Modulation of Autophagy-Like Processes by Tumor Viruses

Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved

Concentrations and snow-atmosphere fluxes of reactive nitrogen at Summit, Greenland

Concentrations and fluxes of NOy (total reactive nitrogen), ozone concentrations and fluxes of sensible heat, water vapor, and momentum were measured from May 1 to July 20, 1995 at Summit, Greenland. Median NOy concentrations declined from 947 ppt in May to 444 ppt by July. NOy fluxes were observed into and out of the snow, but the magnitudes were usually below 1 μmol m−2 h−1 because of the low HNO3 concentration and weak turbulence over the snow surface. Some of the highest observed fluxes may be due to temporary storage by equilibrium sorption of peroxyacetylnitrate (PAN) or other organic nitrogen species on ice surfaces in the upper snowpack. Sublimation of snow at the surface or during blowing snow events is associated with efflux of NOy from the snowpack. Because the NOy fluxes during summer at Summit are bidirectional and small in magnitude, the net result of turbulent NOyexchange is insignificant compared to the 2 μmol m−2 d−1 mean input from fresh snow during the summer months. If the arctic NOy reservoir is predominantly PAN (or compounds with similar properties), thermal dissociation of this NOy is sufficient to support the observed flux of nitrate in fresh snow. Very low HNO3 concentrations in the surface layer (1% of total NOy) reflect the poor ventilation of the surface layer over the snowpack combined with the relatively rapid uptake of HNO3 by fog, falling snow, and direct deposition to the snowpack

Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice

BACKGROUND: The detection of bitter-tasting compounds by the gustatory system is thought to alert animals to the presence of potentially toxic food. Some, if not all, bitter stimuli activate specific taste receptors, the T2Rs, which are expressed in subsets of taste receptor cells on the tongue and palate. However, there is evidence for both receptor-dependent and -independent transduction mechanisms for a number of bitter stimuli, including quinine hydrochloride (QHCl) and denatonium benzoate (DB). RESULTS: We used brief-access behavioral taste testing of BXD/Ty recombinant inbred (RI) mouse strains to map the major quantitative trait locus (QTL) for taste sensitivity to QHCl. This QTL is restricted to a ~5 Mb interval on chromosome 6 that includes 24 genes encoding T2Rs (Tas2rs). Tas2rs at this locus display in total 307 coding region single nucleotide polymorphisms (SNPs) between the two BXD/Ty RI parental strains, C57BL/6J (quinine-sensitive) and DBA/2J (quinine insensitive); approximately 50% of these mutations are silent. Individual RI lines contain exclusively either C57BL/6J or DBA/2J Tas2r alleles at this locus, and RI lines containing C57BL/6J Tas2r alleles are more sensitive to QHCl than are lines containing DBA/2J alleles. Thus, the entire Tas2r cluster comprises a large haplotype that correlates with quinine taster status. CONCLUSION: These studies, the first using a taste-salient assay to map the major QTL for quinine taste, indicate that a T2R-dependent transduction cascade is responsible for the majority of strain variance in quinine taste sensitivity. Furthermore, the large number of polymorphisms within coding exons of the Tas2r cluster, coupled with evidence that inbred strains exhibit largely similar bitter taste phenotypes, suggest that T2R receptors are quite tolerant to variation

Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of bitter stimuli

BACKGROUND: Common inbred mouse strains are genotypically diverse, but it is still poorly understood how this diversity relates to specific differences in behavior. To identify quantitative trait genes that influence taste behavior differences, it is critical to utilize assays that exclusively measure the contribution of orosensory cues. With a few exceptions, previous characterizations of behavioral taste sensitivity in inbred mouse strains have generally measured consumption, which can be confounded by post-ingestive effects. Here, we used a taste-salient brief-access procedure to measure taste sensitivity to eight stimuli characterized as bitter or aversive in C57BL/6J (B6) and DBA/2J (D2) mice. RESULTS: B6 mice were more sensitive than D2 mice to a subset of bitter stimuli, including quinine hydrochloride (QHCl), 6-n-propylthiouracil (PROP), and MgCl(2). D2 mice were more sensitive than B6 mice to the bitter stimulus raffinose undecaacetate (RUA). These strains did not differ in sensitivity to cycloheximide (CYX), denatonium benzoate (DB), KCl or HCl. CONCLUSION: B6-D2 taste sensitivity differences indicate that differences in consumption of QHCl, PROP, MgCl(2 )and RUA are based on immediate orosensory cues, not post-ingestive effects. The absence of a strain difference for CYX suggests that polymorphisms in a T2R-type taste receptor shown to be differentially sensitive to CYX in vitro are unlikely to differentially contribute to the CYX behavioral response in vivo. The results of these studies point to the utility of these common mouse strains and their associated resources for investigation into the genetic mechanisms of taste

Quantum Dynamics in Atomic-Fountain Experiments for Measuring the Electric Dipole Moment of the Electron with Improved Sensitivity

An improved measurement of the electron electric dipole moment (EDM) appears feasible using groundstate alkali atoms in an atomic fountain in which a strong electric field, which couples to a conceivable EDM, is applied perpendicular to the fountain axis. In a practical fountain, the ratio of the atomic tensor Stark shift to the Zeeman shift is a factor μ ~ 100.We expand the complete time-evolution operator in inverse powers of this ratio; complete results are presented for atoms of total spin F = 3, 4, and 5. For a specific set of entangled hyperfine sublevels (coherent states), potential systematic errors enter only as even powers of 1/μ, making the expansion rapidly convergent. The remaining EDM-mimicking effects are further suppressed in a proposed double-differential setup, where the final state is interrogated in a differential laser configuration, and the direction of the strong electric field also is inverted. Estimates of the signal available at existing accelerator facilities indicate that the proposed apparatus offers the potential for a drastic improvement in EDM limits over existing measurements, and for constraining the parameter space of supersymmetric (SUSY) extensions of the Standard Model

Heterogeneous Sensory Innervation and Extensive Intrabulbar Connections of Olfactory Necklace Glomeruli

The mammalian nose employs several olfactory subsystems to recognize and transduce diverse chemosensory stimuli. These subsystems differ in their anatomical position within the nasal cavity, their targets in the olfactory forebrain, and the transduction mechanisms they employ. Here we report that they can also differ in the strategies they use for stimulus coding. Necklace glomeruli are the sole main olfactory bulb (MOB) targets of an olfactory sensory neuron (OSN) subpopulation distinguished by its expression of the receptor guanylyl cyclase GC-D and the phosphodiesterase PDE2, and by its chemosensitivity to the natriuretic peptides uroguanylin and guanylin and the gas CO2. In stark contrast to the homogeneous sensory innervation of canonical MOB glomeruli from OSNs expressing the same odorant receptor (OR), we find that each necklace glomerulus of the mouse receives heterogeneous innervation from at least two distinct sensory neuron populations: one expressing GC-D and PDE2, the other expressing olfactory marker protein. In the main olfactory system it is thought that odor identity is encoded by a combinatorial strategy and represented in the MOB by a pattern of glomerular activation. This combinatorial coding scheme requires functionally homogeneous sensory inputs to individual glomeruli by OSNs expressing the same OR and displaying uniform stimulus selectivity; thus, activity in each glomerulus reflects the stimulation of a single OSN type. The heterogeneous sensory innervation of individual necklace glomeruli by multiple, functionally distinct, OSN subtypes precludes a similar combinatorial coding strategy in this olfactory subsystem

Afferent activity to necklace glomeruli is dependent on external stimuli

<p>Abstract</p> <p>Background</p> <p>The main olfactory epithelium (MOE) is a complex organ containing several functionally distinct subpopulations of sensory neurons. One such subpopulation is distinguished by its expression of the guanylyl cyclase GC-D. The axons of GC-D-expressing (GC-D+) neurons innervate 9–15 "necklace" glomeruli encircling the caudal main olfactory bulb (MOB). Chemosensory stimuli for GC-D+ neurons include two natriuretic peptides, uroguanylin and guanylin, and CO₂. However, the biologically-relevant source of these chemostimuli is unclear: uroguanylin is both excreted in urine, a rich source of olfactory stimuli for rodents, and expressed in human nasal epithelium; CO₂is present in both inspired and expired air.</p> <p>Findings</p> <p>To determine whether the principal source of chemostimuli for GC-D+ neurons is external or internal to the nose, we assessed the consequences of removing external chemostimuli for afferent activity to the necklace glomeruli. To do so, we performed unilateral naris occlusions in <it>Gucy2d-Mapt-lacZ </it>^+/-mice [which express a β-galactosidase (β-gal) reporter specifically in GC-D+ neurons] followed by immunohistochemistry for β-gal and a glomerular marker of afferent activity, tyrosine hydroxylase (TH). We observed a dramatic decrease in TH immunostaining, consistent with reduced or absent afferent activity, in both necklace and non-necklace glomeruli ipsilateral to the occluded naris.</p> <p>Conclusion</p> <p>Like other MOB glomeruli, necklace glomeruli exhibit a large decrease in afferent activity upon removal of external stimuli. Thus, we conclude that activity in GC-D+ neurons, which specifically innervate necklace glomeruli, is not dependent on internal stimuli. Instead, GC-D+ neurons, like other OSNs in the MOE, primarily sense the external world.</p

Monellin (MNEI) at 1.15 Å resolution

The crystal structure of the sweet protein MNEI at 1.15 Å resolution reveals networks of alternate conformations and stably bound negative ions

Electron electric dipole moment experiment using electric-field quantized slow cesium atoms

A proof-of-principle electron electric dipole moment (e-EDM) experiment using slow cesium atoms, nulled magnetic fields, and electric field quantization has been performed. With the ambient magnetic fields seen by the atoms reduced to less than 200 pT, an electric field of 6 MV/m lifts the degeneracy between states of unequal mF and, along with the low (approximately 3 m/s) velocity, suppresses the systematic effect from the motional magnetic field. The low velocity and small residual magnetic field have made it possible to induce transitions between states and to perform state preparation, analysis, and detection in regions free of applied static magnetic and electric fields. This experiment demonstrates techniques that may be used to improve the e-EDM limit by two orders of magnitude, but it is not in itself a sensitive e-EDM search, mostly due to limitations of the laser system.Comment: 9 pages, 8 figures, accepted for publication in Phys. Rev.