Regulation of Expression of B7 by Murine Langerhans Cells: A Direct Relationship Between B7 mRNA Levels and the Level of Surface Expression of B7 by Langerhans Cells

Cultured BALB/c epidermal Langerhans cells express high levels of the costimulatory molecule B7 on their surfaces relative to levels expressed on fresh Langerhans cells. Quantitation of relative amounts of B7 mRNA in fresh epidermal cells and cultured epidermal cells following amplification of mRNA signals via reverse transcriptase – polymerase chain reaction, hybridization of PCR products with radiolabeled internal oligonucleotide probes, resolution of hybrids in non-denaturing polyacrylamide gels, and detection by autoradiography revealed dramatically (approximately one thousandfold) higher levels of B7 mRNA in cultured epidermal cells (10-40% 1-A+) as compared with fresh epidermal cells (1 – 4% I-A+). Levels of B7 mRNA in cultured epidermal cells were also substantially greater than those detected in a reference B lymphoma cell line (CH-1). Analysis of 87 mRNA expression in subpopulations of cultured epidermal cells demonstrated that essentially all of the B7 mRNA was present in Langerhans cells; cells bearing I-A and CD45 antigens. Cultured keratinocytes did not contain appreciable amounts of B7 mRNA. These results are consistent with previous data regarding surface expression of 87 by cLC and also demonstrate that fLC are essentially devoid of B7 mRNA and surface protein

Skeletal Muscle PGC-1β Signaling is Sufficient to Drive an Endurance Exercise Phenotype and to Counteract Components of Detraining in Mice

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy

Small-polaron hopping conductivity in bilayer manganite La1.2_{1.2}Sr1.8_{1.8}Mn2_{2}O7_{7}

We report anisotropic resistivity measurements on a La$_{1.2}$Sr$_{1.8}$Mn$_{2}$O$_{7}$ single crystal over a temperature $T$ range from 2 to 400 K and in magnetic fields $H$ up to 14 T. For $T\geq 218$ K, the temperature dependence of the zero-field in-plane $\rho_{ab}(T)$ resistivity obeys the adiabatic small polaron hopping mechanism, while the out-of-plane $\rho_{c}(T)$ resistivity can be ascribed by an Arrhenius law with the same activation energy. Considering the magnetic character of the polarons and the close correlation between the resistivity and magnetization, we developed a model which allows the determination of $\rho_{ab,c}(H,T)$. The excellent agreement of the calculations with the measurements indicates that small polarons play an essential role in the electrical transport properties in the paramagnetic phase of bilayer manganites.Comment: 4 pages, 3 figures, to appear in Physical Review

Heterogeneous N2O5 Uptake During Winter: Aircraft Measurements During the 2015 WINTER Campaign and Critical Evaluation of Current Parameterizations

Nocturnal dinitrogen pentoxide (N2O5) heterogeneous chemistry impacts regional air quality and the distribution and lifetime of tropospheric oxidants. Formed from the oxidation of nitrogen oxides, N2O5 is heterogeneously lost to aerosol with a highly variable reaction probability, γ(N2O5), dependent on aerosol composition and ambient conditions. Reaction products include soluble nitrate (HNO3 or NO3−) and nitryl chloride (ClNO2). We report the first‐ever derivations of γ(N2O5) from ambient wintertime aircraft measurements in the critically important nocturnal residual boundary layer. Box modeling of the 2015 Wintertime INvestigation of Transport, Emissions, and Reactivity (WINTER) campaign over the eastern United States derived 2,876 individual γ(N2O5) values with a median value of 0.0143 and range of 2 × 10−5 to 0.1751. WINTER γ(N2O5) values exhibited the strongest correlation with aerosol water content, but weak correlations with other variables, such as aerosol nitrate and organics, suggesting a complex, nonlinear dependence on multiple factors, or an additional dependence on a nonobserved factor. This factor may be related to aerosol phase, morphology (i.e., core shell), or mixing state, none of which are commonly measured during aircraft field studies. Despite general agreement with previous laboratory observations, comparison of WINTER data with 14 literature parameterizations (used to predict γ(N2O5) in chemical transport models) confirms that none of the current methods reproduce the full range of γ(N2O5) values. Nine reproduce the WINTER median within a factor of 2. Presented here is the first field‐based, empirical parameterization of γ(N2O5), fit to WINTER data, based on the functional form of previous parameterizations

Pain in the Past and Pleasure in the Future : The Development of Past-Future Preferences for Hedonic Goods

It seems self-evident that people prefer painful experiences to be in the past and pleasurable experiences to lie in the future. Indeed, it has been claimed that, for hedonic goods, this preference is absolute (Sullivan, 2018). Yet very little is known about the extent to which people demonstrate explicit preferences regarding the temporal location of hedonic experiences, about the developmental trajectory of such preferences, and about whether such preferences are impervious to differences in the quantity of envisaged past and future pain or pleasure. We find consistent evidence that, all else being equal, adults and children aged 7 and over prefer pleasure to lie in the future and pain in the past and believe that other people will too. They also predict that other people will be happier when pleasure is in the future rather than the past but sadder when pain is the future rather than the past. Younger children have the same temporal preferences as adults for their own painful experiences, but prefer their pleasure to lie in the past, and do not predict that others’ levels of happiness or sadness vary dependent on whether experiences lie in the past or the future. However, from the age of 7, temporal preferences were typically abandoned at the earliest opportunity when the quantity of past pain or pleasure was greater than the quantity located in the future. Past-future preferences for hedonic goods emerge early developmentally but are surprisingly flexible

THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage

Background and Purpose A ruptured intracranial aneurysm (IA) is the leading cause of a subarachnoid hemorrhage (SAH). This study seeks to define a specific gene whose mutation leads to disease. Methods More than 500 IA probands and 100 affected families were enrolled and clinically characterized. Whole exome sequencing was performed on a large family, revealing a segregating THSD1 mutation. THSD1 was sequenced in other probands and controls. Thsd1 loss-of-function studies in zebrafish and mice were used for in vivo analyses, and functional studies performed using an in vitro endothelial cell model. Results A nonsense mutation in THSD1 (thrombospondin type-1 domain-containing protein 1) was identified that segregated with the 9 affected (3 suffered SAH; 6 had unruptured IA) and 13 unaffected family members (LOD score 4.69). Targeted THSD1 sequencing identified mutations in 8 of 507 unrelated IA probands, including 3 who had suffered SAH (1.6% [95% CI, 0.8%–3.1%]). These THSD1 mutations/rare variants were highly enriched in our IA patient cohort relative to 89,040 chromosomes in ExAC database (p\u3c0.0001). In zebrafish and mice, Thsd1 loss-of-function caused cerebral bleeding (which localized to the subarachnoid space in mice) and increased mortality. Mechanistically, THSD1 loss impaired endothelial cell focal adhesion to the basement membrane. These adhesion defects could be rescued by expression of wild-type THSD1 but not THSD1 mutants identified in IA patients. Conclusions This report identifies THSD1 mutations in familial and sporadic IA patients, and shows that THSD1 loss results in cerebral bleeding in two animal models. This finding provides new insight into IA and SAH pathogenesis and provides new understanding of THSD1 function, which includes endothelial cell to extracellular matrix adhesion

Anomalous spin susceptibility and magnetic polaron formation in the double exchange systems

The magnetic susceptibility and spin-spin correlation of the double-exchange model for doped manganites are investigated through the Monte Carlo calculations on the three-dimensional lattice model. Deviations of the susceptibility from the Curie-Weiss behavior above the ferromagnetic ordering temperature $T_c$ seem to indicate a formation of local ferromagnetic clusters in the vicinity of $T_c$, which is consistent with recent electron paramagnetic resonance experiments for La$_{2/3}$Ca$_{1/3}$MnO$_3$. A further analysis of the spin-spin correlations show the ferromagnetic cluster size to be three-to-four lattice spacings, suggesting that the charge carriers may form magnetic polarons.Comment: 5 pages, 5 figures, Late

Effects of Age, Race, and Ethnicity on the Optic Nerve and Peripapillary Region Using Spectral-Domain OCT 3D Volume Scans

Purpose: To evaluate the effects of age, race, and ethnicity on the optic nerve and peripapillary retina using spectral-domain optical coherence tomography (SD-OCT) three-dimensional (3D) volume scans in normal subjects. Methods: This is a cross-sectional study performed at a single institution in Boston. All patients received retinal nerve fiber layer (RNFL) scans and an optic nerve 3D volume scan. The SD-OCT software calculated peripapillary RNFL thickness, retinal thickness (RT), and retinal volume (RV). Custom-designed software calculated neuroretinal rim minimum distance band (MDB) thickness and area. Results: There were 272 normal subjects, including 175 whites, 40 blacks, 40 Asians, and 17 Hispanics. Rates of age-related decline were 2.3%, 2.0%, 1.7%, 3.3%, and 4.3% per decade for RNFL, RT, RV, MDB neuroretinal rim thickness, and MDB area, respectively. The RNFL was most affected by racial and ethnic variations, with Asians having thicker global, superior, and inferior RNFL, Hispanics having thicker inferior RNFL, and blacks having thinner temporal RNFL, compared to whites. For MDB thickness and area, Asians had smaller nasal values and blacks had smaller temporal values. Peripapillary RT and RV parameters were not influenced by race and ethnicity. Conclusions: All of the parameters exhibited age-related declines. RNFL, MDB thickness, and MDB area demonstrated racial and ethnic variations, while peripapillary RT and RV did not. Translational Relevance: This study demonstrates that both normal aging and ethnicity affect several novel 3D OCT parameters used to diagnose and monitor glaucoma (i.e., RT, RV, and MDB), and this should be factored in when making clinical decisions based on these parameters