Epithelial dynamics shed light on mechanisms underlying ear canal defects

Defects in ear canal development can cause severe hearing loss as sound waves fail to reach the middle ear. Here we reveal new mechanisms that control human canal development and highlight for the first time the complex system of canal closure and reopening. These processes can be perturbed in mutant mice and in explant culture, mimicking the defects associated with canal aplasia. The more superficial part of the canal forms from an open primary canal that closes and then reopens. In contrast, the deeper part of the canal forms from an extending solid meatal plate that opens later. Closure and fusion of the primary canal was linked to loss of periderm, with failure in periderm formation in Grhl3 mutant mice associated with premature closure of the canal. Conversely, inhibition of cell death in the periderm resulted in an arrest of closure. Once closed, re-opening of the canal occurred in a wave, triggered by terminal differentiation of the epithelium. Understanding these complex processes involved in canal development sheds light on the underlying causes of canal aplasia

Challenges of determining frequency and magnitudes of explosive eruptions even with an unprecedented stratigraphy

Through decades of field studies and laboratory analyses, Volcán de Colima, Mexico has one of the best known proximal eruption stratigraphies of any volcano, yet the frequency and magnitudes of previous eruptions are still poorly resolved. Hazard assessments based on models of well-known, well-mapped recent eruptions may appear to have low uncertainty, but may be biased by the nature of those events. We present a comprehensive stratigraphy of explosive eruption deposits combining new data collected as part of this study together with published and unpublished data. For the first time we have been able to model five of the best exposed and cross-correlated pre-historical Holocene explosive events at Volcán de Colima. By modelling the volumes and magnitudes of Holocene eruptions at Volcán de Colima, we are able to improve estimations of the potential range of magnitudes of future explosive eruptions, which can be incorporated into hazard assessments for nearby communities. Based on recent studies we demonstrate that these volumes may be underestimated by at least an order of magnitude, and show that even with an exceptionally well-defined stratigraphic record our understanding of the full range of explosive eruptions may still be biased

Canopy fruit location can affect olive oil quality in Arbequina hedgerow orchards

The effect of location of fruit in canopies of hedgerow olive trees (Olea europaea L., cv. ‘Arbequina’) on quality of virgin oil was tested by analyzing oils extracted from different height layers and faces of 9 olive hedgerows (6 North-South oriented and 3 East-West). Although sensory attributes were not different other oil quality parameters may be significantly modified by fruit position. In some hedgerows, oils extracted from fruits harvested from higher layers exhibited significantly higher stability against oxidation, along with higher palmitic acid, linoleic acid and phenol contents, but lower oleic acid content. Oils extracted from fruits harvested from East and North facing hedgerows oriented North-South and East-West, respectively, exhibited higher oleic contents and lower saturated and polyunsaturated fatty acid contents. The mean phenol content of oils extracted from fruits from a North-South oriented hedgerow was significantly greater from one of the East-West oriented hedgerows. These findings may be relevant for the design of future olive hedgerows destined for olive oil production

Querying metric spaces with bit operations

Funding: This work was supported by ESRC grant ES/L007487/1 “Administrative Data Research Centre—Scotland".Metric search techniques can be usefully characterised by the time at which distance calculations are performed during a query. Most exact search mechanisms use a “just-in-time” approach where distances are calculated as part of a navigational strategy. An alternative is to use a “one-time” approach, where distances to a fixed set of reference objects are calculated at the start of each query. These distances are typically used to re-cast data and queries into a different space where querying is more efficient, allowing an approximate solution to be obtained. In this paper we use a “one-time” approach for an exact search mechanism. A fixed set of reference objects is used to define a large set of regions within the original space, and each query is assessed with respect to the definition of these regions. Data is then accessed if, and only if, it is useful for the calculation of the query solution. As dimensionality increases, the number of defined regions must increase, but the memory required for the exclusion calculation does not. We show that the technique gives excellent performance over the SISAP benchmark data sets, and most interestingly we show how increases in dimensionality may be countered by relatively modest increases in the number of reference objects used.Postprin

Effect of solvent on the hydrogenation of 4-phenyl-2-butanone over Pt based catalysts

In part I of this study, experimental data were presented for the hydrogenation of 4-phenyl-2-butanone with a 4% Pt/TiO2 catalyst where the reaction rate and selectivity (ketone vs. aromatic ring) varied with solvent. In this paper, a rigorous kinetic model is presented utilising these data, incorporating statistical analysis methods to strengthen the foundations of mechanistically sound kinetic models. A fundamental kinetic model for the system is presented and a 2-site model was determined to be most appropriate, describing aromatic hydrogenation (postulated to be over a platinum site) and ketone hydrogenation (at the platinum titania interface). Solvent choice has little impact on the ketone hydrogenation rate constant but strongly impacts aromatic hydrogenation due to solvent-catalyst interaction. Reaction selectivity is also correlated to a fitted product adsorption constant parameter. This kinetic analysis method is the first of its kind demonstrating the role of solvents in influencing reactant adsorption and reaction selectivity.We acknowledge EPSRC for funding as part of the CASTech grant (EP/G011397/1) and the Department of Employment and Learning for a studentship (IM). NSB was funded by a PhD scholarship from the University of Birmingham. SKW was supported by an Engineering Doctorate Studentship in Formulation Engineering at the University of Birmingham sponsored by the EPSRC (EP/G036713/1) and Johnson Matthey.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jcat.2015.06.00

Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue

<p>Abstract</p> <p>Background</p> <p>Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG) tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel.</p> <p>Results</p> <p>After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H) immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; <it>P </it>< 0.0002) and size (-45%; <it>P </it>< 0.0001) of pNF-H-immunoreactive neurons after oxaliplatin treatment. pNF-H-immunoreactive neurons had overlapping size profiles and co-localisation with neurons displaying cell body immunoreactivity for parvalbumin, non-phospho-specific neurofilament medium subunit (NF-M) and non-phospho-specific neurofilament heavy subunit (NF-H), in control DRG. However, there were no significant changes in the numbers of neurons with immunoreactivity for parvalbumin (4.6%, <it>P </it>= 0.82), NF-M (-1%, <it>P </it>= 0.96) or NF-H (0%; <it>P </it>= 0.93) after oxaliplatin treatment, although the sizes of parvalbumin (-29%, <it>P </it>= 0.047), NF-M (-11%, <it>P </it>= 0.038) and NF-H (-28%; <it>P </it>= 0.0033) immunoreactive neurons were reduced. In an independent comparison of different chemotherapeutic agents, the number of pNF-H-immunoreactive neurons was significantly altered by oxaliplatin (-77.2%; <it>P </it>< 0.0001) and cisplatin (-35.2%; <it>P </it>= 0.03) but not by carboplatin or paclitaxel, and their mean cell body area was significantly changed by oxaliplatin (-31.1%; <it>P </it>= 0.008) but not by cisplatin, carboplatin or paclitaxel.</p> <p>Conclusion</p> <p>This study has demonstrated a specific pattern of loss of pNF-H immunoreactivity in rat DRG tissue that corresponds with the relative neurotoxicity of oxaliplatin, cisplatin and carboplatin. Loss of pNF-H may be mechanistically linked to oxaliplatin-induced neuronal atrophy, and serves as a readily measureable endpoint of its neurotoxicity in the rat model.</p

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

Inferring Ecological Processes from Taxonomic, Phylogenetic and Functional Trait β-Diversity

Understanding the influences of dispersal limitation and environmental filtering on the structure of ecological communities is a major challenge in ecology. Insight may be gained by combining phylogenetic, functional and taxonomic data to characterize spatial turnover in community structure (β-diversity). We develop a framework that allows rigorous inference of the strengths of dispersal limitation and environmental filtering by combining these three types of β-diversity. Our framework provides model-generated expectations for patterns of taxonomic, phylogenetic and functional β-diversity across biologically relevant combinations of dispersal limitation and environmental filtering. After developing the framework we compared the model-generated expectations to the commonly used “intuitive” expectation that the variance explained by the environment or by space will, respectively, increase monotonically with the strength of environmental filtering or dispersal limitation. The model-generated expectations strongly departed from these intuitive expectations: the variance explained by the environment or by space was often a unimodal function of the strength of environmental filtering or dispersal limitation, respectively. Therefore, although it is commonly done in the literature, one cannot assume that the strength of an underlying process is a monotonic function of explained variance. To infer the strength of underlying processes, one must instead compare explained variances to model-generated expectations. Our framework provides these expectations. We show that by combining the three types of β-diversity with model-generated expectations our framework is able to provide rigorous inferences of the relative and absolute strengths of dispersal limitation and environmental filtering. Phylogenetic, functional and taxonomic β-diversity can therefore be used simultaneously to infer processes by comparing their empirical patterns to the expectations generated by frameworks similar to the one developed here