The location of olfactory receptors within olfactory epithelium is independent of odorant volatility and solubility

<p>Abstract</p> <p>Background</p> <p>Our objective was to study the pattern of olfactory receptor expression within the dorsal and ventral regions of the mouse olfactory epithelium. We hypothesized that olfactory receptors were distributed based on the chemical properties of their ligands: e.g. receptors for polar, hydrophilic and weakly volatile odorants would be present in the dorsal region of olfactory epithelium; while receptors for non-polar, more volatile odorants would be distributed to the ventral region. To test our hypothesis, we used micro-transplantation of cilia-enriched plasma membranes derived from dorsal or ventral regions of the olfactory epithelium into Xenopus oocytes for electrophysiological characterization against a panel of 100 odorants.</p> <p>Findings</p> <p>Odorants detected by ORs from the dorsal and ventral regions showed overlap in volatility and water solubility. We did not find evidence for a correlation between the solubility and volatility of odorants and the functional expression of olfactory receptors in the dorsal or ventral region of the olfactory epithelia.</p> <p>Conclusions</p> <p>No simple clustering or relationship between chemical properties of odorants could be associated with the different regions of the olfactory epithelium. These results suggest that the location of ORs within the epithelium is not organized based on the physico-chemical properties of their ligands.</p

Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever

Lassa fever (LF), caused by Lassa virus (LASV), is a viral hemorrhagic fever for which no approved vaccine or potent antiviral treatment is available. LF is a WHO priority disease and, together with rabies, a major health burden in West Africa. Here we present the development and characterization of an inactivated recombinant LASV and rabies vaccine candidate (LASSARAB) that expresses a codon-optimized LASV glycoprotein (coGPC) and is adjuvanted by a TLR-4 agonist (GLA-SE). LASSARAB elicits lasting humoral response against LASV and RABV in both mouse and guinea pig models, and it protects both guinea pigs and mice against LF. We also demonstrate a previously unexplored role for non-neutralizing LASV GPC-specific antibodies as a major mechanism of protection by LASSARAB against LF through antibody-dependent cellular functions. Overall, these findings demonstrate an effective inactivated LF vaccine and elucidate a novel humoral correlate of protection for LF.NIH grants R01 AI105204 to M.J.S., by the Jefferson Vaccine Center, and by the Fundação para a Ciência e Tecnologia (FCT) scholarship PD/BD/105847/2014 (to T.A.-M.). This work was also funded in part through the NIAID Division of Intramural Research and the NIAID Division of Clinical Research, Battelle Memorial Institute’s prime contract with the U.S. National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272200700016Iinfo:eu-repo/semantics/publishedVersio

Modes of Aβ toxicity in Alzheimer’s disease

Alzheimer’s disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide

South Atlantic heat transport at 11°S

Hydrographic data along 11°S occupied in 1983 by the R.V. OCEANUS are used together with various wind climatologies to estimate the annual average transport of heat at this latitude. Some motivation for expecting fairly well-defined estimates at this latitude compared to others comes from the absence of a strong western boundary current. Results include flow in four layers representing the thermocline, Antarctic Intermediate Water, North Atlantic Deep Water, and Antarctic Bottom Water, using zero velocity reference level choices based on property distributions. The annual average heat transport is estimated to be 0.6 ± 0.17 x 1015 W. Previous estimates of the transport at 8–16°S range from 0.2 PW to greater than 1 PW. Interannual variability from the wind field alone leads to interannual heat transport variability of about 0.05 PW. Comparisons with other recent studies at 45–30°S and 11°N are made

Mixing and convection in the Greenland Sea from a tracer-release experiment

Convective vertical mixing in restricted areas of the subpolar oceans, such as the Greenland Sea, is thought to be the process responsible for forming much of the dense water of the ocean interior. Deep-water formation varies substantially on annual and decadal timescales, and responds to regional climate signals such as the North Atlantic Oscillation; its variations may therefore give early warning of changes in the thermohaline circulation that may accompany climate change8. Here we report direct measurements of vertical mixing, by convection and by turbulence, from a sulphur hexafluoride tracer-release experiment in the central Greenland Sea gyre. In summer, we found rapid turbulent vertical mixing of about 1.1 cm2 s-1. In the following late winter, part of the water column was mixed more vigorously by convection, indicated by the rising and vertical redistribution of the tracer patch in the centre of the gyre. At the same time, mixing outside the gyre centre was only slightly greater than in summer. The results suggest that about 10% of the water in the gyre centre was vertically transported in convective plumes, which reached from the surface to, at their deepest, 1,200–1,400 m. Convection was limited to a very restricted area, however, and smaller volumes of water were transported to depth than previously estimated. Our results imply that it may be the rapid year-round turbulent mixing, rather than convection, that dominates vertical mixing in the region as a whole