Stoichiometry of the murine γδ T cell receptor

The T cell receptor for antigen (TCR) complex is organized into two functional domains: the antigen-binding clonotypic heterodimer and the signal-transducing invariant CD3 and TCRζ chains. In most vertebrates, there are two different clonotypic heterodimers (TCRαβ and TCRγδ) that define the αβ and γδ T cell lineages, respectively. αβ- and γδTCRs also differ in their invariant chain subunit composition, in that αβTCRs contain CD3γɛ and CD3δɛ dimers, whereas γδTCRs contain only CD3γɛ dimers. This difference in subunit composition of the αβ- and γδTCRs raises the question of whether the stoichiometries of these receptor complexes are different. As the stoichiometry of the murine γδTCR has not been previously investigated, we used two quantitative immunofluorescent approaches to determine the valency of TCRγδ heterodimers and CD3γɛ dimers in surface murine γδTCR complexes. Our results support a model of murine γδTCR stoichiometry in which there are two CD3γɛ dimers for every TCRγδ heterodimer

Fluorescence Imaging of Underexpanded Jets and Comparison with CFD

An experimental study of underexpanded and highly underexpanded axisymmetric nitrogen free jets seeded with 0.5% nitric oxide (NO) and issuing from a sonic orifice was conducted at NASA Langley Research Center. Reynolds numbers based on nozzle exit conditions ranged from 770 to 35,700, and nozzle exit-to-ambient jet pressure ratios ranged from 2 to 35. These flows were non-intrusively visualized with a spatial resolution of approximately 0.14 mm x 0.14 mm x 1 mm thick and a temporal resolution of 1 s using planar laser-induced fluorescence (PLIF) of NO, with the laser tuned to the strongly-fluorescing UV absorption bands of the Q1 band head near 226.256 nm. Three laminar cases were selected for comparison with computational fluid dynamics (CFD). The cases were run using GASP (General Aerodynamic Simulation Program) Version 4. Comparisons of the fundamental wavelength of the jet flow showed good agreement between CFD and experiment for all three test cases, while comparisons of Mach disk location and Mach disk diameter showed good agreement at lower jet pressure ratios, with a tendency to slightly underpredict these parameters with increasing jet pressure ratio

Sudden collapse of a colloidal gel

Metastable gels formed by weakly attractive colloidal particles display a distinctive two-stage time-dependent settling behavior under their own weight. Initially a space-spanning network is formed that for a characteristic time, which we define as the lag time \taud, resists compaction. This solid-like behavior persists only for a limited time. Gels whose age \tw is greater than \taud yield and suddenly collapse. We use a combination of confocal microscopy, rheology and time-lapse video imaging to investigate both the process of sudden collapse and its microscopic origin in an refractive-index matched emulsion-polymer system. We show that the height $h$ of the gel in the early stages of collapse is well described by the surprisingly simple expression, h(\ts) = \h0 - A \ts^{3/2}, with \h0 the initial height and \ts = \tw-\taud the time counted from the instant where the gel first yields. We propose that this unexpected result arises because the colloidal network progressively builds up internal stress as a consequence of localized rearrangement events which leads ultimately to collapse as thermal equilibrium is re-established.Comment: 14 pages, 11 figures, final versio

Effects of pH on redox proxies in a Jurassic rift lake : implications for interpreting environmental records in deep time

This work was supported at the University of California, Riverside by the NSF-EAR FESD Program and the NASA Astrobiology Institute under Cooperative Agreement No. NNA15BB03A issued through the Science Mission Directorate. We thank Roger Buick (UW) for financial support of the carbon and nitrogen isotope work. EES acknowledges support from a NASA postdoctoral fellowship, as well as valuable discussions about the Newark basin with Charlotte B. Schreiber. GDL thanks the Agouron Institute for providing funding for the Waters Autospec GC-MS instrument at UCR.It is widely agreed that the Earth’s atmosphere and oceans have undergone major redox changes over the last 2.5 billion years. However, the magnitude of these shifts remains a point of debate because it is difficult to reconstruct concentrations of dissolved O2 from indirect proxies in sedimentary archives. In this study, we show that an additional complicating factor that is rarely considered may be the pH of the water column. We analyzed rock samples from the early Jurassic Towaco Formation in the Newark basin (eastern USA), comprising deposits of a rift lake that became temporarily redox stratified. New biomarker evidence points to increasingly saline aquatic conditions during the second half of the lake’s history, with a salinity stratification that induced redox stratification, including evidence for water column anoxia, and that state may also explain the disappearance of macrofauna at this time. Distinctive lipid biomarker assemblages and stable nitrogen isotope data support previous mineralogical indications that the lake was alkaline (pH ≥ 9) during its saline episode. Despite the biomarker and macrofaunal evidence for anoxia, ratios of Fe/Al and FeHR/FeT show only small to no enrichments in the anoxic horizon compared to oxic facies in the same section – counter to what is commonly observed in anoxic marine settings. Molybdenum, As, V, U and to some degree Cd show enrichments in the anoxic interval, whereas Co, Ni, Cu, Zn and Cr do not. These patterns are most parsimoniously explained by differential pH effects on the solubility of these elements. Extrapolating from these observations in lacustrine strata, we speculate that a secular increase in seawater pH over Earth’s history as recently proposed may have helped modulate the magnitude of trace metal enrichments in marine shales, although other factors such as atmospheric and oceanic redox likely dominated the observed enrichment patterns. Further, a decrease in the solubility of ferrous iron, a major O2 sink, with increasing pH may have contributed to ocean oxygenation. In summary, our results highlight the potential importance of pH in influencing global biogeochemical cycles for multiple elements and for the interpretation of ancient nitrogen isotope signatures.PostprintPeer reviewe

Angiotensin II-inhibition:effect on Alzheimer's pathology in the aged triple transgenic mouse

Reducing excessive accumulation of amyloid-β (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies, and inhibition of angiotensin-converting enzyme (ACE) may delay onset or progression of AD. The effects of an ACE-inhibitor (ACE-I) and an angiotensin II receptor blocker (ARB) on Aβ and tau pathology in a triple transgenic (3xTGAD) mouse model of AD were investigated. 9-10month 3xTGAD mice were treated with ARB, ACE-I or vehicle for 6 months. Mean arterial blood pressure (MABP) was measured periodically and mice were assessed behaviourally. Aβ, phospho-tau, amyloid precursor protein (APP) and ACE activity were analysed. MABP was significantly reduced at 2 weeks and 3 months in the ACE-I group and at 3 months in the ARB group, compared to vehicle. Neither drug altered performance of 3xTGAD mice in Morris Water Maze or T-maze, nor were Aβ, tau immunolabelling or APP levels altered. ACE-I significantly reduced ACE activity in kidney. Prolonged treatment with ACE-I or ARB does not affect Aβ or phospho-tau accumulation in brains of aged 3xTGAD mice