Annotation-based meta-analysis of microarray experiments

We are developing software applications to perform meta-analysis of microarray experiments based on standardized experiment annotations aiming to identify similar experiments and cluster experiments. The applications were tested on files obtained from the ArrayExpress public repository. Annotation terms were used to compute experiment dissimilarities to find experiments related to a query experiment. These applications may motivate efforts of bench biologists to better annotate experiments

Penning collisions of laser-cooled metastable helium atoms

We present experimental results on the two-body loss rates in a magneto-optical trap of metastable helium atoms. Absolute rates are measured in a systematic way for several laser detunings ranging from -5 to -30 MHz and at different intensities, by monitoring the decay of the trap fluorescence. The dependence of the two-body loss rate coefficient $\beta$ on the excited state ($2^3P_2$) and metastable state ($2^3S_1$) populations is also investigated. From these results we infer a rather uniform rate constant $K_{sp}=(1{\pm}0.4)\times10^{-7}$ cm$^3$/s.Comment: 8 pages, 9 figures, Revte

The Effectiveness of Exercise Interventions Supported by Telerehabilitation For Recently Hospitalized Adult Medical Patients: A Systematic Review

Objective: To evaluate the effectiveness of exercise interventions delivered via telerehabilitation (via videoconference) for recently hospitalized adult medical patients. Data sources: A search was undertaken across six databases for English language publications from inception to May 2020. Methods: Studies were selected if they included an exercise intervention for recently hospitalized adults, delivered by a physiotherapist via videoconference. Two reviewers independently screened 1,122 articles (21 full text screening) and assessed methodological quality using the Downs and Black Checklist. A narrative synthesis of the included studies was undertaken. Results: Three studies met eligibility criteria involving 201 participants with chronic heart failure or chronic obstructive pulmonary disease. Findings demonstrated limited evidence supporting the effectiveness of exercise delivered via telerehabilitation in improving physical function and patient reported quality of life outcomes in recently hospitalized medical patients. Telerehabilitation in this setting was also associated with high attendance rates and patient satisfaction. Conclusions: Findings provide preliminary support for the benefits of exercise interventions delivered via telerehabilitation for recently hospitalized medical patients. Results do need to be interpreted with caution as further high-quality studies specific to this method of exercise intervention delivery are needed

Visual characterization of associative quasitrivial nondecreasing operations on finite chains

In this paper we provide visual characterization of associative quasitrivial nondecreasing operations on finite chains. We also provide a characterization of bisymmetric quasitrivial nondecreasing binary operations on finite chains. Finally, we estimate the number of functions belonging to the previous classes.Comment: 25 pages, 18 Figure

Elimination of degenerate trajectory of single atom strongly coupled to the tilted cavity TEM10 mode

We demonstrate the trajectory measurement of the single neutral atoms deterministically using a high-finesse optical micro-cavity. Single atom strongly couples to the high-order transverse vacuum TEM_{10} mode, instead of the usual TEM_{00} mode, and the parameter of the system is (g_{10},\kappa ,\gamma )=2\pi \times (20.5,2.6,2.6)MHz. The atoms simply fall down freely from the magneto-optic trap into the cavity modes and the trajectories of the single atoms are linear. The transmission spectrums of atoms passing through the TEM10 mode are detected by a single photon counting modules and well fitted. Thanks to the tilted cavity transverse TEM10 mode, which is inclined to the vertical direction about 45 degrees and it helps us, for the first time, to eliminate the degenerate trajectory of the single atom falling through the cavity and get the unique atom trajectory. Atom position with high precision of 0.1{\mu}m in the off-axis direction (axis y) is obtained, and the spatial resolution of 5.6{\mu}m is achieved in time of 10{\mu}s along the vertical direction (axis x). The average velocity of the atoms is also measured from the atom transits, which determines the temperature of the atoms in magneto-optic trap, 186{\mu}K {\pm} 19{\mu}K.Comment: 13 pages, 5figure

Proteomic Analysis of Hippocampal Dentate Granule Cells in Frontotemporal Lobar Degeneration: Application of Laser Capture Technology

Frontotemporal lobar degeneration (FTLD) is the most common cause of dementia with pre-senile onset, accounting for as many as 20% of cases. A common subset of FTLD cases is characterized by the presence of ubiquitinated inclusions in vulnerable neurons (FTLD-U). While the pathophysiological mechanisms underlying neurodegeneration in FTLD-U have not yet been elucidated, the presence of inclusions in this disease indicates enhanced aggregation of one or several proteins. Moreover, these inclusions suggest altered expression, processing, or degradation of proteins during FTLD-U pathogenesis. Thus, one approach to understanding disease mechanisms is to delineate the molecular changes in protein composition in FTLD-U brain. Using a combined approach consisting of laser capture microdissection (LCM) and high-resolution liquid chromatography-tandem mass spectrometry (LC–MS/MS), we identified 1252 proteins in hippocampal dentate granule cells excised from three post-mortem FTLD-U and three unaffected control cases processed in parallel. Additionally, we employed a labeling-free quantification technique to compare the abundance of the identified proteins between FTLD-U and control cases. Quantification revealed 54 proteins with selective enrichment in FTLD-U, including TAR–DNA binding protein 43 (TDP-43), a recently identified component of ubiquitinated inclusions. Moreover, 19 proteins were selectively decreased in FTLD-U. Subsequent immunohistochemical analysis of TDP-43 and three additional protein candidates suggests that our proteomic profiling of FTLD-U dentate granule cells reveals both inclusion-associated proteins and non-aggregated disease-specific proteins. Application of LCM is a valuable tool in the molecular analysis of complex tissues, and its application in the proteomic characterization of neurodegenerative disorders such as FTLD-U may be used to identify proteins altered in disease

Epidithiodiketopiperazines inhibit protein degradation by targeting Proteasome Deubiquitinase Rpn11

The 26S proteasome is the major proteolytic machine for breaking down cytosolic and nuclear proteins in eukaryotes. Due to the lack of a suitable assay, it is difficult to measure routinely and quantitatively the breakdown of proteins by the 26S proteasome in vitro. In the present study, we developed an assay to monitor proteasome-mediated protein degradation. Using this assay, we discovered that epidithiodiketopiperazine (ETPs) blocked the degradation of our model substrate in vitro. Further characterization revealed that ETPs inhibited proteasome function by targeting the essential proteasomal deubiquitinase Rpn11 (POH1/PSMD14). ETPs also inhibited other JAMM (JAB1/MPN/Mov34 metalloenzyme) proteases such as Csn5 and AMSH. An improved ETP with fewer non-specific effects, SOP11, stabilized a subset of proteasome substrates in cells, induced the unfolded protein response, and led to cell death. SOP11 represents a class of Rpn11 inhibitor and provides an alternative route to develop proteasome inhibitors. [Abstract copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Site-specific ubiquitination exposes a linear motif to promote interferon-α receptor endocytosis

Ligand-induced endocytosis and lysosomal degradation of cognate receptors regulate the extent of cell signaling. Along with linear endocytic motifs that recruit the adaptin protein complex 2 (AP2)–clathrin molecules, monoubiquitination of receptors has emerged as a major endocytic signal. By investigating ubiquitin-dependent lysosomal degradation of the interferon (IFN)-α/β receptor 1 (IFNAR1) subunit of the type I IFN receptor, we reveal that IFNAR1 is polyubiquitinated via both Lys48- and Lys63-linked chains. The SCFβTrcp (Skp1–Cullin1–F-box complex) E3 ubiquitin ligase that mediates IFNAR1 ubiquitination and degradation in cells can conjugate both types of chains in vitro. Although either polyubiquitin linkage suffices for postinternalization sorting, both types of chains are necessary but not sufficient for robust IFNAR1 turnover and internalization. These processes also depend on the proximity of ubiquitin-acceptor lysines to a linear endocytic motif and on its integrity. Furthermore, ubiquitination of IFNAR1 promotes its interaction with the AP2 adaptin complex that is required for the robust internalization of IFNAR1, implicating cooperation between site-specific ubiquitination and the linear endocytic motif in regulating this process