Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

Photon Management in Two-Dimensional Disordered Media

Elaborating reliable and versatile strategies for efficient light coupling between free space and thin films is of crucial importance for new technologies in energy efficiency. Nanostructured materials have opened unprecedented opportunities for light management, notably in thin-film solar cells. Efficient coherent light trapping has been accomplished through the careful design of plasmonic nanoparticles and gratings, resonant dielectric particles and photonic crystals. Alternative approaches have used randomly-textured surfaces as strong light diffusers to benefit from their broadband and wide-angle properties. Here, we propose a new strategy for photon management in thin films that combines both advantages of an efficient trapping due to coherent optical effects and broadband/wide-angle properties due to disorder. Our approach consists in the excitation of electromagnetic modes formed by multiple light scattering and wave interference in two-dimensional random media. We show, by numerical calculations, that the spectral and angular responses of thin films containing disordered photonic patterns are intimately related to the in-plane light transport process and can be tuned through structural correlations. Our findings, which are applicable to all waves, are particularly suited for improving the absorption efficiency of thin-film solar cells and can provide a novel approach for high-extraction efficiency light-emitting diodes

The effect of prior walking on coronary heart disease risk markers in South Asian and European men.

Purpose: Heart disease risk is elevated in South Asians possibly due to impaired postprandial metabolism. Running has been shown to induce greater reductions in postprandial lipaemia in South Asian than European men but the effect of walking in South Asians is unknown. Methods: Fifteen South Asian and 14 White European men aged 19-30 years completed two, 2-d trials in a randomised crossover design. On day 1, participants rested (control) or walked for 60 min at approximately 50% maximum oxygen uptake (exercise). On day 2, participants rested and consumed two high fat meals over a 9h period during which 14 venous blood samples were collected. Results: South Asians exhibited higher postprandial triacylglycerol (geometric mean (95% confidence interval) 2.29(1.82 to 2.89) vs. 1.54(1.21 to 1.96) mmol·L-1·hr-1), glucose (5.49(5.21 to 5.79) vs. 5.05(4.78 to 5.33) mmol·L-1·hr-1), insulin (32.9(25.7 to 42.1) vs. 18.3(14.2 to 23.7) µU·mL-1·hr-1) and interleukin-6 (2.44(1.61 to 3.67) vs. 1.04(0.68 to 1.59) pg·mL-1·hr-1) than Europeans (all ES ≥ 0.72, P≤0.03). Between-group differences in triacylglycerol, glucose and insulin were not significant after controlling for age and percentage body fat. Walking reduced postprandial triacylglycerol (1.79(1.52 to 2.12) vs. 1.97(1.67 to 2.33) mmol·L-1·hr-1) and insulin (21.0(17.0 to 26.0) vs. 28.7(23.2 to 35.4) µU·mL-1·hr-1) (all ES ≥ 0.23. P≤0.01), but group differences were not significant. Conclusions: Healthy South Asians exhibited impaired postprandial metabolism compared with White Europeans, but these differences were diminished after controlling for potential confounders. The small-moderate reduction in postprandial triacylglycerol and insulin after brisk walking was not different between the ethnicities

The Induction of MicroRNA Targeting IRS-1 Is Involved in the Development of Insulin Resistance under Conditions of Mitochondrial Dysfunction in Hepatocytes

BACKGROUND: Mitochondrial dysfunction induces insulin resistance in myocytes via a reduction of insulin receptor substrate-1 (IRS-1) expression. However, the effect of mitochondrial dysfunction on insulin sensitivity is not understood well in hepatocytes. Although research has implicated the translational repression of target genes by endogenous non-coding microRNAs (miRNA) in the pathogenesis of various diseases, the identity and role of the miRNAs that are involved in the development of insulin resistance also remain largely unknown. METHODOLOGY: To determine whether mitochondrial dysfunction induced by genetic or metabolic inhibition causes insulin resistance in hepatocytes, we analyzed the expression and insulin-stimulated phosphorylation of insulin signaling intermediates in SK-Hep1 hepatocytes. We used qRT-PCR to measure cellular levels of selected miRNAs that are thought to target IRS-1 3' untranslated regions (3'UTR). Using overexpression of miR-126, we determined whether IRS-1-targeting miRNA causes insulin resistance in hepatocytes. PRINCIPAL FINDINGS: Mitochondrial dysfunction resulting from genetic (mitochondrial DNA depletion) or metabolic inhibition (Rotenone or Antimycin A) induced insulin resistance in hepatocytes via a reduction in the expression of IRS-1 protein. In addition, we observed a significant up-regulation of several miRNAs presumed to target IRS-1 3'UTR in hepatocytes with mitochondrial dysfunction. Using reporter gene assay we confirmed that miR-126 directly targeted to IRS-1 3'UTR. Furthermore, the overexpression of miR-126 in hepatocytes caused a substantial reduction in IRS-1 protein expression, and a consequent impairment in insulin signaling. CONCLUSIONS/SIGNIFICANCE: We demonstrated that miR-126 was actively involved in the development of insulin resistance induced by mitochondrial dysfunction. These data provide novel insights into the molecular basis of insulin resistance, and implicate miRNA in the development of metabolic disease

The Survey of Water and Ammonia in the Galactic Center (SWAG): Molecular Cloud Evolution in the Central Molecular Zone

The Survey of Water and Ammonia in the Galactic Center (SWAG) covers the Central Molecular Zone (CMZ) of the Milky Way at frequencies between 21.2 and 25.4 GHz obtained at the Australia Telescope Compact Array at $\sim 0.9$ pc spatial and $\sim 2.0$ km s$^{-1}$ spectral resolution. In this paper, we present data on the inner $\sim 250$ pc ($1.4^\circ$) between Sgr C and Sgr B2. We focus on the hyperfine structure of the metastable ammonia inversion lines (J,K) = (1,1) - (6,6) to derive column density, kinematics, opacity and kinetic gas temperature. In the CMZ molecular clouds, we find typical line widths of $8-16$ km s$^{-1}$ and extended regions of optically thick ($\tau > 1$) emission. Two components in kinetic temperature are detected at $25-50$ K and $60-100$ K, both being significantly hotter than dust temperatures throughout the CMZ. We discuss the physical state of the CMZ gas as traced by ammonia in the context of the orbital model by Kruijssen et al. (2015) that interprets the observed distribution as a stream of molecular clouds following an open eccentric orbit. This allows us to statistically investigate the time dependencies of gas temperature, column density and line width. We find heating rates between $\sim 50$ and $\sim 100$ K Myr$^{-1}$ along the stream orbit. No strong signs of time dependence are found for column density or line width. These quantities are likely dominated by cloud-to-cloud variations. Our results qualitatively match the predictions of the current model of tidal triggering of cloud collapse, orbital kinematics and the observation of an evolutionary sequence of increasing star formation activity with orbital phase

A Novel, Low-Volume Method for Organ Culture of Embryonic Kidneys That Allows Development of Cortico-Medullary Anatomical Organization

Here, we present a novel method for culturing kidneys in low volumes of medium that offers more organotypic development compared to conventional methods. Organ culture is a powerful technique for studying renal development. It recapitulates many aspects of early development very well, but the established techniques have some disadvantages: in particular, they require relatively large volumes (1–3 mls) of culture medium, which can make high-throughput screens expensive, they require porous (filter) substrates which are difficult to modify chemically, and the organs produced do not achieve good cortico-medullary zonation. Here, we present a technique of growing kidney rudiments in very low volumes of medium–around 85 microliters–using silicone chambers. In this system, kidneys grow directly on glass, grow larger than in conventional culture and develop a clear anatomical cortico-medullary zonation with extended loops of Henle

The Molecular Gas Environment in the 20 KMS−1 Cloud in the Central Molecular Zone

We recently reported a population of protostellar candidates in the 20 kms−1 cloud in the Central Molecular Zone of the Milky Way, traced by H2O masers in gravitationally bound dense cores. In this paper, we report high-angular-resolution (_3′′) molecular line studies of the environment of star formation in this cloud. Maps of various molecular line transitions as well as the continuum at 1.3 mm are obtained using the Submillimeter Array. Five NH3 inversion lines and the 1.3 cm continuum are observed with the Karl G. Jansky Very Large Array. The interferometric observations are complemented with single-dish data. We find that the CH3OH, SO, and HNCO lines, which are usually shock tracers, are better correlated spatially with the compact dust emission from dense cores among the detected lines. These lines also show enhancement in intensities with respect to SiO intensities toward the compact dust emission, suggesting the presence of slow shocks or hot cores in these regions. We find gas temperatures of &100 K at 0.1-pc scales based on RADEX modelling of the H2CO and NH3 lines. Although no strong correlations between temperatures and linewidths/H2O maser luminosities are found, in high-angular-resolution maps we notice several candidate shock heated regions offset from any dense cores, as well as signatures of localized heating by protostars in several dense cores. Our findings suggest that at 0.1-pc scales in this cloud star formation and strong turbulence may together affect the chemistry and temperature of the molecular gas

Human Herpesvirus-8 Infection Leads to Expansion of the Preimmune/Natural Effector B Cell Compartment

BACKGROUND: Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS) and of some lymphoproliferative disorders of B cells. Most malignancies develop after long-lasting viral dormancy, and a preventing role for both humoral and cellular immune control is suggested by the high frequency of these pathologies in immunosuppressed patients. B cells, macrophages and dendritic cells of peripheral lymphoid organs and blood represent the major reservoir of HHV-8. Due to the dual role of B cells in HHV-8 infection, both as virus reservoir and as agents of humoral immune control, we analyzed the subset distribution and the functional state of peripheral blood B cells in HHV-8-infected individuals with and without cKS. METHODOLOGY/PRINCIPAL FINDINGS: Circulating B cells and their subsets were analyzed by 6-color flow cytometry in the following groups: 1- patients HHV-8 positive with classic KS (cKS) (n = 47); 2- subjects HHV-8 positive and cKS negative (HSP) (n = 10); 3- healthy controls, HHV-8 negative and cKS negative (HC) (n = 43). The number of B cells belonging to the preimmune/natural effector compartment, including transitional, pre-naïve, naïve and MZ-like subsets, was significantly higher among HHV-8 positive subjects, with or without cKS, while was comparable to healthy controls in the antigen-experienced T-cell dependent compartment. The increased number of preimmune/natural effector B cells was associated with increased resistance to spontaneous apoptosis, while it did not correlate with HHV-8 viral load. CONCLUSIONS/SIGNIFICANCE: Our results indicate that long-lasting HHV-8 infection promotes an imbalance in peripheral B cell subsets, perturbing the equilibrium between earlier and later steps of maturation and activation processes. This observation may broaden our understanding of the complex interplay between viral and immune factors leading HHV-8-infected individuals to develop HHV-8-associated malignancies

The JCMT BISTRO Survey: The Magnetic Field Strength in the Orion A Filament

We determine the magnetic field strength in the OMC 1 region of the Orion A filament via a new implementation of the Chandrasekhar-Fermi method using observations performed as part of the James Clerk Maxwell Telescope (JCMT) B-Fields In Star-Forming Region Observations (BISTRO) survey with the POL-2 instrument. We combine BISTRO data with archival SCUBA-2 and HARP observations to find a plane-of-sky magnetic field strength in OMC 1 of B_pos=6.6±4.7 mG, where δB_pos=4.7 mG represents a predominantly systematic uncertainty. We develop a new method for measuring angular dispersion, analogous to unsharp masking. We find a magnetic energy density of ~1.7×10^-7 Jm^-3 in OMC 1, comparable both to the gravitational potential energy density of OMC 1 (~10^-7 Jm^-3), and to the energy density in the Orion BN/KL outflow (~10^-7 Jm^-3). We find that neither the Alfvén velocity in OMC 1 nor the velocity of the super-Alfvénic outflow ejecta is sufficiently large for the BN/KL outflow to have caused large-scale distortion of the local magnetic field in the ~500-year lifetime of the outflow. Hence, we propose that the hour-glass field morphology in OMC 1 is caused by the distortion of a primordial cylindrically-symmetric magnetic field by the gravitational fragmentation of the filament and/or the gravitational interaction of the BN/KL and S clumps. We find that OMC 1 is currently in or near magnetically-supported equilibrium, and that the current large-scale morphology of the BN/KL outflow is regulated by the geometry of the magnetic field in OMC 1, and not vice versa

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions