The identification of novel orally active mGluR5 antagonist GSK2210875

The identification of novel orally active mGluR5 antagonist GSK2210875 is described.     

Antibacterial activity and biocompatibility of a chitosan-γ-poly(glutamic acid) polyelectrolyte complex hydrogel

In this study, we prepared a polyelectrolyte complex (PEC) hydrogel comprising chitosan as the cationic polyelectrolyte and γ-poly(glutamic acid) (γ-PGA) as the anionic polyelectrolyte. Fourier transform infrared spectroscopy revealed that ionic complex interactions existed in the chitosan-γ-PGA PEC hydrogels. The compressive modulus increased upon increasing the degree of complex formation in the chitosan-γ-PGA PEC hydrogel; the water uptake decreased upon increasing the degree of complex formation. At the same degree of complex formation, the compressive modulus was larger for the chitosan-dominated PEC hydrogels; the water uptake was larger for the γ-PGA-dominated ones. Scanning electron microscopy images revealed the existence of interconnected porous structures (pore size: 30-100 μm) in all of the chitosan-γ-PGA PEC hydrogels. The chitosan-γ-PGA PEC hydrogels also exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, in vitro cell culturing of 3T3 fibroblasts revealed that all the chitosan-γ-PGA PEC hydrogels were effective in promoting cell proliferation, especially the positively charged ones (chitosan-dominated). Therefore, the chitosan-γ-PGA polyelectrolyte hydrogel appears to have potential as a new material for biomedical applications.     

Effects of hypoxia on genioglossus and scalene reflex responses to brief pulses of negative upper-airway pressure during wakefulness and sleep in healthy men.

Hypoxia can depress ventilation, respiratory load sensation, and the cough reflex, and potentially other protective respiratory reflexes such as respiratory muscle responses to increased respiratory load. In sleep-disordered breathing, increased respiratory load and hypoxia frequently coexist. This study aimed to examine the effects of hypoxia on the reflex responses of 1) the genioglossus (the largest upper airway dilator muscle) and 2) the scalene muscle (an obligatory inspiratory muscle) to negative-pressure pulse stimuli during wakefulness and sleep. We hypothesized that hypoxia would impair these reflex responses. Fourteen healthy men, 19-42 yr old, were studied on two separate occasions, approximately 1 wk apart. Bipolar fine-wire electrodes were inserted orally into the genioglossus muscle, and surface electrodes were placed overlying the left scalene muscle to record EMG activity. In random order, participants were exposed to mild overnight hypoxia (arterial oxygen saturation approximately 85%) or medical air. Respiratory muscle reflex responses were elicited via negative-pressure pulse stimuli (approximately -10 cmH(2)O at the mask, 250-ms duration) delivered in early inspiration during wakefulness and sleep. Negative-pressure pulse stimuli resulted in a short-latency activation followed by a suppression of the genioglossus EMG that did not alter with hypoxia. Conversely, the predominant response of the scalene EMG to negative-pressure pulse stimuli was suppression followed by activation with more pronounced suppression during hypoxia compared with normoxia (mean +/- SE suppression duration 64 +/- 6 vs. 38 +/- 6 ms, P = 0.006). These results indicate differential sensitivity to the depressive effects of hypoxia in the reflex responsiveness to sudden respiratory loads to breathing between these two respiratory muscles.     

Temperature downshift increases recombinant cytokine titer in Streptomyces lividans fermentation

Recombinant human interleukin-3 (rhIL-3) production by a Streptomyces lividans strain is subject to severe proteolytic degradation. Human interleukin-3 (rhIL-3) concentration in the culture supernatant typically reaches 100–120 mg l^–1 about 20 h after inoculation, but the titer drops rapidly as the result of proteolysis. Reducing the culture temperature at this point has a dramatic effect on product yield, increasing the final concentration in the supernatant at least two-fold.     

Electromyography of trunk muscles in isometric graded axial rotation.

This study was conducted to determine the pattern, magnitude, and phasic inter-relationship of the trunk muscles in maximal isometric and graded isometric axial rotational contractions and compare them with those previously observed from the same subjects in the same experimental session in dynamic conditions. In 50 normal young healthy subjects (27 male and 23 female), after a suitable skin preparation, bipolar silver-silver chloride recessed pregelled surface electrodes were placed on external oblique, internal oblique, rectus abdominis, pectoralis major, latissimus dorsi, erector spinae at T(10) and L(3) levels bilaterally with 2 cm interelectrode distance. EMG signals from grounded subjects were suitably preamplified and amplified by a fully isolated system. These subjects were stabilized in an upright-seated posture in the Axial Rotation Tester (AROT), which was placed in isometric mode for force and rotation output from the AROT. The 14 channels of EMG, the force and the rotation were sampled at 1 kHz. The subjects initially registered their isometric maximal voluntary contraction (MVC) on both sides which was used for reference and then performed their 25%, 50% and 75% of MVC bilaterally in an isometric mode in a random order. The EMG magnitude, the slope of the rise of the EMG, and the phasic interrelationship of muscles were analyzed. The results showed that female sample generated only 65% of torque of their male counterparts. There were no significant differences between the male and the female samples in the EMG variables. Exertions to the left and to the right were not significantly different from each other for the measured variables. However, the magnitude contribution of the muscles and the slope of rise of EMG were significantly different in two directions (p<0.001). The phasic interrelationship of the external obliques, the latissimus dorsi and the erector spinae were different from other muscles (p<0.01). With the increasing grades of contraction the latissimus dorsi and the external obliques increased their magnitude significantly whereas that of the erectores spinae underwent a decrease in proportionate terms (but not in absolute magnitude) suggesting their role as stabilizers but not as rotators.     

Isolation and cross‐species amplification of microsatellite loci in the freshwater minnow Zacco pachycephalus (Teleostei: Cyprinidae) for diversity and conservation genetic analysis

Asian minnows of the genus Zacco are dominant fish in various freshwater ecosystems. Two species, Zacco pachycephalus and Z. platypus, occur in Taiwan and are favourite targets for local sport anglers. The introduction of Zacco fish into nonindigenous habitats in Taiwan has become a conservation issue. We developed eight polymorphic microsatellites for Z. pachycephalus (average H_E = 0.779) and these microsatellites were applicable to Z. platypus, which showed a comparable polymorphic level (average H_E = 0.784). These loci can be used as genetic markers for identifying conservation units and studying population differentiation for both Zacco species.