Search

Background: The commercialization of space travel will soon lead to many more people living and working in unique built environments similar to the International Space Station, which is a specialized closed environment that contains its own indoor microbiome. Unintended microbial growth can occur in these environments as in buildings on Earth from elevated moisture, such as from a temporary ventilation system failure. This growth can drive negative health outcomes and degrade building materials. We need a predictive approach for modeling microbial growth in these critical indoor spaces., Results: Here, we demonstrate that even short exposures to varying elevated relative humidity can facilitate rapid microbial growth and microbial community composition changes in dust from spacecraft. We modeled fungal growth in dust from the International Space Station using the time-of-wetness framework with activation and deactivation limited growth occurring at 85% and 100% relative humidity, respectively. Fungal concentrations ranged from an average of 4.4 × 10 6 spore equivalents per milligram of dust in original dust with no exposure to relative humidity to up to 2.1 × 10 10 when exposed to 100% relative humidity for 2 weeks. As relative humidity and time-elevated increased, fungal diversity was significantly reduced for both alpha (Q < 0.05) and beta (R 2  = 0.307, P = 0.001) diversity metrics. Bacteria were unable to be modeled using the time-of-wetness framework. However, bacterial communities did change based on constant relative humidity incubations for both beta (R 2  = 0.22, P = 0.001) and alpha diversity decreasing with increasing moisture starting at 85% relative humidity (Q < 0.05)., Conclusion: Our results demonstrate that moisture conditions can be used to develop and predict changes in fungal growth and composition onboard human-occupied spacecraft. This predictive model can be expanded upon to include other spacecraft environmental factors such as microgravity, elevated carbon dioxide conditions, and radiation exposure. Understanding microbial growth in spacecraft can help better protect astronaut health, fortify spacecraft integrity, and promote planetary protection as human activity increases in low-Earth orbit, the moon, Mars, and beyond. Video Abstract., (© 2024. The Author(s).)

Human occupied built environments are no longer confined to Earth. In fact, there have been humans living and working in low-Earth orbit on the International Space Station (ISS) since November 2000. With NASA's Artemis missions and the age of commercial space stations set to begin, more human-occupied spacecraft than ever will be in Earth's orbit and beyond. On Earth and in the ISS, microbes, especially fungi, can be found in dust and grow when unexpected, elevated moisture conditions occur. However, we do not yet know how indoor microbiomes in Earth-based homes and in the ISS differ due to their unique set of environmental conditions. Here we show that bacterial and fungal communities are different in dust collected from vacuum bags on Earth and the ISS, with Earth-based homes being more diverse (465 fungal OTUs and 237 bacterial ASVs) compared to the ISS (102 fungal OTUs and 102 bacterial ASVs). When dust from these locations were exposed to varying equilibrium relative humidity conditions (ERH), there were also significant fungal community composition changes as ERH and time elevated increased (Bray Curtis: R 2  = 0.35, P = 0.001). These findings can inform future spacecraft design to promote healthy indoor microbiomes that support crew health, spacecraft integrity, and planetary protection., (© 2024. The Author(s).)

Environmental surveillance of pathogens underlying infectious disease is critical to ensure public health. Recent efforts to track SARS-CoV-2 have utilized wastewater sampling to infer community trends in viral abundance and variant composition. Indoor dust has also been used for building-level inferences, though to date no sequencing data providing variant-scale resolution have been reported from dust samples, and strategies to monitor circulating variants in dust are needed to help inform public health decisions. In this study, we demonstrate that SARS-CoV-2 lineages can be detected and sequenced from indoor bulk dust samples. We collected 93 vacuum bags from April 2021 to March 2022 from buildings on The Ohio State University's (OSU) Columbus campus, and the dust was used to develop and apply an amplicon-based whole-genome sequencing protocol to identify the variants present and estimate their relative abundances. Three variants of concern were detected in the dust: Alpha, Delta, and Omicron. Alpha was found in our earliest sample in April 2021 with an estimated frequency of 100%. Delta was the primary variant present from October of 2021 to January 2022, with an average estimated frequency of 91% (±1.3%). Omicron became the primary variant in January 2022 and was the dominant strain in circulation through March with an estimated frequency of 87% (±3.2%). The detection of these variants on OSU's campus correlates with the circulation of these variants in the surrounding population (Delta p<0.0001 and Omicron p = 0.02). Overall, these results support the hypothesis that dust can be used to track COVID-19 variants in buildings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Van Dusen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Osteosarcoma (OS) is the most common primary malignancy of the bone, highly aggressive and metastasizing, and it mainly affects children and adolescents. The current standard of care for OS is a combination of surgery and chemotherapy. However, these treatment options are not always successful, especially in cases of metastatic or recurrent osteosarcomas. For this reason, research into new therapeutic strategies is currently underway, and immunotherapies have received considerable attention. Mifamurtide stands out among the most studied immunostimulant drugs; nevertheless, there are very conflicting opinions on its therapeutic efficacy. Here, we aimed to investigate mifamurtide efficacy through in vitro and in vivo experiments. Our results led us to identify a new possible target useful to improve mifamurtide effectiveness on metastatic OS: the cytokine interleukin-10 (IL-10). We provide experimental evidence that the synergic use of an anti-IL-10 antibody in combination with mifamurtide causes a significantly increased mortality rate in highest-grade OS cells and lower metastasis in an in vivo model compared with mifamurtide alone. Overall, our data suggest that mifamurtide in combination with an anti-IL-10 antibody could be proposed as a new treatment protocol to be studied to improve the outcomes of OS patients.

Neuroblastoma (NB) is a heterogeneous extracranial tumor occurring in childhood. A distinctive feature of NB tumors is their neuroendocrine ability to secrete catecholamines, which in turn, via β-adrenergic receptors ligation, may affect different signaling pathways in tumor microenvironment (TME). It was previously demonstrated that specific antagonism of β3-adrenergic receptor (β3-AR) on NB tumor cells affected tumor growth and progression. Here, in a murine syngeneic model of NB, we aimed to investigate whether the β3-AR modulation influenced the host immune system response against tumor. Results demonstrated that β3-AR antagonism lead to an immune response reactivation, partially dependent on the PD-1/PD-L1 signaling axis involvement. Indeed, β3-AR blockade on tumor-infiltrating lymphocytes (TILs) dampened their ability to secrete IFN-γ, which in turn reduced the PD-L1 expression, caused by TILs infiltration, on NB tumor cells. Further investigations, through a genomic analysis on NB patients, showed that high ADRB3 gene expression correlates with worse clinical outcome compared to the low expression group, and that ADRB3 gene expression affects different immune-related pathways. Overall, results indicate that β3-AR in NB TME is able to modulate the interaction between tumor and host immune system, and that its antagonism hits multiple pro-tumoral signaling pathways., (© 2023. The Author(s).)

β3-adrenergic receptor (β3-AR) is the last β-adrenoceptor subtype identified. β3-AR is widely expressed and regulates numerous physiological processes, and it is also a potential target for the treatment of many diseases, including cancers. For some types of cancers, bone marrow transplant (BMT) represents a valid therapeutic support, especially in the case of the necessity of high-dose chemotherapy and radiotherapy. For a successful BMT, it is necessary that a donor's hematopoietic stem cells (HSCs) correctly reach the staminal niche in the recipient's bone marrow (BM) and contribute to restore normal hematopoiesis in order to rapidly repopulate BM and provide all the healthy blood cells of which the patient needs. Generally, it takes a long time. Control and accelerate homing and engraftment of HSCs could represent a helpful approach to avoid the complications and undesirable effects of BMT. The evidence that the β-adrenergic system has a role in the BM can be found in different studies, and this leads us to hypothesize that studying this field could be interesting to meliorate the most critical aspects of a BMT. Here, we collected the data present in literature about the role of β3-AR in the BM with the purpose of discovering a possible utility of β3-AR modulation in regulating HSC trafficking and hematopoiesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nastasi, Bruno, Favre and Calvani.)

Resuspension of dust from flooring is a major source of human exposure to microbial contaminants, but the persistence of viruses on dust and carpet and the contribution to human exposure are often unknown. The goal of this work is to determine viability of MS2 and Phi6 bacteriophages on cut carpet, looped carpet, and house dust both over time and after cleaning. Bacteriophages were nebulized onto carpet or dust in artificial saliva. Viability was measured at 0, 1, 2, 3, 4, 24, and 48 h and after cleaning by vacuum, steam, hot water extraction, and disinfection. MS2 bacteriophages showed slower viability decay rates in dust (-0.11 hr -1 ), cut carpet (-0.20 hr -1 ), and looped carpet (-0.09 hr -1 ) compared to Phi6 (-3.36 hr -1 , -1.57 hr -1 , and -0.20 hr -1 , respectively). Viable viral concentrations were reduced to below the detection limit for steam and disinfection for both MS2 and Phi6 (p < 0.05), while vacuuming and hot water extraction showed no significant changes in concentration from uncleaned carpet (p > 0.05). These results demonstrate that MS2 and Phi6 bacteriophages can remain viable in carpet and dust for several hours to days, and cleaning with heat and disinfectants may be more effective than standard vacuuming., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ongoing disease surveillance is a critical tool to mitigate viral outbreaks, especially during a pandemic. Environmental monitoring has significant promise even following widespread vaccination among high-risk populations. The goal of this work is to demonstrate molecular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monitoring in bulk floor dust and related samples as a proof of concept of a noninvasive environmental surveillance methodology for coronavirus disease 2019 (COVID-19) and potentially other viral diseases. Surface swab, passive sampler, and bulk floor dust samples were collected from the rooms of individuals positive for COVID-19, and SARS-CoV-2 was measured with quantitative reverse transcription-PCR (RT-qPCR) and two digital PCR (dPCR) methods. Bulk dust samples had a geometric mean concentration of 163 copies/mg of dust and ranged from nondetects to 23,049 copies/mg of dust detected using droplet digital PCR (ddPCR). An average of 89% of bulk dust samples were positive for the virus by the detection methods compared to 55% of surface swabs and fewer on the passive sampler (19% carpet, 29% polystyrene). In bulk dust, SARS-CoV-2 was detected in 76%, 93%, and 97% of samples measured by qPCR, chip-based dPCR, and droplet dPCR, respectively. Detectable viral RNA in the bulk vacuum bags did not measurably decay over 4 weeks, despite the application of a disinfectant before room cleaning. Future monitoring efforts should further evaluate RNA persistence and heterogeneity in dust. This study did not measure virus infectivity in dust or potential transmission associated with dust. Overall, this work demonstrates that bulk floor dust is a potentially useful matrix for long-term monitoring of viral disease in high-risk populations and buildings. IMPORTANCE Environmental surveillance to assess pathogen presence within a community is proving to be a critical tool to protect public health, and it is especially relevant during the ongoing COVID-19 pandemic. Importantly, environmental surveillance tools also allow for the detection of asymptomatic disease carriers and for routine monitoring of a large number of people as has been shown for SARS-CoV-2 wastewater monitoring. However, additional monitoring techniques are needed to screen for outbreaks in high-risk settings such as congregate care facilities. Here, we demonstrate that SARS-CoV-2 can be detected in bulk floor dust collected from rooms housing infected individuals. This analysis suggests that dust may be a useful and efficient matrix for routine surveillance of viral disease., (Copyright © 2021 Renninger et al.)

Mold growth indoors is associated with negative human health effects, and this growth is limited by moisture availability. Dust deposited in carpet is an important source of human exposure due to potential elevated resuspension compared to hard floors. However, we need an improved understanding of fungal growth in dust and carpet to better estimate human exposure. The goal of this study was to compare fungal growth quantity and morphology in residential carpet under different environmental conditions, including equilibrium relative humidity (ERH) (50%, 85%, 90%, 95%, 100%), carpet fiber material (nylon, olefin, wool) and presence/absence of dust. We analyzed incubated carpet and dust samples from three Ohio homes for total fungal DNA, fungal allergen Alt a 1, and fungal morphology. Dust presence and elevated ERH (≥85%) were the most important variables that increased fungal growth. Elevated ERH increased mean fungal DNA concentration (P < 0.0001), for instance by approximately 1000 times at 100% compared to 50% ERH after two weeks. Microscopy also revealed more fungal growth at higher ERH. Fungal concentrations were up to 100 times higher in samples containing house dust compared to no dust. For fiber type, olefin had the least total fungal growth, and nylon had the most total fungi and A. alternata growth in unaltered dust. Increased ERH conditions were associated with increased Alt a 1 allergen concentration. The results of this study demonstrate that ERH, presence/absence of house dust, and carpet fiber type influence fungal growth and allergen production in residential carpet, which has implications for human exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Carpet and rugs currently represent about half of the United States flooring market and offer many benefits as a flooring type. How carpets influence our exposure to both microorganisms and chemicals in indoor environments has important health implications but is not well understood. The goal of this manuscript is to consolidate what is known about how carpet impacts indoor chemistry and microbiology, as well as to identify the important research gaps that remain. After describing the current use of carpet indoors, questions focus on five specific areas: 1) indoor chemistry, 2) indoor microbiology, 3) resuspension and exposure, 4) current practices and future needs, and 5) sustainability. Overall, it is clear that carpet can influence our exposures to particles and volatile compounds in the indoor environment by acting as a direct source, as a reservoir of environmental contaminants, and as a surface supporting chemical and biological transformations. However, the health implications of these processes are not well known, nor how cleaning practices could be optimized to minimize potential negative impacts. Current standards and recommendations focus largely on carpets as a primary source of chemicals and on limiting moisture that would support microbial growth. Future research should consider enhancing knowledge related to the impact of carpet in the indoor environment and how we might improve the design and maintenance of this common material to reduce our exposure to harmful contaminants while retaining the benefits to consumers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Troy Virgo is an employee of and has financial interests in Shaw Industries, which manufactures carpet. David Wilkinson is an employee of and has financial interests in Tarkett, which manufactures carpet. John Downey is associated with the Cleaning Industry Research Institute, which is a 501c3 nonprofit research institute and professional technical institute. All other authors declare no competing interests.

Hydraulic fracturing is the prevailing method for enhancing recovery of hydrocarbon resources from unconventional shale formations, yet little is understood regarding the microbial impact on biogeochemical cycling in natural-gas wells. Although the metabolisms of certain fermentative bacteria and methanogenic archaea that dominate in later produced fluids have been well studied, few details have been reported on microorganisms prevelant during the early flowback period, when oxygen and other surface-derived oxyanions and nutrients become depleted. Here, we report the isolation, genomic and phenotypic characterization of Marinobacter and Arcobacter bacterial species from natural-gas wells in the Utica-Point Pleasant and Marcellus Formations coupled to supporting geochemical and metagenomic analyses of produced fluid samples. These unconventional hydrocarbon system-derived Marinobacter sp. are capable of utilizing a diversity of organic carbon sources including aliphatic and aromatic hydrocarbons, amino acids, and carboxylic acids. Marinobacter and Arcobacter can metabolize organic nitrogen sources and have the capacity for denitrification and dissimilatory nitrate reduction to ammonia (DNRA) respectively; with DNRA and ammonification processes partially explaining high concentrations of ammonia measured in produced fluids. Arcobacter is capable of chemosynthetic sulfur oxidation, which could fuel metabolic processes for other heterotrophic, fermentative, or sulfate-reducing community members. Our analysis revealed mechanisms for growth of these taxa across a broad range of salinities (up to 15% salt), which explains their enrichment during early natural-gas production. These results demonstrate the prevalence of Marinobacter and Arcobacter during a key maturation phase of hydraulically fractured natural-gas wells, and highlight the significant role these genera play in biogeochemical cycling for this economically important energy system.

The complex [PtMe(dpa)(Me(2)SO)](+)(CF(3)SO(3))(-) (dpa = bis(2-pyridyl)amine) crystallizes in the monoclinic space group P2(1)/c with a = 11.010(2) Å, b = 18.366(2) Å, c = 10.333(5) Å, beta = 111.62(2) degrees, and Z = 4. Least-squares refinement of the structure led to an R factor of 2.41%. To avoid steric repulsions, the chelate six-membered ring assumes a boat configuration in which the two pyridyl rings are folded with a dihedral angle of 46.4(1) degrees. There is a strong hydrogen-bonding interaction involving the amine hydrogen (N3) and a triflate anion oxygen O3, 2.898(5) Å. The tendency by the NH group of the ligand moiety to attract anions is maintained in a solution of nonpolar solvents. Tight ion-pairs of structure similar to that in the solid state are formed with PF(6)(-), BF(4)(-), CF(3)SO(3)(-), and Cl(-) in chloroform, as shown by the strong dependence of the chemical shifts of the NH, H(3), and H(3') protons of the dpa ligand on the nature of the counterion. (19)F{(1)H} HOESY experiments on [PtMe(dpa)(Me(2)SO)](+)(PF(6))(-) in CD(2)Cl(2) confirmed that the preferential position of the counterion is close to the NH proton. The absorption spectra are also strongly affected by the nature of the counterion. This allowed for a stopped-flow measure of the PF(6)(-) for Cl(-) exchange rate at the NH site, which is a bimolecular process with k(2) = 96.4 +/- 4 M(-)(1) s(-)(1). The cation [PtMe(dpa)(Me(2)SO)](+) shows acidic properties in water (pK(a) = 12.1 +/- 0.2, at 25 degrees C, &mgr; = 0.1 M, NaNO(3)), and the corresponding amido species [PtMe(dpa-H)(Me(2)SO)] can be isolated on basification. Ion-pairing and full deprotonation of the amine ligand have remarkably little effect on the reactivity, as shown by the comparison of the rates of isotopic exchange of dimethyl sulfoxide of these species followed by (1)H NMR in chloroform. The rates of substitution of dimethyl sulfoxide from [PtMe(dpa)(Me(2)SO)](+) by various charged nucleophiles were measured in methanol, where ion-pairing effects are absent, and compared with those of the parent [PtMe(phen)(Me(2)SO)](+) (phen = 1,10-phenanthroline) complex. Because of the reduced capacity of electron withdrawal from the metal of the ancillary ligand, the dpa complex is less reactive and possesses a minor nucleophilic discrimination ability compared with the phen complex.

A series of monoalkyl square-planar complexes of the type [Pt(N-N)(CH(3))(Me(2)SO)]PF(6) (1-14), where N-N represents chelating diamines or diimines of widely different steric and electronic characteristics, was synthesized, and the complexes were fully characterized as solids and in solution. The substrates were tailored to offer only one site of exchange to a neutral molecule, i.e. Me(2)SO, in a noncoordinating solvent. No evidence for fluxionality of the N-N ligands was found, except for the case of complex 11 formed by 2,9-dimethyl-1,10-phenanthroline. In solution this complex is fluxional with the phenanthroline oscillating between nonequivalent bidentate modes by a mechanism which involves rupture of the metal-nitrogen bond and rapid interconversion of two coordinatively unsaturated T-shaped 14-electron three-coordinate molecular fragments. Rates of this fluxion were measured by NMR spectroscopy from the exchange effects on the (1)H signals of the methyl and aromatic hydrogens. The DeltaG() value for the fluxion is 49.6 +/- 4 kJ mol(-)(1). Dimethyl sulfoxide exchange with all the complexes has been studied as a function of ligand concentration by (1)H NMR line-broadening, isotopic labeling, and magnetization transfer experiments with deuterated acetone as the solvent. Second-order rate constants were obtained from linear plots of k(obs) vs [Me(2)SO] and activation parameters were obtained from exchange experiments carried out at different temperatures. Second-order kinetics and negative entropies of activation indicate an associative mechanism. The lability of dimethyl sulfoxide in the complexes depends in a rather unexpected and spectacular way upon the nature of the coordinate N-N ligands, the difference in reactivity between the first (N-N = N,N,N',N'-tetramethyl-1,2-diaminoethane, k(2)(298) = (1.15 +/- 0.1) x 10(-)(6) mol(-)(1) s(-)(1)) and the last (N-N = 2,9-dimethyl-1,10-phenanthroline, k(2)(298) = (3.81 +/- 0.005) x10(4) mol(-)(1) s(-)(1)) members of the series being greater than 10 orders of magnitude, as a result of a well-known phenomenon of steric retardation (for the first complex) and an unprecedented case of steric acceleration (for the last complex). Other factors of primary importance in controlling the reactivity are (i) the presence of an extensive pi system on the ligand N-N, (ii) the ease with which this pi system interacts with nonbonding d electrons of the metal, and (iii) the flexibility and ease of elongation of the chelate bite distance. The basicity plays a somewhat minor role, except in the restricted range of the same class of compounds such as substituted phenanthrolines.