Specialized mechanoreceptor systems in rodent glabrous skin

Rodents use their forepaws to actively interact with their tactile environment. Studies on the physiology and anatomy of glabrous skin that makes up the majority of the forepaw are almost non-existent in the mouse. Here we developed a preparation to record from single sensory fibers of the forepaw and compared anatomical and physiological receptor properties to those of the hind paw glabrous and hairy skin. We found that the mouse forepaw skin is equipped with a very high density of mechanoreceptors; > 3 fold more than hind paw glabrous skin. In addition, rapidly adapting mechanoreceptors that innervate Meissner's corpuscles of the forepaw were several-fold more sensitive to slowly moving mechanical stimuli compared to their counterparts in the hind paw glabrous skin. All other mechanoreceptors types as well as myelinated nociceptors had physiological properties that were invariant regardless of which skin area they occupied. We discovered a novel D-hair receptor innervating a small group of hairs in the middle of the hind paw glabrous skin in mice. These glabrous skin D-hair receptors were direction sensitive albeit with an orientation sensitivity opposite to that described for hairy skin D-hair receptors. Glabrous skin hairs do not occur in all rodents, but are present in North American and African rodent species that diverged more than 65 million years ago. The function of these specialized hairs is unknown, but they are nevertheless evolutionarily very ancient. Our study reveals novel physiological specializations of mechanoreceptors in the glabrous skin that likely evolved to facilitate tactile exploration. This article is protected by copyright. All rights reserved

Genetic studies in sunflower broomrape

Much research has been conducted to identify sources of genetic resistance to sunflower broomrape (Orobanche cumana Wallr.) and to study their mode of inheritance. However, studies on the parasite have been scarce. This manuscript reviews three genetic studies in sunflower broomrape. First, the inheritance of the absence of pigmentation in a natural mutant of this species with yellow plant color phenotype was studied. In a first stage, lines from the unpigmented mutant and a normally pigmented population were developed by several generations of self-pollination. Plants of both lines were crossed and the F1, F2, and F3 generations were evaluated. The results indicated that plant pigmentation is controlled by a partially dominant allele at a single locus. Second, the unpigmented mutant was used to evaluate outcrossing potential of the species. Two experiments in which single unpigmented plants were surrounded by normally pigmented plants were conducted under pot and field conditions. The cross-fertilization rate was estimated as the percentage of F1 hybrids in the progenies of unpigmented plants, which averaged 21.5% in the pot and 28.8% in the field experiment. The results indicated that, under the conditions of this study, the species was not strictly self-pollinated. Finally, the inheritance of avirulence was studied in crosses of plants from lines of O. cumana races E and F, developed by several generations of self-pollination. The F1 and F3 generations were evaluated on the differential line P-1380 carrying the race-E resistance gene Or5. The results suggested that race E avirulence and race F virulence on P-1380 are allelic and controlled by a single locus, which confirmed the gene-for-gene theory for the O. cumana-sunflower interaction.The manuscript reviews research partially funded by Fundación Ramón Areces, Madrid. The contribution of Dr. Enrique Quesada Moraga, entomologist from the University of Córdoba, Spain, to taxonomic classification of pollinators is gratefully acknowledged. R. Pineda-Martos was the recipient of a PhD fellowship from the Spanish National Research Council (CSIC) (JAEPre_08_00370)Peer Reviewe

Lack of evidence for participation of TMEM150C in sensory mechanotransduction

The membrane protein TMEM150C has been proposed to form a mechanosensitive ion channel that is required for normal proprioceptor function. Here, we examined whether expression of TMEM150C in neuroblastoma cells lacking Piezo1 is associated with the appearance of mechanosensitive currents. Using three different modes of mechanical stimuli, indentation, membrane stretch, and substrate deflection, we could not evoke mechanosensitive currents in cells expressing TMEM150C. We next asked if TMEM150C is necessary for the normal mechanosensitivity of cutaneous sensory neurons. We used an available mouse model in which the Tmem150c locus was disrupted through the insertion of a LacZ cassette with a splice acceptor that should lead to transcript truncation. Analysis of these mice indicated that ablation of the Tmem150c gene was not complete in sensory neurons of the dorsal root ganglia (DRG). Using a CRISPR/Cas9 strategy, we made a second mouse model in which a large part of the Tmem150c gene was deleted and established that these Tmem150c(-/-) mice completely lack TMEM150C protein in the DRGs. We used an ex vivo skin nerve preparation to characterize the mechanosenstivity of mechanoreceptors and nociceptors in the glabrous skin of the Tmem150c(-/-) mice. We found no quantitative alterations in the physiological properties of any type of cutaneous sensory fiber in Tmem150c(-/-) mice. Since it has been claimed that TMEM150C is required for normal proprioceptor function, we made a quantitative analysis of locomotion in Tmem150c(-/-) mice. Here again, we found no indication that there was altered gait in Tmem150c(-/-) mice compared to wild-type controls. In summary, we conclude that existing mouse models that have been used to investigate TMEM150C function in vivo are problematic. Furthermore, we could find no evidence that TMEM150C forms a mechanosensitive channel or that it is necessary for the normal mechanosensitivity of cutaneous sensory neurons

NO2 climatology in the northern subtropical region: diurnal, seasonal and interannual variability

Daily NO2 vertical column density (VCD) has been routinely measured by zenith sky spectroscopy at the subtropical station of Izaña (28° N, 16° W) since 1993 in the framework of the Network for the Detection of Atmospheric Composition Change (NDACC). Based on 14 years of data the first low latitude NO2 VCD climatology has been established and the main characteristics from short timescales of one day to interannual variability are presented. Instrumental descriptions and different sources of errors are described in detail. The observed diurnal cycle follows that expected by gas-phase NOx chemistry, as can be shown by the good agreement with a vertically integrated chemical box model, and is modulated by solar radiation. The seasonal evolution departs from the phase of the hours of daylight, indicating the signature of upper stratospheric temperature changes. From the data record (1993–2006) no significant long-term trends in NO2 VCD can be inferred. Comparison of the ground-based data sets with nadir-viewing satellite spectrometers shows excellent agreement for SCIAMACHY with differences between both datasets of 1.1%. GOME displays unrealistic features with the largest discrepancies during summer. The ground-based data are compared with long-term output of the SLIMCAT 3-D chemical transport model (CTM). The basic model, forced by ECMWF (ERA-40) analyses, captures the observed NO2 annual cycle but significantly underestimates the spring/summer maximum (by 12% at sunset and up to 25% at sunrise). In a model run which uses assimilation of satellite CH4 profiles to constrain the model long-lived tracers the agreement is significantly improved. This improvement in modelled column NO2 is due to better modelled NOy profiles and points to transport errors in the ECMWF ERA-40 reanalyses.Routine measurements have been possible thanks to the funding provided by the projects QUILT (EU EVK2-CT2000-0059) SCOUT-O3 (EU 505390-GOCE-CT-2004), TROMPETA (MCyT CGL2004-03669) and is on-going through GEOMON (EU FP6-2005-Global-4- 036677)

Toll-Like Receptors in Secondary Obstructive Cholangiopathy

Secondary obstructive cholangiopathy is characterized by intra- or extrahepatic bile tract obstruction. Liver inflammation and structural alterations develop due to progressive bile stagnation. Most frequent etiologies are biliary atresia in children, and hepatolithiasis, postcholecystectomy bile duct injury, and biliary primary cirrhosis in adults, which causes chronic biliary cholangitis. Bile ectasia predisposes to multiple pathogens: viral infections in biliary atresia; Gram-positive and/or Gram-negative bacteria cholangitis found in hepatolithiasis and postcholecystectomy bile duct injury. Transmembrane toll-like receptors (TLRs) are activated by virus, bacteria, fungi, and parasite stimuli. Even though TLR-2 and TLR-4 are the most studied receptors related to liver infectious diseases, other TLRs play an important role in response to microorganism damage. Acquired immune response is not vertically transmitted and reflects the infectious diseases history of individuals; in contrast, innate immunity is based on antigen recognition by specific receptors designated as pattern recognition receptors and is transmitted vertically through the germ cells. Understanding the mechanisms for bile duct inflammation is essential for the future development of therapeutic alternatives in order to avoid immune-mediated destruction on secondary obstructive cholangiopathy. The role of TLRs in biliary atresia, hepatolithiasis, bile duct injury, and primary biliary cirrhosis is described in this paper

The Rossiter-McLaughlin effect in Exoplanet Research

The Rossiter-McLaughlin effect occurs during a planet's transit. It provides the main means of measuring the sky-projected spin-orbit angle between a planet's orbital plane, and its host star's equatorial plane. Observing the Rossiter-McLaughlin effect is now a near routine procedure. It is an important element in the orbital characterisation of transiting exoplanets. Measurements of the spin-orbit angle have revealed a surprising diversity, far from the placid, Kantian and Laplacian ideals, whereby planets form, and remain, on orbital planes coincident with their star's equator. This chapter will review a short history of the Rossiter-McLaughlin effect, how it is modelled, and will summarise the current state of the field before describing other uses for a spectroscopic transit, and alternative methods of measuring the spin-orbit angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from ‘‘Instituto de Salud Carlos III’’ (ISCIII), Spain