Respiratory Syncytial Virus-Like Nanoparticle Vaccination Induces Long-Term Protection Without Pulmonary Disease by Modulating Cytokines and T-cells Partially Through Alveolar Macrophages

The mechanisms of protection against respiratory syncytial virus (RSV) are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs]) have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs) in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV) or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL)-4+ T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon-γ, which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration

Dokaz protutijela protiv velikog metilja Fasciola hepatica u goveda na otoku Ulleung, Koreja.

We performed a cross-sectional study to estimate the seroprevalence of Fasciola hepatica in herds of cattle on Ulleung island, Korea. Blood samples were collected from randomly selected cattle and the sera were separated and analysed with an ELISA to detect antibodies against F. hepatica. The positive samples were classified as mildly, moderately or strongly positive. Out of 405 cattle sera assessed, 38 (9.4%) were seropositive for antibodies against F. hepatica. From these, 2.5% each were moderately or strongly positive and 4.4% were mildly positive. A significantly higher seroprevalence (P<0.05) was observed in young animals (<2 y old, 15.3%) compared to adults (≥2 y old, 5.4%), while no significant difference in seropositivity was found between male and female animals. This is the the first report of F. hepatica seroprevalence in cattle herds in Korea. These findings may be used to establish a base-line of information for future investigations focused on the significance of F. hepatica in Korea.Provedeno je presječno istraživanje radi procjene seroprevalencije invadiranosti velikim metiljem Fasciola hepatica u stadima goveda na otoku Ulleung u Koreji. Uzorci krvi bili su uzeti od nasumce odabranih goveda, a odvojeni uzorci seruma bili su pretraženi imunoenzimnim testom na prisutnost protutijela specifičnih za velikog metilja. Pozitivni uzorci bili su svrstani u skupine: slabo, umjereno i jako pozitivni. Od 405 pretraženih uzoraka seruma, 38 (9,4%) je bilo pozitivnih na protutijela specifična za metilj F. hepatica. Od toga je 2,5% uzoraka bilo umjereno ili jako pozitivno, a 4,4% slabo pozitivno. Značajno veća seroprevalencija (P<0,05) ustanovljena je u mladih životinja (u dobi manjoj od dvije godine, 15,3%) u usporedbi s odraslima (≥2 godine, 5,4%), dok nije ustanovljena značajna razlika u seropozitivnosti između mužjaka i ženki. Ovo je prvo izvješće o seroprevalenciji velikog metilja u stadima goveda u Koreji. Nalazi mogu biti od koristi za buduća istraživanja o značenju velikog metilja F. hepatica u Koreji

Dokaz protutijela protiv velikog metilja Fasciola hepatica u goveda na otoku Ulleung, Koreja.

We performed a cross-sectional study to estimate the seroprevalence of Fasciola hepatica in herds of cattle on Ulleung island, Korea. Blood samples were collected from randomly selected cattle and the sera were separated and analysed with an ELISA to detect antibodies against F. hepatica. The positive samples were classified as mildly, moderately or strongly positive. Out of 405 cattle sera assessed, 38 (9.4%) were seropositive for antibodies against F. hepatica. From these, 2.5% each were moderately or strongly positive and 4.4% were mildly positive. A significantly higher seroprevalence (P<0.05) was observed in young animals (<2 y old, 15.3%) compared to adults (≥2 y old, 5.4%), while no significant difference in seropositivity was found between male and female animals. This is the the first report of F. hepatica seroprevalence in cattle herds in Korea. These findings may be used to establish a base-line of information for future investigations focused on the significance of F. hepatica in Korea.Provedeno je presječno istraživanje radi procjene seroprevalencije invadiranosti velikim metiljem Fasciola hepatica u stadima goveda na otoku Ulleung u Koreji. Uzorci krvi bili su uzeti od nasumce odabranih goveda, a odvojeni uzorci seruma bili su pretraženi imunoenzimnim testom na prisutnost protutijela specifičnih za velikog metilja. Pozitivni uzorci bili su svrstani u skupine: slabo, umjereno i jako pozitivni. Od 405 pretraženih uzoraka seruma, 38 (9,4%) je bilo pozitivnih na protutijela specifična za metilj F. hepatica. Od toga je 2,5% uzoraka bilo umjereno ili jako pozitivno, a 4,4% slabo pozitivno. Značajno veća seroprevalencija (P<0,05) ustanovljena je u mladih životinja (u dobi manjoj od dvije godine, 15,3%) u usporedbi s odraslima (≥2 godine, 5,4%), dok nije ustanovljena značajna razlika u seropozitivnosti između mužjaka i ženki. Ovo je prvo izvješće o seroprevalenciji velikog metilja u stadima goveda u Koreji. Nalazi mogu biti od koristi za buduća istraživanja o značenju velikog metilja F. hepatica u Koreji

GAIT ASYMMETRY IN CHILDREN WITH DOWN SYNDROME

It has been reported that approximately 80% of children with Down syndrome (OS) exhibit gait problems (Matteo, 2002), characterized by flat-footed contact with no heel-strike, excessive abduction of the leg in the swing phase, and abnormal knee and hip f1exions throughout the gait cycle (Parker et aI., 1986). Due to muscle hypotonia, muscle weakness, !igamentous laXity, and other orthopedic abnormalities, different gait characteristics exist. The purpose of this study was to investigate the gait (walking and running) asymmetry in children with OS

A Novel sLRP6E1E2 Inhibits Canonical Wnt Signaling, Epithelial-to-Mesenchymal Transition, and Induces Mitochondria-Dependent Apoptosis in Lung Cancer

Aberrant activation of the Wnt pathway contributes to human cancer progression. Antagonists that interfere with Wnt ligand/receptor interactions can be useful in cancer treatments. In this study, we evaluated the therapeutic potential of a soluble Wnt receptor decoy in cancer gene therapy. We designed a Wnt antagonist sLRP6E1E2, and generated a replication-incompetent adenovirus (Ad), dE1-k35/sLRP6E1E2, and a replication-competent oncolytic Ad, RdB-k35/sLRP6E1E2, both expressing sLRP6E1E2. sLRP6E1E2 prevented Wnt-mediated stabilization of cytoplasmic β-catenin, decreased Wnt/β-catenin signaling and cell proliferation via the mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways. sLRP6E1E2 induced apoptosis, cytochrome c release, and increased cleavage of PARP and caspase-3. sLRP6E1E2 suppressed growth of the human lung tumor xenograft, and reduced motility and invasion of cancer cells. In addition, sLRP6E1E2 upregulated expression of epithelial marker genes, while sLRP6E1E2 downregulated mesenchymal marker genes. Taken together, sLRP6E1E2, by inhibiting interaction between Wnt and its receptor, suppressed Wnt-induced cell proliferation and epithelial-to-mesenchymal transition

Systems Biology from Virus to Humans

Natural infection and then recovery are considered to be the most effective means for hosts to build protective immunity. Thus, mimicking natural infection of pathogens, many live attenuated vaccines such as influenza virus, and yellow fever vaccine 17D were developed and have been successfully used to induce protective immunity. However, humans fail to generate long-term protective immunity to some pathogens after natural infection such as influenza virus, respiratory syncytial virus (RSV), and human immunodeficiency virus (HIV) even if they survive initial infections. Many vaccines are suboptimal since much mortality is still occurring, which is exampled by influenza and tuberculosis. It is critically important to increase our understanding on protein components of pathogens and vaccines as well as cellular and host responses to infections and vaccinations. Here, we highlight recent advances in gene transcripts and protein analysis results in the systems biology to enhance our understanding of viral pathogens, vaccines, and host cell responses

THE EFFECT OF 12-WEEK STRENGTH TRAINING ON GAIT CHARACTERISTICS IN ADOLESCENT WITH DOWN SYNDROME: A SINGLE CASE STUDY

It has been reported that approximately 80% of individuals with Down syndrome (DS) exhibit abnormal gait characteristics. They are exhibited by flat-footed contact with no heel-strike, excessive abduction of the leg in the swing phase, and abnormal knee and hip flexion throughout the gait cycle (Matteo, 2002). The purpose of this study was to examine the influence of a 12-week strength training program on the gait characteristics during walking by an adolescent with DS

Recombinant Influenza Virus Carrying the Conserved Domain of Respiratory Syncytial Virus (RSV) G Protein Confers Protection Against RSV Without Inflammatory Disease

Respiratory syncytial virus (RSV) is one of the most important causes for viral lower respiratory tract disease in humans. There is no licensed RSV vaccine. Here, we generated recombinant influenza viruses (PR8/RSV. HA-G) carrying the chimeric constructs of hemagglutinin (HA) and central conserved-domains of the RSV G protein. PR8/RSV.HA-G virus showed lower pathogenicity without compromising immunogenicity in mice. Single intranasal inoculation of mice with PR8/RSV.HA-G induced IgG2a isotype dominant antibodies and RSV neutralizing activity. Mice with single intranasal inoculation of PR8/RSV.HA-G were protected against RSV infection as evidenced by significant reduction of lung viral loads to a detection limit upon RSV challenge. PR8/RSV.HA-G inoculation of mice did not induce pulmonary eosinophilia and inflammation upon RSV infection. These findings support a concept that recombinant influenza viruses carrying the RSV G conserved-domain can be developed as a promising RSV vaccine candidate without pulmonary disease

Indoor formaldehyde removal over CMK-3

The removal of formaldehyde at low concentrations is important in indoor air pollution research. In this study, mesoporous carbon with a large specific surface area was used for the adsorption of low-concentration indoor formaldehyde. A mesoporous carbon material, CMK-3, was synthesized using the nano-replication method. SBA-15 was used as a mesoporous template. The surface of CMK-3 was activated using a 2N H2SO4 solution and NH3 gas to prepare CMK-3-H2SO4 and CMK-3-NH3, respectively. The activated samples were characterized by N2 adsorption-desorption, X-ray diffraction, and X-ray photoelectron spectroscopy. The formaldehyde adsorption performance of the mesoporous carbons was in the order of CMK-3-NH3 > CMK-3-H2SO4 > CMK-3. The difference in the adsorption performance was explained by oxygen and nitrogen functional groups formed during the activation process and by the specific surface area and pore structure of mesoporous carbon