Virus Infection Impairs Fungal Response to Stress: Effect of Salt

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Infection with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1) weakens the resistance of biofilms of common A. fumigatus reference strain Af293 in intermicrobial competition with Pseudomonas aeruginosa, and sensitizes A. fumigatus for antifungal effects of nikkomycin Z. We compared the sensitivity of two virus-infected (VI) and one virus-free (VF) Af293 strains to hypertonic salt. Salt stress impairs the growth of VI and VF at all times; VF control growth always exceeds VI, and VF growth in salt always exceeds VI. Since VF growth exceeds VI in the presence and absence of salt, we also examined growth in salt as a percentage of control growth. Initially, as a percentage of control, VI exceeded VF, but at 120 h VF began to exceed VI consistently even by this measure; thus, at that time the growth of VF in salt surges in relation to control growth, or, alternatively, its growth in salt persists compared to the relative inhibition of VI. In summary, virus infection impairs the response of A. fumigatus to several different stresses, including hypertonic salt.Peer reviewe

Single photon source characterization with a superconducting single photon detector

Superconducting single photon detectors (SSPD) based on nanopatterned niobium nitride wires offer single photon counting at fast rates, low jitter, and low dark counts, from visible wavelengths well into the infrared. We demonstrate the first use of an SSPD, packaged in a commercial cryocooler, for single photon source characterization. The source is an optically pumped, microcavity-coupled InGaAs quantum dot, emitting single photons on demand at 902 nm. The SSPD replaces the second silicon Avalanche Photodiode (APD) in a Hanbury-Brown Twiss interferometer measurement of the source second-order correlation function, g (2) (tau). The detection efficiency of the superconducting detector system is >2 % (coupling losses included). The SSPD system electronics jitter is 170 ps, versus 550 ps for the APD unit, allowing the source spontaneous emission lifetime to be measured with improved resolution.Comment: 8 page

Freeing Aspergillus fumigatus of Polymycovirus Infection Renders It More Resistant to Competition with Pseudomonas aeruginosa Due to Altered Iron-Acquiring Tactics

A virus-free (VF) A. fumigatus isolate has been shown to be resistant in competition with Pseudomonas as compared to the isogenic line infected with Aspergillus fumigatus polymycovirus 1 (AfuPmV-1), and this phenotype was apparently related to alterations in iron metabolism. Here we investigated further the mechanisms underpinning this phenotype. The extracellular siderophore profiles of five isogenic VF and virus-infected (VI) strains were sampled at 24, 31, 48, 54, and 72 h in submerged cultures and quantitatively examined by liquid chromatography and mass spectrometry. Intracellular profiles of conidia and cultures at the stationary growth phase were defined. VF A. fumigatus demonstrated the best fitness represented by the fastest onset of its exponential growth when grown on an iron-limited mineral medium. The exponential phase and transitional production phase of the extracellular triacetylfusarinine C (TafC) were achieved at 24 and 31 h, respectively, contrary to VI strains, which acted more slowly. As a result, the TafC reservoir was consumed sooner in the VF strain. Additionally, the VF strain had lower ferricrocin and higher hydroxyferricrocin content in the pellet during the stationary phase. All of these differences were significant (Kruskal–Wallis, p 0.01). In our study, the siderophore reservoir of a VF strain was consumed sooner, improving the fitness of the VF strain in competition with P. aeruginosa.Peer reviewedFinal Published versio

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal splenic-placenta-fetal brain axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (IL-6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of IL-6 in Chrna7 mutant mice. We found that the basal level of IL-6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7+/− offspring. The Chrna7+/− offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after maternal infection

Micropatterned Cell–Cell Interactions Enable Functional Encapsulation of Primary Hepatocytes in Hydrogel Microtissues

Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental cues such as cell–cell interactions and cell–matrix interactions. In this work, we sought to incorporate phenotypically stable hepatocytes into three-dimensional (3D) microtissues, which, in turn, could be deployed in drug-screening platforms such as multiwell plates and diverse organ-on-a-chip devices. We first utilize micropatterning on collagen I to specify cell–cell interactions in two-dimensions, followed by collagenase digestion to produce well-controlled aggregates for 3D encapsulation in polyethylene glycol (PEG) diacrylate. Using this approach, we examined the influence of homotypic hepatocyte interactions and composition of the encapsulating hydrogel, and achieved the maintenance of liver-specific function for over 50 days. Optimally preaggregated structures were subsequently encapsulated using a microfluidic droplet-generator to produce 3D microtissues. Interactions of engineered hepatic microtissues with drugs was characterized by flow cytometry, and yielded both induction of P450 enzymes in response to prototypic small molecules and drug–drug interactions that give rise to hepatotoxicity. Collectively, this study establishes a pipeline for the manufacturing of 3D hepatic microtissues that exhibit stabilized liver-specific functions and can be incorporated into a wide array of emerging drug development platforms.National Institutes of Health (U.S.) (Grant UH2 EB017103)National Institutes of Health (U.S.) (Grant R01 EB008396)National Institutes of Health (U.S.) (Grant R01 DK85713)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)American Gastroenterological Association (Research Scholar Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship (1122374

Generation of degenerate, factorizable, pulsed squeezed light at telecom wavelengths

We characterize a periodically poled KTP crystal that produces an entangled, two-mode, squeezed state with orthogonal polarizations, nearly identical, factorizable frequency modes, and few photons in unwanted frequency modes. We focus the pump beam to create a nearly circular joint spectral probability distribution between the two modes. After disentangling the two modes, we observe Hong-Ou-Mandel interference with a raw (background corrected) visibility of 86 % (95 %) when an 8.6 nm bandwidth spectral filter is applied. We measure second order photon correlations of the entangled and disentangled squeezed states with both superconducting nanowire single-photon detectors and photon-number-resolving transition-edge sensors. Both methods agree and verify that the detected modes contain the desired photon number distributions

Vascular smooth muscle cell apoptosis in aneurysmal, occlusive, and normal human aortas

AbstractPurpose: Apoptosis is a physiologic mechanism of cell death that regulates mass and architecture in many tissues. Apoptosis has been described as a feature in human vascular atherosclerosis and large vessel structural integrity. We examined the extent of vascular smooth muscle cell (VSMC) apoptosis in aneurysmal, occlusive, and normal human aortic tissue. Methods: Tissue samples of aneurysmal, occlusive, and normal human infrarenal aorta were evaluated. DNA fragmentation detection methods, immunohistochemistry, and DNA electrophoresis determined VSMC density, VSMC apoptosis, and apoptosis markers. Apoptotic cells and VSMC nuclei were counted with the use of computer-generated image analysis. Aortic subtypes were compared statistically by analysis of variance. Results: Seventeen aneurysmal, ten occlusive, and five normal human aortas were evaluated. By α1-actin immunostaining, VSMC density was least in aneurysmal aortas (271.8 ± 13.5 cells/high-power field [HPF]) compared with occlusive aorta (278.2 ± 39.4 cells/HPF) and normal aortas (291.0 ± 25.4 cells/HPF; P = not significant). Presence of apoptotic VSMCs was demonstrated by terminal deoxynucleotidyl transferase fragment end labeling and propidium iodide nuclear staining. VSMC apoptosis was greatest within aneurysmal aortas with 11.7 ± 1.5 cells/HPF compared with occlusive aortas with 3.3 ± 0.8 cells/HPF (P <.05) and normal aortas with 3.75 ± 4.6 cells/HPF (P <.05). Significant differences in apoptosis markers, p53 or bcl-2, could not be demonstrated by immunohistochemistry or DNA electrophoresis in aortic subtypes. Conclusion: Apoptosis of VSMCs is increased and VSMC density is decreased within the medial layer of aneurysmal aortic tissue. Structural degeneration of aortic tissue at the cellular level contributes to aneurysmal formation. (J Vasc Surg 2000;31:567-576.