Structure-function study of ubiquitin c-terminal hydrolase L1 (UCH-L1) by NMR spectroscopy - insights into UCH-L1 mutation's association with the risk of Parkinson's disease

Poster Presentation: P72Protein ubiquitination and deubiquitination, play important roles in many aspects of cellular mechanisms. Its defective regulation results in diseases that range from developmental abnormalities to neurodegenerative diseases and cancer. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a protein of 223 amino acids, which is highly abundant in brain, constituting up to 2% of total brain proteins. Although it was originally characterized as a deubiquitinating enzyme, recent studies indicate that it also functions as a ubiquitin ligase and a mono-Ub stabilizer. Down-regulation and extensive oxidative modifications of UCH-L1 have been observed in the brains of Alzheimer’s disease and Parkinson’s disease (PD) patients. Of importance, I93M and S18Y point mutations in the UCH-L1 gene have been reported to be linked to susceptibility to and protection from PD respectively. Hence, the structure of UCH-L1 and the effects of disease associated mutations on the structure and function are of considerable interest. Our circular dichroism studies suggest that the S18Y point mutation only slightly perturbs the structure while a significant decrease in the α-helical content is observed in the I93M mutant. We have determined the solution structure of S18Y and mapping its interaction with ubiquitin by chemical shift perturbation approach. The electrostatic surface potential analysis reveals that the interaction between ubiquitin and UCH-L1-S18Y is primarily electrostatic in nature, with negatively charged residues on the surface of UCH-L1-S18Y interacting with the positively charged residues on the basic face of ubiquitin. Although the active site and the L8 loop in UCH-L1-S18Y adopts conformations similar to that observed in the crystal structure of UCH-L1-WT, both the altered hydrogen bond network and surface charge distributions have demonstrated that the S18Y substitution could lead to profound structural changes. In particular, the difference in the dimeric interfaces of the wild-type and the S18Y mutant has shown that mutation can significantly affect the distribution of the surface-exposed residues involved in the dimeric interface. Such observed difference might weaken the stability of the UCH-L1 dimer and hence may explain the reduced dimerization-dependent ligase activity of UCH-L1-S18Y in comparison to UCH-L1-WT.postprin

Nonclassicality of photon-added squeezed vacuum and its decoherence in thermal environment

We study the nonclassicality of photon-added squeezed vacuum (PASV) and its decoherence in thermal environment in terms of the sub-Poissonian statistics and the negativity of Wigner function (WF). By converting the PASV to a squeezed Hermite polynomial excitation state, we derive a compact expression for the normalization factor of m-PASV, which is an m-order Legendre polynomial of squeezing parameter r. We also derive the explicit expression of WF of m-PASV and find the negative region of WF in phase space. We show that there is an upper bound value of r for this state to exhibit sub-Poissonian statistics increasing as m increases. Then we derive the explicit analytical expression of time evolution of WF of m-PASV in the thermal channel and discuss the loss of nonclassicality using the negativity of WF. The threshold value of decay time is presented for the single PASV.Comment: 14 pages and 7 figure

Field distribution of epidural electrical stimulation

Epidural electrical stimulation has been applied in clinics for many years. However, there is still a concern about possible injury to spinal nerves. This study investigated electrical field and current density distribution during direct epidural electrical stimulation. Field distribution models were theoretically deduced, while the distribution of potentials and current were analyzed. The current density presented an increase of 70-80%, with one peak value ranging from -85 degrees to 85 degrees between the two stimulated poles. The effect of direct epidural electrical stimulation is mainly on local tissue surrounding the electrodes, concentrated around the two stimulated positions.postprin

A dynamic prediction model for intraoperative somatosensory evoked potential monitoring

This study proposed a support vector regression model applied in prediction of intraoperative somatosensory evoked potential changes associated with physiological and anesthetic changes. This model was developed from probability distribution and support vector machines. The predicted results showed that observed and predicted SEP has similar variation trend with different values, with acceptable errors. With this prediction model, changes of SEP in correlation with non-surgical factors were estimated. Not only the prediction accuracy of SEP has been improved, but also provides the reliability of the classification. It will be helpful to develop an intelligent monitor model based expert system that can make a reliable decision for the potential spinal injury.published_or_final_versio

Trial-to-trial latency variability of somatosensory evoked potentials as a prognostic indicator for surgical management of cervical spondylotic myelopathy

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Usefulness of time-frequency patterns of somatosensory evoked potentials in identification of the location of spinal cord injury

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Radiative Transfer Modeling of Lyman Alpha Emitters. I. Statistics of Spectra and Luminosity

We combine a cosmological reionization simulation with box size of 100Mpc/h on a side and a Monte Carlo Lyman-alpha (Lya) radiative transfer code to model Lyman Alpha Emitters (LAEs) at z~5.7. The model introduces Lya radiative transfer as the single factor for transforming the intrinsic Lya emission properties into the observed ones. Spatial diffusion of Lya photons from radiative transfer results in extended Lya emission and only the central part with high surface brightness can be observed. Because of radiative transfer, the appearance of LAEs depends on density and velocity structures in circumgalactic and intergalactic media as well as the viewing angle, which leads to a broad distribution of apparent (observed) Lya luminosity for a given intrinsic Lya luminosity. Radiative transfer also causes frequency diffusion of Lya photons. The resultant Lya line is asymmetric with a red tail. The peak of the Lya line shifts towards longer wavelength and the shift is anti-correlated with the apparent to intrinsic Lya luminosity ratio. The simple radiative transfer model provides a new framework for studying LAEs. It is able to explain an array of observed properties of z~5.7 LAEs in Ouchi et al. (2008), producing Lya spectra, morphology, and apparent Lya luminosity function (LF) similar to those seen in observation. The broad distribution of apparent Lya luminosity at fixed UV luminosity provides a natural explanation for the observed UV LF, especially the turnover towards the low luminosity end. The model also reproduces the observed distribution of Lya equivalent width (EW) and explains the deficit of UV bright, high EW sources. Because of the broad distribution of the apparent to intrinsic Lya luminosity ratio, the model predicts effective duty cycles and Lya escape fractions for LAEs.Comment: 28 pages, 22 figures, accepted for publication in ApJ, revised according to the referee's comment

The effect of cigarette price increase on the cigarette consumption in Taiwan: evidence from the National Health Interview Surveys on cigarette consumption

BACKGROUND: This study uses cigarette price elasticity to evaluate the effect of a new excise tax increase on cigarette consumption and to investigate responses from various types of smokers. METHODS: Our sample consisted of current smokers between 17 and 69 years old interviewed during an annual face-to-face survey conducted by Taiwan National Health Research Institutes between 2000 to 2003. We used Ordinary Least Squares (OLS) procedure to estimate double logarithmic function of cigarette demand and cigarette price elasticity. RESULTS: In 2002, after Taiwan had enacted the new tax scheme, cigarette price elasticity in Taiwan was found to be -0.5274. The new tax scheme brought about an average annual 13.27 packs/person (10.5%) reduction in cigarette consumption. Using the cigarette price elasticity estimate from -0.309 in 2003, we calculated that if the Health and Welfare Tax were increased by another NT$ 3 per pack and cigarette producers shifted this increase to the consumers, cigarette consumption would be reduced by 2.47 packs/person (2.2%). The value of the estimated cigarette price elasticity is smaller than one, meaning that the tax will not only reduce cigarette consumption but it will also generate additional tax revenues. Male smokers who had no income or who smoked light cigarettes were found to be more responsive to changes in cigarette price. CONCLUSIONS: An additional tax added to the cost of cigarettes would bring about a reduction in cigarette consumption and increased tax revenues. It would also help reduce incidents smoking-related illnesses. The additional tax revenues generated by the tax increase could be used to offset the current financial deficiency of Taiwan's National Health Insurance program and provide better public services

Solar influenced late Holocene temperature changes on the northern Tibetan Plateau

Considerable efforts have been made to extend temperature records beyond the instrumental period through proxy reconstructions, in order to further understand the mechanisms of past climate variability. Yet, the global coverage of existing temperature records is still limited, especially for some key regions like the Tibetan Plateau and for earlier times including the Medieval Warm Period (MWP). Here we present decadally-resolved, alkenone-based, temperature records from two lakes on the northern Tibetan Plateau. Characterized by marked temperature variability, our records provide evidence that temperatures during the MWP were slightly higher than the modern period in this region. Further, our temperature reconstructions, within age uncertainty, can be well correlated with solar irradiance changes, suggesting a possible link between solar forcing and natural climate variability, at least on the northern Tibetan Plateau. © 2013 The Author(s).published_or_final_versio

Assimilable organic carbon (AOC) variation in reclaimed water: Insight on biological stability evaluation and control for sustainable water reuse

© 2018 Elsevier Ltd This review highlights the importance of conducting biological stability evaluation due to water reuse progression. Specifically, assimilable organic carbon (AOC) has been identified as a practical indicator for microbial occurrence and regrowth which ultimately influence biological stability. Newly modified AOC bioassays aimed for reclaimed water are introduced. Since elevated AOC levels are often detected after tertiary treatment, the review emphasizes that actions can be taken to either limit AOC levels prior to disinfection or conduct post-treatment (e.g. biological filtration) as a supplement to chemical oxidation based approaches (e.g. ozonation and chlorine disinfection). During subsequent distribution and storage, microbial community and possible microbial regrowth caused by complex interactions are discussed. It is suggested that microbial surveillance, AOC threshold values, real-time field applications and surrogate parameters could provide additional information. This review can be used to formulate regulatory plans and strategies, and to aid in deriving relevant control, management and operational guidance