IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

Proteomic analysis of swine serum following highly virulent classical swine fever virus infection

<p>Abstract</p> <p>Background</p> <p>Classical swine fever virus (CSFV) belongs to the genus <it>Pestivirus </it>within the family <it>Flaviviridae</it>. Virulent strains of classical swine fever virus (CSFV) cause severe disease in pigs characterized by immunosuppression, thrombocytopenia and disseminated intravascular coagulation, which causes significant economic losses to the pig industry worldwide.</p> <p>Methods</p> <p>To reveal proteomic changes in swine serum during the acute stage of lethal CSFV infection, 5 of 10 pigs were inoculated with the virulent CSFV Shimen strain, the remainder serving as uninfected controls. A serum sample was taken at 3 days post-infection from each swine, at a stage when there were no clinical symptoms other than increased rectal temperatures (≥40°C). The samples were treated to remove serum albumin and immunoglobulin (IgG), and then subjected to two-dimension differential gel electrophoresis.</p> <p>Results</p> <p>Quantitative intensity analysis revealed 17 protein spots showing at least 1.5-fold quantitative alteration in expression. Ten spots were successfully identified by MALDI-TOF MS or LTQ MS. Expression of 4 proteins was increased and 6 decreased in CSFV-infected pigs. Functions of these proteins included blood coagulation, anti-inflammatory activity and angiogenesis.</p> <p>Conclusion</p> <p>These proteins with altered expression may have important implications in the pathogenesis of classical swine fever and provide a clue for identification of biomarkers for classical swine fever early diagnosis.</p

Soft Leptogenesis in Higgs Triplet Model

We consider the minimal supersymmetric triplet seesaw model as the origin of neutrino masses and mixing as well as of the baryon asymmetry of the Universe, which is generated through soft leptogenesis employing a CP violating phase and a resonant behavior in the supersymmetry breaking sector. We calculate the full gauge--annihilation cross section for the Higgs triplets, including all relevant supersymmetric intermediate and final states, as well as coannihilations with the fermionic superpartners of the triplets. We find that these gauge annihilation processes strongly suppress the resulting lepton asymmetry. As a consequence of this, successful leptogenesis can occur only for a triplet mass at the TeV scale, where the contribution of soft supersymmetry breaking terms enhances the CP and lepton asymmetry. This opens up an interesting opportunity for testing the model in future colliders.Comment: 17 pages, 5 figures; version accepted for publicatio

Exploring Sharing Economy Success: Resource-Based View and the Role of Resource Complementarity in Business Value Co-Creation

In recent years, the sharing economy has been grown increasingly as an important means to achieve sustainable competitive advantage. With the support of mobile phone devices and the ubiquitous application of “SOLOMO (social, location, mobile)” concept, the emerging sharing economy hubs increase the pool of potential service providers and sellers by leveraging networked technology to change how market participants engage in a specific transaction. Several successful examples, such as Uber, Airbnb or live streaming platforms, demonstrate that such phenomenon will continue to generate immense interests and receive growing practical and academic attentions for the next decades. In order to meet the needs of heterogeneous network users or buyers, platform owners seek to promote and exploit the network resources from providers and facilitate the transactions. Therefore, the holistic network performance improves and values are co-created when the presence of platform owner complements network members each other. Though the importance of the above mentioned resource complementarity can be well-recognized from many practical evidences and academic studies, the role and empirical evidence of resource complementarity in facilitating the cocreation value and the impact on subsequent performance under sharing economy context is still not well understood. Moreover, sharing economy network is a new and distinct type of organization form and separates from markets and hierarchies, it still requires unique theories and research approaches for providing deeper insights. Value can be co-created by complementary alignment of mutual resources, but the degree to which value generation occurs is still subject to contextual factors. Therefore, the objective of this study is to present a holistic view to illuminate relationships among resource complementarity, relational capabilities (including relational embeddedness and ambidextrous competence), subsequent performance and cooperation continuance intention based on the perspective of resource-based view. 367 respondents from well-known online streaming platform were collected. We find that all hypotheses are supported, except that relational embeddedness has no any significant effect on financial performance. From this study, we hope to contribute nascent knowledge for sharing economy phenomenon and value co-creation with online marketing and information management disciplines scholarly, and provide fruitful insights to the design of an effective value-creating ecosystem application platform through our study for practitioners

Spectrum of the S-wave fully-heavy tetraquark states

In present work, spectrum of the $S$-wave fully-heavy tetraquark states $QQ\bar{Q}\bar{Q}$ ($Q=c,b$), i.e., $cc\bar{c}\bar{c}$, $bb\bar{b}\bar{b}$, $cc\bar{b}\bar{b}$/$bb\bar{c}\bar{c}$, $bc\bar{c}\bar{c}$/ $cc\bar{b}\bar{c}$, $bb\bar{c}\bar{b}$/$cb\bar{b}\bar{b}$, and $bc\bar{b}\bar{c}$ are systematically investigated within an nonrelativistic constituent quark model, in which the Instanton-induced and one-gluon-exchange interactions are taken into account as the residual spin-dependent hyperfine interaction. Our results show that the states with $cc\bar{c}\bar{c}$ and $bb\bar{b}\bar{b}$ components could be located around $6500$ MeV and $19200$ MeV, respectively. Based on our calculations, the new $X(6900)$ state observed by LHCb may be not a ground $cc\bar{c}\bar{c}$ tetraquark state, while it could be an orbitally or radially excited state of $cc\bar{c}\bar{c}$ system. On the other hand, the recently reported $X(6600)$ state by CMS and ATLAS can be explained as a ground $cc\bar{c}\bar{c}$ tetraquark state with spin-parity $J^{PC} =0^{++}$.Comment: Version to appear in Eur. Phys. J.

Strategies for Preventing Drug Recidivism Cycle in Taiwan

Drug abuse is currently a worldwide problem and Taiwan is no exception. Drug abuse is a disease that must be treated on the basis of evidence (United Nations Office on Drugs and Crime 2007; World Health Organisation 2004). In order to reduce the damage caused by drug abuse to the nation, society and people, the government not only developed two anti-drug strategies - that of supply eradication and demand reduction - but since May 1994, has mobilised relevant government departments to take assertive action. Some of the actions include law enforcement enhancement, anti-drug enforcement and drug rehabilitation utilisation. In 2005, new anti-drug programs, such as the sterile needle exchange program and substitution therapy program, were also introduced. The cities implementing the Harm Reduction Program (HR Program) showed lower HIV infection rates in comparison to others without the HR Program. The income and employment conditions of drug addicted patients receiving Methadone Maintenance Treatment have been improved. The future drug policies in Taiwan will focus on drug rehabilitation (treatment), anti-drug actions (prevention) and law enforcement (punishment). The educational system, community recovery and aftercare for drug addicts will also be indispensable (WHO/UNODC/UNAIDS 2004)