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SummaryThe DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair.

Aged blood vessels accelerate systemic aging; SIRT7 gene therapy rejuvenates blood vessels and promotes longevity in aging model., Vascular dysfunction is a typical characteristic of aging, but its contributing roles to systemic aging and the therapeutic potential are lacking experimental evidence. Here, we generated a knock-in mouse model with the causative Hutchinson-Gilford progeria syndrome (HGPS) LmnaG609G mutation, called progerin. The Lmnaf/f;TC mice with progerin expression induced by Tie2-Cre exhibit defective microvasculature and neovascularization, accelerated aging, and shortened life span. Single-cell transcriptomic analysis of murine lung endothelial cells revealed a substantial up-regulation of inflammatory response. Molecularly, progerin interacts and destabilizes deacylase Sirt7; ectopic expression of Sirt7 alleviates the inflammatory response caused by progerin in endothelial cells. Vascular endothelium–targeted Sirt7 gene therapy, driven by an ICAM2 promoter, improves neovascularization, ameliorates aging features, and extends life span in Lmnaf/f;TC mice. These data support endothelial dysfunction as a primary trigger of systemic aging and highlight gene therapy as a potential strategy for the clinical treatment of HGPS and age-related vascular dysfunction.

The gamma-type inhibitor of snake venom phospholipase A2 (PLIγ) is expressed extensively in livers of both venomous and non-venomous snakes. It is not clear why PLIγs from different snake species possess diverse activities. To obtain high activity PLIγs and interpret the sequence-function relationships, we used DNA shuffling to hybridize the PLIγs of Sinonatrix annularis (saPLIγ) and Elaphe carinata (ecPLIγ). Chimera PLIγs (cPLIγ) of ∼550 bp were obtained by a series of gene manipulations including DNase I digestion, primer-free PCR, and PCR amplification with PLIγs primer pair. After successful insertion of cPLIγs into pCANTAB5e phage vector, the transformed TG1 strain of Esherichia coli was achieved. The cPLIγ phage library was produced and panned in a five-pace snake venom-coated immune tube. Three high affinity cPLIγ isoforms survived two rounds of panning. Prokaryote expression by the pET28c vector was employed for production of the three cPLIγs and the two parental PLIγs. These all showed anti-hemorrhage activity with cPLIγ 2 demonstrating superior inhibition to the parent PLIγs. Sequence alignment showed that the three kinds of cPLIγ were produced by gene splicing of S. annularis and E. carinata at different sites. Primary sequence changes brought regional changes in secondary and tertiary structure, which may explain the differences in PLIγ activity.

Most of the detection methods against DDoS attacks are based on periodic detection, which leads to high communication overhead, untimely detection, and slow attack response. This paper proposes a passive abnormality detection approach. First, we record the two flow-table characteristics of the regular switches. Then, based on dynamic threshold method and Grubbs outlier test method, we make a determination of abnormal switches. This method reduces the amount of data duplication and regular traffic collection. Moreover, we use Support Vector Machine (SVM) algorithm to evaluate the performance of the passive anomaly detection method. The experiment results show a better performance than active period DDoS attack detection approaches.

Circadian clock relies on a transcription and translation feedback loop (TTFL). Two transcription factors, i.e. Bmal1 and Clock, activate the transcription of Period (Per) and Cryptochrome (Cry), which inhibit their own transcription when accumulated to a critical concentration. NAD+-dependent deacylase Sirt1 deacetylates Bmal1 and Per2 to regulate circadian rhythms. Sirt6 interacts with Bmal1 to regulate clock-controlled gene (CCG) expression by local chromatin remodeling. Whether Sirt6 directly modify clock components is elusive. Here, we found that loss of Sirt6 jeopardizes circadian phase. At molecular level, Sirt6 interacts with and deacetylates Per2, thus preventing its proteasomal degradation. These data highlight an important function of Sirt6 in the direct regulation of TTFL and circadian rhythms.

The central pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes peripheral oscillators to coordinate physiological and behavioural activities throughout the body. How circadian phase coherence between the SCN and the periphery is controlled is not well understood. Here, we identify hepatic SIRT7 as an early responsive element to light that ensures circadian phase coherence in the mouse liver. The SCN-driven body temperature (BT) oscillation induces rhythmic expression of HSP70, which promotes SIRT7 ubiquitination and proteasomal degradation. Acute temperature challenge dampens the BT oscillation and causes an advanced liver circadian phase. Further, hepatic SIRT7 deacetylates CRY1, promotes its FBXL3-mediated degradation and regulates the hepatic clock and glucose homeostasis. Loss of Sirt7 in mice leads to an advanced liver circadian phase and rapid entrainment of the hepatic clock upon daytime-restricted feeding. These data identify a BT-HSP70-SIRT7-CRY1 axis that couples the mouse hepatic clock to the central pacemaker and ensures circadian phase coherence and glucose homeostasis.

The biological clock is generated in the hypothalamic suprachiasmatic nucleus (SCN), which synchronizes peripheral oscillators to coordinate physiological and behavioral activities throughout the body. Disturbance of circadian phase coherence between the central and peripheral could disrupt rhythms and thus cause diseases and aging. Here, we identified hepatic Sirt7 as an early element responsive to light, which ensures the phase coherence in mouse liver. Loss of Sirt7 leads to advanced liver circadian phase; restricted feeding in daytime entrains hepatic clock more rapidly in Sirt7-/- mice compared to wild-types. Molecularly, a light-driven body temperature (BT) oscillation induces rhythmic expression of Hsp70, which binds to and promotes the ubiquitination and proteasomal degradation of Sirt7. Sirt7 rhythmically deacetylates Cry1 on K565/579 and promotes Fbxl3-mediated degradation, thus coupling hepatic clock to the central pacemaker. Together, our data identify a novel BT/Hsp70-Sirt7-Cry1 axis, which transmits biological timing cues from the central to the peripheral and ensures circadian phase coherence in livers.

The gamma-type inhibitor of snake venom phospholipase A

SaPLIγ is a natural phospholipase A

Background: The gamma-type phospholipase A2 inhibitor (ΡLIγ) is a natural protein commonly found in snake serum, which can neutralize pathophysiological effects of snake venom phospholipases A2. Therefore, this protein is a potential candidate to the development of a novel antivenom. To the best of our knowledge, there is no antibody currently available for PLIγ identification and characterization. Methods: Bioinformatics prediction of epitope using DNAStar software was performed based on the sequence of Sinonatrix annularis PLIγ (SaPLIγ). The best epitope 151CPVLRLSNRTHEANRNDLIKVA172 was chosen and synthesized, and then conjugated to keyhole limpet hemocyanin and bovine serum albumin for use as an immunogen and plate-coating antigen, respectively. Results: Eighteen IgG anti-PLIγ mAb hybridoma cell strains were obtained, and all the mAbs had positive interaction with recombinant His6-PLIγ and natural SaPLIγ. Moreover, the mAb from 10E9 strain was also successfully used for the immunodetection of other snake serum PLIγs. cDNA sequence alignment of those PLIγs from different snake species showed that their epitope segments were highly homologous. Conclusions: The successful preparation of anti-PLIγmAb is significant for further investigation on the relationship between the structure and function of PLIγs, as well as the interaction between PLIγs and PLA2s.

In this paper, the preparation and the test of the endothermic properties of modified expanded graphitebased CaxZny(OH)2(x+y) composite materials are reported, which is promised to be used for heat storage. Coprecipitation method is employed to prepare the modified expanded graphite-based CaxZny(OH)2(x+y) composite materials for heat storage. Ca(OH)2 is dissolved in water first, and a certain amount of ZnO is added into the Ca(OH)2 solution to get a milky suspension; thereafter the modified expanded graphite is immersed into the milky suspension to prepare the composite materials by way of physical adsorption. Furthermore, differential scanning calorimetric analyzer is used to analyze the endothermic properties of the material. The results show that the endothermic enthalpy of the composite material is about 1000 J/g with lower decomposition temperature.

Phospholipid scramblases (PLSCRs) are the conserved calcium-binding, type II transmembrane proteins synthesized in all eukaryotic organisms. In mammals, these proteins play essential roles in various physiological processes, especially in the immune responses. However, the existence of PLSCRs and their biological functions in planarian are still unknown at present. In this study, a new member of PLSCRs was identified in planarian Dugesia japonica (D. japonica), named DjPLSCR. The sequence analysis revealed that it contains an opening reading frame consisting of 726bp encoding a putative protein of 241 amino acids with a predicted molecular mass of ~28.7kDa and an isoelectric point of 6.21. Whole-mount in situ hybridization showed that mRNAs of DjPLSCR are predominantly expressed in adult and regenerative pharynx which is an important organ of immune system in planarians. Importantly, we found that the transcription level of DjPLSCR was significantly upregulated when planarians were stimulated with the pathogen-associated molecular patterns [polyinosinic-polycytidylic acid, lipopolysaccharide, peptidoglycan and β-glucan], suggesting that DjPLSCR is involved in the immune response upon pathogen invasion. Our findings provide the first experimental insights into the characteristics and potential functions of PLSCR in planarians.

With the proliferation of mobile device and applications, a large number of mobility management solutions have been proposed to support mobility in IP networks. Mobile IP and its derivatives are basically network layer solutions for terminal mobility problems. However, there are several shortages in those solutions, such as large overhead, high latency, lack of scalability and weak security. Software Defined Networking (SDN) provides a flexible centralized approach to handle mobility in IP networks. In this paper, we propose a network based secure mobility management architecture. SDN controller manages the mobility with full authority and controls OpenFlow Switches to forward packets for mobile nodes in optimal path. The implementation and test results show a better delay and throughput performance during the handover process.

Recently, research for Future Internet has been proposed and carried out in order to address two kinds of issues. First, the existing Internet protocol does not use new identifiers, and secondly the Internet protocol should be improved to meet usage requirements. Internet Protocol version 6 (IPv6) has been applied to fix the second issue. IPv6 has almost infinite address space. In addition, it has a significant feature in that it allows the host to generate and configure its own IPv6 addresses. We call that feature the Stateless Address Auto Configuration (SLAAC). However, this feature has drawbacks with respect to security for the network management system. Illegal hosts or unauthorized hosts could access the network and attack critical equipment, such as financial or industrial IT infrastructure. Users are exposed to such attacks as identity theft. In order to solve this issue, a host management method is needed to control and protect from illegal or unauthorized hosts. In this paper, we developed and implemented a mechanism for collecting host information and blocking specific hosts using features of ICMPv6. This proposal is tested and implemented in Korea Advance Research Network (KOREN). Through this, our solution covers the mechanisms to control host which is illegal or unauthorized in local network. Therefore, it can be protection from any Virus, DDOS and etc.

IPv6 has been developed to deal with the increase in number of hosts in the Internet. IPv6 address can be assigned to any network devices. IPv6 provides new function called SLAAC (Stateless Address Auto Configuration). SLAAC is a significant feature for host itself generating and configuring own addresses to enable communication. But this feature has drawbacks in term of security and management of networks. In this paper, we propose a blocking mechanism for malicious hosts using the feature of RA message in ICMPv6 (Internet Control Message Protocol version 6). It was experimented using Emulab testbed environment. And the result show that it can block malicious hosts successfully.

International audience; Throughout the last decade, overlay multicast is a hot issue for media distribution services. High bandwidth consumption and multi-source multicasting in widely distributed networks is a critical issue for a wide range of applications including video conferencing, multi-party games, content distribution etc. A number of research projects have explored to use multicast as an efficient and scalable mechanism to deal with group oriented communications. However, there are still some limitations, such as long latency, duplicated packet transmission at certain points and lack of network equipment functionality support. With the appearance of Software Defined Networking, represented by OpenFlow devices, network control and management becomes possible to remote administrators. With the support of OpenFlow, it is possible to do some optimizations of existing media distribution mechanisms in overlay networks. In this paper, we proposed a novel method to improve the traditional overlay multicast relay networks with available limited number of OpenFlow devices, to cut down the bandwidth expenditures and perform a good control and management of media distribution services.

Thermal energy storage has very important prospects in many applications related to the use of renewable energies (solar energy, etc.) or other energy sources, such as waste heat from industrial processes. Thermochemical storage is very attractive for long-term storage, since it could be conducted at room temperature without energy losses. In the present paper, a novel nanocomposite material, Ca2−αZnα(OH)4, is prepared using coprecipitation methodology and is characterized by XRD and DSC tests. The XRD result shows that the grain size of the nano-composite ranges from 40 nm to 95 nm. The DSC test result shows that the nano-composite exhibits high thermal storage capacity: 764.5 J/g at α = 0.8555. Its thermal decomposition temperature was found to be approximately 180º. Itwas found possible to recover 63.25% of the stored heat energy.

After the VDSL (Very High-bit-rate Digital Subscriber Line) system enters into fast mode, not all the tones have the same margin. In order to cope with the crosstalk noise, Bit Swap is utilized to swap the tone pairs: the one has a high margin while the other one has a relatively low margin. Although the Bit Swap has been proposed before, there is no Bit Swap established on EOC(Embedded Operational Channel) and the scheme proposes coarse and fine SNR margin tuning algorithm. The paper presents the architecture and process of Bit Swap based on EOC and also implements the algorithm to adjust the margin for tones calculated to be swapped. After thoroughly tested, the test results show that the proposed scheme functions well. Compared with the scheme without Bit Swap, it greatly improves the performance against crosstalk noise and can reduce the RS errors to zero.

Applying supply chain management is an effective approach to solve pork quality and safety problems in China at present, and it is the key of high quality pork supply chain management to form and improve quality and safety control abilities for supply chain core enterprises. On the basis of representing the construction of quality safety control abilities of core enterprises, this paper analyses the formation mechanism of quality and safety control abilities of core enterprises in high quality pork supply chain, from aspects of dynamic mechanism, conduction mechanism, realization mechanism, Incentive and restriction mechanism, and promotion and guarantee mechanism

In this paper, the conception of effective co-opetition mechanism in high quality pork supply chain has been analyzed. The evolutional processes of co-opetition mechanism and related influencing factors have been studied by using the dual population evolutionary game theory. The result showed that evolution of co-opetition is influenced by 8 factors, which are cooperation cost, cooperation income, coefficient of income distribution, decrease of cooperative risk, coefficient of risk compensation, probability of risk, management scale, and coefficients of either encouragement or punishment. It also suggested that the achievement of effective competition-cooperation of high quality pork supply chain would be improved by decreasing cooperation costs, increasing cooperation incomes, and building the equitable and effective systems of income distribution, risk compensation, as well as encouragement and punishment.