Computational approaches for understanding the diagnosis and treatment of Parkinson's disease

This study describes how the application of evolutionary algorithms (EAs) can be used to study motor function in humans with Parkinson's disease (PD) and in animal models of PD. Human data is obtained using commercially available sensors via a range of non-invasive procedures that follow conventional clinical practice. EAs can then be used to classify human data for a range of uses, including diagnosis and disease monitoring. New results are presented that demonstrate how EAs can also be used to classify fruit flies with and without genetic mutations that cause Parkinson's by using measurements of the proboscis extension reflex. The case is made for a computational approach that can be applied across human and animal studies of PD and lays the way for evaluation of existing and new drug therapies in a truly objective way

Myristoylated CIL-7 regulates ciliary extracellular vesicle biogenesis

The cilium both releases and binds to extracellular vesicles (EVs). EVs may be used by cells as a form of intercellular communication and mediate a broad range of physiological and pathological processes. The mammalian polycystins (PCs) localize to cilia, as well as to urinary EVs released from renal epithelial cells. PC ciliary trafficking defects may be an underlying cause of autosomal dominant polycystic kidney disease (PKD), and ciliary–EV interactions have been proposed to play a central role in the biology of PKD. In Caenorhabditis elegans and mammals, PC1 and PC2 act in the same genetic pathway, act in a sensory capacity, localize to cilia, and are contained in secreted EVs, suggesting ancient conservation. However, the relationship between cilia and EVs and the mechanisms generating PC-containing EVs remain an enigma. In a forward genetic screen for regulators of C. elegans PKD-2 ciliary localization, we identified CIL-7, a myristoylated protein that regulates EV biogenesis. Loss of CIL-7 results in male mating behavioral defects, excessive accumulation of EVs in the lumen of the cephalic sensory organ, and failure to release PKD-2::GFP-containing EVs to the environment. Fatty acylation, such as myristoylation and palmitoylation, targets proteins to cilia and flagella. The CIL-7 myristoylation motif is essential for CIL-7 function and for targeting CIL-7 to EVs. C. elegans is a powerful model with which to study ciliary EV biogenesis in vivo and identify cis-targeting motifs such as myristoylation that are necessary for EV–cargo association and function

Child caries management: A randomized controlled trial in dental practice

This multicenter 3-arm, parallel-group, patient-randomized controlled trial compared clinical effectiveness of 3 treatment strategies over 3 y for managing dental caries in primary teeth in UK primary dental care. Participants aged 3 to 7 y with at least 1 primary molar with dentinal carious lesion were randomized across 3 arms (1:1:1 via centrally administered system with variable-length random permuted blocks): C+P, conventional carious lesion management (complete carious tooth tissue removal and restoration placement) with prevention; B+P, biological management (sealing in carious tooth tissue restoratively) with prevention; and PA, prevention alone (diet, plaque removal, fluorides, and fissure sealants). Parents, children, and dentists were not blind to allocated arm. Co–primary outcomes were 1) the proportion of participants with at least 1 episode of dental pain and/or infection and 2) the number of episodes of dental pain and/or infection during follow-up (minimum, 23 mo). In sum, 1,144 participants were randomized (C+P, n = 386; B+P, n = 381; PA, n = 377) by 72 general dental practitioners, of whom 1,058 (C+P, n = 352; B+P, n = 352; PA, n = 354) attended at least 1 study visit and were included in the primary analysis. The median follow-up was 33.8 mo (interquartile range, 23.8 to 36.7). Proportions of participants with at least 1 episode of dental pain and/or infection were as follows: C+P, 42%; B+P, 40%; PA, 45%. There was no evidence of a difference in incidence of dental pain and/or infection when B+P (adjusted risk difference [97.5% CI]: −2% [−10% to 6%]) or PA (4% [−4% to 12%]) was compared with C+P. The mean (SD) number of episodes of dental pain and/or infection were as follows: C+P, 0.62 (0.95); B+P, 0.58 (0.87); and PA, 0.72 (0.98). Superiority could not be concluded for number of episodes between B+P (adjusted incident rate ratio (97.5% CI): 0.95 [0.75 to 1.21]) or PA (1.18 [0.94 to 1.48]) and C+P. In conclusion, there was no evidence of a difference among the 3 treatment approaches for incidence or number of episodes of dental pain and/or infection experienced by these participants with high caries risk and established disease (trial registration: ISRCTN77044005)

PTF11iqb: cool supergiant mass-loss that bridges the gap between Type IIn and normal supernovae

The supernova (SN) PTF11iqb was initially classified as a Type IIn event caught very early after explosion. It showed narrow Wolf–Rayet (WR) spectral features on day 2 (as in SN 1998S and SN 2013cu), but the narrow emission weakened quickly and the spectrum morphed to resemble Types II-L and II-P. At late times, H? exhibited a complex, multipeaked profile reminiscent of SN 1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN 1998S, although with somewhat weaker interaction with circumstellar material (CSM) at early times, and stronger interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for CSM interaction (with a mass-loss rate of roughly 10?4 M? yr?1) added to the light curve of a normal SN II-P. The underlying plateau requires a progenitor with an extended hydrogen envelope like a red supergiant at the moment of explosion, consistent with the slow wind speed (<80?km?s?1) inferred from narrow H? emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum – meaning that the presence of such WR features does not necessarily indicate a WR-like progenitor. Overall, PTF11iqb bridges SNe IIn with weaker pre-SN mass-loss seen in SNe II-L and II-P, implying a continuum between these types

PTF11iqb: cool supergiant mass-loss that bridges the gap between Type IIn and normal supernovae

The supernova (SN) PTF11iqb was initially classified as a Type IIn event caught very early after explosion. It showed narrow Wolf–Rayet (WR) spectral features on day 2 (as in SN 1998S and SN 2013cu), but the narrow emission weakened quickly and the spectrum morphed to resemble Types II-L and II-P. At late times, H? exhibited a complex, multipeaked profile reminiscent of SN 1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN 1998S, although with somewhat weaker interaction with circumstellar material (CSM) at early times, and stronger interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for CSM interaction (with a mass-loss rate of roughly 10?4 M? yr?1) added to the light curve of a normal SN II-P. The underlying plateau requires a progenitor with an extended hydrogen envelope like a red supergiant at the moment of explosion, consistent with the slow wind speed (<80?km?s?1) inferred from narrow H? emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum – meaning that the presence of such WR features does not necessarily indicate a WR-like progenitor. Overall, PTF11iqb bridges SNe IIn with weaker pre-SN mass-loss seen in SNe II-L and II-P, implying a continuum between these types

BAs and boride III-V alloys

Boron arsenide, the typically-ignored member of the III-V arsenide series BAs-AlAs-GaAs-InAs is found to resemble silicon electronically: its Gamma conduction band minimum is p-like (Gamma_15), not s-like (Gamma_1c), it has an X_1c-like indirect band gap, and its bond charge is distributed almost equally on the two atoms in the unit cell, exhibiting nearly perfect covalency. The reasons for these are tracked down to the anomalously low atomic p orbital energy in the boron and to the unusually strong s-s repulsion in BAs relative to most other III-V compounds. We find unexpected valence band offsets of BAs with respect to GaAs and AlAs. The valence band maximum (VBM) of BAs is significantly higher than that of AlAs, despite the much smaller bond length of BAs, and the VBM of GaAs is only slightly higher than in BAs. These effects result from the unusually strong mixing of the cation and anion states at the VBM. For the BAs-GaAs alloys, we find (i) a relatively small (~3.5 eV) and composition-independent band gap bowing. This means that while addition of small amounts of nitrogen to GaAs lowers the gap, addition of small amounts of boron to GaAs raises the gap (ii) boron ``semi-localized'' states in the conduction band (similar to those in GaN-GaAs alloys), and (iii) bulk mixing enthalpies which are smaller than in GaN-GaAs alloys. The unique features of boride III-V alloys offer new opportunities in band gap engineering.Comment: 18 pages, 14 figures, 6 tables, 61 references. Accepted for publication in Phys. Rev. B. Scheduled to appear Oct. 15 200

Recommendations to encourage participation of individuals from diverse backgrounds in psychiatric genetic studies

We present innovative research practices in psychiatric genetic studies to ensure representation of individuals from diverse ancestry, sex assigned at birth, gender identity, age, body shape and size, and socioeconomic backgrounds. Due to histories of inappropriate and harmful practices against marginalized groups in both psychiatry and genetics, people of certain identities may be hesitant to participate in research studies. Yet their participation is essential to ensure diverse representation, as it is incorrect to assume that the same genetic and environmental factors influence the risk for various psychiatric disorders across all demographic groups. We present approaches developed as part of the Eating Disorders Genetics Initiative (EDGI), a study that required tailored approaches to recruit diverse populations across many countries. Considerations include research priorities and design, recruitment and study branding, transparency, and community investment and ownership. Ensuring representation in participants is costly and funders need to provide adequate support to achieve diversity in recruitment in prime awards, not just as supplemental afterthoughts. The need for diverse samples in genetic studies is critical to minimize the risk of perpetuating health disparities in psychiatry and other health research. Although the EDGI strategies were designed specifically to attract and enroll individuals with eating disorders, our approach is broadly applicable across psychiatry and other fields

Heavy Quarks and Heavy Quarkonia as Tests of Thermalization

We present here a brief summary of new results on heavy quarks and heavy quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma Thermalization" Workshop in Vienna, Austria in August 2005, directly following the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop (Vienna August 2005) Proceeding

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Nuclear Modification of Electron Spectra and Implications for Heavy Quark Energy Loss in Au+Au Collisions at sqrt(s_NN)=200 GeV

The PHENIX experiment has measured mid-rapidity transverse momentum spectra (0.4 < p_T < 5.0 GeV/c) of electrons as a function of centrality in Au+Au collisions at sqrt(s_NN)=200 GeV. Contributions from photon conversions and from light hadron decays, mainly Dalitz decays of pi^0 and eta mesons, were removed. The resulting non-photonic electron spectra are primarily due to the semi-leptonic decays of hadrons carrying heavy quarks. Nuclear modification factors were determined by comparison to non-photonic electrons in p+p collisions. A significant suppression of electrons at high p_T is observed in central Au+Au collisions, indicating substantial energy loss of heavy quarks.Comment: 330 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm