24 research outputs found
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A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response
The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell-intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic
Very High Channel Conductivity in Low-Defect AlN/GaN High Electron Mobility Transistor Structures
Low defect AlN/GaN high electron mobility transistor (HEMT) structures, with very high values of electron mobility (\u3e1800 cm2/V s) and sheet charge density (\u3e3×1013 cm−2), were grown by rf plasma-assisted molecular beam epitaxy (MBE) on sapphire and SiC, resulting in sheet resistivity values down to ∼ 100 Ω/◻ at room temperature. Fabricated 1.2 μm gate devices showed excellent current-voltage characteristics, including a zero gate saturation current density of ∼ 1.3 A/mm and a peak transconductance of ∼ 260 mS/mm. Here, an all MBE growth of optimized AlN/GaN HEMT structures plus the results of thin-film characterizations and device measurements are presented
Siglec-E is a negative regulator of acute pulmonary neutrophil recruitment induced by LPS
Recognition of invading bacterial pathogens by human peripheral
blood cd T-cells is attributed to their unique TCR-mediated detection
of the microbial metabolite, HMB-PP, although the exact mechanism
behind cd T-cell access to this activating ligand is largely unclear. The
response of cd T-cells to HMB-PP is likely to occur at early stages of
infection and collectively with cells of the innate immune system. Here
we assessed the crosstalk of autologous Vc9/Vd2 T-cells, neutrophils
and monocytes in response to HMB-PP producing (e.g. Klebsiella
pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Mycobacterium
smegmatis) and HMB-PP deficient live bacteria (e.g. Staphylococcus
aureus, Enterococcus faecalis, Chryseobacterium indologenes,
Listeria innocua). Neutrophils harbouring HMB-PP producing but not
HMB-PP deficient bacteria induced CD69 on Vc9/Vd2 T-cells and
secretion of IFN-c and TNF-a. In addition, activation of Vc9/Vd2 Tcells
only occurred with Listeria innocua transfected with HMB-PP
synthase but not with HMB-PP deficient L. innocua wild-type, demonstrating
that the response of Vc9/Vd2 T-cells to neutrophils harbouring
phagocytosed bacteria depended on the ability of these
bacteria to produce HMB-PP. Transwell experiments showed that Vc9/
Vd2 T-cells responded directly to soluble HMB-PP released from infected
neutrophils and that cell-cell contact with monocytes was required
for optimum activation. HMB-PP responsive Vc9/Vd2 T-cells
also rescued neutrophils from spontaneous apoptosis and stimulated
them to upregulate CD11b, shed CD62L, and release IL-8. Our findings
link the essential innate function of pathogen clearance by neutrophils
to the activation of cd T-cells, implicating an unconventional
mechanism of pathogen recognition with the ability to potentiate innate
and adaptive immunity.
BSI 2010 Abstracts Selected for Poster Presentation
The Hexachlorocerate(III) Anion: A Potent, Benchtop Stable, and Readily Available Ultraviolet A Photosensitizer for Aryl Chlorides
The hexachlorocerate(III) anion,
[Ce<sup>III</sup>Cl<sub>6</sub>]<sup>3–</sup>, was found to
be a potent photoreductant in
acetonitrile solution with an estimated excited-state reduction potential
of −3.45 V versus Cp<sub>2</sub>Fe<sup>0/+</sup>. Despite a
short lifetime of 22.1(1) ns, the anion exhibited a photoluminescence
quantum yield of 0.61(4) and fast quenching kinetics toward organohalogens
allowing for its application in the photocatalytic reduction of aryl
chloride substrates
ZnCdO/ZnMgO and ZnO/AlGaN Heterostructures for UV and Visible Light Emitters
This paper reviews of some of the progress made in the development of ZnO-based light emitting diodes (LEDs). n-ZnO/p-AlGaN-based heterostructures have been successfully for the fabrication of UV emitting LEDs that have operated at temperatures up to 650K, suggesting an excitonic origin for the optical transitions. RF-plasma-assisted molecular beam epitaxy has been used to grow epitaxial CdxZn1-xO films on GaN/sapphire structure. These films have a single-crystal wurtzite structure as demonstrated by structural and compositional analysis. High quality CdxZn1-xO films were grown with up to x=0.78 mole fraction as determined by RBS and SIMS techniques. Optical emission ranging from purple (Cd0.05Zn0.95O) to yellow (Cd0.29Zn0.71O) was observed. Compositional fluctuations in a Cd0.16Zn0.84O films were not detected by spatially resolved CL measurements, although intensity fluctuation with features of ∼0.5 μm diameter were seen on the intensity maps. Time resolved photoluminescence shows multi-exponential decay with 21 psec. and 49±3 psec. lifetimes, suggesting that composition micro-fluctuations may be present in Cd0.16Zn0.84O film
ZnCdO/ZnMgO and ZnO/AlGaN Heterostructures for UV and Visible Light Emitters
This paper reviews of some of the progress made in the development of ZnO-based light emitting diodes (LEDs). n-ZnO/p-AlGaN-based heterostructures have been successfully for the fabrication of UV emitting LEDs that have operated at temperatures up to 650K, suggesting an excitonic origin for the optical transitions. RF-plasma-assisted molecular beam epitaxy has been used to grow epitaxial CdxZn1-xO films on GaN/sapphire structure. These films have a single-crystal wurtzite structure as demonstrated by structural and compositional analysis. High quality CdxZn1-xO films were grown with up to x=0.78 mole fraction as determined by RBS and SIMS techniques. Optical emission ranging from purple (Cd0.05Zn0.95O) to yellow (Cd0.29Zn0.71O) was observed. Compositional fluctuations in a Cd0.16Zn0.84O films were not detected by spatially resolved CL measurements, although intensity fluctuation with features of ∼0.5 μm diameter were seen on the intensity maps. Time resolved photoluminescence shows multi-exponential decay with 21 psec. and 49±3 psec. lifetimes, suggesting that composition micro-fluctuations may be present in Cd0.16Zn0.84O film