UV LED wastewater disinfection: The future is upon us.

The world's first full-scale, 280 nm UV LED reactor for wastewater disinfection was tested at flows of 545 and 817 m day. The system achieved > 3 average log reduction of total coliform at 545 m day and the 817 m day flow rate achieved over > 2.5 average log reduction for all operational conditions.

Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response.

Cutting Edge: Cytosolic Receptor AIM2 Is Induced by Peroxisome Proliferator-activated Receptor γ following Mycobacterium tuberculosis Infection of Human Macrophages but Does Not Contribute to IL-1β Release.

AIM2 (absent in melanoma 2), an inflammasome component, mediates IL-1β release in murine macrophages and cell lines. AIM2 and IL-1β contribute to murine control of Mycobacterium tuberculosis (M.tb) infection, but AIM2's impact in human macrophages, the primary niche for M.

Considerations and Approaches for Cancer Immunotherapy in the Aging Host.

Advances in cancer immunotherapy are improving treatment successes in many distinct cancer types. Nonetheless, most tumors fail to respond. Age is the biggest risk for most cancers, and the median population age is rising worldwide.

Alternative splicing of the SUMO1/2/3 transcripts affects cellular SUMOylation and produces functionally distinct SUMO protein isoforms.

Substantial increases in the conjugation of the main human SUMO paralogs, SUMO1, SUMO2, and SUMO3, are observed upon exposure to different cellular stressors, and such increases are considered important to facilitate cell survival to stress. Despite their critical cellular role, little is known about how the levels of the SUMO modifiers are regulated in the cell, particularly as it relates to the changes observed upon stress. Here we characterize the contribution of alternative splicing towards regulating the expression of the main human SUMO paralogs under normalcy and three different stress conditions, heat-shock, cold-shock, and Influenza A Virus infection.

Pharmacological tumor PDL1 depletion with chlorambucil treats ovarian cancer and melanoma: improves antitumor immunity and renders anti-PDL1-resistant tumors anti-PDL1-sensitive through NK cell effects.

Background: Tumor intracellular programmed cell death ligand-1 (PDL1) mediates pathologic signals that regulate clinical treatment responses distinctly from surface-expressed PDL1 targeted by αPDL1 immune checkpoint blockade antibodies.

Methods: We performed a drug screen for tumor cell PDL1 depleting drugs that identified Food and Drug Administration (FDA)-approved chlorambucil and also 9-[2-(phosphonomethoxy)ethyl] guanine. We used in vitro and in vivo assays to evaluate treatment and signaling effects of pharmacological tumor PDL1 depletion focused on chlorambucil as FDA approved, alone or plus αPDL1.

Genomic and phenotypic analyses suggest moderate fitness differences among Zika virus lineages.

RNA viruses have short generation times and high mutation rates, allowing them to undergo rapid molecular evolution during epidemics. However, the extent of RNA virus phenotypic evolution within epidemics and the resulting effects on fitness and virulence remain mostly unknown. Here, we screened the 2015-2016 Zika epidemic in the Americas for lineage-specific fitness differences.

Immersive ultraviolet disinfection of E. coli and MS2 phage on woven cotton textiles.

Immersive ultraviolet disinfection provides a chemical-free technology for safer textiles, surfaces, and public spaces by inactivating communicable pathogens. This study examined immersive UV disinfection, using a disinfection cabinet, of E. coli and MS2 that was inoculated on white cotton T-shirts.

Pharmacologic Tumor PDL1 Depletion with Cefepime or Ceftazidime Promotes DNA Damage and Sensitivity to DNA-Damaging Agents.

The interaction between tumor surface-expressed PDL1 and immune cell PD1 for the evasion of antitumor immunity is well established and is targeted by FDA-approved anti-PDL1 and anti-PD1 antibodies. Nonetheless, recent studies highlight the immunopathogenicity of tumor-intrinsic PDL1 signals that can contribute to the resistance to targeted small molecules, cytotoxic chemotherapy, and αPD1 immunotherapy. As genetic PDL1 depletion is not currently clinically tractable, we screened FDA-approved drugs to identify those that significantly deplete tumor PDL1.

Tumor Intrinsic PD-L1 Promotes DNA Repair in Distinct Cancers and Suppresses PARP Inhibitor-Induced Synthetic Lethality.

Unlabelled: BRCA1-mediated homologous recombination is an important DNA repair mechanism that is the target of FDA-approved PARP inhibitors, yet details of BRCA1-mediated functions remain to be fully elucidated. Similarly, immune checkpoint molecules are targets of FDA-approved cancer immunotherapies, but the biological and mechanistic consequences of their application are incompletely understood. We show here that the immune checkpoint molecule PD-L1 regulates homologous recombination in cancer cells by promoting BRCA1 nuclear foci formation and DNA end resection.

Specificity of UV-C LED disinfection efficacy for three N95 respirators.

The recent surge in the use of UV technology for personal protective equipment (PPE) has created a unique learning opportunity for the UV industry to deepen surface disinfection knowledge, especially on surfaces with complex geometries, such as the N95 filter facepiece respirators (FFR). The work outlined in this study addresses the interconnectedness of independent variables (e.g.

Reversing Post-Infectious Epigenetic-Mediated Immune Suppression.

The immune response must balance the pro-inflammatory, cell-mediated cytotoxicity with the anti-inflammatory and wound repair response. Epigenetic mechanisms mediate this balance and limit host immunity from inducing exuberant collateral damage to host tissue after severe and chronic infections. However, following treatment for these infections, including sepsis, pneumonia, hepatitis B, hepatitis C, HIV, tuberculosis (TB) or schistosomiasis, detrimental epigenetic scars persist, and result in long-lasting immune suppression.

Assessing the impact of multiple ultraviolet disinfection cycles on N95 filtering facepiece respirator integrity.

During the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs) were recommended to protect healthcare workers when providing care to infected patients. Despite their single-use disposable nature, the need to disinfect and repurpose FFRs is paramount during this global emergency. The objectives of this study were to (1) determine if UV treatment has an observable impact on respirator integrity; (2) test the impact of UV treatment on N95 FFR user fit; and (3) test the impact of UV treatment on FFR integrity.

Source Water Characteristics and Building-specific Factors Influence Corrosion and Point of Use Water Quality in a Decentralized Arctic Drinking Water System.

Access to clean and safe drinking water is a perpetual concern in Arctic communities because of challenging climatic conditions, limited options for the transportation of equipment and process chemicals, and the ongoing effects of colonialism. Water samples were gathered from multiple locations in a decentralized trucked drinking water system in Nunavut, Canada, over the course of one year. The results indicate that point of use drinking water quality was impacted by conditions in the source water and in individual buildings and strongly suggest that lead and copper measured at the tap were related to corrosion of onsite premise plumbing components.

Inactivation of biofilm-bound Pseudomonas aeruginosa bacteria using UVC light emitting diodes (UVC LEDs).

Ultraviolet light emitting diodes (UV LEDs) are a promising technology for the disinfection of water and wetted surfaces, but research into these applications remains limited. In the drinking water field, UV LEDs emitting at wavelengths ranging from 254 nm to 285 nm (UVC LEDs) have been shown to be effective for the inactivation of numerous pathogens and pathogen surrogate organisms at UV doses comparable to conventional germicidal UV lamps. Surface disinfection with UV light, from UVC LEDs or from conventional UV lamps, is not as well understood.

Molecular signatures of the primitive prostate stem cell niche reveal novel mesenchymal-epithelial signaling pathways.

Background: Signals between stem cells and stroma are important in establishing the stem cell niche. However, very little is known about the regulation of any mammalian stem cell niche as pure isolates of stem cells and their adjacent mesenchyme are not readily available. The prostate offers a unique model to study signals between stem cells and their adjacent stroma as in the embryonic prostate stem cell niche, the urogenital sinus mesenchyme is easily separated from the epithelial stem cells.

High aldehyde dehydrogenase activity: a novel functional marker of murine prostate stem/progenitor cells.

We have shown previously that prostatic stem/progenitor cells can be purified from isolated prostate ducts, based on their high expression of the Sca-1 surface antigen. We now report that high levels of aldehyde dehydrogenase (ALDH) activity are present in a subset of prostate epithelial cells that coexpress a number of antigens found on stem/progenitor cells of other origins (CD9, Bcl-2, CD200, CD24, prominin, Oct 3/4, ABCG2, and nestin). Almost all of these cells expressing high levels of ALDH activity also express Sca-1 and a third of them express high levels of this antigen.

Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer.

Background: The global gene expression profiles of adult and fetal murine prostate stem cells were determined to define common and unique regulators whose misexpression might play a role in the development of prostate cancer.

Methodology/principal Findings: A distinctive core of transcriptional regulators common to both fetal and adult primitive prostate cells was identified as well as molecules that are exclusive to each population. Elements common to fetal and adult prostate stem cells include expression profiles of Wnt, Shh and other pathways identified in stem cells of other organs, signatures of the aryl-hydrocarbon receptor, and up-regulation of components of the aldehyde dehydrogenase/retinoic acid receptor axis.

Axin2 expression identifies progenitor cells in the murine prostate.

Background: We previously reported that prostatic stem/progenitor cells are concentrated in the proximal region of prostatic ducts and express stem cell antigen 1 (Sca-1). As Wnt signaling is important for the maintenance of stem cells, we determined whether Sca-1 expressing cells also express Axin2, as Axin2 expression is highly suggestive of active Wnt signaling.

Methods: Axin2 promoter reporter mice were used for whole mount and fluorescence activated cell sorting (FACS) analysis to determine its expression in the prostate.

Hypoxia suppresses runx2 independent of modeled microgravity.

Bone loss is a consequence of skeletal unloading as seen in bed rest and space flight. Unloading decreases oxygenation and osteoblast differentiation/function in bone. Previously we demonstrated that simulation of unloading in vitro, by culturing differentiating mouse osteoblasts in a horizontal rotating wall vessel (RWV), results in suppressed expression of runx2, a master transcriptional regulator of osteoblast differentiation.

Aryl hydrocarbon receptor-mediated activity of particulate organic matter from the Paso del Norte airshed along the U.S.-Mexico border.

In this study, we determined the biologic activity of dichloromethane-extracted particulate matter < 10 micro m in aerodynamic diameter (PM10) obtained from filters at three sites in the Paso del Norte airshed, which includes El Paso, Texas, USA; Juarez, Chihuahua, Mexico, and Sunland Park, New Mexico, USA. The extracts were rich in polycyclic aromatic hydrocarbons (PAHs) and had significant biologic activity, measured using two in vitro assay systems: ethoxyresorufin-(O-deethylase (EROD) induction and the aryl hydrocarbon-receptor luciferase reporter system. In most cases, both EROD (5.

Simulated microgravity suppresses osteoblast phenotype, Runx2 levels and AP-1 transactivation.

Conditions of disuse such as bed rest, space flight, and immobilization result in decreased mechanical loading of bone, which is associated with reduced bone mineral density and increased fracture risk. Mechanisms involved in this process are not well understood but involve the suppression of osteoblast function. To elucidate the influence of mechanical unloading on osteoblasts, a rotating wall vessel (RWV) was employed as a ground based model of simulated microgravity.

Parathyroid hormone stimulates fra-2 expression in osteoblastic cells in vitro and in vivo.

PTH and PTH-related protein (PTHrP) are key mediators of skeletal development and homeostasis through their activation of the PTH-1 receptor. Previous studies have found that several AP-1 family members are regulated by PTH, such as c-fos, fra-1, and c-jun. There are numerous genes in the bone microenvironment that contain AP-1 sites, and different Fos family members are reported to have opposing transcriptional activities at AP-1 sites.

Increased bar minigene mRNA stability during cell growth inhibition.

Bacteriophage lambda is unable to grow vegetatively on Escherichia coli mutants defective in peptidyl-tRNA hydrolase (Pth) activity. Mutations which allow phage growth on the defective host have been located at regions named bar in the lambda genome. Expression of wild-type bar regions from plasmid constructs results in inhibition of protein synthesis and lethality to Pth-defective cells.

lambda bar minigene-mediated inhibition of protein synthesis involves accumulation of peptidyl-tRNA and starvation for tRNA.

Expression of the bacteriophage lambda two-codon, AUG AUA, barI minigene (bar+) leads to the arrest of protein synthesis in cells defective in peptidyl-tRNA hydrolase (Pth). It has been hypothesized that translation of the bar+ transcript provokes premature release and accumulation of peptidyl-tRNA (p-tRNA). Inhibition of protein synthesis would then result from either starvation of sequestered tRNA or from toxicity of accumulated p-tRNA.