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► Hydrolytic enzymes are the first step in the removal of wastewater organic matter. ► Changes in enzyme activities in a SFBBR exposed to saline wastewater were examined. ► High ...salinity of wastewater significantly reduced hydrolytic rates of the biofilms.
The effect of salinity on the hydrolytic enzymatic activities (acid phosphatase, alkaline phosphatase, glucosidase, protease and esterase) released by the microorganisms in a submerged fixed bed bioreactor for real urban wastewater treatment was investigated. The influence of salt (NaCl) on the enzymatic activities was evaluated in four different experiments with concentrations of NaCl of 0, 3.7, 24.1 and 44.1g/L, remaining constant all other operating parameters of the bioreactor. The results show that enzymatic activities were reduced when the salinity was increased in the influent and consequently the biotransformation of organic matter in the submerged fixed bed bioreactor significantly decreased. A redundancy analysis was performed to evaluate the relationships between enzymatic activities and physic-chemical parameters analyzed in the influent. According to the results obtained with the Monte Carlo permutation test, salinity and sampling day significantly contributed to explain the variation of enzymatic activities, showing a negative correlation.
Infiltrating and tissue-resident myeloid cells are essential regulators of innate and adaptive immunity. During inflammation, and in response to microbial products, these cells can adapt to ...microenvironmental conditions and acquire specialized functions, including phagocytosis and the production of proinflammatory cytokines. Such myeloid plasticity is driven, in part, by epigenetic dynamics that can sustain stable phenotypes after activation, and which may lead to maladaptive cell polarization states associated with inflammation and autoimmunity. Here, we review recent reports describing epigenetic mechanisms linked to such polarization states and innate immune memory (tolerance and training) in monocyte and macrophage lineages. We discuss how these mechanisms might be targeted to develop putative immunomodulatory tools that might be used to treat a variety of immune-mediated diseases.
Epigenetic mechanisms control the balance between a resting state and the activation of monocytes/macrophages in the presence of inflammatory stimuli. These mechanisms are also essential to induce and maintain polarization and innate immune memory after activation.
Epigenetic targeting of these processes can ameliorate inflammation and tissue damage in experimental models of immune and inflammatory diseases, including rheumatoid arthritis, asthma, encephalomyelitis, chronic kidney disease, and cancer.
The epigenetic landscape confers a long-lasting immune memory on microglia that has been associated with the severity of certain neurodegenerative and neuroinflammatory diseases. Peripheral administration of low-dose LPS induces long-lasting innate immune memory in microglia through epigenetic mechanisms.
Phytoplankton size structure is key for the ecology and biogeochemistry of pelagic ecosystems, but the relationship between cell size and maximum growth rate (μmax) is not yet well understood. We ...used cultures of 22 species of marine phytoplankton from five phyla, ranging from 0.1 to 106 μm3 in cell volume (Vcell), to determine experimentally the size dependence of growth, metabolic rate, elemental stoichiometry and nutrient uptake. We show that both μmax and carbon‐specific photosynthesis peak at intermediate cell sizes. Maximum nitrogen uptake rate (VmaxN) scales isometrically with Vcell, whereas nitrogen minimum quota scales as Vcell0.84. Large cells thus possess high ability to take up nitrogen, relative to their requirements, and large storage capacity, but their growth is limited by the conversion of nutrients into biomass. Small species show similar volume‐specific VmaxN compared to their larger counterparts, but have higher nitrogen requirements. We suggest that the unimodal size scaling of phytoplankton growth arises from taxon‐independent, size‐related constraints in nutrient uptake, requirement and assimilation.
Generalized lymphatic anomaly (GLA) is a vascular disorder characterized by diffuse or multifocal lymphatic malformations (LMs). The etiology of GLA is poorly understood. We identified four distinct ...somatic
variants (Glu542Lys, Gln546Lys, His1047Arg, and His1047Leu) in tissue samples from five out of nine patients with GLA. These same
variants occur in
-related overgrowth spectrum and cause hyperactivation of the PI3K-AKT-mTOR pathway. We found that the mTOR inhibitor, rapamycin, prevented lymphatic hyperplasia and dysfunction in mice that expressed an active form of
(His1047Arg) in their lymphatics. We also found that rapamycin reduced pain in patients with GLA. In conclusion, we report that somatic activating
mutations can cause GLA, and we provide preclinical and clinical evidence to support the use of rapamycin for the treatment of this disabling and deadly disease.
The airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via respiratory fluids and droplets suggests that mouthwashes containing substances with virucidal activity ...can help reduce viral spread. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to assess the virucidal activity of cetylpyridinium chloride (CPC) mouthwashes. Outpatients who tested positive for SARS-CoV-2 infection with or without symptoms were randomized to perform washes and gargles for 1 min with 15 mL of either colored distilled water or 0.07% CPC (Vitis CPC Protect) mouthwash. The study outcomes were the SARS-CoV-2 log10 viral RNA load and the nucleocapsid protein levels, both in saliva at 1 and 3 h after the intervention. In total, 118 patients were enrolled and randomized (mean SD, age 46 14 y). Thirteen of 118 participants (11%) did not complete follow-up or had insufficient sample volume for testing and were excluded from the analysis. The assessment of the viral load showed no significant differences between groups at any of the investigated points. However, the levels of SARS-CoV-2 nucleocapsid protein of lysed viruses were significantly higher in the CPC group compared with the control group at 1 h (adjusted difference 269.3 pg/mL; 95% confidence interval CI, 97.1–441.5) and at 3 h postintervention (561.1 pg/mL; 95% CI, 380.0–742.2). In nonhospitalized patients with asymptomatic or mild symptomatic SARS-CoV-2 infection, a 0.07% CPC mouthwash, compared to placebo, was associated with a significant increase of nucleocapsid protein levels in saliva, indicating enhanced disruption of viral particles.
Extracellular vesicles (EVs) are membrane-bound nanovesicles delivered by different cellular lineages under physiological and pathological conditions. Although these vesicles have shown relevance as ...biomarkers for a number of diseases, their isolation and detection still has several technical drawbacks, mainly related with problems of sensitivity and time-consumed. Here, we reported a rapid and multiple-targeted lateral flow immunoassay (LFIA) system for the detection of EVs isolated from human plasma. A range of different labels (colloidal gold, carbon black and magnetic nanoparticles) was compared as detection probe in LFIA, being gold nanoparticles that showed better results. Using this platform, we demonstrated that improvements may be carried out by incorporating additional capture lines with different antibodies. The device exhibited a limit of detection (LOD) of 3.4×106EVs/µL when anti-CD81 and anti-CD9 were selected as capture antibodies in a multiple-targeted format, and anti-CD63 labeled with gold nanoparticles was used as detection probe. This LFIA, coupled to EVs isolation kits, could become a rapid and useful tool for the point-of-care detection of EVs, with a total analysis time of two hours.
•A multiplex lateral flow immunoassay for Extracellular vesicles detection has been developed.•Colloidal gold and additional capture lines provided the best sensitivity.•The limit of detection was of 3.4×06EVs/µL with anti-CD81 and anti-CD9 as capture antibodies.•This platform allows Point-of-care measurements based on biological vesicles determination.
The oncostatic effects of melatonin correlate with increased reactive oxygen species (ROS) levels, but how melatonin induces this ROS generation is unknown. In the present study, we aimed to ...elucidate the two seemingly opposing actions of melatonin regarding its relationship with free radicals. We analyzed the effects of melatonin on head and neck squamous cell carcinoma cell lines (Cal‐27 and SCC‐9), which were treated with 0.5 or 1 mM melatonin. We further examined the potential effects of melatonin to induce ROS and apoptosis in Cal‐27 xenograft mice. Here we report that melatonin mediates apoptosis in head and neck cancer by driving mitochondrial reverse electron transport (RET) to induce ROS production. Melatonin‐induced changes in tumoral metabolism led to increased mitochondrial activity, which, in turn, induced ROS‐dependent mitochondrial uncoupling. Interestingly, mitochondrial complex inhibitors, including rotenone, abolished the ROS elevation indicating that melatonin increased ROS generation via RET. Melatonin also increased membrane potential and CoQ10H2/CoQ10 ratio to elevate mitochondrial ROS production, which are essential conditions for RET. We found that genetic manipulation of cancer cells with alternative oxidase, which transfers electrons from QH2 to oxygen, inhibited melatonin‐induced ROS generation, and apoptosis. RET restored the melatonin‐induced oncostatic effect, highlighting the importance of RET as the site of ROS production. These results illustrate that RET and ROS production are crucial factors in melatonin's effects in cancer cells and establish the dual effect of melatonin in protecting normal cells and inducing apoptosis in cancer cells.
Microbial communities of natural subaerial biofilms developed on granitic historic buildings of a World Heritage Site (Santiago de Compostela, NW Spain) were characterized and cultured in liquid BG11 ...medium. Environmental barcoding through next-generation sequencing (Pacific Biosciences) revealed that the biofilms were mainly composed of species of Chlorophyta (green algae) and Ascomycota (fungi) commonly associated with rock substrata. Richness and diversity were higher for the fungal than for the algal assemblages and fungi showed higher heterogeneity among samples. Cultures derived from natural biofilms showed the establishment of stable microbial communities mainly composed of Chlorophyta and Cyanobacteria. Although most taxa found in these cultures were not common in the original biofilms, they are likely common pioneer colonizers of building stone surfaces, including granite. Stable phototrophic multi-species cultures of known microbial diversity were thus obtained and their reliability to emulate natural colonization on granite should be confirmed in further experiments.
The design of new strategies to increase the effectiveness of the antibacterial treatments is a main goal in public health. So, the aim of the study was to achieve a local antibacterial directed ...therapy as novel alternative allowing both, the delivery of the drug at the target, while minimizing undesirable side effects, thus anticipating an enhanced effectiveness. Hence, we have developed an innovative nanoformulation composed by biomimetic magnetic nanoparticles functionalized with the antimicrobial peptide AS-48 and its potential against Gram-positive and Gram-negative bacteria, either by itself or combined with magnetic hyperthermia has been investigated. Besides, the physical properties, binding efficiency, stability and mechanism of action of this nanoassembly are analyzed. Remarkably, the nanoassembly has a strong bactericidal effect on Gram-positive bacteria, but surprisingly also on E. coli and, finally, when combined with magnetic hyperthermia, on P. aeruginosa and K. pneumoniae. The results obtained represent a breakthrough since it allows a local treatment of infections, reducing and concentrating the dose of antimicrobial compounds, avoiding secondary effects, including the resistance generation and particularly because the combination with magnetic hyperthermia helps sensitizing resistant bacteria to the bactericidal effect of AS-48. Thus, this new formulation should be considered a promising tool in the antibacterial fight.
Capillary malformation‐arteriovenous malformation (CM‐AVM) is caused by germline RASA1 and EPHB4 alterations. RASA1 intralesional second hits have also been reported. Here we report RASA1 ...constitutional mosaicism, defined here as the presence of a mosaic variant in all cell types of an individual, in two patients with CM‐AVM. High‐throughput sequencing was used to search for RASA1 pathogenic variants in blood samples from two unrelated patients with CM‐AVM. An affected tissue sample from one of the patients was also analyzed. Both patients showed different nonsense RASA1 variants in mosaic, ranging from 7% to 21.5%, in blood samples and in the corresponding affected tissue sample from one of the patients. In conclusion, we report for the first time the presence of RASA1 constitutional mosaicism in CM‐AVM. Constitutional mosaicism has implications for accurate molecular diagnosis and recurrence risk and helps to explain the great phenotypic variability in CM‐AVM.
Constitutional mosaicism in RASA1‐related capillary malformation‐arteriovenous malformation.
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