3D-interologs: an evolution database of physical protein- protein interactions across multiple genomes

<p>Abstract</p> <p>Background</p> <p>Comprehensive exploration of protein-protein interactions is a challenging route to understand biological processes. For efficiently enlarging protein interactions annotated with residue-based binding models, we proposed a new concept "3D-domain interolog mapping" with a scoring system to explore all possible protein pairs between the two homolog families, derived from a known 3D-structure dimmer (template), across multiple species. Each family consists of homologous proteins which have interacting domains of the template for studying domain interface evolution of two interacting homolog families.</p> <p>Results</p> <p>The 3D-interologs database records the evolution of protein-protein interactions database across multiple species. Based on "3D-domain interolog mapping" and a new scoring function, we infer 173,294 protein-protein interactions by using 1,895 three-dimensional (3D) structure heterodimers to search the UniProt database (4,826,134 protein sequences). The 3D- interologs database comprises 15,124 species and 283,980 protein-protein interactions, including 173,294 interactions (61%) and 110,686 interactions (39%) summarized from the IntAct database. For a protein-protein interaction, the 3D-interologs database shows functional annotations (e.g. Gene Ontology), interacting domains and binding models (e.g. hydrogen-bond interactions and conserved residues). Additionally, this database provides couple-conserved residues and the interacting evolution by exploring the interologs across multiple species. Experimental results reveal that the proposed scoring function obtains good agreement for the binding affinity of 275 mutated residues from the ASEdb. The precision and recall of our method are 0.52 and 0.34, respectively, by using 563 non-redundant heterodimers to search on the Integr8 database (549 complete genomes).</p> <p>Conclusions</p> <p>Experimental results demonstrate that the proposed method can infer reliable physical protein-protein interactions and be useful for studying the protein-protein interaction evolution across multiple species. In addition, the top-ranked strategy and template interface score are able to significantly improve the accuracies of identifying protein-protein interactions in a complete genome. The 3D-interologs database is available at <url>http://3D- interologs.life.nctu.edu.tw</url>.</p

Nocturnal CPAP improves walking capacity in COPD patients with obstructive sleep apnoea

BACKGROUND: Exercise limitation is an important issue in patients with chronic obstructive pulmonary disease (COPD), and it often co-exists with obstructive sleep apnoea (overlap syndrome). This study examined the effects of nocturnal continuous positive airway pressure (CPAP) treatment on walking capacity in COPD patients with or without obstructive sleep apnoea. METHODS: Forty-four stable moderate-to-severe COPD patients were recruited and completed this study. They all underwent polysomnography, CPAP titration, accommodation, and treatment with adequate pressure. The incremental shuttle walking test was used to measure walking capacity at baseline and after two nights of CPAP treatment. Urinary catecholamine and heart rate variability were measured before and after CPAP treatment. RESULTS: After two nights of CPAP treatment, the apnoea-hypopnoea index and oxygen desaturation index significantly improved in both overlap syndrome and COPD patients, however these changes were significantly greater in the overlap syndrome than in the COPD group. Sleep architecture and autonomic dysfunction significantly improved in the overlap syndrome group but not in the COPD group. CPAP treatment was associated with an increased walking capacity from baseline from 226.4 ± 95.3 m to 288.6 ± 94.6 m (P < 0.05), and decreased urinary catecholamine levels, pre-exercise heart rate, oxygenation, and Borg scale in the overlap syndrome group. An improvement in the apnoea-hypopnoea index was an independent factor associated with the increase in walking distance (r = 0.564). CONCLUSION: Nocturnal CPAP may improve walking capacity in COPD patients with overlap syndrome. TRIAL REGISTRATION: NCT0091426

MicroRNA-146a Alleviates Experimental Autoimmune Anterior Uveitis in the Eyes of Lewis Rats

Purpose. This study aimed to determine the effect and roles of microRNA (miRNA, miR) treatment in experimental autoimmune anterior uveitis (EAAU). Materials and Methods. Uveitis was induced in Lewis rats by simultaneous injections of bovine melanin-associated antigen into the hind footpad and the intraperitoneal cavity. The animals were injected intravitreally with low-dose (0.5 μg) or high-dose (1.5 μg) miR-146a. The clinical scores, leukocyte count in the aqueous humor, and histology were assessed. Cytokine changes were evaluated by relative mRNA expression and enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) was assessed by immunofluorescence and Western blotting. Evaluation of the DNA-binding activity of NF-κB was performed by electrophoretic mobility shift assay (EMSA). Results. Treatment with miR-146a significantly attenuated clinical scores and leukocyte infiltration in a dose-dependent manner, a result that was compatible with histological findings. Following miR-146a injections, downregulation of interleukin- (IL-) 1β, IL-6, and IL-12 and interferon- (IFN-) γ and upregulation of IL-10 and IL-17 were noted. The decreased NF-κB expression on immunofluorescence and Western blotting and reduced DNA-binding activity on EMSA were demonstrated following miR-146a treatment. Conclusions. miR-146a effectively reduced intraocular inflammation in EAAU through the inhibition of NF-κB. miR-146a might be a new treatment choice for uveitis

Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation

Polarization Dependence Suppression of Optical Fiber Grating Sensor in a π-Shifted Sagnac Loop Interferometer

In the sensing applications of optical fiber grating, it is necessary to reduce the transmission-type polarization dependence to isolate the sensing parameter. It is experimentally shown that the polarization-dependent spectrum of acousto-optic long-period fiber grating sensors can be suppressed in the transmission port of a π-shifted Sagnac loop interferometer. General expressions for the transmittance and reflectance are derived for transmission-type, reflection-type, and partially reflecting/transmitting-type polarization-dependent optical devices. The compensation of polarization dependence through the counter propagation in the Sagnac loop interferometer is quantitatively measured for a commercial in-line polarizer and an acousto-optic long-period fiber grating sensor

Perforated Sigmoid Colon Cancer within an Irreducible Inguinal Hernia: a Case Report

A perforated sigmoid colon cancer within an inguinal hernia is extremely rare. This unexpected finding is usually discovered during surgery and causes an unavoidable septic evolution. Here, we describe the case of an 84-year-old man who presented with fever, abdominal distension, and a painful, enlarged, left scrotum. A CT showed a left, incarcerated, inguinal hernia containing a perforated sigmoid adenocarcinoma (which was confirmed by histopathology). The possibility of an irreducible inguinal hernia in association with perforated sigmoid colon cancer should be considered in the array of diagnoses. A pre-operative CT scan would be helpful in facilitating an accurate diagnosis

RSC96 Schwann Cell Proliferation and Survival Induced by Dilong through PI3K/Akt Signaling Mediated by IGF-I

Schwann cell proliferation is critical for the regeneration of injured nerves. Dilongs are widely used in Chinese herbal medicine to remove stasis and stimulate wound-healing functions. Exactly how this Chinese herbal medicine promotes tissue survival remains unclear. The aim of the present study was to investigate the molecular mechanisms by which Dilong promote neuron regeneration. Our results show that treatment with extract of Dilong induces the phosphorylation of the insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway, and activates protein expression of cell nuclear antigen (PCNA) in a time-dependent manner. Cell cycle analysis showed that G1 transits into the S phase in 12–16 h, and S transits into the G2 phase 20 h after exposure to earthworm extract. Strong expression of cyclin D1, cyclin E and cyclin A occurs in a time-dependent manner. Small interfering RNA (siRNA)-mediated knockdown of PI3K significantly reduced PI3K protein expression levels, resulting in Bcl2 survival factor reduction and a marked blockage of G1 to S transition in proliferating cells. These results demonstrate that Dilong promotes the proliferation and survival of RSC96 cells via IGF-I signaling. The mechanism is mainly dependent on the PI3K protein