Role of human metapneumovirus and respiratory syncytial virus in asthma exacerbations: where are we now?

Since its discovery in 2001, human metapneumovirus (hMPV) has been identified as an important cause of respiratory tract infection in young children, second only to the closely related respiratory syncytial virus (RSV). Clinical evidence suggests that hMPV is associated with acute exacerbations of asthma in both children and adults, and may play a role in initiating asthma development in children. Animal models have demonstrated that airway hyperresponsiveness (AHR) and inflammation are triggered following hMPV infection, and hMPV is able to persist in vivo by inhibiting innate immune responses and causing aberrant adaptive responses. In this review, we discuss the prevalence of hMPV infection in pediatric and adult populations and its potential role in asthma exacerbation. We also review recent advances made in animal models to determine immune responses following hMPV infection, and compare to what is known about RSV.

Dissecting the cis and trans elements that regulate adjacent-gene coregulation in Saccharomyces cerevisiae.

The relative positions that genes occupy on their respective chromosomes can play a critical role in determining how they are regulated at the transcriptional level. For example, a significant fraction of the genes from a variety of coregulated gene sets, including the ribosomal protein (RP) and the rRNA and ribosome biogenesis (RRB) regulons, exist as immediate, adjacent gene pairs. These gene pairs occur in all possible divergent, tandem, and convergent orientations. Adjacent-gene pairing in these regulons is associated with a tighter transcriptional coregulation than is observed for nonpaired genes of the same regulons. In order to define the cis and trans factors that regulate adjacent-gene coregulation (AGC), we conducted a mutational analysis of the convergently oriented RRB gene pair MPP10-YJR003C. We observed that coupled corepression of the gene pair under heat shock was abrogated when the two genes were separated by an actively expressed RNA polymerase (Pol) II transcription unit (the LEU2 gene) but not when the inserted LEU2 gene was repressed. In contrast, the insertion of an RNA Pol III-transcribed tRNA (Thr) gene did not disrupt the coregulated repression of MPP10 and YJR003C. A targeted screen of mutants defective in regulating chromosome architecture revealed that the Spt20, Snf2, and Chd1 proteins were required for coupling the repression of YJR003C to that of MPP10. Nucleosome occupancy assays performed across the MPP10 and YJR003C promoter regions revealed that the mechanism of corepression of the gene pair was not related to the repositioning of nucleosomes across the respective gene promoters.

Sample Processing and Concentration Methods for Viruses from Foods and the Environment Prior to Detection.

Viruses are the leading cause of foodborne illness globally. Concentration of viruses from samples is important for detection because viral contamination of foods often occurs at low levels. In general, virus concentration methods can be classified as either nonspecific, exploiting the relatively homogeneous physicochemical properties of the virus to separate/concentrate it from the sample matrix, or specific, relying on recognition elements such as antibodies to specifically capture and separate viruses from foods. Numerous nonspecific and specific techniques for virus concentration have been reported, each with its own advantages and limitations. Factors to consider can include reagent and equipment costs, time-to-result, ease of use, and potential to eliminate matrix-associated inhibitors. The purpose of this review is to survey the different foodborne virus concentration techniques and their efficacy in various food and environmental matrices as well as discuss some emerging techniques for purification and concentration of viral pathogens from food samples.

Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells.

Introduction: Diet-induced obesity has been shown to decrease the abundance of Turicibacter, a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of Turicibacter potentially influential in the protection of intestinal tumorigenesis. Recently, Antrodia camphorata (AC), a medicinal fungus native to Taiwan, has emerged as a promising candidate for complementary and alternative cancer therapy. Small molecules and polysaccharides derived from AC have been reported to possess health-promoting effects, including anti-cancer properties. Methods: Bacterial culture followed with cell culture were used in this study to determine the role of Turicibacter in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with Turicibacter fermentation. Results: Turicibacter fermentation and the addition of AC polysaccharide led to a significant increase in the production of nutrients and metabolites, including α-ketoglutaric acid and lactic acid (p < 0.05). Treatment of Turicibacter fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including Tph1, Htr1d, Htr2a, Htr2b, and Htr2c (p < 0.05), and Wnt-signaling related protein and downstream gene expressions, such as phospho-GSK-3ß, active ß-catenin, c-Myc, Ccnd1, and Axin2 (p < 0.05). Additionally, it triggered the highest generation of reactive oxygen species (ROS), which activated PI3K/Akt and MAPK/Erk signaling and resulted in cleaved caspase-3 expression. In comparison, the treatment of AC polysaccharide without Turicibacter fermentation displayed a lesser effect. Discussion: Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and Wnt-signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by Turicibacter fermentation.

Assessment of SARS-CoV-2 surrogate inactivation on surfaces and in air using UV and blue light-based intervention technologies.

The COVID-19 pandemic has created an urgent need to utilize existing and develop new intervention technologies for SARS-CoV-2 inactivation on surfaces and in the air. Ultraviolet (UV) technology has been shown to be an effective antimicrobial intervention. Here a study was conducted to determine the efficacy of commercially available UV and blue light-based devices for inactivating HCoV-229E, a surrogate of SARS-CoV-2. The results indicate that two UV devices designed for surface disinfection, with doses of 8.07 µJ/cm2 for the 254 nm device and 20.61 µJ/cm2 for the 275 nm device, were efficient in inactivating 4.94 logs of surface inoculated HCoV-229E. Additionally, a 222 nm UV device with intended ceiling-based operation was effective in inactivating 1.7 logs of the virus inoculated on surface, with a dose of 6 mJ/cm2. A ceiling-based device designed to emit blue light at 405 nm was found to produce 89% reduction in HCoV-229E inoculated on a surface for a dose of 78 J/cm2. Finally, the UV based 222 nm device was found to produce a 90% reduction in the concentration of airborne HCoV-229E, at a 55 µJ/cm2 dose. These results are indicative of the great potential of using UV based technology for the control of SARS-CoV-2.Implications: An important avenue of arresting COVID-19 and future pandemics caused by infectious pathogens is through environmental disinfection. To this effect, the study presented here evaluates commercially available UV and blue light based antimicrobial devices for their ability to kill the human coronavirus HCoV-229E, a surrogate of SARS-CoV-2, on surfaces and in air. The results indicate that two handheld UV devices produced complete inactivation of surface viral inoculum and a UVC ceiling based device produced 1 log reduction in HCoV-229E in air. These results imply the efficacy of UV technology as an antimicrobial tool, especially for rapid disinfection of indoor air.

Inactivating SARS-CoV-2 Surrogates on Surfaces Using Engineered Water Nanostructures Incorporated with Nature Derived Antimicrobials.

The continuing cases of COVID-19 due to emerging strains of the SARS-CoV-2 virus underscore the urgent need to develop effective antiviral technologies. A crucial aspect of reducing transmission of the virus is through environmental disinfection. To this end, a nanotechnology-based antimicrobial platform utilizing engineered water nanostructures (EWNS) was utilized to challenge the human coronavirus 229E (HCoV-229E), a surrogate of SARS-CoV-2, on surfaces. The EWNS were synthesized using electrospray and ionization of aqueous solutions of antimicrobials, had a size in the nanoscale, and contained both antimicrobial agents and reactive oxygen species (ROS). Various EWNS were synthesized using single active ingredients (AI) as well as their combinations. The results of EWNS treatment indicate that EWNS produced with a cocktail of hydrogen peroxide, citric acid, lysozyme, nisin, and triethylene glycol was able to inactivate 3.8 logs of HCoV-229E, in 30 s of treatment. The delivered dose of antimicrobials to the surface was measured to be in pico to nanograms. These results indicate the efficacy of EWNS technology as a nano-carrier for delivering a minuscule dose while inactivating HCoV-229E, making this an attractive technology against SARS-CoV-2.

Failure to Detect SARS-CoV-2 RNA in the Air During Active Labor in Mothers Who Recently Tested Positive.

The risk of potential SARS-CoV-2 transmission by infected mothers during labor and delivery has not been investigated in-depth. This work collected air samples close to (respiratory droplets) and more distant from (aerosol generation) unvaccinated patients who had previously tested positive for SARS-CoV-2 during labor within 5 days of a positive test. All but one of the patients wore masks during the delivery, and delivery was carried out in either birthing or negative pressure isolation rooms. Our work failed to detect SARS-CoV-2 RNA in any air samples for all of the six patients who gave birth vaginally, despite validation of the limit of detection of the samplers. In sum, this brief report provides initial evidence that the risk of airborne transmission of SARS-CoV-2 during labor may be mitigated by the use of masks and high ventilation rates common in many modern U.S. medical facilities; however more work is needed to fully evaluate the risk of SARS-CoV-2 transmission during labor and maternal pushing.

Geldanamycin-inspired compounds induce direct trans-differentiation of human mesenchymal stem cells to neurons.

Inspired from geldanamycin, the synthesis of a new series of 20-membered macrocyclic compounds is developed. The key features in our design are (i) retention of the fragment having the precise chiral functional groups of geldanamycin at C10, C11, C12 and C14, and (ii) replacement of an olefin moiety with the ester group, and the quinoid sub-structure with the triazole ring. The southern fragment needed for the macrocyclic ring formation was obtained from Evans' syn aldol as the key reaction and with the use of D-mannitol as the cheap source of a chiral starting material. For the synthesis of the northern fragment, we utilized l-ascorbic acid, which provided the desired chiral functional groups at C6 and C7. Further, the chain extension completed the synthesis of the northern fragment. In our approach, the crucial 20 membered macrocyclic ring was formed employing the click chemistry. When tested for their ability to directly trans-differentiate human mesenchymal stem cells to neurons, two novel compounds (20a and 7) from this series were identified and this was further validated by the presence of specific neuronal biomarkers (i.e. nestin, agrin and RTN4).