Evaluation of Salmonella Gallinarum ghost formulated with Montanide™ ISA 70 VG adjuvant as a vaccine against fowl typhoid

Escherichia coli heat-labile enterotoxin B subunit (LTB) protein is a potent adjuvant. Salmonella Gallinarum ghosts carrying LTB (S. Gallinarum-LTB ghosts) were genetically constructed using a plasmid, pJHL187-LTB, designed for the co-expression of the LTB and E lysis proteins. This study evaluates the immunopotentiating effects of Montanide™ ISA 70 VG on S. Gallinarum-LTB ghost vaccination against fowl typhoid. Five-week-old layer chickens were injected intramuscularly with sterile PBS (non-immunised control, Group A), S. Gallinarum-LTB ghost (Group B) or S. Gallinarum-LTB ghost emulsified with Montanide™ ISA 70 VG adjuvant (Group C). Chickens from both Groups B and C showed significant induction of antigen-specific systemic IgG response compared to controls; in addition, Group C showed enhanced induction of systemic IgG response compared to Group B. We observed significant induction of antigen-specific lymphocyte proliferative response and increased mRNA levels of Th1 cytokines (IFN-γ and IL2) in both Groups B and C. Furthermore, in the challenge experiment with a virulent strain of S. Gallinarum, Group C showed higher survival rates compared with other groups. These results indicate that vaccination with the S. Gallinarum-LTB ghost in combination with Montanide™ ISA 70 VG may enhance the protective immunity against fowl typhoid

Surveillance of avian influenza virus type A in semi-scavenging ducks in Bangladesh

BACKGROUND: Ducks are the natural reservoir of influenza A virus and the central host for highly pathogenic avian influenza (H5N1), while domestic ducks rearing in semi-scavenging system could serve as re-assortment vessels for re-emerging new subtypes of influenza viruses between birds to human. Avian influenza virus (AIV) surveillance in Bangladesh has been passive, relying on poultry farmers to report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results of an active surveillance effort focusing on the semi-scavenging ducks are presented. RESULT: A total of 2100 cloacal swabs and 2100 sera were collected from semi-scavenging ducks from three wintering-sites of Bangladesh during three successive winter seasons, December through February in the years between 2009 and 2012. Virus isolation and identification were carried out from the cloacal swabs by virus propagation in embryonated hen eggs followed by amplification of viral RNA using Avian influenza virus (AIV) specific RT-PCR. The overall prevalence of avian influenza type A was 22.05% for swab samples and 39.76% ducks were sero-positive for avian influenza type A antibody. Extremely low sero-prevalence (0.09%) of AIV H5N1 was detected. CONCLUSIONS: Based on our surveillance results, we conclude that semi-scavenging ducks in Bangladesh might play important role in transmitting Avian Influenza virus (AIV) type A. However, the current risk of infection for humans from domestic ducks in Bangladesh is negligible. We believe that this relatively large dataset over three winters in Bangladesh might create a strong foundation for future studies of AIV prevalence, evolution, and ecology in wintering sites around the globe

500 MS/s 4-Bit Flash ADC with Complementary Architecture

This paper proposes a 500 MS/s 4-bit flash analog-to-digital converter (ADC) featuring a differential input voltage range of 1.2 Vpp operating at a supply voltage of 1.2 V. Although the proposed circuit utilizes a conventional flash ADC structure, its track and hold circuit, driving buffer, and preamp circuits corresponding to the analog stages are designed using complementary architecture to attain a sufficient swing range even at a low supply voltage. Notably, the proposed structure satisfies the error requirements. The error source of the flash ADC, such as the comparator’s input referred offset, did not degrade its performance, while the use of a calibration circuit, characterized by power consumption and area burdens and increased complexity, could also be avoided. Therefore, the proposed flash ADC met the error requirements, such as the comparator’s input referred offset, without the need for calibration circuits. The chip, fabricated using the TSMC 65 nm process, covers an area of 1,160 × 950 μm2 and consumes 78 mW of power. Furthermore, its signal-to-noise and distortion ratio and spurious-free dynamic range were measured to be 23.36 dB and 30.26 dB, respectively, at a sampling frequency of 500 MHz

Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.The research was supported by the Republic of Korea (Government-wide R&D Fund project for infectious disease research (GFID), HG18C0084)

The Roles and Perspectives of Toll-Like Receptors and CD4+ Helper T Cell Subsets in Acute Viral Encephalitis

Acute viral encephalitis caused by neurotrophic viruses, such as mosquito-borne flaviviruses, is an emerging and re-emerging disease that represents an immense global health problem. Considerable progression has been made in understanding the pathogenesis of acute viral encephalitis, but the immune-pathological processes occurring during the progression of encephalitis and the roles played by various molecules and cellular components of the innate and adaptive systems still remain undefined. Recent findings reveal the significant contribution of Toll-like receptors (TLRs) and regulatory CD4+ T cells in the outcomes of infectious diseases caused by neurotrophic viruses. In this review, we discuss the ample evidence focused on the roles of TLRs and CD4+ helper T cell subsets on the progression of acute viral encephalitis. Finally, we draw attention to the importance of these molecules and cellular components in defining the pathogenesis of acute viral encephalitis, thereby providing new therapeutic avenues for this disease

Identification of a Bacterial-Like HslVU Protease in the Mitochondria of Trypanosoma brucei and Its Role in Mitochondrial DNA Replication

ATP-dependent protease complexes are present in all living organisms, including the 26S proteasome in eukaryotes, Archaea, and Actinomycetales, and the HslVU protease in eubacteria. The structure of HslVU protease resembles that of the 26S proteasome, and the simultaneous presence of both proteases in one organism was deemed unlikely. However, HslVU homologs have been identified recently in some primordial eukaryotes, though their potential function remains elusive. We characterized the HslVU homolog from Trypanosoma brucei, a eukaryotic protozoan parasite and the causative agent of human sleeping sickness. TbHslVU has ATP-dependent peptidase activity and, like its bacterial counterpart, has essential lysine and N-terminal threonines in the catalytic subunit. By epitope tagging, TbHslVU localizes to mitochondria and is associated with the mitochondrial genome, kinetoplast DNA (kDNA). RNAi of TbHslVU dramatically affects the kDNA by causing over-replication of the minicircle DNA. This leads to defects in kDNA segregation and, subsequently, to continuous network growth to an enormous size. Multiple discrete foci of nicked/gapped minicircles are formed on the periphery of kDNA disc, suggesting a failure in repairing the gaps in the minicircles for kDNA segregation. TbHslVU is a eubacterial protease identified in the mitochondria of a eukaryote. It has a novel function in regulating mitochondrial DNA replication that has never been observed in other organisms

ICAR: endoscopic skull‐base surgery

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Rosmarinic acid induces rabbit articular chondrocyte differentiation by decreases matrix metalloproteinase-13 and inflammation by upregulating cyclooxygenase-2 expression

Abstract Background Matrix metalloproteinases (MMPs) are known to play an important role in the degradation of the extracellular matrix and the pathological progression of osteoarthritis (OA). The natural polyphenolic compound rosmarinic acid (Ros. A) has been shown to suppress the inhibitory activity of matrix metalloproteinases (MMPs). However, the effects of Ros. A on OA have not been investigated. Methods In the current study, primary articular chondrocytes were cultured from rabbit articular cartilage and treated with Ros. A. Phenotypic characterization was performed by western blotting to assess specific markers, prostaglandin E2 (PGE2) assays, and alcian blue staining to measure sulfated-proteoglycan production. Results We report that in rabbit articular chondrocytes, Ros. A increased type II collagen, sulfated-proteoglycan, cyclooxygenase-2 (COX-2), and PGE2 production in a dose- and time-dependent manner. Furthermore, Ros. A suppressed the expression of MMP-13. In addition, treatment with Ros A activated extracellular signal-regulated kinase (ERK)-1/2 and p38 kinase signaling pathways. Inhibition of MMP-13 enhanced Ros. A-induced type II collagen expression and sulfated-proteoglycan synthesis but COX-2 and PGE2 production were unchanged. Ros. A-mediated up-regulation of ERK phosphorylation was abolished by the MEK inhibitor, PD98059, which prevented induction of the associated inflammatory response. Inhibition of p38 kinase with SB203580 enhanced the increase in type II collagen expression via Ros. A-mediated down-regulation of MMP-13. Conclusions Results suggest that ERK-1/2 regulates Ros. A-induced inflammation and that p38 regulates differentiation by inhibiting MMP-13 in rabbit articular chondrocytes