The Molecular Mechanism Of Alpha-Synuclein Dependent Regulation Of Protein Phosphatase 2A Activity

Background/Aims: Alpha-synuclein (α-Syn) is a neuronal protein that is highly implicated in Parkinson\u27s disease (PD), and protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase that is associated with neurodegenerative diseases, such as PD. α-Syn can directly upregulate PP2A activity, but the underling mechanism remains unclear. Therefore, we investigated the molecular mechanism of α-Syn regulating PP2A activity. Methods: α-Syn and its truncations were expressed in E.coli, and purified by affinity chromatography. PP2A Cα and its mutants were expressed in recombinant baculovirus, and purified by affinity chromatography combined with gel filtration chromatography. The interaction between α-Syn and PP2A Cα was detected by GST pull-down assay. PP2A activity was investigated by the colorimetric assay. Results: The hydrophobic non-amyloid component (NAC) domain of α-Syn interacted with PP2A Cα and upregulated its activity. α-Syn aggregates reduced its ability to upregulate PP2A activity, since the hydrophobic domain of α-Syn was blocked during aggregation. Furthermore, in the hydrophobic center of PP2A Cα, the residue of I123 was responsible for PP2A to interact with α-Syn, and its hydrophilic mutation blocked its interaction with α-Syn as well as its activity upregulation by α-Syn. Conclusions: α-Syn bound to PP2A Cα by the hydrophobic interaction and upregulated its activity. Blocking the hydrophobic domain of α-Syn or hydrophilic mutation on the residue I123 in PP2A Cα all reduced PP2A activity upregulation by α-Syn. Overall, we explored the mechanism of α-Syn regulating PP2A activity, which might offer much insight into the basis underlying PD pathogenesis

Denial of service mitigation approach for IPv6-enabled smart object networks

Denial of service (DoS) attacks can be defined as any third-party action aiming to reduce or eliminate a network's capability to perform its expected functions. Although there are several standard techniques in traditional computing that mitigate the impact of some of the most common DoS attacks, this still remains a very important open problem to the network security community. DoS attacks are even more troublesome in smart object networks because of two main reasons. First, these devices cannot support the computational overhead required to implement many of the typical counterattack strategies. Second, low traffic rates are enough to drain sensors' battery energy making the network inoperable in short times. To realize the Internet of Things vision, it is necessary to integrate the smart objects into the Internet. This integration is considered an exceptional opportunity for Internet growth but, also, a security threat, because more attacks, including DoS, can be conducted. For these reasons, the prevention of DoS attacks is considered a hot topic in the wireless sensor networks scientific community. In this paper, an approach based on 6LowPAN neighbor discovery protocol is proposed to mitigate DoS attacks initiated from the Internet, without adding additional overhead on the 6LoWPAN sensor devices.This work has been partially supported by the Instituto de Telecomunicacoes, Next Generation Networks and Applications Group (NetGNA), Portugal, and by National Funding from the FCT - Fundacao para a Ciencia e Tecnologia through the Pest-OE/EEI/LA0008/2011.Oliveira, LML.; Rodrigues, JJPC.; De Sousa, AF.; Lloret, J. (2013). Denial of service mitigation approach for IPv6-enabled smart object networks. Concurrency and Computation: Practice and Experience. 25(1):129-142. doi:10.1002/cpe.2850S129142251Gershenfeld, N., Krikorian, R., & Cohen, D. (2004). The Internet of Things. Scientific American, 291(4), 76-81. doi:10.1038/scientificamerican1004-76Akyildiz, I. F., Su, W., Sankarasubramaniam, Y., & Cayirci, E. (2002). Wireless sensor networks: a survey. Computer Networks, 38(4), 393-422. doi:10.1016/s1389-1286(01)00302-4Karl, H., & Willig, A. (2005). Protocols and Architectures for Wireless Sensor Networks. doi:10.1002/0470095121IEEE Std 802.15.4-2006 Part 15.4: wireless medium access control (MAC) and physical layer (PHY) specificationsfor low-rate wireless personal area networks (LR-WPANs) 2006ZigBee Alliance ZigBee Specification 2007WirelessHARThomepage 2012 http://www.hartcomm.org/Hui, J. W., & Culler, D. E. (2008). Extending IP to Low-Power, Wireless Personal Area Networks. IEEE Internet Computing, 12(4), 37-45. doi:10.1109/mic.2008.79Kushalnagar N Montenegro G Schumacher C IPv6 over Low-Power Wireless Personal Area Networks (6LoWPANs): Overview, Assumptions, Problem Statement, and Goals 2007Montenegro G Kushalnagar N Hui J Culler D Transmission of IPv6 Packets over IEEE 802.15.4 Networks 2007Shelby Z Thubert P Hui J Chakrabarti S Bormann C Nordmark E 6LoWPAN Neighbor Discovery 2011Zhou, L., Chao, H.-C., & Vasilakos, A. V. (2011). Joint Forensics-Scheduling Strategy for Delay-Sensitive Multimedia Applications over Heterogeneous Networks. IEEE Journal on Selected Areas in Communications, 29(7), 1358-1367. doi:10.1109/jsac.2011.110803Roman, R., & Lopez, J. (2009). Integrating wireless sensor networks and the internet: a security analysis. Internet Research, 19(2), 246-259. doi:10.1108/10662240910952373Wang, Y., Attebury, G., & Ramamurthy, B. (2006). A survey of security issues in wireless sensor networks. IEEE Communications Surveys & Tutorials, 8(2), 2-23. doi:10.1109/comst.2006.315852Xiaojiang Du, & Hsiao-Hwa Chen. (2008). Security in wireless sensor networks. IEEE Wireless Communications, 15(4), 60-66. doi:10.1109/mwc.2008.4599222Pelechrinis, K., Iliofotou, M., & Krishnamurthy, S. V. (2011). Denial of Service Attacks in Wireless Networks: The Case of Jammers. IEEE Communications Surveys & Tutorials, 13(2), 245-257. doi:10.1109/surv.2011.041110.00022Zhou, L., Wang, X., Tu, W., Muntean, G., & Geller, B. (2010). Distributed scheduling scheme for video streaming over multi-channel multi-radio multi-hop wireless networks. IEEE Journal on Selected Areas in Communications, 28(3), 409-419. doi:10.1109/jsac.2010.100412Lin, K., Lai, C.-F., Liu, X., & Guan, X. (2010). Energy Efficiency Routing with Node Compromised Resistance in Wireless Sensor Networks. Mobile Networks and Applications, 17(1), 75-89. doi:10.1007/s11036-010-0287-xLi, H., Lin, K., & Li, K. (2011). Energy-efficient and high-accuracy secure data aggregation in wireless sensor networks. Computer Communications, 34(4), 591-597. doi:10.1016/j.comcom.2010.02.026Oliveira, L. M. L., de Sousa, A. F., & Rodrigues, J. J. P. C. (2011). Routing and mobility approaches in IPv6 over LoWPAN mesh networks. International Journal of Communication Systems, 24(11), 1445-1466. doi:10.1002/dac.1228Narten T Nordmark E Simpson W Soliman H Neighbor Discovery for IP version 6 (IPv6) 2007Singh H Beebee W Nordmark E IPv6 Subnet Model: The Relationship between Links and Subnet Prefixes 2010Roman, R., Lopez, J., & Gritzalis, S. (2008). Situation awareness mechanisms for wireless sensor networks. IEEE Communications Magazine, 46(4), 102-107. doi:10.1109/mcom.2008.4481348Sakarindr, P., & Ansari, N. (2007). Security services in group communications over wireless infrastructure, mobile ad hoc, and wireless sensor networks. IEEE Wireless Communications, 14(5), 8-20. doi:10.1109/mwc.2007.4396938Tsao T Alexander R Dohler M Daza V Lozano A A Security Framework for Routing over Low Power and Lossy Networks 2009Karlof C Wagner D Secure Routing in Wireless Sensor Networks: Attacks and Countermeasures First IEEE International Workshop on Sensor Network Protocols and Applications 2003 113 127 10.1109/SNPA.2003.1203362Hui J Thubert P Compression Format for IPv6 Datagrams in 6LoWPAN Networks 2009Elaine Shi, & Perrig, A. (2004). Designing Secure Sensor Networks. IEEE Wireless Communications, 11(6), 38-43. doi:10.1109/mwc.2004.1368895Akkaya, K., & Younis, M. (2005). A survey on routing protocols for wireless sensor networks. Ad Hoc Networks, 3(3), 325-349. doi:10.1016/j.adhoc.2003.09.01

Possible association between SIRT1 single nucleotide polymorphisms and predisposition to antisocial personality traits in Chinese adolescents

Accumulating evidence suggests an association between the SIRT1 gene and human psychiatric disorders. The aim of the study was to investigate the association between SIRT1 and predisposition to antisocial personality traits (ASP) in Chinese adolescents. Participants consisted of 327 controls and 261 juvenile offenders who were diagnosed with predisposition to ASP according to the Personality Diagnostic Questionnaire. Four tag single nucleotide polymorphisms (tagSNPs) of SIRT1, namely rs12778366, rs7896005, rs10823112, and rs4746720, were genotyped. Association analysis between individual SNPs and ASP risk revealed the CC genotype of rs4746720 to be significantly associated with reduced risk of ASP (OR = 0.51, 95% CI = 0.33–0.77, adjusted P = 0.007). Haplotype analysis showed the TAAC haplotype was associated with reduced susceptibility to ASP (OR = 0.72, 95% CI = 0.57–0.91, P = 0.005). Moreover, rs4746720 variants were found to not only have a direct impact on ASP susceptibility but also modulate the effect of alcohol consumption (Y = 0.022X + 0.431 vs. Y = −0.066X + 0.387). The present study is the first to report a significant association between SIRT1 polymorphisms and ASP in adolescents. This finding is expected to aid in the development of effective interventions for this socially and personally costly disorder.The study was supported by the National Natural Science Foundation of China (grant number: 81373022 and 81573172).Published versio

Association of internet addiction With nonsuicidal self-injury among adolescents in China

© 2020 The Authors. Published by American Medical Association. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: 10.1001/jamanetworkopen.2020.6863Importance: Both nonsuicidal self-injury (NSSI), defined as the direct, deliberate damage of one's body tissue without suicidal intent, and internet addiction among adolescents are public health concerns. However, the possible association of NSSI with internet addiction is not well understood. Objective: To examine the occurrence of internet addiction with NSSI and any sex differences among Chinese adolescents. Design, Setting, and Participants: A multicenter, cross-sectional, survey study was conducted from February 18 to October 15, 2015, among adolescents aged 11 to 20 years from 343 classes in 45 public high schools across 5 provinces of China. Data analysis was performed from August 1, 2018, to March 1, 2019. Exposures: Possible internet addiction and internet addiction. Main Outcomes and Measures: Less-frequent (1-4 times) NSSI and more-frequent (≥5 times) NSSI were surveyed using the Chinese version of the Functional Assessment of Self-Mutilation. Results: A total of 15 623 students (8043 male [51.5%] and 7580 female [48.5%]) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) participated. Of these, 4670 participants (29.9%) met the criteria for possible internet addiction and 509 participants (3.3%) met the criteria for internet addiction. A total of 2667 students (17.1%) engaged in less-frequent NSSI, while 1798 students (11.5%) engaged in more-frequent NSSI in the 12 months preceding the survey. Both possible internet addiction and internet addiction were associated with less-frequent or more-frequent NSSI. The adjusted odds ratios were 1.29 (95% CI, 1.17-1.42) for possible internet addiction and 1.41 (95% CI, 1.11-1.80) for internet addiction for less-frequent NSSI; for more-frequent NSSI, the adjusted odds ratios were 1.75 (95% CI, 1.56-1.96) for possible internet addiction and 2.66 (95% CI, 2.10-3.38) for internet addiction. These associations were similarly observed among age groups of 11 to 14, 15 to 17, and 18 to 20 years. No sex disparities were found in the associations of internet addiction with NSSI, except among adolescents aged 11 to 14 years, where the odds ratios for possible internet addiction with less-frequent NSSI were higher in male adolescents (1.53; 95% CI, 1.25-1.88) than female adolescents (1.13; 95% CI, 0.90-1.47). Conclusion and Relevance: Internet addiction appears to be associated with NSSI, and the findings of this study suggest that the association was similar between male adolescents and female adolescents. These data suggest that evaluation of the risk of NSSI for adolescents in association with internet addiction may help health care professionals in developing preventive interventions for NSSI.This study was supported by grants from National Natural Science Foundation of China (81773457, 81302445 [Dr Tang], and 81373022 [Dr Yu]), and a European Union grant from Horizon 2020 MSCA (DEMAIRPO 799247 [Drs Tang and Chen]).Published versio

Prevalence of and risk factors for non-suicidal self-injury in rural China: Results from a nationwide survey in China

Background Non-suicidal self-injury (NSSI) is a highly prevalent and serious public health problem among adolescents worldwide. However, to date there were no studies assessing the prevalence of NSSI defined by suggested DSM-5 criteria among Chinese adolescents. We aimed to conduct a nationwide survey to explore the prevalence of and risk factors for NSSI among school-based adolescents in rural China. Methods A total sample of 15,623 adolescents in rural China were enrolled by using a multistage sampling method. Data was collected by self-report questionnaires including demographic characteristics, neglect, maltreatment, loneliness, resilience, social support and emotional management ability. NSSI was defined by suggested DSM-5 criteria, according to which the engagement in self-injury took place more than 5 times a year. Multinomial logistic regression models were used to estimate the association between risk factors and NSSI. Results There were 12.2% of adolescents (n = 1908) met the suggested DSM-5 criteria. Approximately 29% reported a history of NSSI at least once during the last year. Significant differences were found in several demographic factors including gender, ethnicity, grade, and family structure between adolescents with and without experiencing NSSI. The top three NSSI behaviors among adolescents with NSSI experience were hitting self, pinching, and pulling hair, with a prevalence rate of 16.7%, 14.1% and 11.2%, respectively. Female, Han ethnicity, fathers’ education level, neglect, maltreatment, loneliness, social support, suicidal behaviors and emotional management ability were significantly associated with NSSI by multivariate analysis. No significant relationship was found between resilience and risk of NSSI. Limitation The DSM-5 has proposed 6 groups of criteria for NSSI, we only used criteria on frequency given its more accepted feasibility and pragmatic application. Consequently, it may different from other prevalence that estimated by other criteria. Conclusion To the best of our knowledge, this is the first study reporting prevalence of NSSI defined by suggested DSM-5 criteria among adolescent in rural China. In comparison to finding from the similar samples of adolescents, Chinese rural adolescents seem to have a relative higher prevalence. The potential risk factors for NSSI include female, father's education, Han ethnicity, psychosocial factors and suicide behaviors. More evidence for further understanding of context of the occurrence, improving access to health care utilization, and identifying the role of psychosocial factors and family relationship, is needed for the prevention and management of NSSI.Published versio

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead