We previously reported a novel polymeric surface coating, namely, HaloFilm™ that can immobilize and extend the antimicrobial activity of chlorine on surfaces. In this study, we demonstrated the ...continuous antiviral efficacy of HaloFilm when applied on stainless steel and cotton gauze as two representative models for non‐porous and porous surfaces against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Forty‐eight hours post HaloFilm application and chlorination and 2 h post the viral challenge, the inoculum titre was reduced by 2.25 ± 0.33 and ≥4.36 ± 0.23 log10 TCID50 on non‐porous and porous surfaces, respectively. The half‐life of the virus was shorter (13.86 min) on a HaloFilm‐coated surface than what has been reported on copper (46.44 min).
Significance and Impact of Study: Chlorine is a widely used antimicrobial agent due to its broad spectrum and potent efficacy, low cost, abundancy, and history of safe use. This work describes a unique, non‐antimicrobial polymeric coating, Halofilm™, which, in conjunction with chlorine disinfectants, demonstrates extended activity against SARS‐CoV‐2 virus on a stainless steel and cotton gauze. Ease of application combined with the quick drying properties of HaloFilm solutions would enable its use in many standard cleaning and disinfection practices across a variety of institutional and home settings.
ABSTRACT
GW190425 is the second of two binary neutron star (BNS) merger events to be significantly detected by the Laser Interferometer Gravitational Wave (GW) Observatory (LIGO), Virgo and the ...Kamioka Gravitational Wave (KAGRA) detector network. With a detection only in LIGO Livingston, the skymap containing the source was large and no plausible electromagnetic counterpart was found in real-time searching in 2019. Here, we summarize Asteroid Terrestrial-Impact Last Alert System (ATLAS) and Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) wide-field optical coverage of the skymap beginning within 1 and 3 h, respectively, of the GW190425 merger time. More recently, a potential coincidence between GW190425 and a fast radio burst FRB 20190425A has been suggested, given their spatial and temporal coincidences. The smaller sky localization area of FRB 20190425A and its dispersion measure led to the identification of a likely host galaxy, UGC 10667 at a distance of 141 ± 10 Mpc. Our optical imaging covered the galaxy 6.0 h after GW190425 was detected and 3.5 h after the FRB 20190425A. No optical emission was detected and further imaging at +1.2 and +13.2 d also revealed no emission. If the FRB 20190425A and GW190425 association were real, we highlight our limits on kilonova emission from a BNS merger in UGC 10667. The model for producing FRB 20190425A from a BNS merger involves a supramassive magnetized neutron star spinning down by dipole emission on the time-scale of hours. We show that magnetar-enhanced kilonova emission is ruled out by optical upper limits. The lack of detected optical emission from a kilonova in UGC 10667 disfavours, but does not disprove, the FRB–GW link for this source.
Tumor cells aberrantly express chemokines and/or chemokine receptors, and some may promote tumor growth and metastasis. We examined the expression and function of chemokine receptor CXCR3 in a ...syngeneic murine model of metastatic breast cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell lines examined. All human breast cancer cell lines examined also expressed CXCR3, as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant murine mammary tumor cell line 66.1 resulted in intracellular calcium mobilization and chemotaxis in vitro. To test the hypothesis that tumor metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this antimetastatic activity was compromised in mice depleted of natural killer cells. Systemic administration of AMG487 also inhibited experimental lung metastasis. In contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary tumors was not affected by receptor antagonism. These studies indicate that murine mammary tumor cells express CXCR3 which facilitates the development of lung metastases. These studies also indicate for the first time that a small molecular weight antagonist of CXCR3 has the potential to inhibit tumor metastasis.
Chemical dispersants can be a useful tool to mitigate oil spills, but the potential risks to sensitive estuarine species should be carefully considered. To improve the decision making process, more ...information is needed regarding the effects of oil spill dispersants on the health of coastal ecosystems under variable environmental conditions such as salinity. The effects of salinity on the toxicity of two oil dispersants, Corexit® 9500 and Finasol® OSR 52, were examined in this study. Corexit® 9500 was the primary dispersant used during the 2010 Deepwater Horizon oil spill event, while Finasol® OSR 52 is another dispersant approved for oil spill response in the U.S., yet considerably less is known regarding its toxicity to estuarine species. The grass shrimp, Palaemonetes pugio, was used as a model estuarine species. It is a euryhaline species that tolerates salinities from brackish to full strength seawater. Adult and larval life stages were tested with each dispersant at three salinities, 5, 20, and 30 ppt. Median acute lethal toxicity thresholds and oxidative stress responses were determined. The toxicity of both dispersants was significantly influenced by salinity, with greatest toxicity observed at the lowest salinity tested. Larval shrimp were significantly more sensitive than adult shrimp to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Oxidative stress in adult shrimp, as measured by increased lipid peroxidation activity, occurred with exposure to both dispersants. These data will assist environmental managers in making informed decisions regarding dispersant use in future oil spills.
•oil dispersant toxicity may vary with abiotic conditions.•toxicity values for two oil dispersants determined at various salinities.•increasing salinity decreased dispersant toxicity in the grass shrimp, P. pugio.•larval P. pugio were more sensitive to dispersants than adult P. pugio.
Coccolithoviruses employ a suite of glycosphingolipids (GSLs) to successfully infect the globally important coccolithophore Emiliania huxleyi. Lipid rafts, chemically distinct membrane lipid ...microdomains that are enriched in GSLs and are involved in sensing extracellular stimuli and activating signalling cascades through protein–protein interactions, likely play a fundamental role in host–virus interactions. Using combined lipidomics, proteomics and bioinformatics, we isolated and characterized the lipid and protein content of lipid rafts from control E. huxleyi cells and those infected with EhV86, the type strain for Coccolithovirus. Lipid raft‐enriched fractions were isolated and purified as buoyant, detergent‐resistant membranes (DRMs) in OptiPrep density gradients. Transmission electron microscopy of vesicle morphology, polymerase chain reaction amplification of the EhV major capsid protein gene and immunoreactivity to flotillin antisera served as respective physical, molecular and biochemical markers. Subsequent lipid characterization of DRMs via high performance liquid chromatography‐triple quadrapole mass spectrometry revealed four distinct GSL classes. Parallel proteomic analysis confirmed flotillin as a major lipid raft protein, along with a variety of proteins affiliated with host defence, programmed cell death and innate immunity pathways. The detection of an EhV86‐encoded C‐type lectin‐containing protein confirmed that infection occurs at the interface between lipid rafts and cellular stress/death pathways via specific GSLs and raft‐associated proteins.
Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) are indicators of a poor prognosis in breast cancer. Using several independent publicly available breast cancer gene expression ...databases, we investigated other members of the PGE2 pathway. PGE2 is produced by COX-2 and actively exported by multiple drug resistance-associated protein 4 (MRP4) into the extracellular microenvironment, where PGE2 can bind four cognate EP receptors (EP1–EP4) and initiate diverse biological signaling pathways. Alternatively, PGE2 is imported via the prostaglandin transporter (PGT) and metabolized by 15-prostaglandin dehydrogenase (15-PGDH/HPGD). We made the novel observation that MRP4, PGT, and 15-PGDH are differentially expressed among distinct breast cancer molecular subtypes; this finding was confirmed in independent datasets. In triple-negative breast cancer, the observed gene expression pattern (high COX-2, high MRP4, low PGT, and low 15-PGDH) would favor high levels of tumor-promoting PGE2 in the tumor microenvironment that may contribute to the overall poor prognosis of triple-negative breast cancer.
To determine which type of egg-laying hen housing was best for the chickens, the workers in those housing systems, the environment, and society based on food safety and affordability, a combined ...research project involving egg suppliers, food manufacturers, food service representatives, and food retailers, as well as research institutions and nongovernmental organizations, was performed. This study reports the hen health and welfare portion based upon veterinary health inspections and compared mortality rates, skeletal abnormalities, causes of death determined by necropsy, and titers to infectious bronchitis and Newcastle disease viruses. Birds were housed on a preexisting Midwest layer complex, which consisted of conventional cages (CC). New houses were built adjacent to the CC house where enriched colony cages (EC) and an aviary system (AV) were installed. Two flock cycles from housing to 78 wk of age were followed. Total mortality was greatest for AV, while CC and EC birds were similar. Keel bone fractures were greatest for AV, next greatest for EC, and least for CC birds. Other skeletal abnormalities were greatest for AV birds. Birds dying from being caught in the structure, pick out, and persecution was most frequent for AV and next most frequent for EC, but nonexistent with CC birds. Infectious pododermatitis (bumblefoot) was most frequent for AV, next most frequent for EC, and essentially nonexistent for CC birds. There was little to no effect on antibody titers based upon housing type. Based upon these findings, it appears that EC housing is better for the health and welfare of egg-laying chickens than CC or AV housing.
Purpose. Previous studies have demonstrated an association between melatonin status and both refractive error and axial length in young adult myopes. This study aimed to determine if this ...relationship extends to a younger adolescent cohort. Methods. Healthy children aged 12–15 years provided morning saliva samples before attending Ulster University (55°N) for cycloplegic autorefraction and axial length measures. Participants completed questionnaires describing recent sleep habits and physical activity. Salivary melatonin was quantified using high-performance liquid chromatography-tandem mass spectrometry. Data collection for all participants occurred over a 1-week period (April 2021). Results. Seventy participants aged 14.3 (95% CI: 14.2—14.5) years were categorised by spherical equivalent refraction SER (range: −5.38DS to +1.88DS) into two groups; myopic SER ≤ −0.50DS (n = 22) or nonmyopic −0.50DS < SER ≤ +2.00DS (n = 48). Median morning salivary melatonin levels were 4.52 pg/ml (95% CI: 2.60–6.02) and 4.89 pg/ml (95% CI: 3.18–5.66) for myopic and nonmyopic subjects, respectively, and did not differ significantly between refractive groups (P = 0.91). Melatonin levels were not significantly correlated with SER, axial length, sleep, or activity scores (Spearman’s rank, all P > 0.39). Higher levels of physical activity were associated with higher sleep quality (Spearman’s rank, ρ = −0.28, P = 0.02). Conclusion. The present study found no significant relationship between morning salivary melatonin levels and refractive error or axial length in young adolescents. This contrasts with outcomes from a previous study of adults with comparable methodology, season of data collection, and geographical location. Prospective studies are needed to understand the discrepancies between adult and childhood findings and evaluate whether melatonin levels in childhood are indicative of an increased risk for future onset of myopia and/or faster axial growth trajectories and myopia progression in established myopes. Future work should opt for a comprehensive dim-light melatonin onset protocol to determine circadian phase.
Lentiviral vectors (LVs) are a powerful tool for gene and cell therapy and human embryonic kidney cells (HEK293) have been extensively used as a platform for production of these vectors. Like most ...cells and cellular tissues, HEK293 cells release extracellular vesicles (EVs). EVs released by cells share similar size, biophysical characteristics and even a biogenesis pathway with cell-produced enveloped viruses, making it a challenge to efficiently separate EVs from LVs. Thus, EVs co-purified with LVs during downstream processing, are considered "impurities" in the context of gene and cell therapy. A greater understanding of EVs co-purifying with LVs is needed to enable improved downstream processing. To that end, EVs from an inducible lentivirus producing cell line were studied under two conditions: non-induced and induced. EVs were identified in both conditions, with their presence confirmed by transmission electron microscopy and Western blot. EV cargos from each condition were then further characterized by a multi-omic approach. Nineteen proteins were identified by mass spectrometry as potential EV markers to differentiate EVs in LV preparations. Lipid composition of EV preparations before and after LV induction showed similar enrichment in phosphatidylserine. RNA cargos in EVs showed enrichment in transcripts involved in viral processes and binding functions. These findings provide insights on the product profile of lentiviral preparations and could support the development of improved separation strategies aimed at removing co-produced EVs.
Annual Emiliania huxleyi blooms (along with other coccolithophorid species) play important roles in the global carbon and sulfur cycles. E. huxleyi blooms are routinely terminated by large, ...host-specific dsDNA viruses, (Emiliania huxleyi Viruses; EhVs), making these host-virus interactions a driving force behind their potential impact on global biogeochemical cycles. Given projected increases in sea surface temperature due to climate change, it is imperative to understand the effects of temperature on E. huxleyi's susceptibility to viral infection and its production of climatically active dimethylated sulfur species (DSS). Here we demonstrate that a 3°C increase in temperature induces EhV-resistant phenotypes in three E. huxleyi strains and that successful virus infection impacts DSS pool sizes. We also examined cellular polar lipids, given their documented roles in regulating host-virus interactions in this system, and propose that alterations to membrane-bound surface receptors are responsible for the observed temperature-induced resistance. Our findings have potential implications for global biogeochemical cycles in a warming climate and for deciphering the particular mechanism(s) by which some E. huxleyi strains exhibit viral resistance.
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