Na(V)1.5 sodium channel window currents contribute to spontaneous firing in olfactory sensory neurons

Olfactory sensory neurons (OSNs) fire spontaneously as well as in response to odor; both forms of firing are physiologically important. We studied voltage-gated Na+ channels in OSNs to assess their role in spontaneous activity. Whole cell patch-clamp recordings from OSNs demonstrated both tetrodotoxin-sensitive and tetrodotoxin-resistant components of Na+ current. RT-PCR showed mRNAs for five of the nine different Na+ channel α-subunits in olfactory tissue; only one was tetrodotoxin resistant, the so-called cardiac subtype NaV1.5. Immunohistochemical analysis indicated that NaV1.5 is present in the apical knob of OSN dendrites but not in the axon. The NaV1.5 channels in OSNs exhibited two important features: 1) a half-inactivation potential near −100 mV, well below the resting potential, and 2) a window current centered near the resting potential. The negative half-inactivation potential renders most NaV1.5 channels in OSNs inactivated at the resting potential, while the window current indicates that the minor fraction of noninactivated NaV1.5 channels have a small probability of opening spontaneously at the resting potential. When the tetrodotoxin-sensitive Na+ channels were blocked by nanomolar tetrodotoxin at the resting potential, spontaneous firing was suppressed as expected. Furthermore, selectively blocking NaV1.5 channels with Zn2+ in the absence of tetrodotoxin also suppressed spontaneous firing, indicating that NaV1.5 channels are required for spontaneous activity despite resting inactivation. We propose that window currents produced by noninactivated NaV1.5 channels are one source of the generator potentials that trigger spontaneous firing, while the upstroke and propagation of action potentials in OSNs are borne by the tetrodotoxin-sensitive Na+ channel subtypes.This work was aided by support from Boston University, the Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD) P30 DC-04657; D. Restrepo, principal investigator], and NIDCD Grants DC-04863 to V. Dionne and DC-006070 to D. Restrepo and T. E. Finger. (Boston University; P30 DC-04657 - Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD)]; DC-04863 - Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD)]; DC-006070 - Rocky Mountain Taste and Smell Center Core for Cellular Visualization and Analysis [National Institute on Deafness and Other Communication Disorders (NIDCD)])https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122723/Accepted manuscrip

Faraday rotation spectra of bismuth-substituted ferrite garnet films with in-plane magnetization

Single crystalline films of bismuth-substituted ferrite garnets have been synthesized by the liquid phase epitaxy method where GGG substrates are dipped into the flux. The growth parameters are controlled to obtain films with in-plane magnetization and virtually no domain activity, which makes them excellently suited for magnetooptic imaging. The Faraday rotation spectra were measured across the visible range of wavelengths. To interprete the spectra we present a simple model based on the existence of two optical transitions of diamagnetic character, one tetrahedral and one octahedral. We find excellent agreement between the model and our experimental results for photon energies between 1.77 and 2.53 eV, corresponding to wavelengths between 700 and 490 nm. It is shown that the Faraday rotation changes significantly with the amount of substituted gallium and bismuth. Furthermore, the experimental results suggest that the magnetooptic response changes linearly with the bismuth substitution.Comment: 15 pages, 6 figures, published in Phys. Rev.

Error analysis of Tide Gauge Benchmark Monitoring (TIGA) Analysis Center stacked solutions

In 2013 the International GNSS Service (IGS) Tide Gauge Benchmark Monitoring (TIGA) Working Group (WG) started their reprocessing campaign, which proposes to re-analyze all relevant Global Positioning System (GPS) observations from 1995 to the end of 2013. This re-processed dataset will provide high quality estimates of land motions, enabling regional and global high-precision geophysical/geodetic studies. Several of the individual TIGA Analysis Centers (TACs) have completed processing the full history of GPS observations recorded by the IGS global network, as well as, many other GPS stations at or close to tide gauges, which are available from the TIGA data center at the University of La Rochelle (www.sonel.org). The TAC solutions contain a total of over 700 stations. This study focuses on the evaluations of any systematic error present in the three TIGA analysis center (TAC) SINEX solutions: the British Isles continuous GNSS Facility – University of Luxembourg consortium (BLT), the GeoForschungsZentrum (GFZ) Potsdam, and of the University of La Rochelle (ULR). We have analyzed the residual position time series of the individual TAC a combination of automatic and manual discontinuity identification, applying a post-seismic deformation model adopted from ITRF2014 for those stations that are affected by earthquakes, followed by the stacking of the daily solution of the individual TAC into a long term linear frame. We have carried out the error analysis using the Combination and Analysis of Terrestrial Reference Frame (CATREF) software package. The TIGA Combination Centre (TCC) at the University of Luxembourg (UL) is responsible for providing a combined solution with a global set of vertical land movement estimates

Investigating patterns of straying and mixed stock exploitation of sea trout, Salmo trutta, in rivers sharing an estuary in south-west England

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.For effective management, information on the stock composition of a fishery is essential. Here, the utility of a resident trout, Salmon trutta L, microsatellite baseline to determine the origins of sea trout entering the rivers Tamar, Tavy and Lynher in south-west England is highlighted – all share a common estuary and have major runs of sea trout. There is a high degree of geographical structuring of the genetic variation in the baseline rivers. Testing with simulated and real data sets showed fish can be assigned to reporting group with a high degree of accuracy. Mixed stock analysis of >1000 sea trout showed that fish entering the Tamar and Tavy constituted mixed stocks. Significantly, in the Tamar, non-natal origin sea trout are restricted to the lower catchment. As well as providing insight into sea trout behaviour, this study also has important implications for the management of recreational rod and line fisheries.This research forms part of the Atlantic AquaticResource Conservation (AARC) project and was funded via the European Union 2007–2013 Atlantic Area Pro-gramme, an INTERREG III B initiat ive; additional funding for this project was provided by the Atlantic SalmonTrust

Hepatitis B virus X protein impedes the DNA repair via its association with transcription factor, TFIIH

<p>Abstract</p> <p>Background</p> <p>Hepatitis B virus (HBV) infections play an important role in the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. HBx is known to interact with DNA helicase components of TFIIH, a basal transcriptional factor and an integral component of DNA excision repair.</p> <p>Results</p> <p>In this study, the functional relevance of this association was further investigated in the context to DNA repair. By site-directed mutagenesis HBx's critical residues for interaction with TFIIH were identified. Similarly, TFIIH mutants lacking ATPase domain and the conserved carboxyl-terminal domain failed to interact with HBx. Yeast and mammalian cells expressing HBx^wtconferred hypersensitivity to UV irradiation, which is interpreted as a basic deficiency in nucleotide excision repair. HBx^mut120(Glu to Val) was defective in binding to TFIIH and failed to respond to UV.</p> <p>Conclusions</p> <p>We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, thereby contributing to HCC development.</p

Disentangling the effects of evolutionary, demographic, and environmental factors influencing genetic structure of natural populations: Atlantic herring as a case study

The spatial structuring of intraspecific genetic diversity is the result of random genetic drift, natural selection, migration, mutation, and their interaction with historical processes. The contribution of each has been typically difficult to estimate, but recent advances in statistical genetics have provided valuable new investigative tools to tackle such complexity. Using a combination of such methods, we examined the roles of environment (i.e., natural selection), random genetic processes (i.e., drift), and demography and life histories (e. g., feeding migrations) on population structure of a widely distributed and abundant marine pelagic fish of economic importance, Atlantic herring (Clupea harengus). Individuals were collected during peak spawning time from 19 spawning locations spanning the region from the western North Sea to the eastern Baltic Sea (N = 1859, eight microsatellite loci). We carried out separate analyses of neutral and selected genetic variation, which allowed us to establish that the two most important factors affecting population structure were selection due to salinity at spawning sites and feeding migrations. The genetic signal left by the demographic history of herring, on the other hand, seems to have been largely eroded, which is not surprising given the large reproductive potential and presumed enormous local effective population sizes of pelagic fish that constrain the effect of stochastic processes. The approach we used can in principle be applied to any abundant and widely distributed aquatic or terrestrial species.</p

On the Scientific Applications of IGS Products: An Assessment of the Reprocessed TIGA Solutions and Combined Products

Global sea levels have risen since the early 19th century and this rise is likely to accelerate through the 21st century and beyond. Much of the past information on sea level rise stems from the instrumental records of tide gauges, which measure changes in sea level relative to a tide gauge benchmark (TGBM) situated on land. In order to assess regional or global sea level changes the vertical land movements (VLM) at the tide gauge and its TGBM need to be monitored. GNSS, in particular GPS, has been recognized as one space-geodetic technique to provide highly accurate estimates of VLM in a geocentric reference frame for tide gauges and their TGBMs. As it turned out, this scientific application of GNSS poses the most stringent requirements on the consistency and homogeneity on the data, processing strategies, satellite products, bias models and reference frames used in the analysis of GNSS measurements. Under the umbrella of the International GNSS Service (IGS), the Tide Gauge Benchmark Monitoring (TIGA) Working Group (WG) has the objective to provide highly-accurate positions and VLM estimates for a global network of tide gauges contributing to the Global Sea Level Observing System (GLOSS) and the Permanent Service for Mean Sea Level (PSMSL). As such TIGA forms an important contribution of the IGS to the goals of the Global Geodetic Observing System (GGOS), the Global Climate Observing System (GCOS) and the World Climate Research Programme (WCRP). To achieve the TIGA-WG objectives, five TIGA Analysis Centers (TACs) contributed re-processed global GPS network solutions to TIGA, employing the latest bias models and processing strategies in accordance with the second IGS re-processing campaign (repro2). These individual TAC solutions were then used to compute the combined products by the TIGA Combination Centre (TCC) at the University of Luxembourg using an in-house modified version of the CATREF software package. In this study, we present and internally evaluate the individual TAC and TIGA combined products. We investigate station positions, scale and origin biases, including their frequency content. We also externally evaluate the combined products, particularly the VLM estimates, using solutions from the ITRF2008, ITRF2014 and the glacial isostatic adjustment model ICE-6G (VM5a). Finally, we draw some conclusions on the recent advances and remaining limitations of the various IGS products required for the challenging application to sea level studies

A Global Vertical Land Movement Data Set from a Combination of Global Navigation Satellite System Solutions

Coastal sea-level measurements by tide gauges provide the longest instrumental records of sea-levels with some stretching from the 19th century to present. The derived mean sea-level (MSL) records provide sea-level relative to a nearby tide gauge benchmark (TGBM), which allows for the continuation of this record in time after, for example, equipment modifications. Any changes in the benchmark levels induced by vertical land movements (VLM) affect the MSL records and hence the computed sea-levels. In the past, MSL records affected by VLM were often excluded from further analyses or the VLM were modelled using numerical models of the glacial isostatic adjustment (GIA) process. Over the last two decades Global Navigation Satellite System (GNSS), in particular Global Positioning System (GPS), measurements at or close to tide gauges and the development of the associated processing strategies, have made it possible to obtain estimates of VLM in a geocentric reference system, such as the International Terrestrial Reference Frame release 2008 (ITRF2008) that approach the required accuracy for sea-level studies. Furthermore, the GPS-derived VLM estimates have been shown to improve estimates of sea-level change compared to those using the aforementioned GIA models as these models cannot predict local subsidence or uplift. The International GNSS Service (IGS) Tide Gauge Benchmark Monitoring (TIGA) Working Group has recently re-processed the global GNSS data set from its archive (1000+ stations for 1995-2014) to provide VLM estimates tuned for the sea-level community. To achieve this, five TIGA Analysis Centers (TAC) contributed their reprocessed global GPS network solutions to the WG, all employing the latest bias models and processing strategies in accordance with the second re-processing compaign (repro2) of the IGS. These individual solutions were then combined by the TIGA Combination Center (TCC) to produce, for the first time, a TIGA combined solution (Release 0.99). This combined solution allows an evaluation of each individual TAC solution while also providing a means to gauge the quality and reliability of the combined solution, which is generally regarded as superior to the individual TAC solutions. Using time series analysis methods, estimates of VLM can then be derived from the daily position estimates, which are sub-sequentially employed to investigate coastal sea-levels. In this study, we show results from the evaluation of the relevant solutions, provide an evaluation of the TIGA VLM estimates and give examples of their impact on sea-level estimates for selected tide gauges from around the world. The TAC and TIGA combined solutions, as well as the derived VLM data sets are available from the IGS TIGA WG and will be accessible through SONEL (www.sonel.org) in the near future