Gentamicin, genetic variation and deafness in preterm children.

Hearing loss in children born before 32 weeks of gestation is more prevalent than in full term infants. Aminoglycoside antibiotics are routinely used to treat bacterial infections in babies on neonatal intensive care units. However, this type of medication can have harmful effects on the auditory system. In order to avoid this blood levels should be maintained in the therapeutic range. However in individuals with a mitochondrial genetic variant (m.1555A > G), permanent hearing loss can occur even when drug levels are within normal limits. The aim of the study is to investigate the burden that the m.1555A > G mutation represents to deafness in very preterm infants

Geology and Wine 11. Terroir of the Western Snake River Plain, Idaho, USA

This article explores the unique combination of factors that shape the terroir of Idaho's principal wine grape-growing district. Most Idaho wine grape vineyards are located in the Western Snake River Plain (WSRP) rift basin (~43°N, ~117°W) on soils derived from lake, river, volcanic and wind-blown sediments. The underlying Tertiary and Quaternary rocks record the geologic history of ancient Lake Idaho, its interaction with basaltic volcanism, and subsequent Pleistocene fluvial processes and catastrophic floods. The arid to semi-arid, mid-latitude steppe climate of the WSRP provides fewer growing degree days than American Viticultural Areas (AVAs) in Walla Walla, Washington and Napa Valley, California, but still allows cultivation of Vitis vinifera grapes. Other differences include lower precipitation, higher solar radiation during the growing season, and greater threat of cold injury. Wine grapes grown in the WSRP require irrigation, and irrigation is used to manage canopy size and manipulate vine physiology. Wine grape acreage in Idaho has increased dramatically since 1993 and is estimated, in 2003, at about 500 ha with the white wine cultivars Riesling, Chardonnay, and Gewürztraminer comprising about 60% of production, and Cabernet Sauvignon, Merlot and Syrah as principal red wine cultivars. RÉSUMÉ Le présent article porte sur la combinaison particulière de facteurs qui définit le terroir du principal district viticole de l'État d'Idaho. La plupart des vignobles de l'Idaho sont situés dans le bassin de fossé tectonique (~43°N, ~117°O) de la Western Snake River Plain (WSRP), sur des sols formés de sédiments lacustres, fluviatiles, volcaniques et éoliens. Les couches tertiaires et quaternaires sousjacentes témoignent des événements constitutifs de l'histoire géologique de l'ancien lac Idaho, de phénomènes interactifs dont il a été le théâtre, soit un volcanisme basaltique, ainsi que des processus fluviatiles et des inondations catastrophiques pléistocènes. Bien que le climat aride à semi-aride de steppe en altitude moyenne de la WSRP comporte moins de degrés-jours de croissance que les zone les zones viticoles étasuniennes (AVA) de Walla Walla de l'État de Washhington et de la vallée de Napa de l'État de Californie, il permet tout de même la culture des raisins de Vitis vinifera. De plus, cette région reçoit moins de précipitations, plus d'ensoleillement durant la saison de croissance, et elle est davantage exposée aux meurtrissures du froid. Les vignes de raisins de cuve cultivés dans la WSRP doivent être irriguées, l'irrigation permettant d'agir sur l'ampleur du feuillage et sur la physiologie du vin. La superficie de culture du raisin de cuve en Idaho s'est considérablement accrue depuis 1993 pour atteindre 500 ha environ en 2003, les cultivars à vin blanc de Riesling, Chardonnay, et Gewürztraminer constituant 60 % de la production, et ceux du Cabernet Sauvignon, du Merlot et du Syrah constituant les principaux cultivars à vin rouge

Early Badenian transgression on the outer flank of Western Carpathian Foredeep, Hluchov area, Czech Republic

This multidisciplinary study, based on borehole cores from the Hluchov area in Czech Republic, docu- ments an early Badenian marine transgression on the outer flank of the Western Carpathian Foredeep . The shallow-marine deposits represent coastal transgression over a terrestrial topography of weathered pre-Cenozoic bedrock. The lower facies association (FA1) consists of siliciclastic sediment derived from local substrate erosion. Facies indicate a wave-dominated environment with unstable bottom, variable rate of sediment supply and an incremental rise of relative sea level. The upper facies association (FA2) consists of carbonates indicating a major landward shift of shoreline, decline in siliciclastic input and further sea-level rise. The succession represents a transgressive to highstand systems tract. The maximum flooding surface, ca . 1 m above the FA1/FA2 boundary, is signified by an anomalous decrease in K and Th, an increased Th/K ratio and highest U concentration. The heavy-mineral assemblages in FA1 confirm local sediment provenance, whereas those in FA2 indicate broader sediment derivation, including volcanic component from contemporaneous rhyolitic to rhyodacitic eruptions. The deposits contain a wide range of marine fauna, with the foraminifers and molluscs indicating an early Badenian age. Molluscs, bryozoans and echinoderms indicate a normal-salinity environment with a decreasing hydraulic energy. Foraminifers indicate salinity fluctua- tions in the lowest part of the succession. The isotopic composition of mollusc shells shows marked inter-species differences and a general negative shift in the d 13 C and d 18 O values, indicating diagenetic alteration. The impact of diagenetic processes appears to have been controlled by sedimentary facies. The highly negative d 13 C and d 18 O values correspond to sediment layers with the highest Th/K ratios and hence low clay content. Sediment permea- bility was thus probably crucial in controlling the differential circulation and impact of diagenetic fluids

Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord

<p>Abstract</p> <p>Background</p> <p>Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration and subsequent nociceptive behavior that has been described as a model of osteoarthritis (OA) pain. Central sensitization through activation of mitogen activated protein kinases (MAPKs) is recognized as a pathogenic mechanism in chronic pain. In the present studies, induction of central sensitization as indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 phosphorylation, was assessed in the MIA-OA model.</p> <p>Results</p> <p>Behaviorally, MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks post-MIA treatment. In the same animals, activation of phospho ERK1/2 was gradually increased, reaching a significant level at post injection week 3. Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection week 1 and decreased, but remained elevated, thereafter. Double labeling from 3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but not astrocytes. Additionally, there was increased ipsilateral expression of microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force and pERK1/2 induction in MIA-OA rats.</p> <p>Conclusion</p> <p>Results of these studies support the role of MAPK activation in the progression and maintenance of central sensitization in the MIA-OA experimental pain model.</p

Functional Assessment of Variants Associated with Wolfram Syndrome

Wolfram Syndrome (WS) is a heterogeneous multisystem neurodegenerative disorder with two allelic variations in addition to a separate subtype known as WS type 2. The wide phenotypic spectrum of WS includes diabetes mellitus and optic atrophy which is often accompanied by diabetes insipidus, deafness, urological and neurological complications in combination or in isolation. To date, the understanding of the genotype phenotype relationship in this complex syndrome remains poorly understood. In this study we identified and explored the functionality of rare and novel variants in the two causative WS genes WFS1 and CISD2 by assessing the effects of the mutations on the encoded proteins Wolframin and ERIS, in a cohort of 12 patients with autosomal recessive WS, dominant WS and WS type 2. The identified pathogenic variants included missense changes, frameshift deletions and insertions in WFS1 and an exonic deletion in CISD2 which all altered the respective encoded protein in a manner that did not correlate to the phenome previously described. These observations suggest the lack of genotype phenotype correlation in this complex syndrome and the need to explore other molecular genetic mechanisms. Additionally, our findings highlight the importance of functionally assessing variants for their pathogenicity to tackle the problem of increasing variants of unknown significance (VUS) in the public genetic databases

Moving from a Product-Based Economy to a Service-Based Economy for a More Sustainable Future

Traditionally, economic growth and prosperity have been linked with the availability, production and distribution of tangible goods as well as the ability of consumers to acquire such goods. Early evidence regarding this connection dates back to Adam Smith's Wealth of Nations (1776), in which any activity not resulting in the production of a tangible good is characterized as unproductive of any value." Since then, this coupling of economic value and material production has been prevalent in both developed and developing economies throughout the world. One unintended consequence of this coupling has been the exponential increase in the amount of solid waste being generated. The reason is that any production and consumption of material goods eventually generates the equivalent amount of (or even more) waste. Exacerbating this problem is the fact that, with today's manufacturing and supply chain management technologies, it has become cheaper to dispose and replace most products rather than to repair and reuse them. This has given rise to what some call a disposable society." To put things in perspective: In 2012 households in the U.K. generated approximately 22 thousand tons of waste, which amounted to 411 kg of waste generated per person (Department for Environment, Food & Rural Affairs, 2015). During the same time period, households in the U.S. generated 251 million tons of waste, which is equivalent to a person generating approximately 2 kg of waste every day (U.S. Environmental Protection Agency, 2012). Out of these 251 million tons of total waste generated, approximately 20% of the discarded items were categorized as durable goods. The disposal of durable goods is particularly worrisome because they are typically produced using material from non- renewable resources such as iron, minerals, and petroleum-based raw materials

Properties of the Galactic population of cataclysmic variables in hard X-rays

We measure the spatial distribution and hard X-ray luminosity function of cataclysmic variables (CVs) using the INTEGRAL all-sky survey in the 17-60 keV energy band. The vast majority of the INTEGRAL detected CVs are intermediate polars with luminosities in the range 10^{32}-10^{34} erg/sec. The scale height of the Galactic disk population of CVs is found to be 130{+90}{-50} pc. The CV luminosity function measured with INTEGRAL in hard X-rays is compatible with that previously determined at lower energies (3--20 keV) using a largely independent sample of sources detected by RXTE (located at |b|>10deg as opposed to the INTEGRAL sample, strongly concentrated to the Galactic plane). The cumulative 17-60 keV luminosity density of CVs per unit stellar mass is found to be (1.3+/-0.3)x10^{27} erg/sec/Msun and is thus comparable to that of low-mass X-ray binaries in this energy band. Therefore, faint but numerous CVs are expected to provide an important contribution to the cumulative hard X-ray emission of galaxies.Comment: 8 pages, 8 figures. Submitted to A&

The Energetics of Molecular Gas in NGC 891 from H2 and FIR Spectroscopy

We have studied the molecular hydrogen energetics of the edge-on spiral galaxy NGC\,891, using a 34-position map in the lowest three pure rotational H$_2$ lines observed with the Spitzer Infrared Spectrograph. The S(0), S(1), and S(2) lines are bright with an extinction corrected total luminosity of $\sim2.8 \times 10^{7}$ L$_{\odot}$, or 0.09\% of the total-infrared luminosity of NGC\,891. The H$_2$ line ratios are nearly constant along the plane of the galaxy -- we do not observe the previously reported strong drop-off in the S(1)/S(0) line intensity ratio in the outer regions of the galaxy, so we find no evidence for the very massive cold CO-free molecular clouds invoked to explain the past observations. The H$_2$ level excitation temperatures increase monotonically indicating more than one component to the emitting gas. More than 99\% of the mass is in the lowest excitation (T$_{ex}$ $\sim$125 K) ``warm'' component. In the inner galaxy, the warm H$_2$ emitting gas is $\sim$15\% of the CO(1-0)-traced cool molecular gas, while in the outer regions the fraction is twice as high. This large mass of warm gas is heated by a combination of the far-UV photons from stars in photo-dissociation regions (PDRs) and the dissipation of turbulent kinetic energy. Including the observed far-infrared [OI] and [CII] fine-structure line emission and far-infrared continuum emission in a self-consistent manner to constrain the PDR models, we find essentially all of the S(0) and most (70\%) of the S(1) line arises from low excitation PDRs, while most (80\%) of the S(2) and the remainder of the S(1) line emission arises from low velocity microturbulent dissipation.Comment: Accepted for publication in The Astrophysical Journal. Figure 10 available at http://www.physics.uoc.gr/~vassilis/papers/ngc891.pd

Mitochondrial m.1584A 12S m62A rRNA methylation in families with m.1555A>G associated hearing loss.

The mitochondrial DNA mutation m.1555A>G predisposes to hearing loss following aminoglycoside antibiotic exposure in an idiosyncratic dose-independent manner. However, it may also cause maternally inherited hearing loss in the absence of aminoglycoside exposure or any other clinical features (non-syndromic hearing loss). Although m.1555A>G was identified as a cause of deafness more than twenty years ago, the pathogenic mechanism of this mutation of ribosomal RNA remains controversial. Different mechanistic concepts have been proposed. Most recently, evidence from cell lines and animal models suggested that patients with m.1555A>G may have more 12S rRNA N6, N6-dimethyladenosine (m(6) 2A) methylation than controls, so-called 'hypermethylation'. This has been implicated as a pathogenic mechanism of mitochondrial dysfunction but has yet to be validated in patients. 12S m(6) 2A rRNA methylation, by the mitochondrial transcription factor 1 (TFB1M) enzyme, occurs at two successive nucleotides (m.1584A and m.1583A) in close proximity to m.1555A>G. We examined m(6) 2A methylation in 14 patients with m.1555A>G, and controls, and found all detectable 12S rRNA transcripts to be methylated in both groups. Moreover, different RNA samples derived from the same patient (lymphocyte, fibroblast and lymphoblast) revealed that only transformed cells contained some unmethylated 12S rRNA transcripts, with all detectable 12S rRNA transcripts derived from primary samples m(6) 2A-methylated. Our data indicate that TFB1M 12S m(6) 2A rRNA hypermethylation is unlikely to be a pathogenic mechanism and may be an artefact of previous experimental models studied. We propose that RNA methylation studies in experimental models should be validated in primary clinical samples to ensure that they are applicable to the human situation