Impact of harmful algal bloom severity on bacterial communities in a full-scale biological filtration system for drinking water treatment.

The occurrence of harmful algal blooms (HABs) in freshwater environments has been expanded worldwide with growing frequency and severity. HABs can pose a threat to public water supplies, raising concerns about safety of treated water. Many studies have provided valuable information about the impacts of HABs and management strategies on the early-stage treatment processes (e.g., pre-oxidation and coagulation/flocculation) in conventional drinking water treatment plants (DWTPs). However, the potential effect of HAB-impacted water in the granular media filtration has not been well studied. Biologically-active filters (BAFs), which are used in drinking water treatment and rely largely on bacterial community interactions, have not been examined during HABs in full-scale DWTPs. In this study, we assessed the bacterial community structure of BAFs, functional profiles, assembly processes, and bio-interactions in the community during both severe and mild HABs. Our findings indicate that bacterial diversity in BAFs significantly decreases during severe HABs due to the predominance of bloom-associated bacteria (e.g., Spingopyxis, Porphyrobacter, and Sphingomonas). The excitation-emission matrix combined with parallel factor analysis (EEM-PARAFAC) confirmed that filter influent affected by the severe HAB contained a higher portion of protein-like substances than filter influent samples during a mild bloom. In addition, BAF community functions showed increases in metabolisms associated with intracellular algal organic matter (AOM), such as lipids and amino acids, during severe HABs. Further ecological process and network analyses revealed that severe HAB, accompanied by the abundance of bloom-associated taxa and increased nutrient availability, led to not only strong stochastic processes in the assembly process, but also a bacterial community with lower complexity in BAFs. Overall, this study provides deeper insights into BAF bacterial community structure, function, and assembly in response to HABs.

Field and laboratory studies of fluorescence-based technologies for real-time tracking of cyanobacterial cell lysis and potential microcystins release.

Elevated levels of dissolved microcystins (MCs) in source water due to rapid cell lysis of harmful cyanobacterial blooms may pose serious challenges for drinking water treatment. Catastrophic cell lysis can result from outbreaks of naturally-occurring cyanophages - as documented in Lake Erie during the Toledo water crisis of 2014 and in 2019, or through the application of algaecides or water treatment chemicals. Real-time detection of cyanobacterial cell lysis in source water would provide a valuable tool for drinking water plant and reservoir managers. In this study we explored two real-time fluorescence-based devices, PhycoSens and PhycoLA, that can detect unbound phycocyanin (uPC) as a potential indication of cell lysis and MCs release. The PhycoSens was deployed at the Low Service pump station of the City of Toledo Lake Erie drinking water treatment plant from July 15 to October 19, 2022 during the annual cyanobacteria bloom season. It measured major algal groups and uPC in incoming lake water at 15-min intervals during cyanobacteria dominant and senescence periods. Intermittent uPC detections from the PhycoSens over a three-month period coincided with periods of increasing proportions of extracellular MCs relative to total (intracellular and extracellular) MCs, indicating potential for uPC use as an indicator of cyanobacterial cell integrity. Following exposures of laboratory-cultured MCs-producing Microcystis aeruginosa NIES-298 (120 µg chlorophyll/L) to cyanophage Ma-LMM01, copper sulfate (0.5 and 1 mg Cu/L), sodium carbonate peroxyhydrate (PAK® 27, 6.7 and 10 mg H2O2/L), and potassium permanganate (2.5 and 4 mg/L), appearance of uPC coincided with elevated fractions of extracellular MCs. The PhycoLA was used to monitor batch samples collected daily from Lake Erie water exposed to algaecides in the laboratory. Concurrence of uPC signal and surge of dissolved MCs was observed following 24-h exposures to copper sulfate and PAK 27. Overall results indicate the appearance of uPC is a useful indicator of the onset of cyanobacterial cell lysis and the release of MCs when MCs are present.

An assessment of a biosensor system for the quantification of microcystins in freshwater cyanobacterial blooms.

Microcystin-producing cyanobacterial blooms are a global issue threatening drinking water supplies and recreation on lakes and beaches. Direct measurement of microcystins is the only way to ensure waters have concentrations below guideline concentrations; however, analyzing water for microcystins takes several hours to days to obtain data. We tested LightDeck Diagnostics' bead beater cell lysis and two versions of the quantification system designed to give microcystin concentrations within 20 min and compared it to the standard freeze-thaw cycle lysis method and ELISA quantification. The bead beater lyser was only 30 % effective at extracting microcystins compared to freeze-thaw. When considering freeze-thaw samples analyzed in 2021, there was good agreement between ELISA and LightDeck version 2 (n = 152; R2 = 0.868), but the LightDeck slightly underestimated microcystins (slope of 0.862). However, we found poor relationships between LightDeck version 2 and ELISA in 2022 (n = 49, slopes 0.60 to 1.6; R2 < 0.6) and LightDeck version 1 (slope = 1.77 but also a high number of less than quantifiable concentrations). After the quantification issues are resolved, combining the LightDeck system with an already-proven rapid lysis method (such as microwaving) will allow beach managers and water treatment operators to make quicker, well-informed decisions.

Impact of the COVID-19 Pandemic on Adolescent Self-Harm: Based on a National Emergency Department Information System.

Republic of Korea's suicide rate is the highest among Organization for Economic Co-operation and Development countries. In Republic of Korea, suicide is the leading cause of death among young people aged 10-19 years. This study aimed to identify changes in patients aged 10-19 years who visited the emergency department in Republic of Korea after inflicting self-harm over the past five years and to compare the situations before and after the outbreak of the COVID-19 pandemic. Analysis of government data revealed that the average daily visits per 100,000 were 6.25, 8.18, 13.26, 15.31, and 15.71 from 2016 to 2020, respectively. The study formed four groups for further analysis, with the population divided by sex and age (10-14 and 15-19 years old). The late-teenage female group showed the sharpest increase and was the only group that continued to increase. A comparison of the figures 10 months before and after the outbreak of the pandemic revealed a statistically significant increase in self-harm attempts by only the late-teenage female group. Meanwhile, visits (per day) in the male group did not increase, but the rates of death and ICU admission increased. Additional studies and preparations that account for age and sex are warranted.

Review: Current understanding on biological filtration for the removal of microcystins.

Harmful algal blooms (HABs) have become a global problem not only in aquatic habitats but also in public health and safety due to the production of cyanotoxins as their secondary metabolites. Among the various identified cyanotoxin groups, microcystins (MCs) are one of the most prevalent cyanotoxin detected during HABs. Different strategies including advanced physical and chemical treatment processes have been developed to mitigate the threat of cyanotoxins in water utilities, but these have revealed certain limitations in terms of high operational costs, low removal efficacy, and harmful by-products formation. Recently, biological filtration systems (BFS) have gained attention for safe drinking water production as they can treat various natural organic matter (NOM) and emerging contaminants through a highly efficient and environmentally sustainable process. However, limited attention has been given to understand the current research progress, research challenges, and knowledge gaps for the successful implementation of BFS for MC removal. Therefore, in this review, currently identified MC biodegradation pathways and MC-degrading microorganisms with their degradation rates are summarized, which may be pivotal for studying bioaugmented BFS to enhance the MC removal during HABs. Moreover, both laboratory and field studies on BFS for MC removal are reviewed, followed by a discussion of current challenges and future research needs for the practical application of BFS.

Low-voltage Activating K+ Channels in Cochlear Afferent Nerve Fiber Dendrites.

Cochlear afferent nerve fibers (ANF) are the first neurons in the ascending auditory pathway. We investigated the low-voltage activating K+ channels expressed in ANF dendrites using isolated rat cochlear segments. Whole cell patch clamp recordings were made from the dendritic terminals of ANFs. Outward currents activating at membrane potentials as low as -64 mV were observed in all dendrites studied. These currents were inhibited by 4-aminopyridine (4-AP), a blocker known to preferentially inhibit low-voltage activating K+ currents (IKL) in CNS auditory neurons and spiral ganglion neurons. When the dendritic IKL was blocked by 4-AP, the EPSP decay time was significantly prolonged, suggesting that dendritic IKL speeds up the decay of EPSPs and likely modulates action potentials of ANFs. To reveal molecular subtype of dendritic IKL, α-dendrotoxin (α-DTX), a selective inhibitor for Kv1.1, Kv1.2, and Kv1.6 containing channels, was tested. α-DTX inhibited 23±9% of dendritic IKL. To identify the α-DTXsensitive and α-DTX-insensitive components of IKL, immunofluorescence labeling was performed. Strong Kv1.1- and Kv1.2-immunoreactivity was found at unmyelinated dendritic segments, nodes of Ranvier, and cell bodies of most ANFs. A small fraction of ANF dendrites showed Kv7.2- immunoreactivity. These data suggest that dendritic IKL is conducted through Kv1.1and Kv1.2 channels, with a minor contribution from Kv7.2 and other as yet unidentified channels.

Impacts of algal organic matter and humic substances on microcystin-LR removal and their biotransformation during the biodegradation process.

The application of bioaugmentation (i.e., injection of contaminant-degrading microorganisms) has shown its potential to remove harmful cyanotoxins like microcystin-LR (MC-LR) from drinking water sources. However, the natural organic matter (NOM) present in both natural and engineered water systems might affect the bacterial biodegradation of MC-LR. Therefore, for the successful application of bioaugmentation for MC-LR removal in water treatment, it is important to understand NOM effects on MC-LR biodegradation. In this study, the impact of NOM [algal organic matter (AOM) and humic substances (HS)] on MC-LR biodegradation was evaluated in the presence of varying concentrations of NOM by monitoring MC-LR biodegradation kinetics. The changes in NOM composition during MC-LR biodegradation were also characterized by a five-component Parallel factor (PARAFAC) model using 336 excitation-emission matrix (EEM) spectra collected at different sampling points. Our results showed decreases in MC-LR biodegradation rate of 1.6-and 3.4-fold in the presence of AOM and HS, respectively. The expression of the functional mlrA gene exhibited a similar trend to the MC-LR degradation rate at different NOM concentrations. EEM-PARAFAC analyses and NOM molecular size fractionation results indicated a relatively greater production of terrestrial humic-like components (57%) and a decrease of protein-like components. Two-dimensional correlation spectroscopy (2D-COS) analyses further confirmed that low molecular weight protein-like components were initially utilized by bacteria, followed by the formation of higher molecular weight humic-like components, likely due to microbial metabolism.

Analysis of Postoperative Outcomes in Patients with Intermittent Exotropia According to Preoperative Change of Angle of Deviation.

PURPOSE: The correlation between the existence of the preoperative condition of ≥10 prism diopters (PD) in patients with basic type of intermittent exotropia (IXT) and postoperative outcomes was analyzed. METHODS: The medical records of patients that underwent surgery for IXT were analyzed retrospectively. The analysis was conducted by dividing the patients into a group with change of <10 PD (group 1) and ≥10 PD (group 2) before the time of the surgery. Patients who received at least 6 months of follow-up after surgery were included. The age, sex, angle of deviation and stereoacuity of the patients were studied. Surgical success was defined as exodeviation of <10 PD or esodeviation of <4 PD at the final visit after the surgery. The correlation between clinical factors and surgical success rate was analyzed by using correlative analysis. RESULTS: A total of 129 patients participated in the study. There were 108 (83.7%) and 21 (16.3%) patients in groups 1 and 2, respectively. There were 89 (82.4%) and 17 (80.1%) patients with surgical successes in groups 1 and 2, respectively (p = 0.18). Moreover, 13 (12.0%) patients in group 1 and three (14.3%) patients in group 2 required reoperation, showing no significant difference (p = 0.12). There was no statistically significant correlation between surgical success and preoperative change of angle of deviation <10 PD (odds ratio, 1.78; p = 0.17). CONCLUSIONS: Among the patients with basic type of IXT subjected to the analysis, 16.3% had a change of ≥10 PD before surgery, and there was no significant correlation between surgical success and preoperative change of angle of deviation.

Ecological insights into assembly processes and network structures of bacterial biofilms in full-scale biologically active carbon filters under ozone implementation.

To address the adverse effects of harmful algal blooms, there are increased demands over the implementation of ozone coupled with biologically active carbon (BAC) filters in the drinking water treatment plants. Although the microbial biofilms are vital elements to support the proper performance of BAC filters, except for taxonomic affiliations, little is known about the assembly mechanisms of microbial communities in the full-scale BAC filters. This study aimed to examine how the assembly processes and their associated factors (e.g., influent characteristics, biological interactions) drive the temporal dynamics of bacterial communities in full-scale BAC filters, which underwent ozone implementation (five consecutive seasons from 2017 to 2018). The results revealed that along with the increase of bacterial taxonomic richness and evenness, stochastic processes became more crucial to determine the bacterial community assembly in the summer and autumn after ozone implementation (relative contribution: 61.23% and 83.75%, respectively). Moreover, their corresponding networks possessed simple network structures with lower modularity than other seasons, which implied lesser biological interactions among bacterial populations. The correlation between taxonomic and predicted functional diversities using functional redundancy index indicated that relatively high levels of bacterial functional redundancy (>0.83) were generally present in BAC filters. However, compared to other seasons, significantly higher degrees of functional redundancy existed in the summer and autumn after ozone implementation (0.85 ± 0.01 and 0.86 ± 0.01, respectively). Overall, this work improves our understanding of the microbial ecology of full-scale BAC filters by providing a conceptual framework that characterizes bacterial biofilm assembly processes relevant to performance optimization of full-scale BAC filters.

The role of biofilms on the formation and decay of disinfection by-products in chlor(am)inated water distribution systems.

This study investigated the role of biofilms on the formation and decay of disinfection by-products (DBPs) in chlorine (Cl2) or monochloramine (NH2Cl) disinfected reactors under the conditions related to drinking water distribution systems (DWDSs). Biofilm analysis results revealed that at 0.5 mg/L of disinfectant residual, both Cl2 and NH2Cl were not effective to remove biofilms. As the disinfectant residual increased, biofilms could be eradicated by Cl2, while remaining biofilms were still present even under the highest allowable NH2Cl dose (4 mg/L) for 25 days. Low DBP formation was observed under the recommended minimum Cl2 residual (0.5 mg/L), which could be attributed to limited Cl2 reactions with biofilms, as well as a combination of the volatilization and biodegradation of DBPs. However, when Cl2 residuals reached 2 mg/L, DBP concentrations in bulk water increased sharply beyond the DBP formation of the feed solution, with trihalomethanes and haloacetic acids being the most prevalent DBP species. The sharp increase was temporary for 15 days because of the removal of biofilms. For unregulated DBPs, high levels of haloacetonitriles were observed as attached biofilms reacted with the increased Cl2 dose and provided an additional organic nitrogen source for nitrogenous DBP formation. When maximum Cl2 residual (4 mg/L) was applied, no further increase of DBPs was observed because of biofilm eradication. For NH2Cl disinfection, the DBP levels were much lower than those of Cl2 disinfection, with small differences in DBP formation for different NH2Cl residuals. Overall, this study provides insights into optimizing disinfection protocols for water utilities by balancing the benefits of disinfection application for biofilm control with minimized toxic DBP formation in DWDSs.

Taxonomic and Genotypical Heterogeneity of Microcystin degrading Bacterioplankton in Western Lake Erie.

Microcystins (MCs) are among the predominant cyanotoxins that are primarily degraded by heterotrophic bacteria in various freshwater environments, including Lake Erie, a Laurentian Great Lake. However, despite the prevalence of MCs in Lake Erie basins, our knowledge about the taxonomic diversity of local MC-degrading bacteria is largely limited. The current study obtained thirty-four MC-degrading bacterial pure isolates from Lake Erie surface water and characterized their taxonomical and phenotypic identities as well as their MC-degradation rates under different pH, temperature, availability of organic substrates and with other MC-degrading isolates. Obtained MC-degrading isolates included both Gram-positive (18 isolates of Actinobacteria and Firmicutes) and Gram-negative bacteria (16 isolates of Gamma-proteobacteria); and 7 of these isolates were motile, and 13 had the capacity to form biofilms. In general, MC-degradation rates of the isolates were impacted by temperature and pH but insensitive to the presence of cyanobacterial exudates. At the optimal temperature (30-35°C) and pH (7-8), individual isolates degraded MC-LR, the most abundant MC isomer, at an average of 0.20 µg/mL/hr. With additions of cyanobacterial exudates, only Pseudomonas sp. LEw-2029, a non-motile biofilm maker, showed increased MC degradation (0.25 µg/mL/hr). Five out of nine tested dual culture mixtures showed rises in MC degradation rates than their corresponding monocultures; the highest rate reached 0.40 µg/mL/hr for the pair LEw-(1132 + 2029). PCR amplification of mlrA genes yielded negative results for all isolates; subsequent enzyme assay-Mass Spectrum analysis identified no product associated with the mlr gene-based MC degradation pathway. Collectively, our results demonstrated that a diversity of indigenous Lake Erie bacteria can degrade MCs via a novel mlr-independent pathway. Obtained MC degraders, especially Pseudomonas sp. LEw-2029, may serve as candidates for the development of biological filters to remove cyanotoxins in water treatment systems.

Impact of algal organic matter on the performance, cyanotoxin removal, and biofilms of biologically-active filtration systems.

The occurrence of harmful algal blooms dominated by toxic cyanobacteria has induced continuous loadings of algal organic matter (AOM) and toxins in drinking water treatment plants. However, the impact of AOM on the active biofilms and microbial community structures of biologically-active filtration (BAF), which directly affects the contaminant removal, is not well understood. In this study, we systematically examined the effects of AOM on BAF performance and bacterial biofilm formation over 240 days, tracing the removal of specific AOM components, a cyanotoxin [microcystin-LR (MC-LR)], and microbial community responses. The component analysis (excitation and emission matrix analysis) results for AOM revealed that terrestrial humic-like substances showed the highest removal among all the identified components and were strongly correlated to MC-LR removal. In addition, reduced empty bed contact time and deactivation of biofilms significantly decreased BAF performances for both AOM and MC-LR. The active biofilm, bacterial community structure, and mlrA gene (involved in microcystin degradation) abundance demonstrated that bacterial biofilm composition responded to AOM and MC-LR, in which Rhodocyclaceae, Saprospiraceae, and Comamonadaceae were dominant. In addition, MC-LR biodegradation appeared to be more active at the top than at the bottom layer in BAF. Overall, this study provides deeper insights into the role of biofilms and filter operation on the fate of AOM and MC-LR in BAF.

Involvement of peroxiredoxin 2 in cumulus expansion and oocyte maturation in mice.

Peroxiredoxin 2 (Prdx2), an antioxidant enzyme, is expressed in the ovary during the ovulatory process. The aim of the present study was to examine the physiological role of Prdx2 during ovulation using Prdx2-knockout mice and mouse cumulus-oocyte complex (COC) from WT mice. Two days of treatment of immature mice (21-23 days old) with equine chorionic gonadotrophin and followed by treatment with human chorionic gonadotrophin greatly impaired cumulus expansion and oocyte maturation in Prdx2-knockout but not wild-type mice. Treatment of COCs in culture with conoidin A (50µM), a 2-cys Prdx inhibitor, abolished epiregulin (EPI)-induced cumulus expansion. Conoidin A treatment also inhibited EPI-stimulated signal molecules, including signal transducer and activator of transcription-3, AKT and mitogen-activated protein kinase 1/2. Conoidin A treatment also reduced the gene expression of EPI-stimulated expansion-inducing factors (hyaluronan synthase 2 (Has2), pentraxin 3 (Ptx3), TNF-α induced protein 6 (Tnfaip6) and prostaglandin-endoperoxide synthase 2 (Ptgs2)) and oocyte-derived factors (growth differentiation factor 9 (Gdf9) and bone morphogenetic protein 15 (Bmp15)). Furthermore, conoidin A inhibited EPI-induced oocyte maturation and the activity of connexins 43 and 37. Together, these results demonstrate that Prdx2 plays a role in regulating cumulus expansion and oocyte maturation during the ovulatory process in mice, probably by modulating epidermal growth factor receptor signalling.

Electromagnetic fields for biofouling mitigation in reclaimed water distribution systems.

Biofouling is ubiquitous in reclaimed water distribution systems and causes various industrial, economic, and health issues. This paper investigated the anti-biofouling efficacy of electromagnetic fields (EMFs) for agricultural emitters used for two types of reclaimed water. 16S rRNA gene sequencing and X-ray diffraction were applied to determine the microbial communities and mineral compositions in biofilms. The obtained results revealed that EMF treatment significantly changed the bacterial communities and reduced their diversities in biofilm by affecting water quality parameters. Network analysis results indicated that EMFs were detrimental to the co-occurrence patterns of mutualistic relationships among bacterial species, destroyed the connectivity and complexity of the networks, and inhibited biofilm formation [decreased total biomass and extracellular polymeric substance (EPS) content]. EMF treatment could also decrease the deposition of mineral precipitates, reducing the carbonate and silicate content in biofilm. The decrease of EPS content appeared to reduce biofilm-induced mineral crystallization, while the ion precipitations accelerated by EMFs caused an erosive effect on biofilm. The results demonstrated that EMF treatment is an effective, chemical-free, and anti-biofouling treatment method with great potential for biofouling control in reclaimed water distribution systems.

Assessing the chemical compositions and disinfection byproduct formation of biofilms: Application of fluorescence excitation-emission spectroscopy coupled with parallel factor analysis.

There are increased concerns over the contributions of biofilms to disinfection byproduct (DBP) formation in engineered water systems (EWS). However, monitoring the biomolecular characteristics of biofilms to understand their impacts on DBP formation has been a great challenge as it requires complex analytical techniques. This study aimed to examine the applicability of fluorescence excitation-emission matrices (EEMs) coupled with parallel factor analysis (PARAFAC) to assess the chemical compositions and DBP formation of biofilms. Biofilms were collected from reactors grown on R2A media, as well as two drinking water-related organic substrates such as humic substances and algal organic matter. The chemical composition and formation of carbonaceous and nitrogenous DBPs of biofilms were continuously monitored every 21 days for 168 days and correlated with the derived EEM-PARAFAC components. Results indicated that all biofilm samples comprised mostly of protein-like components (∼90%), and to a lesser extent, humic-like components (∼10%). Strong correlations were generally found between tryptophan-like substances and the studied DBP formation (R2min ≥ 0.76, P < 0.05), indicating that they play a major role in producing biofilm-derived DBPs upon chlorination. Moreover, significant discrepancies between the chemical compositions and DBP formation of biofilms and their corresponding feed solutions were observed, likely due to biotransformation and biosorption processes. Overall, this work highlights that EEM-PARAFAC analysis is a promising tool to monitor the biomolecular characteristics of biofilm components and to predict the subsequent DBP formation in optimizing disinfection protocols for EWS.

Highly Sustained Release of Bactericides from Complex Coacervates.

Materials for preventing harmful bacterial contamination attract widespread interest in areas that include healthcare, home/personal care products, and crop protection. One approach to achieving this functionality is through the sustained release of antibacterial compounds. To this end, we show how putty-like complex coacervates, formed through the association of poly(allylamine hydrochloride) (PAH) with pentavalent tripolyphosphate (TPP) ions, can provide a sustained antibacterial effect by slowly releasing bactericides. Using triclosan (TC) as a model bactericide, we demonstrate that, through their dispersion in the parent PAH solution with nonionic surfactants, hydrophobic biocides can be efficiently and predictably encapsulated within PAH/TPP coacervates. Once encapsulated, the bactericide can be released over multiple months, and the release rates can be readily tuned by varying the bactericide and surfactant compositions used during encapsulation. Through this release, the PAH/TPP coacervates provide sustained bactericidal activity against model Gram-positive and Gram-negative bacteria (Staphylococcus aureus and Escherichia coli) grown under a nutrient-rich condition over at least two weeks. Thereafter, though some partial activity persists after one month, the release slows down and the bactericide-eluting coacervates lose their efficacy. Overall, we show that bactericide release from easy-to-prepare complex coacervates can provide a pathway to sustained disinfection.

MYO1D binds with kinase domain of the EGFR family to anchor them to plasma membrane before their activation and contributes carcinogenesis.

The cell surface receptor tyrosine kinase (RTK) exists in a dynamic state, however, it remains unknown how single membrane-spanning RTK proteins are retained in the plasma membrane before their activation. This study was undertaken to investigate how RTK proteins are anchored in the plasma membrane before they bind with their respective extracellular ligands for activation through protein-protein interaction, co-localization, and functional phenotype studies. Here we show that unconventional myosin-I MYO1D functions to hold members of the EGFR family (except ErbB3) at the plasma membrane. MYO1D binds only with unphosphorylated EGFRs and anchors them to underlying actin cytoskeleton at the plasma membrane. The C-terminal end region of the MYO1D tail domain containing a ß-meander motif is critical for direct binding with kinase domain of the EGFR family, and expression of the tail domain alone suppresses the oncogenic action of full-length MYO1D. Overexpressed MYO1D increases colorectal and breast cancer cell motility and viability through upregulating EGFR level, and thereby promotes colorectal tumor progression in a syngeneic mouse model. MYO1D is upregulated in human colorectal cancer tissues from advanced stages. Collectively, molecular motor MYO1D plays a distinct role in the dynamic regulation of EGFR family levels by holding them at the plasma membrane before their activation. Overexpressed MYO1D contributes to colorectal carcinogenesis possibly as a novel oncogene and thus may serve as an additional target for suppression of RTK signaling in cancer treatment.

Noxa mitochondrial targeting domain induces necrosis via VDAC2 and mitochondrial catastrophe.

Noxa, a Bcl-2 homology 3 (BH3)-only protein of the Bcl-2 family, is responsive to cell stresses and triggers apoptosis by binding the prosurvival Bcl-2-like proteins Mcl1, BclXL, and Bcl2A1. Although the Noxa BH3 domain is necessary to induce apoptosis, the mitochondrial targeting domain (MTD) of Noxa functions as a pronecrotic domain, an inducer of mitochondrial fragmentation, and delivery to mitochondria. In this study, we demonstrate that the extended MTD (eMTD) peptide induces necrotic cell death by interaction with the VDAC2 protein. The eMTD peptide penetrates the cell membrane, causing cell membrane blebbing, cytosolic calcium influx, and mitochondrial swelling, fragmentation, and ROS generation. The MTD domain binds VDACs and opens the mitochondrial permeability transition pore (mPTP) in a CypD-independent manner. The opening of mPTP induced by eMTD is inhibited either by down-regulation of VDAC2 or by the VDACs inhibitor DIDS. These results indicate that the MTD domain of Noxa causes mitochondrial damage by opening mPTP through VDACs, especially VDAC2, during necrotic cell death.