The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

The Thermal Design, Characterization, and Performance of the SPIDER Long-Duration Balloon Cryostat

We describe the SPIDER flight cryostat, which is designed to cool six millimeter-wavelength telescopes during an Antarctic long-duration balloon flight. The cryostat, one of the largest to have flown on a stratospheric payload, uses liquid helium-4 to deliver cooling power to stages at 4.2 and 1.6 K. Stainless steel capillaries facilitate a high flow impedance connection between the main liquid helium tank and a smaller superfluid tank, allowing the latter to operate at 1.6 K as long as there is liquid in the 4.2 K main tank. Each telescope houses a closed cycle helium-3 adsorption refrigerator that further cools the focal planes down to 300 mK. Liquid helium vapor from the main tank is routed through heat exchangers that cool radiation shields, providing negative thermal feedback. The system performed successfully during a 17 day flight in the 2014-2015 Antarctic summer. The cryostat had a total hold time of 16.8 days, with 15.9 days occurring during flight.Comment: 15 pgs, 17 fig

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Treatment of atypical central neurocytoma in a child with high dose chemotherapy and autologous stem cell rescue

The authors describe a 9 month old female with recurrent atypical central neurocytoma and leptomeningeal spread treated with high dose chemotherapy, autologous stem cell rescue, and adjuvant therapy. She had a complete response to therapy and was disease free at 4 years of age until a recurrence 6 months later. The use of intensive chemotherapy followed by autologous stem cell rescue for atypical neurocytoma may be considered as an adjunct to surgical therapy in young patients with atypical neurocytoma not amenable to radiation therapy

Enzymatic Shaving of the Tegument Surface of Live Schistosomes for Proteomic Analysis: A Rational Approach to Select Vaccine Candidates

Adult schistosome parasites can reside in the host bloodstream for decades surrounded by components of the immune system. It was originally proposed that their survival depended on the secretion of an inert bilayer, the membranocalyx, to protect the underlying plasma membrane from attack. We have investigated whether any proteins were exposed on the surface of live worms using incubation with selected hydrolases, in combination with mass spectrometry to identify released proteins. We show that a small number of parasite proteins are accessible to the enzymes and so could represent constituents of the membranocalyx. We also identified several proteins acquired by the parasite on contact with host cells. In addition, components of the cytolytic complement pathway were detected, but these appeared not to harm the worm, indicating that some of its own surface proteins could inhibit the lytic pathway. We suggest that, collectively, the ‘superficial’ parasite proteins may provide good candidates for a schistosome vaccine

Chromosomal evidence for a putative cryptic species in the Gymnotus carapo species-complex (Gymnotiformes, Gymnotidae)

<p>Abstract</p> <p>Background</p> <p>In this study we examined the karyotypes of morphologically indistinguishable populations of the electric knifefish <it>Gymnotus carapo sensu stricto </it>from the Eastern Amazon of Brazil. These were identified unambiguously on the basis of external morphology, meristics, and pigmentation.</p> <p>Results</p> <p>Specimens from one of five localities exhibited a karyotype previously not documented for <it>Gymnotus </it>species in the Amazon basin: 2n = 40 (34M/SM+6ST/A). Samples from the other four localities exhibited a different karyotype: 2n = 42 (30M/SM+12ST/A), which we had previously described. Specimens from all five localities presented constitutive heterochromatin in the centromeric region of almost all chromosomes, including in the distal and interstitial regions. Staining with 4'6-Diamidino-2-phenylindole revealed C-positive banding. In both karyotypes the Nucleolar Organizer Region (NOR) was located on the short arm of pair 20, and Chromomycin A₃stained the NORs. Fluorescent <it>in situ </it>hybridization with telomeric probes showed an Interstitial Telomeric Sequence (ITS) in the proximal short arm of a metacentric pair in the 2n = 40 karyotype.</p> <p>Conclusion</p> <p>The difference between the two karyotypes on the diploid number and chromosome morphology can be explained by rearrangements of the fusion-fission type and also by pericentric inversions. The presence of ITS in a metacentric pair of the 2n = 40 karyotype suggests that the difference in the diploid number of the karyotypes results from a fusion. The consistent 2n = 42 karyotype at four localities suggests an interbreeding population. However, because fusion-fission and pericentric inversions of this nature typically result in reproductive isolation, we speculate that the form with the 2n = 40 karyotype is a different species to that of the 2n = 42 form. Nonetheless, we did not observe evident differences in external morphology, meristics and pigmentation between the two forms, which suggest that they represent cryptic sympatric species in the <it>G. carapo </it>species complex. We speculate that the chromosomal speciation occurred recently, allowing insufficient time for the fixation of other differences following post-zygotic isolation.</p

Discovery of a Novel Activator of KCNQ1-KCNE1 K+ Channel Complexes

KCNQ1 voltage-gated K+ channels (Kv7.1) associate with the family of five KCNE peptides to form complexes with diverse gating properties and pharmacological sensitivities. The varied gating properties of the different KCNQ1-KCNE complexes enables the same K+ channel to function in both excitable and non excitable tissues. Small molecule activators would be valuable tools for dissecting the gating mechanisms of KCNQ1-KCNE complexes; however, there are very few known activators of KCNQ1 channels and most are ineffective on the physiologically relevant KCNQ1-KCNE complexes. Here we show that a simple boronic acid, phenylboronic acid (PBA), activates KCNQ1/KCNE1 complexes co-expressed in Xenopus oocytes at millimolar concentrations. PBA shifts the voltage sensitivity of KCNQ1 channel complexes to favor the open state at negative potentials. Analysis of different-sized charge carriers revealed that PBA also targets the permeation pathway of KCNQ1 channels. Activation by the boronic acid moiety has some specificity for the Kv7 family members (KCNQ1, KCNQ2/3, and KCNQ4) since PBA does not activate Shaker or hERG channels. Furthermore, the commercial availability of numerous PBA derivatives provides a large class of compounds to investigate the gating mechanisms of KCNQ1-KCNE complexes

Immune-Mediated Change in the Expression of a Sexual Trait Predicts Offspring Survival in the Wild

BACKGROUND: The "good genes" theory of sexual selection postulates that females choose mates that will improve their offspring's fitness through the inheritance of paternal genes. In spite of the attention that this hypothesis has given rise to, the empirical evidence remains sparse, mostly because of the difficulties of controlling for the many environmental factors that may covary with both the paternal phenotype and offspring fitness. Here, we tested the hypothesis that offspring sired by males of a preferred phenotype should have better survival in an endangered bird, the houbara bustard (Chlamydotis undulata undulata). METHODOLOGY/PRINCIPAL FINDINGS: We tested if natural and experimentally-induced variation in courtship display (following an inflammatory challenge) predicts the survival of offspring. Chicks were produced by artificial insemination of females, ensuring that any effect on survival could only arise from the transfer of paternal genes. One hundred and twenty offspring were equipped with radio transmitters, and their survival monitored in the wild for a year. This allowed assessment of the potential benefits of paternal genes in a natural setting, where birds experience the whole range of environmental hazards. Although natural variation in sire courtship display did not predict offspring survival, sires that withstood the inflammatory insult and maintained their courtship activity sired offspring with the best survival upon release. CONCLUSIONS: This finding is relevant both to enlighten the debate on "good genes" sexual selection and the management of supportive breeding programs

Protein profiling of the dimorphic, pathogenic fungus, Penicillium marneffei

<p>Abstract</p> <p>Background</p> <p><it>Penicillium marneffei </it>is a pathogenic fungus that afflicts immunocompromised individuals having lived or traveled in Southeast Asia. This species is unique in that it is the only dimorphic member of the genus. Dimorphism results from a process, termed phase transition, which is regulated by temperature of incubation. At room temperature, the fungus grows filamentously (mould phase), but at body temperature (37°C), a uninucleate yeast form develops that reproduces by fission. Formation of the yeast phase appears to be a requisite for pathogenicity. To date, no genes have been identified in <it>P. marneffei </it>that strictly induce mould-to-yeast phase conversion. In an effort to help identify potential gene products associated with morphogenesis, protein profiles were generated from the yeast and mould phases of <it>P. marneffei</it>.</p> <p>Results</p> <p>Whole cell proteins from the early stages of mould and yeast development in <it>P. marneffei </it>were resolved by two-dimensional gel electrophoresis. Selected proteins were recovered and sequenced by capillary-liquid chromatography-nanospray tandem mass spectrometry. Putative identifications were derived by searching available databases for homologous fungal sequences. Proteins found common to both mould and yeast phases included the signal transduction proteins cyclophilin and a RACK1-like ortholog, as well as those related to general metabolism, energy production, and protection from oxygen radicals. Many of the mould-specific proteins identified possessed similar functions. By comparison, proteins exhibiting increased expression during development of the parasitic yeast phase comprised those involved in heat-shock responses, general metabolism, and cell-wall biosynthesis, as well as a small GTPase that regulates nuclear membrane transport and mitotic processes in fungi. The cognate gene encoding the latter protein, designated <it>RanA</it>, was subsequently cloned and characterized. The <it>P. marneffei </it>RanA protein sequence, which contained the signature motif of Ran-GTPases, exhibited 90% homology to homologous <it>Aspergillus </it>proteins.</p> <p>Conclusion</p> <p>This study clearly demonstrates the utility of proteomic approaches to studying dimorphism in <it>P. marneffei</it>. Moreover, this strategy complements and extends current genetic methodologies directed towards understanding the molecular mechanisms of phase transition. Finally, the documented increased levels of RanA expression suggest that cellular development in this fungus involves additional signaling mechanisms than have been previously described in <it>P. marneffei</it>.</p

Non-Adherence in Patients on Peritoneal Dialysis: A Systematic Review

Background: It has been increasingly recognized that non-adherence is an important factor that determines the outcome of peritoneal dialysis (PD) therapy. There is therefore a need to establish the levels of non-adherence to different aspects of the PD regimen (dialysis procedures, medications, and dietary/fluid restrictions). Methods: A systematic review of peer-reviewed literature was performed in PubMed, PsycINFO and CINAHL databases using PRISMA guidelines in May 2013. Publications on non-adherence in PD were selected by two reviewers independently according to predefined inclusion and exclusion criteria. Relevant data on patient characteristics, measures, rates and factors associated with non-adherence were extracted. The quality of studies was also evaluated independently by two reviewers according to a revised version of the Effective Public Health Practice Project assessment tool. Results: The search retrieved 204 studies, of which a total of 25 studies met inclusion criteria. Reported rates of nonadherence varied across studies: 2.6 1353% for dialysis exchanges, 3.9 1385% for medication, and 14.4 1367% for diet/fluid restrictions. Methodological differences in measurement and definition of non-adherence underlie the observed variation. Factors associated with non-adherence that showed a degree of consistency were mostly socio-demographical, such as age, employment status, ethnicity, sex, and time period on PD treatment. Conclusion: Non-adherence to different dimensions of the dialysis regimen appears to be prevalent in PD patients. There is a need for further, high-quality research to explore these factors in more detail, with the aim of informing intervention designs to facilitate adherence in this patient populatio