Investigation of the Differential Contributions of Superficial and Deep Muscles on Cervical Spinal Loads with Changing Head Postures

Cervical spinal loads are predominately influenced by activities of cervical muscles. However, the coordination between deep and superficial muscles and their influence on the spinal loads is not well understood. This study aims to document the changes of cervical spinal loads and the differential contributions of superficial and deep muscles with varying head postures. Electromyography (EMG) of cervical muscles from seventeen healthy adults were measured during maximal isometric exertions for lateral flexion (at 10°, 20° and terminal position) as well as flexion/extension (at 10°, 20°, 30°, and terminal position) neck postures. An EMG-assisted optimization approach was used to estimate the muscle forces and subsequent spinal loads. The results showed that compressive and anterior-posterior shear loads increased significantly with neck flexion. In particular, deep muscle forces increased significantly with increasing flexion. It was also determined that in all different static head postures, the deep muscle forces were greater than those of the superficial muscle forces, however, such pattern was reversed during peak efforts where greater superficial muscle forces were identified with increasing angle of inclination. In summary, the identification of significantly increased spinal loads associated with increased deep muscle activation during flexion postures, implies higher risks in predisposing the neck to occupationally related disorders. The results also explicitly supported that deep muscles play a greater role in maintaining stable head postures where superficial muscles are responsible for peak exertions and reinforcing the spinal stability at terminal head postures. This study provided quantitative data of normal cervical spinal loads and revealed motor control strategies in coordinating the superficial and deep muscles during physical tasks.     

Multi-Q: a fully automated tool for multiplexed protein quantitation

The iTRAQ labeling method combined with shotgun proteomic techniques represents a new dimension in multiplexed quantitation for relative protein expression measurement in different cell states. To expedite the analysis of vast amounts of spectral data, we present a fully automated software package, called Multi-Q, for multiplexed iTRAQ-based quantitation in protein profiling. Multi-Q is designed as a generic platform that can accommodate various input data formats from search engines and mass spectrometer manufacturers. To calculate peptide ratios, the software automatically processes iTRAQ's signature peaks, including peak detection, background subtraction, isotope correction, and normalization to remove systematic errors. Furthermore, Multi-Q allows users to define their own data-filtering thresholds based on semiempirical values or statistical models so that the computed results of fold changes in peptide ratios are statistically significant. This feature facilitates the use of Multi-Q with various instrument types with different dynamic ranges, which is an important aspect of iTRAQ analysis. The performance of Multi-Q is evaluated with a mixture of 10 standard proteins and human Jurkat T cells. The results are consistent with expected protein ratios and thus demonstrate the high accuracy, full automation, and high-throughput capability of Multi-Q as a large-scale quantitation proteomics tool. These features allow rapid interpretation of output from large proteomic datasets without the need for manual validation. Executable Multi-Q files are available on Windows platform at http://ms.iis.sinica.edu.tw/Multi-Q/.     

Statin treatment increases formation of carbon monoxide and bilirubin in mice: a novel mechanism of in vivo antioxidant protection

Heme oxygenase (HO) has a central role in cellular antioxidant defences and vascular protection, and it may mediate pleiotropic actions of drugs used in cardiovascular therapy. We investigated whether long-term use of statins upregulates HO activity and increases carbon monoxide (CO) and bilirubin levels in vivo. Adult FvB mice were given atorvastatin or rosuvastatin (5 mg/kg) daily by i.p. injections for 1, 2, or 3 weeks. HO activity, tissue CO, bilirubin, and antioxidant levels, total plasma bilirubin, and carboxyhemoglobin (COHb) were measured. Fold changes in heart HO activity significantly increased after 1, 2, and 3 weeks of atorvastatin (1.24 +/- 0.06 (p < or = 0.05); 1.29 +/- 0.26 (p < or = 0.03); 1.33 +/- 0.08 (p < 0.01), respectively) and 2 and 3 weeks of rosuvastatin (1.23 +/- 0.20 (p < or = 0.03); 1.63 +/- 0.42 (p < 0.01), respectively). Heart tissue CO and COHb levels also increased after 3 weeks with atorvastatin (1.30 +/- 0.24 (p < or = 0.05); 1.92 +/- 0.17 (p < or = 0.001), respectively) and rosuvastatin (1.47 +/- 0.13 (p < or = 0.004); 1.63 +/- 0.12 (p < or = 0.001), respectively). Significant increases in heart antioxidant levels were observed after statin treatment and corroborated by heart bilirubin content elevations. Antioxidant level increases were abolished by treatment with an HO inhibitor. These findings suggest that the induction of HO and the production of its products, CO and bilirubin, may be a mechanism by which statins exert antioxidant actions and confer cardioprotection in vivo.     

A Novel Small Molecule Inhibitor of Hepatitis C Virus Entry

Small molecule inhibitors of hepatitis C virus (HCV) are being developed to complement or replace treatments with pegylated interferons and ribavirin, which have poor response rates and significant side effects. Resistance to these inhibitors emerges rapidly in the clinic, suggesting that successful therapy will involve combination therapy with multiple inhibitors of different targets. The entry process of HCV into hepatocytes represents another series of potential targets for therapeutic intervention, involving viral structural proteins that have not been extensively explored due to experimental limitations. To discover HCV entry inhibitors, we utilized HCV pseudoparticles (HCVpp) incorporating E1-E2 envelope proteins from a genotype 1b clinical isolate. Screening of a small molecule library identified a potent HCV-specific triazine inhibitor, EI-1. A series of HCVpp with E1-E2 sequences from various HCV isolates was used to show activity against all genotype 1a and 1b HCVpp tested, with median EC₅₀ values of 0.134 and 0.027 µM, respectively. Time-of-addition experiments demonstrated a block in HCVpp entry, downstream of initial attachment to the cell surface, and prior to or concomitant with bafilomycin inhibition of endosomal acidification. EI-1 was equally active against cell-culture adapted HCV (HCVcc), blocking both cell-free entry and cell-to-cell transmission of virus. HCVcc with high-level resistance to EI-1 was selected by sequential passage in the presence of inhibitor, and resistance was shown to be conferred by changes to residue 719 in the carboxy-terminal transmembrane anchor region of E2, implicating this envelope protein in EI-1 susceptibility. Combinations of EI-1 with interferon, or inhibitors of NS3 or NS5A, resulted in additive to synergistic activity. These results suggest that inhibitors of HCV entry could be added to replication inhibitors and interferons already in development.     

Unraveling Geometrical Site Confinement in Highly Efficient Iron‐Doped Electrocatalysts toward Oxygen Evolution Reaction

Introduction of iron in various catalytic systems has served a crucial function to significantly enhance the catalytic activity toward oxygen evolution reaction (OER), but the relationship between material properties and catalysis is still elusive. In this study, by regulating the distinctive geometric sites in spinel, Fe occupies the octahedral sites (Fe³⁺_(Oh)) and confines Co to the tetrahedral site (Co²⁺_(Td)), resulting in a strikingly high activity (η_{j = 10 mA cm}^?2 = 229 mV and η_{j = 100 mA cm}^?2 = 281 mV). Further enrichment of Fe ions would occupy the tetrahedral sites to decline the amount of Co²⁺_(Td) and deteriorate the OER activity. It is also found that similar tafel slope and peak frequency in Bode plot of electrochemical impedance spectroscopy indicate that Co²⁺_(Td) ions are primarily in charge of water oxidation catalytic center. By means of electrochemical techniques and in situ X‐ray absorption spectroscopy, it is proposed that Fe³⁺_(Oh) ions mainly confine cobalt ions to the tetrahedral site to restrain the multipath transfer of cobalt ions during the dynamic structural transformation between spinel and oxyhydroxide, continuously activating the catalytic behavior of Co²⁺_(Td) ions. This material‐related insight provides an indication for the design of highly efficient OER electrocatalysts.