Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19

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Decrease of the hydraulic conductivity of sand columns by Methanosarcina barkeri

The extent to which a methanogen can clog sand columns was examined: two permeameters packed with clean quartz sand were sterilized, saturated with water, inoculated with Methanosarcina barkeri and percolated under upward flow conditions. After approx. 5 months, the hydraulic conductivity of the sand had decreased to 3% and 25% of the highest values measured earlier. At that point, gas-filled regions in the sand were clearly visible through the transparent walls of the permeameters, and methane bubbles were continuously released from the columns into the effluent. Scanning electron microscopy observations and biomass assays indicated that cell mass accumulation did not contribute significantly to the observed decrease of the hydraulic conductivity. This decrease was therefore attributed to pore blocking due to the entrapment of methane bubbles.D. Sanchez de Lozada and P. Baveye are with the Department of Soil, Crop and Atmospheric Sciences, Bradfield Hall, Cornell University, Ithaca, NY 13853, USA; P. Vandevivere is with the College of Marine Studies, University of Delaware, Lewes, DE 19958, USA. S. Zinder is with the Department of Microbiology, Rice Hall, Cornell University, Ithaca, NY 14853, USA.     

Advertising individual identity by mother and adolescent contact calls in Siberian wapiti Cervus elaphus sibiricus

Individualistic contact calls facilitate mother‐offspring reunion after separation. However, in many mammals, both the acoustic structure and individuality of contact calls differ between mother and young. In contrast, in Siberian wapiti Cervus elaphus sibiricus, contact calls are similar in the acoustics between mother and young, whereas effects of this similarity on vocal individuality were not investigated. In this study, we analyzed acoustic differences between closed‐mouth (nasal) and open‐mouth (oral) contact calls and examined individuality of the most usual oral calls of 19 Siberian wapiti (9 hinds and 10 5–6‐month adolescents) emitted in response to mother‐offspring separation. In the oral calls, the values of frequency and power variables were higher than in the nasal calls. Calls of hinds and adolescents did not differ by the maximum fundamental frequency and duration, whereas the peak frequency was higher in the young. Discriminant function analysis (DFA) based on 11 acoustic variables of oral calls accurately classified to individual 92.5% of hind calls and 96.9% of adolescent calls (chi‐square test for differences between hinds and adolescents, p = 0.19). Variables mainly contributing to vocal identity (duration, start, and maximum fundamental frequency) were the same in calls of mothers and adolescents. We conclude that similarities in the acoustics calls of mothers and adolescents mean that they do not differ in their potential for encoding individual identity, suggesting a mutual process of mother‐offspring vocal recognition in Siberian wapiti.     

Metabolism-dependent activation and toxicity of chemicals in nasal glands

The mucosae of the nasal passages contain a large amount of glands which express secretory proteins as well as phase I and phase II biotransformation enzymes. In this review the metabolic activation, covalent binding and toxicity of chemicals in the Bowman's glands in the olfactory mucosa, in the sero-mucous glands in the nasal septum and in the lateral nasal glands and maxillary glands around the maxillary sinuses are discussed. Light microscopic autoradiographic studies have demonstrated a selective covalent binding of nasal toxicants and carcinogens such as halogenated hydrocarbons and N-nitrosamines, especially in the Bowman's glands following a single systemic exposure, suggesting a high rate of metabolic activation of chemicals in these glands. Special attention is put on the herbicide dichlobenil which induces necrosis in the olfactory mucosa following a cytochrome-P450-mediated metabolic activation and covalent binding in the Bowman's glands.     

Staphylococcus aureus adherence to nasal epithelial cells in a physiological in vitro model

Summary Nasal carriage of Staphylococcus aureus represents a risk factor for subsequent invasive infections and interpatient transmission of strains. No physiological in vitro model of nasal epithelial cells is available to study both patient- and bacteria-related characteristics and their interaction, leading to adherence and colonization. Starting with tissues from human nasal polyps, a confluent, squamous, nonkeratinized epithelium in collagen-coated 96-well microtiter plates was obtained after 14 d. This in vitro cell-layer was characterized histologically, ultrastructurally, and immunohistochemically and showed features that were indistinguishable from those observed in the squamous nonkeratinized epithelium found in the posterior part of the vestibulum nasi. Adherence experiments were performed with four different ³H-thymidine-labeled Staphylococcus aureus strains. The effect of bacterial inoculum size, temperature of incubation, and incubation medium were studied. The adherence results were found to be reproducible, reliable and sensitive, allowing detection of small quantitative differences in adherence between the Staphylococcus aureus strains. There was no significant difference in adherence at 23° C and 37° C, nor between the incubation medium M199 and phosphate-buffered saline. Plastic adherence could be reduced and standardized with use of siliconized tips and a constant bacterial inoculum volume of 100 μl/well. This physiological and reliable in vitro cell-culture model offers a unique opportunity to study Staphylococcus aureus adherence to squamous, nonkeratinized nasal epithelial cells and both patient and bacterial characteristics involved in this interaction.     

Blocking gap junctional intercellular communication in myoblasts inhibits myogenin and MRF4 expression

Cells rely heavily on cues from their extracellular environment and other cells to coordinate normal physiological processes, and the exchange of molecules via gap junctions has been suggested as an important avenue for cell-cell communication. Gap junctions are found in virtually all mammalian tissues with the notable exception of adult skeletal muscle. However, since functional gap junctions have been detected during the early stages of muscle development, gap junctional intercellular communication (GJIC) may play an important role in myogenesis. In this study, GJIC in normal L6 myoblasts was inhibited using the known blockers 1-octanal and β-glycyrrhetinic acid (β-GA). Under differentiation promoting conditions, L6 cells fused to form multinucleated myotubes, but when treated with either octanol or β-GA, no fusion was observed. The expression of two muscle regulatory factors (MRFs), myogenin and MRF4, was examined in both the blocked and control cells. As expected, the activation of both the myogenin and MRF4 genes coincided with the onset of differentiation in the control L6 cells. Neither of these genes were turned on in the blocked cells, even when grown under low serum conditions. This inhibition of differentiation by octanol and β-GA was reversible, since the activation of both MRF genes as well as myoblast fusion were observed when the blocking medium was replaced with normal differentiating medium. These results suggest that intercellular communication via gap junctions plays an important role in skeletal muscle development and perhaps in the cell signaling events that trigger the activation of muscle-specific MRF genes. Dev. Genet. 20:133–144. 1997. © 1997 Wiley-Liss, Inc.     

GSK‐3β activation index is a potential indicator for recurrent inflammation of chronic rhinosinusitis without nasal polyps

Chronic rhinosinusitis without nasal polyps (CRSsNP) is one of the most common otorhinolaryngologic diseases worldwide. However, the underlying mechanism remains unclear. In this study, the expression of glycogen synthase kinase 3 (GSK‐3) was quantitatively evaluated in patients with CRSsNP (n = 20) and healthy controls (n = 20). The mRNA levels of GSK‐3α and GSK‐3β were examined by qPCR, the immunoreactivities of GSK‐3β and nuclear factor‐κB (NF‐κB) were examined by immunohistochemistry (IHC) staining, and the protein levels of GSK‐3β, phospho‐GSK‐3β (p‐GSK‐3β, s9) and NF‐κB were examined using Western blot analysis. We found that GSK‐3 was highly expressed in both CRSsNP and control groups without significant difference in both GSK‐3β mRNA and protein levels. However, when compared with healthy control group, the GSK‐3β activation index, defined as the ratio of GSK‐3β over p‐GSK‐3β, was significantly decreased, whereas the NF‐κB protein abundance was significantly increased in CRSsNP group (P < 0.05). Strikingly, the GSK‐3β activation index, was highly correlated with NF‐κB protein level, as well as CT scores in CRSsNP group (P < 0.05). It was also highly correlated with the mRNA expressions of inflammation‐related genes, including T‐bet, IFN‐γ and IL‐4 in CRSsNP group (P < 0.05). Our findings suggest that GSK‐3β activation index, reflecting the inhibitory levels of GSK‐3β through phosphorylation, may be a potential indicator for recurrent inflammation of CRSsNP, and that the insufficient inhibitory phosphorylation of GSK‐3β may play a pivotal role in the pathogenesis of CRSsNP.     

Nasal administration of Lactococcus lactis improves local and systemic immune responses against Streptococcus pneumoniae

Lactococcus lactis NZ9000 is a non-pathogenic non-invasive bacterium extensively used for the delivery of antigens and cytokines at the mucosal level. However, there are no reports concerning the per se immunomodulatory capacity of this strain. The aim of the present study was to investigate the intrinsic immunostimulating properties of the nasal administration of L. lactis NZ9000 in a pneumococcal infection model. Mice were preventively treated with L. lactis (2, 5 or 7 days with 10(8) cells/day per mouse) and then challenged with Streptococcus pneumoniae. The local and the systemic immune responses were evaluated. Our results showed that nasal administration of L. lactis for 5 days (LLN5d) increased the clearance rate of S. pneumoniae from lung and prevented the dissemination of pneumococci into blood. This effect coincided with an upregulation of the innate and specific immune responses in both local and systemic compartments. LLN5d increased phagocyte activation in lung, blood and bone marrow, determined by NBT and peroxidase tests. Anti-pneumococcal immunoglobulin (Ig)A in bronchoalveolar lavages (BAL) and IgG in BAL and serum were increased in the LLN5d group. Lung tissue injury was reduced by LLN5d treatment as revealed by histopathological examination and albumin concentration and lactate dehydrogenase activity in BAL. The adjuvant effect of L. lactis in our infection model would be an important advantage for its use as a delivery vehicle of pneumococcal proteins and nasal immunization with recombinant L. lactis emerges as an effective route of vaccination for both systemic and mucosal immunity against pneumococcal infection.