1,607 research outputs found
Biomimetic intrafibrillar mineralization of type I collagen with intermediate precursors-loaded mesoporous carriers
published_or_final_versio
Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-ÎșB by targeting p65.
Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-ÎșB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-ÎșB stimulator. Here we investigated whether HBoV proteins modulate TNF-α-mediated activation of the NF-ÎșB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-ÎșB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IÎșB kinase alpha (IKKα)-, IÎșB kinase beta (IKKÎČ)-, constitutively active mutant of IKKÎČ (IKKÎČ SS/EE)-, or p65-induced NF-ÎșB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn't interfere with TNF-α-mediated IÎșBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-ÎșB activation. This is the first time that HBoV has been shown to inhibit NF-ÎșB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis
Effects of Post-Translational Modifications of Fibrinogen on Clot Formation, Clot Structure, and Fibrinolysis: A Systematic Review
OBJECTIVE: Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but f
Dimensionality and dynamics in the behavior of C. elegans
A major challenge in analyzing animal behavior is to discover some underlying
simplicity in complex motor actions. Here we show that the space of shapes
adopted by the nematode C. elegans is surprisingly low dimensional, with just
four dimensions accounting for 95% of the shape variance, and we partially
reconstruct "equations of motion" for the dynamics in this space. These
dynamics have multiple attractors, and we find that the worm visits these in a
rapid and almost completely deterministic response to weak thermal stimuli.
Stimulus-dependent correlations among the different modes suggest that one can
generate more reliable behaviors by synchronizing stimuli to the state of the
worm in shape space. We confirm this prediction, effectively "steering" the
worm in real time.Comment: 9 pages, 6 figures, minor correction
Case report of hepatic artery dissection secondary to hepatic artery pseudoaneurysm after living donor liver transplantation
Definition of the ÏW regulon of Bacillus subtilis in the absence of stress
Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF ÏW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF ÏX, ÏY, and ÏM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly ÏW-regulated. Under these conditions, ÏW exhibits a basal level of activity. Subsequently, we verified the ÏW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the ÏW anti-sigma factor RsiW and subsequent activation of the ÏW-regulon. Taken together, our studies identify 89 genes as being strictly ÏW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of ÏW-dependent genes were relatively mild, which implies that ÏW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via ÏW, but that this membrane protease also exerts other important post-transcriptional regulatory functions
Differential down-modulation of HLA class I and II molecule expression on human tumor cell lines upon in vivo transfer
Previous evidence from our laboratory showed that EpsteinâBarr virusâimmortalized lymphoblastoid B cells undergo a prominent down-modulation of HLA-II molecule expression when injected intraperitoneally in SCID mice, while HLA-I remains almost unaffected. Since this phenomenon can alter the experimental outcome of therapeutic protocols of adoptive cell therapy, we decided to evaluate the behavior of MHC antigens in a panel of cell lines belonging to the B- and T-cell lineages, as well as in epithelial tumor cell lines. Cells were administered in mice either intraperitoneally or subcutaneously and recovered 4Â days later for HLA molecule expression analysis. Collected data showed a highly heterogeneous in vivo behavior of the various cell lines, which could alternatively down-modulate, completely abrogate or maintain unchanged the expression of either MHC-I or MHC-II molecules. Moreover, the site of injection impacted differentially on these aspects. Although such phenomena still lack a comprehensive clarification, epigenetic mechanisms are likely to be involved as epigenetic drugs could partially counteract MHC down-modulation in vivo. Nonetheless, it has to be pointed out that careful attention must be paid to the assessment of therapeutic efficacy of translational protocols of adoptive immunotherapy, as modulation of MHC molecules on human target cells when transferred in a mouse environment could readily interfere with the desired and expected therapeutic effects
The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases
Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica; ArgentinaFil: Assis, Juliana. FundaciĂłn Oswaldo Cruz; BrasilFil: Gomes AraĂșjo, FlĂĄvio M.. FundaciĂłn Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. FundaciĂłn Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica; ArgentinaFil: Oliveira, Guilherme. Instituto TecnolĂłgico Vale; Brasil. FundaciĂłn Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂ©dica; Argentin
J Acquir Immune Defic Syndr
BackgroundCervical cancer is a major public health problem in resource-limited settings, particularly among HIV-infected women. Given the challenges of cytology-based approaches, the efficiency of new screening programs need to be assessed.SettingCommunity and hospital-based clinics in Gaborone, Botswana.ObjectiveTo determine the feasibility, and efficiency of the \u201cSee and Treat\u201d approach using Visual Inspection Acetic Acid (VIA) and Enhanced Digital Imaging (EDI) for cervical cancer prevention in HIV-infected women.MethodsA two-tier community-based cervical cancer prevention program was implemented. HIV-infected women were screened by nurses at the community using the VIA/EDI approach. Low-grade lesions were treated with cryotherapy on the same visit.ResultsFrom March 2009 through January 2011, 2,175 patients were screened for cervical cancer at our community-based clinic. 253 (11.6%) were found to have low-grade lesions and received same-day cryotherapy. 1,347 (61.9%) women were considered to have a normal examination and 575 (27.3%) were referred for further evaluation and treatment. Of the 1,347 women initially considered to have normal exams, 267 (19.8%) were recalled based on weekly quality control assessments. 210 (78.6%) of the 267 recalled women and 499 (86.8%) of the 575 referred women were seen at the referral clinic. Of these 709 women, 506 (71.4%) required additional treatment. Overall, 264 CIN stage 2 or 3 were identified and treated, and six micro-invasive cancers identified were referred for further management.ConclusionsOur \u201cSee and Treat\u201d cervical cancer prevention program using the VIA/EDI approach is a feasible, high-output and high-efficiency program, worthy of considering as an additional cervical cancer screening method in Botswana, especially for women with limited access to the current cytology-based screening services.20122014-01-08T00:00:00ZP30 AI045008/AI/NIAID NIH HHS/United StatesU2G PS001949/PS/NCHHSTP CDC HHS/United States1U2GPS001949/PHS HHS/United StatesIP30 AI 45008/AI/NIAID NIH HHS/United States22134146PMC388408
Overview on the phenomenon of two-qubit entanglement revivals in classical environments
The occurrence of revivals of quantum entanglement between separated open
quantum systems has been shown not only for dissipative non-Markovian quantum
environments but also for classical environments in absence of back-action.
While the phenomenon is well understood in the first case, the possibility to
retrieve entanglement when the composite quantum system is subject to local
classical noise has generated a debate regarding its interpretation. This
dynamical property of open quantum systems assumes an important role in quantum
information theory from both fundamental and practical perspectives. Hybrid
quantum-classical systems are in fact promising candidates to investigate the
interplay among quantum and classical features and to look for possible control
strategies of a quantum system by means of a classical device. Here we present
an overview on this topic, reporting the most recent theoretical and
experimental results about the revivals of entanglement between two qubits
locally interacting with classical environments. We also review and discuss the
interpretations provided so far to explain this phenomenon, suggesting that
they can be cast under a unified viewpoint.Comment: 16 pages, 9 figures. Chapter written for the upcoming book "Lectures
on general quantum correlations and their applications
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