-induced decreases in p-ERK. In WT FLS, IL-1β increases ASIC3 mRNA, and when combined with acidic pH enhances [Ca(2+)](i), p-ERK, IL-6 and metalloprotienase mRNA, and cell death. Inhibitors of [Ca(2+)](i) and ERK prevented cell death induced by pH 6.0 in combination with IL-1β in WT FLS.ConclusionsDecreased pH activates ASIC3 resulting in increased [Ca(2+)](i), and decreased p-ERK. Under inflammatory conditions, acidic pH results in enhanced [Ca(2+)](i) and phosphorylation of extracellular signal-regulated kinase that leads to cell death. Thus, activation of ASIC3 on FLS by acidic pH from an inflamed joint could limit synovial proliferation resulting in reduced accumulation of inflammatory mediators and subsequent joint damage

Dynamic Proteomic Analysis of Pancreatic Mesenchyme Reveals Novel Factors That Enhance Human Embryonic Stem Cell to Pancreatic Cell Differentiation

Current approaches in human embryonic stem cell (hESC) to pancreatic beta cell differentiation have largely been based on knowledge gained from developmental studies of the epithelial pancreas, while the potential roles of other supporting tissue compartments have not been fully explored. One such tissue is the pancreatic mesenchyme that supports epithelial organogenesis throughout embryogenesis. We hypothesized that detailed characterization of the pancreatic mesenchyme might result in the identification of novel factors not used in current differentiation protocols. Supplementing existing hESC differentiation conditions with such factors might create a more comprehensive simulation of normal development in cell culture. To validate our hypothesis, we took advantage of a novel transgenic mouse model to isolate the pancreatic mesenchyme at distinct embryonic and postnatal stages for subsequent proteomic analysis. Refined sample preparation and analysis conditions across four embryonic and prenatal time points resulted in the identification of 21,498 peptides with high-confidence mapping to 1,502 proteins. Expression analysis of pancreata confirmed the presence of three potentially important factors in cell differentiation: Galectin-1 (LGALS1), Neuroplastin (NPTN), and the Laminin α-2 subunit (LAMA2). Two of the three factors (LGALS1 and LAMA2) increased expression of pancreatic progenitor transcript levels in a published hESC to beta cell differentiation protocol. In addition, LAMA2 partially blocks cell culture induced beta cell dedifferentiation. Summarily, we provide evidence that proteomic analysis of supporting tissues such as the pancreatic mesenchyme allows for the identification of potentially important factors guiding hESC to pancreas differentiation

LiGaSe2 optical parametric oscillator pumped by a Q-switched Nd:YAG laser

Optical parametric oscillation is demonstrated for the first time with the chalcogenide nonlinear crystal LiGaSe2 pumped by a nanosecond Nd:YAG laser. Angle tuning provides coverage of the 4.8–9.9 μm spectral range in the mid-IR by idler pulses

Gas emissions, minerals, and tars associated with three coal fires, Powder River Basin, USA.

Ground-based surveys of three coal fires and airborne surveys of two of the fires were conducted near Sheridan, Wyoming. The fires occur in natural outcrops and in abandoned mines, all containing Paleocene-age subbituminous coals. Diffuse (carbon dioxide (CO(2)) only) and vent (CO(2), carbon monoxide (CO), methane, hydrogen sulfide (H(2)S), and elemental mercury) emission estimates were made for each of the fires. Additionally, gas samples were collected for volatile organic compound (VOC) analysis and showed a large range in variation between vents. The fires produce locally dangerous levels of CO, CO(2), H(2)S, and benzene, among other gases. At one fire in an abandoned coal mine, trends in gas and tar composition followed a change in topography. Total CO(2) fluxes for the fires from airborne, ground-based, and rate of fire advancement estimates ranged from 0.9 to 780mg/s/m(2) and are comparable to other coal fires worldwide. Samples of tar and coal-fire minerals collected from the mouth of vents provided insight into the behavior and formation of the coal fires

Timing of primary tooth emergence among U.S. racial and ethnic groups

ObjectivesTo compare timing of tooth emergence among groups of American Indian (AI), Black and White children in the United States at 12 months of age.MethodsData were from two sources – a longitudinal study of a Northern Plains tribal community and a study with sites in Indiana, Iowa and North Carolina. For the Northern Plains study, all children (n = 223) were American Indian, while for the multisite study, children (n = 320) were from diverse racial groups. Analyses were limited to data from examinations conducted within 30 days of the child’s first birthday.ResultsAI children had significantly more teeth present (Mean: 7.8, Median: 8.0) than did Whites (4.4, 4.0, P < 0.001) or Blacks (4.5, 4.0, P < 0.001). No significant differences were detected between Black and White children (P = 0.58). There was no significant sex difference overall or within any of the racial groups.ConclusionsTooth emergence occurs at a younger age for AI children than it does for contemporary White or Black children in the United States.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135387/1/jphd12154.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135387/2/jphd12154_am.pd

Development of a Core Curriculum Framework in Cariology for U.S. Dental Schools

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153683/1/jddj002203372016806tb06133x.pd

Integrated Reconnaissance of the Physical and Biogeochemical Characteristics of Jamaica Bay

Researchers at The Earth Institute of Columbia University have carried out an integrated, coordinated pilot reconnaissance of the physical, chemical, geological, and biological systems within Jamaica Bay, entitled "Integrated Reconnaissance of the Physical and Biogeochemical Characteristics of Jamaica Bay." We believe that such an integrated approach is necessary to fully understand the complex inter-relationship of the wetland ecosystem. The program focused on obtaining a synergistic view of the varied elements of Jamaica Bay by carrying out coordinated research in four areas: submarine sediment morphology, sediment and soil sampling, circulation and mixing, and chemical analysis of the Bay waters

The United States of America and Scientific Research

To gauge the current commitment to scientific research in the United States of America (US), we compared federal research funding (FRF) with the US gross domestic product (GDP) and industry research spending during the past six decades. In order to address the recent globalization of scientific research, we also focused on four key indicators of research activities: research and development (R&D) funding, total science and engineering doctoral degrees, patents, and scientific publications. We compared these indicators across three major population and economic regions: the US, the European Union (EU) and the People's Republic of China (China) over the past decade. We discovered a number of interesting trends with direct relevance for science policy. The level of US FRF has varied between 0.2% and 0.6% of the GDP during the last six decades. Since the 1960s, the US FRF contribution has fallen from twice that of industrial research funding to roughly equal. Also, in the last two decades, the portion of the US government R&D spending devoted to research has increased. Although well below the US and the EU in overall funding, the current growth rate for R&D funding in China greatly exceeds that of both. Finally, the EU currently produces more science and engineering doctoral graduates and scientific publications than the US in absolute terms, but not per capita. This study's aim is to facilitate a serious discussion of key questions by the research community and federal policy makers. In particular, our results raise two questions with respect to: a) the increasing globalization of science: “What role is the US playing now, and what role will it play in the future of international science?”; and b) the ability to produce beneficial innovations for society: “How will the US continue to foster its strengths?

In Silico Metabolic Model and Protein Expression of Haemophilus influenzae Strain Rd KW20 in Rich Medium

The intermediary metabolism of Haemophilus influenzae strain Rd KW20 was studied by a combination of protein expression analysis using a recently developed direct proteomics approach, mutational analysis, and mathematical modeling. Special emphasis was placed on carbon utilization, sugar fermentation, TCA cycle, and electron transport of H. influenzae cells grown microaerobically and anaerobically in a rich medium. The data indicate that several H. influenzae metabolic proteins similar to Escherichia coli proteins, known to be regulated by low concentrations of oxygen, were well expressed in both growth conditions in H. influenzae. An in silico model of the H. influenzae metabolic network was used to study the effects of selective deletion of certain enzymatic steps. This allowed us to define proteins predicted to be essential or non-essential for cell growth and to address numerous unresolved questions about intermediary metabolism of H. influenzae. Comparison of data from in vivo protein expression with the protein list associated with a genome-scale metabolic model showed significant coverage of the known metabolic proteome. This study demonstrates the significance of an integrated approach to the characterization of H. influenzae metabolism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63406/1/153623104773547471.pd