1,063 research outputs found
Using phage Lytic Enzymes to Control Pathogenic Bacteria
Our laboratory has developed phage lytic enzymes to prevent infection by specifically destroying disease bacteria on mucous membranes and in blood. Enzymes specific for S. pneumoniae and S. pyogenes have been developed to be used nasally and orally to control these organisms in environments such as hospitals and nursing homes to prevent or markedly reduce serious infections by these pathogens. In addition, a B. anthracis-specific enzyme was developed to kill the vegetative forms of these bacteria in the blood of infected individuals. In animal studies, >80% of mice colonized mucosally or infected intravenously with pathogenic bacteria were decolonized or survived after a single enzyme treatment delivered to the same site of colonization or infection
Pulsed-Laser Irradiation Space Weathering Of A Carbonaceous Chondrite
Grains on the surfaces of airless bodies experience irradiation from solar energetic particles and melting, vaporization and recondensation processes associated with micrometeorite impacts. Collectively, these processes are known as space weathering and they affect the spectral properties, composition, and microstructure of material on the surfaces of airless bodies, e.g. Recent efforts have focused on space weathering of carbonaceous materials which will be critical for interpreting results from the OSIRIS-REx and Hayabusa2 missions targeting primitive, organic-rich asteroids. In addition to returned sample analyses, space weathering processes are quantified through laboratory experiments. For example, the short-duration thermal pulse from hypervelocity micrometeorite impacts have been simulated using pulsed-laser irradiation of target material e.g. Recent work however, has shown that pulsed-laser irradiation has variable effects on the spectral properties and microstructure of carbonaceous chondrite samples. Here we investigate the spectral characteristics of pulsed-laser irradiated CM2 carbonaceous chondrite, Murchison, including the vaporized component. We also report the chemical and structural characteristics of specific mineral phases within the meteorite as a result of pulsed-laser irradiation
Genetic resistance determinants to fusidic acid and chlorhexidine in variably susceptible staphylococci from dogs
Abstract
Background
Concern exists that frequent use of topically-applied fusidic acid (FA) and chlorhexidine (CHX) for canine pyoderma is driving clinically relevant resistance, despite rare description of FA and CHX genetic resistance determinants in canine-derived staphylococci. This study aimed to determine minimum inhibitory concentrations (MICs) and investigate presence of putative resistance determinants for FA and CHX in canine-derived methicillin-resistant (MR) and -susceptible (MS) staphylococci. Plasmid-mediated resistance genes (fusB, fusC, fusD, qacA/B, smr; PCR) and MICs (agar dilution) of FA and CHX were investigated in 578 staphylococci (50 MR S. aureus [SA], 50 MSSA, 259 MR S. pseudintermedius [SP], 219 MSSP) from Finland, U.S.A., North (NUK) and South-East U.K. (SEUK) and Germany. In all isolates with FA MIC ≥64 mg/L (n = 27) fusA and fusE were amplified and sequenced.
Results
FA resistance determinants (fusA mutations n = 24, fusB n = 2, fusC n = 36) were found in isolates from all countries bar U.S.A. and correlated with higher MICs (≥1 mg/L), although 4 SP isolates had MICs of 0.06 mg/L despite carrying fusC. CHX MICs did not correlate with qacA/B (n = 2) and smr (n = 5), which were found in SEUK SA, and SP from NUK and U.S.A.
Conclusions
Increased FA MICs were frequently associated with fusA mutations and fusC, and this is the first account of fusB in SP. Despite novel description of qacA/B in SP, gene presence did not correlate with CHX MIC. Selection pressure from clinical use might increase prevalence of these genetic determinants, but clinical significance remains uncertain in relation to high skin concentrations achieved by topical therapy
Dilute ferrimagnetic semiconductors in Fe-substituted spinel ZnGaO
Solid solutions of nominal composition
[ZnGaO][FeO], of the semiconducting spinel
ZnGaO with the ferrimagnetic spinel FeO have been prepared with
= 0.05, 0.10, and 0.15. All samples show evidence for long-range magnetic
ordering with ferromagnetic hysteresis at low temperatures. Magnetization as a
function of field for the = 0.15 sample is S-shaped at temperatures as high
as 200 K. M\"ossbauer spectroscopy on the = 0.15 sample confirms the
presence of Fe, and spontaneous magnetization at 4.2 K. The magnetic
behavior is obtained without greatly affecting the semiconducting properties of
the host; diffuse reflectance optical spectroscopy indicates that Fe
substitution up to = 0.15 does not affect the position of the band edge
absorption. These promising results motivate the possibility of dilute
ferrimagnetic semiconductors which do not require carrier mediation of the
magnetic moment.Comment: 9 pages and 6 figure
Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure
Background and aims:
Toll-like receptor 4 (TLR4) plays an essential role in mediating organ injury in acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Here we assess whether inhibiting TLR4 signaling can ameliorate liver failure and serve as a potential treatment.
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Material and Methods:
Circulating TLR4 ligands and hepatic TLR4 expression was measured in plasma samples and liver biopsies from patients with cirrhosis. TAK-242 (TLR4 inhibitor) was tested in vivo with 10mg/Kg, i.p. in rodent models of ACLF (bile duct ligation + lipopolysaccharide (LPS); carbontetrachloride + LPS) and ALF (Galactosamine + LPS) and in vitro on immortalized human monocytes (THP-1) and hepatocytes (HHL5).. The in vivo therapeutic effect was assessed by coma free survival, organ injury and cytokine release and in vitro by measuring IL6, IL1b or cell injury (TUNEL), respectively.
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Results:
In patients with cirrhosis, hepatic TLR4 expression was upregulated and circulating TLR4 ligands were increased (p<0.001). ACLF in rodents was associated with a switch from apoptotic cell death in ALF to non-apoptotic forms of cell death. TAK-242 reduced LPS induced cytokine secretion and cell death (p=0.002) in hepatocytes and monocytes in vitro. In rodent models of ACLF, TAK-242 administration improved coma free survival, reduced the degree of hepatocyte cell death in liver p<0.001) and kidneys (p=0.048) and reduced circulating cytokine levels (IL1b p<0.001). In a rodent model of ALF TAK-242 prevented organ injury (p<0.001) and systemic inflammation (IL1b p<0.001).
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Conclusion:
This study shows that TLR4 signaling is a key factor in the development of both ACLF and ALF and its inhibition improves severity of organ injury and outcome. TAK-242 may be of therapeutic relevance in patients with liver failure
High-Density Peptide Arrays with Combinatorial Laser Fusing
Combinatorial laser fusing is a new method to produce high-density peptide arrays with feature sizes as small as 10 mu m. It combines the high spot densities achieved by lithographic methods with the cost-efficiency of biofunctional xerography. The method is also adapted for other small molecules compatible with solid phase synthesis
A MIQE-Compliant Real-Time PCR Assay for Aspergillus Detection
PMCID: PMC3393739This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome
Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials
Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium
Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging
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