Structure and sequence of the human α- -iduronidase gene

In humans, a deficiency of the lysosomal hydrolase α- -iduronidase (IDUA; EC 3.2.1.76) results in the lysosomal storage of the glycosaminoglycans heparan sulfate and dermatan sulfate, thereby causing the lysosomal storage disorder mucopolysaccharidosis type I. The gene for IDUA is split into 14 exons spanning approximately 19 kb. We report the sequence of two noncontiguous segments of the IDUA gene, one 1.8-kb segment containing exons 1 and 2 and surrounding sequences and a second segment of 4.5 kb containing the last 12 exons. The potential promoter for IDUA has only GC box type consensus sequences consistent with a housekeeping promoter and is bounded by an Alu repeat sequence. The first two exons of IDUA are separated by an intron of 566 bp, then there is a large intron of approximately 13 kb, and the last 12 exons are clustered within 4.5 kb. No consensus polyadenylation signal was found in the 3′ untranslated region, although two variant polyadenylation signals are proposed.     

Perceptual constraints on optimal foraging: The effects of variation among foragers

Summary We present a simple model of habitat selection in which individuals differ in their ability to discriminate between resource sites' profitabilities. The model investigates the effects of violating the ideal assumption of the well-known ideal free distribution (IFD). We show that (1) variability in perceptual limits within a population can significantly change the distribution of foraging animals even though the mean perceptual limit is the same, (2) the direction of this change depends on the proportion of the population that choose randomly between resource sites and (3) better perceivers are more likely to be found at individually more profitable sites, which, because of undermatching with respect to the IFD, are also the absolutely more profitable sites. We note that variability in perceptual limits almost always led to an undermatching of organisms to resources, thereby extending previous workers' results implying that the incorporation of any form of perceptual limits leads to undermatching with respect to the IFD.     

Assessment of counting efficiencies for labeled protein and other macromolecules in filter disk assays

A several-fold greater counting efficiency is observed for protein labeled with [³H]leucine than for free [³H]leucine using a conventional filter disk assay. A similar, though less marked, effect is noted for ¹⁴C-labeled molecules. These results are comparable to those reported by others for counting efficiencies of labeled DNA and deoxynucleotides and illustrate the generality of this effect with regard to macromolecules and their low-molecular weight precursors. This phenomenon, presumably due to differences in the distribution of large and small molecules within filters, gives rise to errors in the quantitation of macromolecule synthesis if a counting efficiency identical to that of the precursor is assumed to apply. A convenient method for determining counting efficiencies of various molecules bound to filters is presented which eliminates this problem.     

Angular Precision of Radical Pair Compass Magnetoreceptors

The light-dependent magnetic compass sense of night-migratory songbirds is thought to rely on magnetically sensitive chemical reactions of radical pairs in cryptochrome proteins located in the birds’ eyes. Recently, an information theory approach was developed that provides a strict lower bound on the precision with which a bird could estimate its head direction using only geomagnetic cues and a cryptochrome-based radical pair sensor. By means of this lower bound, we show here how the performance of the compass sense could be optimized by adjusting the orientation of cryptochrome molecules within photoreceptor cells, the distribution of cells around the retina, and the effects of the geomagnetic field on the photochemistry of the radical pair.     

Controlling Hierarchy in Solution‐processed Polymer Solar Cells Based on Crosslinked P3HT

Understanding and controlling the morphology of donor/acceptor blends is critical for the development of solution processable organic solar cells. By crosslinking a poly(3‐n‐hexylthiophene‐2,5‐diyl) (P3HT) film we have been able to spin‐coat [6,6]‐phenyl‐C₆₁‐butyric acid methyl ester (PCBM) onto the film to form a structure that is close to a bilayer, thus creating an ideal platform for investigating interdiffusion in this model system. Neutron reflectometry (NR) demonstrates that without any thermal treatment a smaller amount of PCBM percolates throughout the crosslinked P3HT when compared to a non‐crosslinked P3HT film. Using time‐resolved NR we also show thermal annealing increases the rate of diffusion, resulting in a near‐uniform distribution of PCBM throughout the polymer film. XPS measurements confirm the presence of both P3HT and PCBM at the annealed film's surface indicating that the two components are intermixed. Photovoltaic devices fabricated using this bilayer approach and suitable annealing conditions yielded comparable power conversion efficiencies to bulk heterojunction devices made from the same materials. The crosslinking procedure has also enabled the formation of patterned P3HT films by photolithography. Pillars with feature sizes down to 2 μm were produced and after subsequent deposition of PCBM and thermal annealing devices with efficiencies of up to 1.4% were produced.     

Whether the Weather Drives Patterns of Endemic Amphibian Chytridiomycosis: A Pathogen Proliferation Approach

The pandemic amphibian disease chytridiomycosis often exhibits strong seasonality in both prevalence and disease-associated mortality once it becomes endemic. One hypothesis that could explain this temporal pattern is that simple weather-driven pathogen proliferation (population growth) is a major driver of chytridiomycosis disease dynamics. Despite various elaborations of this hypothesis in the literature for explaining amphibian declines (e.g., the chytrid thermal-optimum hypothesis) it has not been formally tested on infection patterns in the wild. In this study we developed a simple process-based model to simulate the growth of the pathogen Batrachochytrium dendrobatidis (Bd) under varying weather conditions to provide an a priori test of a weather-linked pathogen proliferation hypothesis for endemic chytridiomycosis. We found strong support for several predictions of the proliferation hypothesis when applied to our model species, Litoria pearsoniana, sampled across multiple sites and years: the weather-driven simulations of pathogen growth potential (represented as a growth index in the 30 days prior to sampling; GI₃₀) were positively related to both the prevalence and intensity of Bd infections, which were themselves strongly and positively correlated. In addition, a machine-learning classifier achieved ∼72% success in classifying positive qPCR results when utilising just three informative predictors 1) GI₃₀, 2) frog body size and 3) rain on the day of sampling. Hence, while intrinsic traits of the individuals sampled (species, size, sex) and nuisance sampling variables (rainfall when sampling) influenced infection patterns obtained when sampling via qPCR, our results also strongly suggest that weather-linked pathogen proliferation plays a key role in the infection dynamics of endemic chytridiomycosis in our study system. Predictive applications of the model include surveillance design, outbreak preparedness and response, climate change scenario modelling and the interpretation of historical patterns of amphibian decline.     

Evidence for Enhanced Multisensory Facilitation with Stimulus Relevance: An Electrophysiological Investigation

Currently debate exists relating to the interplay between multisensory processes and bottom-up and top-down influences. However, few studies have looked at neural responses to newly paired audiovisual stimuli that differ in their prescribed relevance. For such newly associated audiovisual stimuli, optimal facilitation of motor actions was observed only when both components of the audiovisual stimuli were targets. Relevant auditory stimuli were found to significantly increase the amplitudes of the event-related potentials at the occipital pole during the first 100 ms post-stimulus onset, though this early integration was not predictive of multisensory facilitation. Activity related to multisensory behavioral facilitation was observed approximately 166 ms post-stimulus, at left central and occipital sites. Furthermore, optimal multisensory facilitation was found to be associated with a latency shift of induced oscillations in the beta range (14–30 Hz) at right hemisphere parietal scalp regions. These findings demonstrate the importance of stimulus relevance to multisensory processing by providing the first evidence that the neural processes underlying multisensory integration are modulated by the relevance of the stimuli being combined. We also provide evidence that such facilitation may be mediated by changes in neural synchronization in occipital and centro-parietal neural populations at early and late stages of neural processing that coincided with stimulus selection, and the preparation and initiation of motor action.     

Experimental infections of Orchitophrya stellarum (Scuticociliata) in American blue crabs (Callinectes sapidus) and fiddler crabs (Uca minax)

Outbreaks of an unidentified ciliate have occurred on several occasions in blue crabs from Chesapeake Bay held during winter months in flow-through systems. The parasite was initially thought to be Mesanophrys chesapeakensis, but molecular analysis identified it as Orchitophyra stellarum, a facultative parasite of sea stars (Asteroidea). We investigated the host-parasite association of O. stellarum in the blue crab host. Crabs were inoculated with the ciliate, or they were held in bath exposures after experimentally induced autotomy of limbs in order to determine potential mechanisms for infection. Crabs inoculated with the ciliate, or exposed to it after experimental autotomy, rapidly developed fatal infections. Crabs that were not experimentally injured, but were exposed to the ciliate, rarely developed infections; thus, indicating that the parasite requires a wound or break in the cuticle as a portal of entry. For comparative purposes, fiddler crabs, Uca minax, were inoculated with the ciliate in a dose-titration experiment. Low doses of the ciliate (10 per crab) were sometimes able to establish infections, but high intensity infections developed quickly at doses over 500 ciliates per crab. Chemotaxis studies were initiated to determine if the ciliate preferentially selected blue crab serum (BCS) over other nutrient sources. Cultures grown on medium with BCS or fetal bovine serum showed some conditioning in their selection for different media, but the outcome in choice experiments indicated that the ciliate was attracted to BCS and not seawater. Our findings indicate that O. stellarum is a facultative parasite of blue crabs. It can cause infections in exposed crabs at 10–15 °C, but it requires a portal of entry for successful host invasion, and it may find injured hosts using chemotaxis.     

Case report of whole genome sequencing in the XY female: identification of a novel <Emphasis Type="Italic">SRY</Emphasis> mutation and revision of a misdiagnosis of androgen insensitivity syndrome

Background

The 46,XY female is characterised by a male karyotype and female phenotype arising due to any interruption in the sexual development pathways in utero. The cause is usually genetic and various genes are implicated.

Case presentation

Herein we describe a 46,XY woman who was first diagnosed with androgen insensitivity syndrome (testicular feminisation) at 18 years; however, this was later questioned due to the presence of intact Müllerian structures. The clinical phenotype suggested several susceptibility genes including SRY, DHH, NR5A1, NR0B1, AR, AMH, and AMHR2. To study candidate genes simultaneously, we performed whole genome sequencing. This revealed a novel and likely pathogenic missense variant (p.Arg130Pro, c.389G>C) in SRY, one of the major genes implicated in complete gonadal dysgenesis, hence securing this condition over androgen insensitivity syndrome as the cause of the patient’s disorder of sexual development.

Conclusion

This case highlights the emerging clinical utility of whole genome sequencing as a tool in differentiating disorders of sexual development.