Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue.

Photochemical switches represent a powerful method for improving pharmacological therapies and controlling cellular physiology. Here we report the photoregulation of GABA(A) receptors (GABA(A)Rs) by a derivative of propofol (2,6-diisopropylphenol), a GABA(A)R allosteric modulator, which we have modified to contain photoisomerizable azobenzene. Using α(1)β(2)γ(2) GABA(A)Rs expressed in Xenopus laevis oocytes and native GABA(A)Rs of isolated retinal ganglion cells, we show that the trans-azobenzene isomer of the new compound (trans-MPC088), generated by visible light (wavelengths ~440 nm), potentiates the γ-aminobutyric acid-elicited response and, at higher concentrations, directly activates the receptors. cis-MPC088, generated from trans-MPC088 by ultraviolet light (~365 nm), produces little, if any, receptor potentiation/activation. In cerebellar slices, MPC088 co-applied with γ-aminobutyric acid affords bidirectional photomodulation of Purkinje cell membrane current and spike-firing rate. The findings demonstrate photocontrol of GABA(A)Rs by an allosteric ligand, and open new avenues for fundamental and clinically oriented research on GABA(A)Rs, a major class of neurotransmitter receptors in the central nervous system

Wavelength Dependence of Solar Flare Irradiation and its Influence on the Thermosphere

The wavelength dependence of solar flare enhancement is one of the important factors determining how the Thermosphere-Ionosphere (T-I) system response to flares. To investigate the wavelength dependence of solar flare, the Flare Irradiance Spectral Model (FISM) has been run for 34 X-class flares. The results show that the percentage increases of solar irradiance at flare peak comparing to pre-flare condition have a clear wavelength dependence. In the wavelength range between 0 - 195 nm, it can vary from 1% to 10000%. The solar irradiance enhancement is largest ( 1000%) in the XUV range (0 - 25 nm), and is about 100% in EUV range (25 - 120 nm). The influence of different wavebands on the T-I system during the October 28th, 2003 flare (X17.2-class) has also been examined using the latest version of National Center for Atmospheric Research (NCAR) Thermosphere- Ionosphere-Electrodynamics General Circulation Model (TIE-GCM). While the globally integrated solar energy deposition is largest in the 0 - 14 nm waveband, the impact of solar irradiance enhancement on the thermosphere at 400 km is largest for 25 - 105 nm waveband. The effect of 122 - 195 nm is small in magnitude, but it decays slowly

ACBD3 functions as a scaffold to organize the Golgi stacking proteins and a Rab33b-GAP

Golgin45 plays important roles in Golgi stack assembly and is known to bind both the Golgi stacking protein GRASP55 and Rab2 in the medial‐Golgi cisternae. In this study, we sought to further characterize the cisternal adhesion complex using a proteomics approach. We report here that Acyl‐CoA binding domain containing 3 (ACBD3) is likely to be a novel binding partner of Golgin45. ACBD3 interacts with Golgin45 via its GOLD domain, while its co‐expression significantly increases Golgin45 targeting to the Golgi. Furthermore, ACBD3 recruits TBC1D22, a Rab33b GTPase activating protein (GAP), to a large multi‐protein complex containing Golgin45 and GRASP55. These results suggest that ACBD3 may provide a scaffolding to organize the Golgi stacking proteins and a Rab33b‐GAP at the medial‐Golgi

Mechanical and physical performance of carbon aerogel reinforced carbon fibre hierarchical composites

Carbon aerogel (CAG) is a potential hierarchical reinforcement to improve the matrix-dominated mechanical properties of continuous carbon fibre reinforced polymer (CFRP) composites in both multifunctional and purely structural applications. When using CAG to reinforce a polyethylene glycol diglycidyl ether (PEGDGE) matrix, the interlaminar shear strength, compressive modulus and strength increased approximately four-fold, whilst the out-of-plane electrical conductivity increased by 118%. These mechanical and electrical performance enhancements significantly improve the multifunctional efficiency of composite structural supercapacitors, which can offer weight savings in transport and other applications. However, CAG also has the potential to reinforce conventional continuous CF composites in purely structural contexts. Here, CAG reinforcement of structural epoxy resin composites marginally increased compressive (1.4%) and tensile (2.7%) moduli respectively, but considerably reduced compressive, tensile and interlaminar shear strengths. Fractographic analysis shows that the reduced performance can be attributed to poor interfacial adhesion; in the future, alternative processing routes may resolve these issues to achieve advances in both moduli and strengths over conventional structural CFRPs

Barriers to accessing TB diagnosis for rural-to-urban migrants with chronic cough in Chongqing, China: A mixed methods study

<p>Abstract</p> <p>Background</p> <p>China is facing a significant tuberculosis epidemic among rural-to-urban migrants, which poses a threat to TB control. This study aimed to understand the health seeking behaviour of and health systems responses to migrants and permanent urban residents suffering from chronic cough, in order to identify the factors influencing delays for both groups in receiving a TB diagnosis in urban China.</p> <p>Methods</p> <p>Combining a prospective cohort study of adult suspect TB patients and a qualitative study, the Piot model was used to analyze the health seeking behaviour of TB suspects among migrants and permanent urban residents, the factors influencing their decision and the responses by general health providers. Methods included a patient survey, focus group discussions with migrants in the general population, qualitative interviews with migrant and permanent resident TB suspects and TB patients as well as key stakeholders related to TB control and the management of migrants.</p> <p>Results</p> <p>Sixty eight percent of migrants delayed for more than two weeks before seeking care for symptoms suggestive of TB, compared to 54% of residents (p < 0.01). When they first decided to seek professional care, migrants were 1.5 times more likely than residents to use less expensive, community-level health services. Only 5% were ultimately referred to a TB dispensary. Major reasons for both patient and provider delay included lack of knowledge and mistrust of the TB control programme, lack of knowledge about TB (patients), and profit-seeking behaviour (providers). In the follow up survey, 61% of the migrants and 41% of the residents who still had symptoms gave up continuing to seek professional care, with a statistically significant difference between the two groups (p < 0.05).</p> <p>Conclusion</p> <p>Rural-to-urban migrants are more likely than permanent residents to delay in seeking care for symptoms suggestive of TB in urban Chongqing. 'Patient-' and 'provider-' related factors interact to pose barriers to TB diagnosis for migrants, including: low awareness, and poor knowledge among both the general public and TB suspects about TB as a disease and about the TB control programme; low financial capacity to pay for care and diagnostic tests; and inadequate use of diagnostic tests and referral to TB dispensaries by general health providers.</p

Berry Phase in Neutrino Oscillations

We study the Berry phase in neutrino oscillations for both Dirac and Majorana neutrinos. In order to have a Berry phase, the neutrino oscillations must occur in a varying medium, the neutrino-background interactions must depend on at least two independent densities, and also there must be CP violation if the neutrino interactions with matter are mediated only by the standard model W and Z boson exchanges which implies that there must be at least three generations of neutrinos. The CP violating Majorana phases do not play a role in generating a Berry phase. We show that a natural way to satisfy the conditions for the generation of a Berry phase is to have sterile neutrinos with active-sterile neutrino mixing, in which case at least two active and one sterile neutrinos are required. If there are additional new CP violating flavor changing interactions, it is also possible to have a non-zero Berry phase with just two generations.Comment: RevTex 16 pages, no figures, new discussions about sterile neutrino added,typos corrected and errors in references correcte

Golgin45-Syntaxin5 Interaction Contributes to Structural Integrity of the Golgi Stack

The unique stacked morphology of the Golgi apparatus had been a topic of intense investigation among the cell biologists over the years. We had previously shown that the two Golgin tethers (GM130 and Golgin45) could, to a large degree, functionally substitute for GRASP-type Golgi stacking proteins to sustain normal Golgi morphology and function in GRASP65/55-double depleted HeLa cells. However, compared to well-studied GM130, the exact role of Golgin45 in Golgi structure remains poorly understood. In this study, we aimed to further characterize the functional role of Golgin45 in Golgi structure and identified Golgin45 as a novel Syntaxin5-binding protein. Based primarily on a sequence homology between Golgin45 and GM130, we found that a leucine zipper-like motif in the central coiled-coil region of Golgin45 appears to serve as a Syntaxin5 binding domain. Mutagenesis study of this conserved domain in Golgin45 showed that a point mutation (D171A) can abrogate the interaction between Golgin45 and Syntaxin5 in pull-down assays using recombinant proteins, whereas this mutant Golgin45 binding to Rab2-GTP was unaffected in vitro. Strikingly, exogenous expression of this Syntaxin5 binding deficient mutant (D171A) of Golgin45 in HeLa cells resulted in frequent intercisternal fusion among neighboring Golgi cisterna, as readily observed by EM and EM tomography. Further, double depletion of the two Syntaxin5-binding Golgin tethers also led to significant intercisternal fusion, while double depletion of GRASP65/55 didn’t lead to this phenotype. These results suggest that certain tether-SNARE interaction within Golgi stack may play a role in inhibiting intercisternal fusion among neighboring cisternae, thereby contributing to structural integrity of the Golgi stack

Structural and functional alterations of the tracheobronchial tree after left upper pulmonary lobectomy for lung cancer

© 2019 The Author(s). Background: Pulmonary lobectomy has been a well-established curative treatment method for localized lung cancer. After left upper pulmonary lobectomy, the upward displacement of remaining lower lobe causes the distortion or kink of bronchus, which is associated with intractable cough and breathless. However, the quantitative study on structural and functional alterations of the tracheobronchial tree after lobectomy has not been reported. We sought to investigate these alterations using CT imaging analysis and computational fluid dynamics (CFD) method. Methods: Both preoperative and postoperative CT images of 18 patients who underwent left upper pulmonary lobectomy are collected. After the tracheobronchial tree models are extracted, the angles between trachea and bronchi, the surface area and volume of the tree, and the cross-sectional area of left lower lobar bronchus are investigated. CFD method is further used to describe the airflow characteristics by the wall pressure, airflow velocity, lobar flow rate, etc. Results: It is found that the angle between the trachea and the right main bronchus increases after operation, but the angle with the left main bronchus decreases. No significant alteration is observed for the surface area or volume of the tree between pre-operation and post-operation. After left upper pulmonary lobectomy, the cross-sectional area of left lower lobar bronchus is reduced for most of the patients (15/18) by 15-75%, especially for 4 patients by more than 50%. The wall pressure, airflow velocity and pressure drop significantly increase after the operation. The flow rate to the right lung increases significantly by 2-30% (but there is no significant difference between each lobe), and the flow rate to the left lung drops accordingly. Many vortices are found in various places with severe distortions. Conclusions: The favorable and unfavorable adaptive alterations of tracheobronchial tree will occur after left upper pulmonary lobectomy, and these alterations can be clarified through CT imaging and CFD analysis. The severe distortions at left lower lobar bronchus might exacerbate postoperative shortness of breath

A balanced homodyne detector for high-rate Gaussian-modulated coherent-state quantum key distribution

We discuss excess noise contributions of a practical balanced homodyne detector in Gaussian-modulated coherent-state (GMCS) quantum key distribution (QKD). We point out the key generated from the original realistic model of GMCS QKD may not be secure. In our refined realistic model, we take into account excess noise due to the finite bandwidth of the homodyne detector and the fluctuation of the local oscillator. A high speed balanced homodyne detector suitable for GMCS QKD in the telecommunication wavelength region is built and experimentally tested. The 3dB bandwidth of the balanced homodyne detector is found to be 104MHz and its electronic noise level is 13dB below the shot noise at a local oscillator level of 8.5*10^8 photon per pulse. The secure key rate of a GMCS QKD experiment with this homodyne detector is expected to reach Mbits/s over a few kilometers.Comment: 22 pages, 11 figure

Design of a new hairpin DNAzyme: The activity controlled by TMPyP4

A new 10-23 hairpin DNAzyme with a G-quadruplex structure stem was designed. The formation and stability of the G-quadruplex structure as the DNAzyme stem in the absence or the presence of TMPyP4 were investigated by UV-visible spectroscopy, circular dichroism (CD) and differential scanning calorimetry (DSC) methods, respectively. The results showed that the stability of this DNAzyme can be enhanced greatly due to the interaction between TMPyP4 and the DNAzyme. The relationship between structural stability and activity of the DNAzyme was studied by in vitro catalytic reaction. The activity of this DNAzyme was regulated by the stability of DNAzyme when TMPyP4 was intercalated into Gquadruplex structure stem. The catalytic activity of the 10-23 hairpin DNAzyme decreased and even inactivated due to the enhanced stability of G-quadruplex structure by TMPyP4 molecules. This DNAzyme is controllable to cleavage substrate and has some potential significance in gene therapy.Key words: 10-23 DNAzyme, hairpin DNAzyme, G-quadruplex structure, TMPyP4