A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling

Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-gamma) receptor signaling. Mal-dependent IFN-gamma receptor (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy. IFN-gamma signaling via Mal was required for phagosome maturation and killing of intracellular Mycobacterium tuberculosis (Mtb). The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB. Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-gamma-related diseases including autoimmunity and cancer

Linear and Second-order Optical Response of the III-V Mono-layer Superlattices

We report the first fully self-consistent calculations of the nonlinear optical properties of superlattices. The materials investigated are mono-layer superlattices with GaP grown on the the top of InP, AlP and GaAs (110) substrates. We use the full-potential linearized augmented plane wave method within the generalized gradient approximation to obtain the frequency dependent dielectric tensor and the second-harmonic-generation susceptibility. The effect of lattice relaxations on the linear optical properties are studied. Our calculations show that the major anisotropy in the optical properties is the result of strain in GaP. This anisotropy is maximum for the superlattice with maximum lattice mismatch between the constituent materials. In order to differentiate the superlattice features from the bulk-like transitions an improvement over the existing effective medium model is proposed. The superlattice features are found to be more pronounced for the second-order than the linear optical response indicating the need for full supercell calculations in determining the correct second-order response.Comment: 9 pages, 4 figures, submitted to Phy. Rev.

Expression of Interleukin-10 in Intestinal Lymphocytes Detected by an Interleukin-10 Reporter Knockin tiger Mouse

SummaryTo identify interleukin-10 (IL-10)-producing cells in vivo, we generated a knockin mouse where an internal ribosome entry site (IRES) green fluorescence protein (GFP) element was inserted immediately before the polyadenylation site of the IL-10 gene. GFP fluorescence in cells from these mice was found to correlate positively with IL-10 protein expression. With this model, we found that after multiple T cell receptor (TCR) stimulations, strong expression of IL-10 was produced specifically by intraepithelial lymphocytes (IEL) in the small intestine and colonic lamina propria lymphocytes (cLPL). We found that anti-CD3 treatment induces T regulatory cell 1 (Tr1)-like cells in small intestinal IEL (sIEL) and led to the accumulation of naturally occurring regulatory T (nTreg) cells in colonic LPL (cLPL). These findings highlight the intestine as a unique site for induction of IL-10-producing T cells, which play a critical role in the regulation of inflammation in the gut

Discrimination Task Reveals Differences in Neural Bases of Tinnitus and Hearing Impairment

We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone

AN ULTRA-FAINT GALAXY CANDIDATE DISCOVERED in EARLY DATA from the MAGELLANIC SATELLITES SURVEY

We report a new ultra-faint stellar system found in Dark Energy Camera data from the first observing run of the Magellanic Satellites Survey (MagLiteS). MagLiteS J0644-5953 (Pictor II or Pic II) is a low surface brightness (μ = 28.5+1 -1 mag arcsec-2 within its half-light radius) resolved overdensity of old and metal-poor stars located at a heliocentric distance of 45+5 -4 kpc. The physical size (r1/2 = 46+15 -11) and low luminosity (Mv = -3.2+0.4 -0.5 mag) of this satellite are consistent with the locus of spectroscopically confirmed ultra-faint galaxies. MagLiteS J0644-5953 (Pic II) is located 11.3+3.1 -0.9 kpc from the Large Magellanic Cloud (LMC), and comparisons with simulation results in the literature suggest that this satellite was likely accreted with the LMC. The close proximity of MagLiteS J0644-5953 (Pic II) to the LMC also makes it the most likely ultra-faint galaxy candidate to still be gravitationally bound to the LMC.Peer reviewe

The mu problem and sneutrino inflation

We consider sneutrino inflation and post-inflation cosmology in the singlet extension of the MSSM with approximate Peccei-Quinn(PQ) symmetry, assuming that supersymmetry breaking is mediated by gauge interaction. The PQ symmetry is broken by the intermediate-scale VEVs of two flaton fields, which are determined by the interplay between radiative flaton soft masses and higher order terms. Then, from the flaton VEVs, we obtain the correct mu term and the right-handed(RH) neutrino masses for see-saw mechanism. We show that the RH sneutrino with non-minimal gravity coupling drives inflation, thanks to the same flaton coupling giving rise to the RH neutrino mass. After inflation, extra vector-like states, that are responsible for the radiative breaking of the PQ symmetry, results in thermal inflation with the flaton field, solving the gravitino problem caused by high reheating temperature. Our model predicts the spectral index to be n_s\simeq 0.96 due to the additional efoldings from thermal inflation. We show that a right dark matter abundance comes from the gravitino of 100 keV mass and a successful baryogenesis is possible via Affleck-Dine leptogenesis.Comment: 27 pages, no figures, To appear in JHE

Ultrafast optical control of entanglement between two quantum dot spins

The interaction between two quantum bits enables entanglement, the two-particle correlations that are at the heart of quantum information science. In semiconductor quantum dots much work has focused on demonstrating single spin qubit control using optical techniques. However, optical control of entanglement of two spin qubits remains a major challenge for scaling from a single qubit to a full-fledged quantum information platform. Here, we combine advances in vertically-stacked quantum dots with ultrafast laser techniques to achieve optical control of the entangled state of two electron spins. Each electron is in a separate InAs quantum dot, and the spins interact through tunneling, where the tunneling rate determines how rapidly entangling operations can be performed. The two-qubit gate speeds achieved here are over an order of magnitude faster than in other systems. These results demonstrate the viability and advantages of optically controlled quantum dot spins for multi-qubit systems.Comment: 24 pages, 5 figure

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Inhibition decorrelates visual feature representations in the inner retina

The retina extracts visual features for transmission to the brain. Different types of bipolar cell split the photoreceptor input into parallel channels and provide the excitatory drive for downstream visual circuits. Mouse bipolar cell types have been described at great anatomical and genetic detail, but a similarly deep understanding of their functional diversity is lacking. Here, by imaging light-driven glutamate release from more than 13,000 bipolar cell axon terminals in the intact retina, we show that bipolar cell functional diversity is generated by the interplay of dendritic excitatory inputs and axonal inhibitory inputs. The resulting centre and surround components of bipolar cell receptive fields interact to decorrelate bipolar cell output in the spatial and temporal domains. Our findings highlight the importance of inhibitory circuits in generating functionally diverse excitatory pathways and suggest that decorrelation of parallel visual pathways begins as early as the second synapse of the mouse visual system