COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome

Item does not contain fulltextMOTIVATION: Complexome profiling combines native gel electrophoresis with mass spectrometry to obtain the inventory, composition and abundance of multiprotein assemblies in an organelle. Applying complexome profiling to determine the effect of a mutation on protein complexes requires separating technical and biological variations from the variations caused by that mutation. RESULTS: We have developed the COmplexome Profiling ALignment (COPAL) tool that aligns multiple complexome profiles with each other. It includes the abundance profiles of all proteins on two gels, using a multi-dimensional implementation of the dynamic time warping algorithm to align the gels. Subsequent progressive alignment allows us to align multiple profiles with each other. We tested COPAL on complexome profiles from control mitochondria and from Barth syndrome (BTHS) mitochondria, which have a mutation in tafazzin gene that is involved in remodeling the inner mitochondrial membrane phospholipid cardiolipin. By comparing the variation between BTHS mitochondria and controls with the variation among either, we assessed the effects of BTHS on the abundance profiles of individual proteins. Combining those profiles with gene set enrichment analysis allows detecting significantly affected protein complexes. Most of the significantly affected protein complexes are located in the inner mitochondrial membrane (mitochondrial contact site and cristae organizing system, prohibitins), or are attached to it (the large ribosomal subunit). AVAILABILITY AND IMPLEMENTATION: COPAL is written in python and is available from http://github.com/cmbi/copal. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Supersymmetric Model of a 2D Long-Range Bose Liquid

The model Hamiltonian of a two-dimensional Bose liquid (proposed earlier by Kane, Kivelson, Lee and Zhang as the Hamiltonian which has Jastrow-type wavefunctions as the ground-state solution), is shown to possess nonrelativistic supersymmetry. For the special value of the coupling constant $\alpha=1/2$ the quantum mechanics described by this Hamiltonian is shown to be equivalent to the dynamics of (complex) eigenvalues of random Gaussian ensemble of normal complex matrices. For general $\alpha$, an exact relation between the equal-time current-current and density-density correlation functions is obtained, and used to derive an asymptotically exact (at low wavevectors q) spectrum of single-particle excitations beyond the superfluid ground-state (realized at low $\alpha$'s). The ground-state at very large $\alpha$ is shown to be of ``Quantum Hexatic" type, possessing long-range orientational order and quasi-long-range translational order but with zero shear modulus. Possible scenaria of the ground-state phase transitions as function of $\alpha$ are discussed.Comment: Revtex; 12 pages, 1 Postscript figur

Insufficient treatment of severe depression in neuromyelitis optica spectrum disorder

OBJECTIVE: To investigate depression frequency, severity, current treatment, and interactions with somatic symptoms among patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this dual-center observational study, we included 71 patients diagnosed with NMOSD according to the International Panel for NMO Diagnosis 2015 criteria. The Beck Depression Inventory (BDI) was classified into severe, moderate, or minimal/no depressive state category. We used the Fatigue Severity Scale to evaluate fatigue. Scores from the Brief Pain Inventory and the PainDETECT Questionnaire were normalized to estimate neuropathic pain. Psychotropic, pain, and immunosuppressant medications were tabulated by established classes. RESULTS: Twenty-eight percent of patients with NMOSD (n = 20) had BDI scores indicative of moderate or severe depression; 48% of patients (n = 34) endorsed significant levels of neuropathic pain. Severity of depression was moderately associated with neuropathic pain (r = 0.341, p < 0.004) but this relationship was confounded by levels of fatigue. Furthermore, only 40% of patients with moderate or severe depressive symptoms received antidepressant medical treatment. Fifty percent of those treated reported persistent moderate to severe depressive symptoms under treatment. CONCLUSIONS: Moderate and severe depression in patients with NMOSD is associated with neuropathic pain and fatigue and is insufficiently treated. These results are consistent across 2 research centers and continents. Future research needs to address how depression can be effectively managed and treated in NMOSD

Impact of densitized lapse slicings on evolutions of a wobbling black hole

We present long-term stable and second-order convergent evolutions of an excised wobbling black hole. Our results clearly demonstrate that the use of a densitized lapse function extends the lifetime of simulations dramatically. We also show the improvement in the stability of single static black holes when an algebraic densitized lapse condition is applied. In addition, we introduce a computationally inexpensive approach for tracking the location of the singularity suitable for mildly distorted black holes. The method is based on investigating the fall-off behavior and asymmetry of appropriate grid variables. This simple tracking method allows one to adjust the location of the excision region to follow the coordinate motion of the singularity.Comment: 10 pages, 8 figure

A drug repurposing screen for whipworms informed by comparative genomics.

Hundreds of millions of people worldwide are infected with the whipworm Trichuris trichiura. Novel treatments are urgently needed as current drugs, such as albendazole, have relatively low efficacy. We have investigated whether drugs approved for other human diseases could be repurposed as novel anti-whipworm drugs. In a previous comparative genomics analysis, we identified 409 drugs approved for human use that we predicted to target parasitic worm proteins. Here we tested these ex vivo by assessing motility of adult worms of Trichuris muris, the murine whipworm, an established model for human whipworm research. We identified 14 compounds with EC50 values of ≤50 μM against T. muris ex vivo, and selected nine for testing in vivo. However, the best worm burden reduction seen in mice was just 19%. The high number of ex vivo hits against T. muris shows that we were successful at predicting parasite proteins that could be targeted by approved drugs. In contrast, the low efficacy of these compounds in mice suggest challenges due to their chemical properties (e.g. lipophilicity, polarity, molecular weight) and pharmacokinetics (e.g. absorption, distribution, metabolism, and excretion) that may (i) promote absorption by the host gastrointestinal tract, thereby reducing availability to the worms embedded in the large intestine, and/or (ii) restrict drug uptake by the worms. This indicates that identifying structural analogues that have reduced absorption by the host, and increased uptake by worms, may be necessary for successful drug development against whipworms

Limits on the monopole magnetic field from measurements of the electric dipole moments of atoms, molecules and the neutron

A radial magnetic field can induce a time invariance violating electric dipole moment (EDM) in quantum systems. The EDMs of the Tl, Cs, Xe and Hg atoms and the neutron that are produced by such a field are estimated. The contributions of such a field to the constants, $\chi$ of the T,P-odd interactions $\chi_e {\bf N} \cdot {\bf s}/s$ and $\chi_N {\bf N} \cdot {\bf I}/I$ are also estimated for the TlF, HgF and YbF molecules (where ${\bf s}$ (${\bf I}$) is the electron (nuclear) spin and ${\bf N}$ is the molecular axis). The best limit on the contact monopole field can be obtained from the measured value of the Tl EDM. The possibility of such a field being produced from polarization of the vacuum of electrically charged magnetic monopoles (dyons) by a Coulomb field is discussed, as well as the limit on these dyons. An alternative mechanism involves chromomagnetic and chromoelectric fields in QCD.Comment: Uses RevTex, 16 pages, 4 postscript figures. An explanation of why there is no orbital contribution to the EDM has been added, and the presentation has been improved in genera