MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting SHMT2.

Purpose: To explore the effects of miR-383-5p and serine hydroxymethyltransferase 2 (SHMT2) on the proliferation and migration of lung adenocarcinoma cells. Methods: SHMT2 expression in lung adenocarcinoma and normal tissues was investigated using The Cancer Genome Atlas database. Immunohistochemical analysis was performed to confirm SHMT2 expression in lung adenocarcinoma and adjacent normal lung tissues. Bioinformatics analysis and luciferase reporter assays were used to analyze the relationship between miR-383-5p and SHMT2 expression. The protein expression levels of SHMT2, vimentin, N-cadherin, E-cadherin, Bcl-2, and cyclinD1 were analyzed using western blotting. The reverse transcription-quantitative polymerase chain reaction was used to detect SHMT2 knockdown efficiency, miR-383-5p overexpression, and inhibition efficiency. The proliferative ability of cells was detected using the Cell Counting Kit-8 assay. The Transwell assay was used to detect the migration ability of cells. Results: SHMT2 expression was significantly increased in patients with lung adenocarcinoma compared to that in control patients; the higher the SHMT2 expression the worse the outcomes were in patients with lung adenocarcinoma. SHMT2 knockdown inhibited the proliferation, migration, and epithelial-mesenchymal transition of lung adenocarcinoma A549 and H1299 cells. MiR-383-5p directly targeted and downregulated SHMT2 in A549 and H1299 cells. The effects of miRNA-383-5p on the proliferation and migration of these cells differed from those of SHMT2. Exogenous overexpression of SHMT2 reversed the miR-383-5p-induced proliferation and migration inhibition in A549 and H1299 cells. Conclusion: MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting and downregulating SHMT2.

Plastoquinone synthesis inhibition by tetrabromo biphenyldiol as a widespread algicidal mechanism of marine bacteria.

Algae and bacteria have complex and intimate interactions in the ocean. Besides mutualism, bacteria have evolved a variety of molecular-based anti-algal strategies. However, limited by the unknown mechanism of synthesis and action of these molecules, these strategies and their global prevalence remain unknown. Here we identify a novel strategy through which a marine representative of the Gammaproteobacteria produced 3,3',5,5'-tetrabromo-2,2'-biphenyldiol (4-BP), that kills or inhibits diverse phytoplankton by inhibiting plastoquinone synthesis and its effect cascades to many other key metabolic processes of the algae. Through comparative genomic analysis between the 4-BP-producing bacterium and its algicidally inactive mutant, combined with gene function verification, we identified the gene cluster responsible for 4-BP synthesis, which contains genes encoding chorismate lyase, flavin-dependent halogenase and cytochrome P450. We demonstrated that in near in situ simulated algal blooming seawater, even low concentrations of 4-BP can cause changes in overall phytoplankton community structure with a decline in dinoflagellates and diatoms. Further analyses of the gene sequences from the Tara Oceans expeditions and 2750 whole genome sequences confirmed the ubiquitous presence of 4-BP synthetic genes in diverse bacterial members in the global ocean, suggesting that it is a bacterial tool potentially widely used in global oceans to mediate bacteria-algae antagonistic relationships.

Combination of epidrugs with immune checkpoint inhibitors in cancer immunotherapy: From theory to therapy.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has revolutionized treatment strategies in multiple types of cancer. However, the resistance and relapse as associated with the extreme complexity of cancer-immunity interactions remain a major challenge to be resolved. Owing to the epigenome plasticity of cancer and immune cells, a growing body of evidence has been presented indicating that epigenetic treatments have the potential to overcome current limitations of immunotherapy, thus providing a rationalefor the combination of ICIs with epigenetic agents (epidrugs). In this review, we first make an overview about the epigenetic regulations in tumor biology and immunodevelopment. Subsequently, a diverse array of inhibitory agents under investigations targeted epigenetic modulators (Azacitidine, Decitabine, Vorinostat, Romidepsin, Belinostat, Panobinostat, Tazemetostat, Enasidenib and Ivosidenib, etc.) and immune checkpoints (Atezolizmab, Avelumab, Cemiplimab, Durvalumb, Ipilimumab, Nivolumab and Pembrolizmab, etc.) to increase anticancer responses were described and the potential mechanisms were further discussed. Finally, we summarize the findings of clinical trials and provide a perspective for future clinical studies directed at investigating the combination of epidrugs with ICIs as a treatment for cancer.

SAC-Net: Learning with weak and noisy labels in histopathology image segmentation.

Deep convolutional neural networks have been highly effective in segmentation tasks. However, segmentation becomes more difficult when training images include many complex instances to segment, such as the task of nuclei segmentation in histopathology images. Weakly supervised learning can reduce the need for large-scale, high-quality ground truth annotations by involving non-expert annotators or algorithms to generate supervision information for segmentation. However, there is still a significant performance gap between weakly supervised learning and fully supervised learning approaches. In this work, we propose a weakly-supervised nuclei segmentation method in a two-stage training manner that only requires annotation of the nuclear centroids. First, we generate boundary and superpixel-based masks as pseudo ground truth labels to train our SAC-Net, which is a segmentation network enhanced by a constraint network and an attention network to effectively address the problems caused by noisy labels. Then, we refine the pseudo labels at the pixel level based on Confident Learning to train the network again. Our method shows highly competitive performance of cell nuclei segmentation in histopathology images on three public datasets. Code will be available at: https://github.com/RuoyuGuo/MaskGA_Net.

Microbial community structures and important taxa across oxygen gradients in the Andaman Sea and eastern Bay of Bengal epipelagic waters.

In oceanic oxygen minimum zones (OMZs), the abundances of aerobic organisms significantly decrease and energy shifts from higher trophic levels to microorganisms, while the microbial communities become critical drivers of marine biogeochemical cycling activities. However, little is known of the microbial ecology of the Andaman Sea and eastern Bay of Bengal (BoB) OMZs. In the present study, a total of 131 samples which from the Andaman Sea and eastern BoB epipelagic waters were analyzed. The microbial community distribution patterns across oxygen gradients, including oxygenic zones (OZs, dissolved oxygen [DO] ≥ 2 mg/L), oxygen limited zones (OLZs, 0.7 mg/L < DO < 2 mg/L), and OMZs (DO ≤ 0.7 mg/L), were investigated. Mantel tests and Spearman's correlation analysis revealed that DO was the most important driver of microbial community structures among several environmental factors. Microbial diversity, richness, and evenness were highest in the OLZs and lowest in the OZs. The microbial community compositions of OZ and OMZ waters were significantly different. Random forest analysis revealed 24 bioindicator taxa that differentiated OZ, OLZ, and OMZ water communities. These bioindicator taxa included Burkholderiaceae, HOC36, SAR11 Clade IV, Thioglobaceae, Nitrospinaceae, SAR86, and UBA10353. Further, co-occurrence network analysis revealed that SAR202, AEGEAN-169, UBA10353, SAR406, and Rhodobacteraceae were keystone taxa among the entire interaction network of the microbial communities. Functional prediction further indicated that the relative abundances of microbial populations involved in nitrogen and sulfur cycling were higher in OMZs. Several microbial taxa, including the Thioglobaceae, Nitrospinaceae, SAR202, SAR406, WPS-2, UBA10353, and Woeseiaceae, may be involved in nitrogen and/or sulfur cycling, while also contributing to oxygen consumption in these waters. This study consequently provides new insights into the microbial community structures and potentially important taxa that contribute to oxygen consumption in the Andaman Sea and eastern BoB OMZ.

Toxicity Effects of Combined Mixtures of BDE-47 and Nickel on the Microalgae Phaeodactylum tricornutum (Bacillariophyceae).

Nickel and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are two environmental pollutants commonly and simultaneously present in aquatic systems. Nickel and BDE-47 are individually toxic to various aquatic organisms. However, their toxicity mechanisms are species-dependent, and the toxic effects of combined mixtures of BDE-47 and nickel have not yet been investigated. The present study investigated the toxic effects of combined mixtures of BDE-47 and nickel in the diatom Phaeodactylum tricornutum. BDE-47 and nickel mixtures significantly decreased cell abundance and photosynthetic efficiency, while these cells' reactive oxygen species (ROS) production significantly increased. The EC50-72 h for BDE-47 and mixtures of BDE-47 and nickel were 16.46 ± 0.93 and 1.35 ± 0.06 mg/L, respectively. Thus, combined mixtures of the two pollutants enhance their toxic effects. Interactions between BDE-47 and nickel were evaluated, revealing synergistic interactions that contributed to toxicity in P. tricornutum. Moreover, transcriptomic analyses revealed photosynthesis, nitrogen metabolism, the biosynthesis of amino acids, the biosynthesis of secondary metabolites, oxoacid metabolism, organic acid metabolism, carboxylic acid metabolism, and oxidation-reduction processes were considerably affected by the mixtures. This study provides evidence for the mechanisms of toxicity from combined BDE-47 and nickel exposure while also improving our understanding of the ecological risks of toxic chemicals on microalgae.

Toxic effect of nickel on microalgae Phaeodactylum tricornutum (Bacillariophyceae).

Nickel acts as an essential trace nutrient or toxicant for organisms, depending on its concentration. The increased concentrations of nickel, due to anthropogenic activity, in the aquatic environment are potential threats to aquatic organisms. However, the knowledge on toxic mechanisms of nickel to microalgae remains incompletely understood. In the present study, we investigated the toxic effects of nickel in the cosmopolitan diatom Phaeodactylum tricornutum via evaluation of physiological and transcriptome responses. The results showed that the median effective concentration-72 h (EC50-72 h) and EC50-96 h of nickel was 2.48 ± 0.33 and 1.85 ± 0.17 mg/L, respectively. The P. tricornutum cell abundance and photosynthesis significantly decreased by 1 mg/L of nickel. Results from photosynthetic parameters including efficiency of the oxygen evolving complex (OEC) of photosystem II (PSII) (Fv/F0), maximum photosynthetic efficiency of PS II (Fv/Fm), electron transport rate (ETR), actual photosynthetic efficiency of PS II (Y(II)), non-photochemical quenching (NPQ), and photochemical quenching (qP) indicated that OEC of PS II might be impaired by nickel. The transcriptome data also reveal that OEC apparatus coding gene PS II oxygen-evolving enhancer protein 2 (PsbP) was regulated by nickel. Moreover, induced reactive oxygen species (ROS) production and chlorophyll a content were also detected under nickel stress. Transcriptome analysis revealed that nickel affected a variety of differentially expressed genes (DEGs) that involved in redox homeostasis, nitrogen metabolisms, fatty acids, and DNA metabolism. However, thiol-disulfide redox system might play important roles in nickel-induced oxidative stress resistance. This study improved the understanding of the toxic effect of nickel on the diatom P. tricornutum.

Detection and Quantification of the Harmful Dinoflagellate Margalefidinium polykrikoides (East Asian Ribotype) in the Coastal Waters of China.

As a marine ichthyotoxic dinoflagellate, Margalefidinium polykrikoides, previously named Cochlodinium polykrikoides, have caused mass mortalities of fish worldwide during blooms. Rapid detection of target species is a prerequisite for the timely monitoring and early warning of harmful algal blooms (HABs). However, it is difficult to achieve rapid identification with traditional methods. The technology of using quantitative real-time PCR (qPCR) to detect and quantify microalgae is relatively mature. Based on the accuracy, rapidity, and sensitivity of qPCR technology, it can be used in the monitoring and development of early warning systems for HABs. From 2017 to 2020, samples were collected from 15 locations off the Chinese coast or from local sea areas. Based on the qPCR detection and analysis, the target species, M. polykrikoides (East Asian ribotype, EAr), was found in samples from Tianjin, Yangtze River estuary, and offshore Fujian (East China Sea). This is the first time that M. polykrikoides (EAr) was detected in the coastal waters of Tianjin. The results reveal a distributive pattern of M. polykrikoides (EAr) along Chinese coastal waters. It is helpful to predict the future diffusion trend of M. polykrikoides (EAr) in the China Sea and provides a practical case for the future construction of monitoring and warning systems for M. polykrikoides and HABs.

Great future or greedy venture: Precision medicine needs philosophy.

INTRODUCTION: Over the past decade, we have witnessed the initiation and implementation of precision medicine (PM), a discipline that promises to individualize and personalize medical management and treatment, rendering them ultimately more precise and effective. Despite of the continuing advances and numerous clinical applications, the potential of PM remains highly controversial, sparking heated debates about its future. METHOD: The present article reviews the philosophical issues and practical challenges that are critical to the feasibility and implementation of PM. OUTCOME: The explanation and argument about the relations between PM and computability, uncertainty as well as complexity, show that key foundational assumptions of PM might not be fully validated. CONCLUSION: The present analysis suggests that our current understanding of PM is probably oversimplified and too superficial. More efforts are needed to realize the hope that PM has elicited, rather than make the term just as a hype.

Comparative transcriptomics of toxin synthesis genes between the non-toxin producing dinoflagellate Cochlodinium polykrikoides and toxigenic Alexandrium pacificum.

In the present study, we extensively characterized potential toxin-related genes, including polyketide synthase (PKS), saxitoxin (STX) and fatty acid synthase (FAS) from the non-toxin producing marine dinoflagellate Cochlodinium polykrikoides, comparing to those of a toxigenic dinoflagellate Alexandrium pacificum. RNA sequencing revealed 50 and 271 PKS contigs from C. polykrikoides and A. pacificum, respectively. According to domain constitute and amino acid alteration, we further classified the dinoflagellate type I PKS genes into 4 sub-groups. Type III PKS was first identified in C. polykrikoides. Interestingly, we detected a large number (242 and 288) of homologs of 18 sxt genes from two studied dinoflagellates. Most of the eight key genes (sxtA, sxtB, sxtD, sxtG, sxtH/T, sxtI, sxtS and sxtU) for STX synthesis were detected in both dinoflatellates, whereas a core STX biosynthesis gene sxtG was not detected in C. polykrikoides. This may partially explain the absence of saxitoxin production in C. polykrikoides. In addition, we identified several type I and type II FAS genes, including FabD, FabF, FabG, FabH, FabI, and FabZ, whereas FabB was not found in C. polykrikoides. Overall, the numbers of the toxin-related genes in C. polykrikoides were less than that of A. pacificum. Phylogenetic analyses showed that type I PKS/FASs of dinoflagellates had close relationships with apicomplexans and bacteria. These suggest that the toxin-related PKS and sxt genes are commonly present in toxigenic and non-toxin producing dinoflagellates, and may be involved not only in the toxin synthesis, but also in other related molecular metabolic functions.

Insight Into the Pico- and Nano-Phytoplankton Communities in the Deepest Biosphere, the Mariana Trench.

As photoautotrophs, phytoplankton are generally present in the euphotic zone of the ocean, however, recently healthy phytoplankton cells were found to be also ubiquitous in the dark deep sea, i.e., at water depths between 2000 and 4000 m. The distributions of phytoplankton communities in much deeper waters, such as the hadal zone, are unclear. In this study, the vertical distribution of the pico- and nano-phytoplankton (PN) communities from the surface to 8320 m, including the epipelagic, mesopelagic, bathypelagic, and hadal zones, were investigated via both 18S and p23S rRNA gene analysis in the Challenger Deep of the Mariana Trench. The results showed that Dinoflagellata, Chrysophyceae, Haptophyta, Chlorophyta, Prochloraceae, Pseudanabaenaceae, Synechococcaceae, and Eustigmatophyceae, etc., were the predominant PN in the Mariana Trench. Redundancy analyses revealed that depth, followed by temperature, was the most important environmental factors correlated with vertical distribution of PN community. In the hadal zone, the PN community structure was considerably different from those in the shallower zones. Some PN communities, e.g., Eustigmatophyceae and Chrysophyceae, which have the heterotrophic characteristics, were sparse in shallower waters, while they were identified with high relative abundance (94.1% and 20.1%, respectively) at the depth of 8320 m. However, the dinoflagellates and Prochloraceae Prochlorococcus were detected throughout the entire water column. We proposed that vertical sinking, heterotrophic metabolism, and/or the transition to resting stage of phytoplankton might contribute to the presence of phytoplankton in the hadal zone. This study provided insight into the PN community in the Mariana Trench, implied the significance of phytoplankton in exporting organic matters from the euphotic to the hadal zone, and also hinted the possible existence of some undetermined energy metabolism (e.g., heterotrophy) of phytoplankton making themselves adapt and survive in the hadal environment.

RuBisCO large subunit gene primers for assessing the CO2-assimilating planktonic community structure in Jiaozhou Bay, China.

The protein coding genes (rbcL/cbbL/cbbM) for RuBisCO large subunit, the most abundant protein on earth that drives biological CO2 fixation, were considered as useful marker genes in characterizing CO2-assimilating plankton. However, their community specificity has hindered comprehensive screening of genetic diversity. In this study, six different rbcL/cbbL/cbbM primers were employed to screen clone libraries to identify CO2-assimilating plankton in Jiaozhou Bay. The following community compositions were observed: the community components in Form I A/B rbcL/cbbL clone library mainly comprised Chlorophyta and Proteobacteria, Form ID2 and ID3 libraries consisted of Bacillariophyta, Form II cbbM library consisted of Proteobacteria and Alveolata, and both Form I green and red libraries included Proteobacteria, respectively. At the genus taxonomic level, no overlaps among these clone libraries were observed, except for ID2 and ID3. Overall, the phytoplankton in Jiaozhou Bay mainly consists of Bacillariophyta, Chlorophyta, Cryptophyta, Haptophyceae and Alveolata. The CO2-assimilating prokaryotes mainly consist of Proteobacteria. Considering the high-sequence specificities of these marker genes, we propose that the joint use of multiple primers may be utilized in unveiling the diversity of CO2-assimilating organisms. In addition, designing novel RuBisCO gene primers that generate longer amplicons and have broader phylogenetic coverage may be necessary in the future.

6.0 K microarray reveals differential transcriptomic responses in the dinoflagellate Prorocentrum minimum exposed to polychlorinated biphenyl (PCB).

Endocrine disrupting chemicals (EDCs) have toxic effects on algae; however, their molecular genomic responses have not been sufficiently elucidated. Here, we evaluated genome-scaled responses of the dinoflagellate alga Prorocentrum minimum exposed to an EDC, polychlorinated biphenyl (PCB), using a 6.0 K microarray. Based on two-fold change cut-off, we identified that 609 genes (∼10.2%) responded to the PCB treatment. KEGG pathway analysis showed that differentially expressed genes (DEGs) were related to ribosomes, biosynthesis of amino acids, spliceosomes, and cellular processes. Many DEGs were involved in cell cycle progression, apoptosis, signal transduction, ion binding, and cellular transportation. In contrast, only a few genes related to photosynthesis and oxidative stress were expressed in response to PCB exposure. This was supported by that fact that there were no obvious changes in the photosynthetic efficiency and reactive oxygen species (ROS) production. These results suggest that PCB might not cause chloroplast and oxidative damage, but could lead to cell cycle arrest and apoptosis. In addition, various signal transduction and transport pathways might be disrupted in the cells, which could further contribute to cell death. These results expand the genomic understanding of the effects of EDCs on this dinoflagellate protist.

Transfer of the small diatoms Thalassiosira proschkinae and T. spinulata to the genus Minidiscus and their taxonomic re-description.

The marine diatoms Thalassiosira proschkinae and T. spinulata are relatively small in size; their taxonomic identities have been debated owing to the diverse morphological variations. In the present study, we isolated both morphotypes from Korean coastal waters and examined their fine structures and conducted molecular sequence comparisons. The morphological and molecular analyses showed that T. proschkinae and T. spinulata were certainly distinct, and phenotypic plasticity of valve structure was not noted. Based on the morphological similarity and phylogenetic relationship, we transferred T. proschkinae and T. spinulata to another genus Minidiscus within Thalassiosirales that includes small-sized species and proposed new combination names, Minidiscus proschkinae (Makarova) Park & Lee comb. nov. and Minidiscus spinulatus (Takano) Park & Lee comb. nov., respectively. The genus description of Minidiscus was emended.

Physiological and biochemical responses of the freshwater green algae Closterium ehrenbergii to the common disinfectant chlorine.

Chlorine (Cl2) is widely used as a disinfectant in water treatment plants and for cleaning swimming pools; it is finally discharged into aquatic environments, possibly causing damage to the non-target organisms in the receiving water bodies. Present study evaluated the effects of the biocide Cl2 to the green alga Closterium ehrenbergii (C. ehrenbergii). Growth rate, chlorophyll a levels, carotenoids, chlorophyll autofluorescence, and antioxidant enzymes were monitored up to 72-h after Cl2 exposure. C. ehrenbergii showed dose-dependent decrease in growth rate and cell division after exposure to Cl2. By using cell counts, the median effective concentration (EC50)-72-h was calculated to be 0.071mgL(-1). Cl2 significantly decreased the pigment levels and chlorophyll autofluorescence intensity, indicating that the photosystem was damaged in C. ehrenbergii. In addition, it increased the production of reactive oxygen species (ROS) in the cells. This stressor significantly increased the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase, and glutathione, and affected the physiology of the cells. These results indicate that Cl2 induces oxidative stress in the cellular metabolic process and leads to physiological and biochemical damages in the green algae. Cl2 discharged in industrial effluents and from water treatment plants may cause harmful effects to the C. ehrenbergii a common freshwater microalgae and other non-target organisms.

Transcriptomic profiles reveal the genome-wide responses of the harmful dinoflagellate Cochlodinium polykrikoides when exposed to the algicide copper sulfate.

BACKGROUND: Harmful algal blooms (HABs) caused by the dinoflagellate Cochlodinium polykrikoides lead to severe environmental impacts in oceans worldwide followed by huge economic losses. Algicide agent copper sulfate (CuSO4) is regard as an economical and effective agent for HABs mitigation; its biochemical and physiological effects were revealed in C. polykrikoides. However, molecular mechanisms of CuSO4 effect on the C. polykrikoides, even other HAB species, have not been investigated. The present study investigated the transcriptional response of C. polykrikoides against CuSO4 treatments, with the aim of providing certain molecular mechanism of CuSO4 effect on the C. polykrikoides blooms. RESULTS: RNA-seq generated 173 million reads, which were further assembled to 191,212 contigs. 43.3 %, 33.9 %, and 15.6 % of contigs were annotated with NCBI NR, GO, and KEGG database, respectively. Transcriptomic analysis revealed 20.6 % differential expressed contigs, which grouped into 8 clusters according to K-means clustering analysis, responding to CuSO4; 848 contigs were up-regulated and 746 contigs were down-regulated more than 2-fold changes from 12 h to 48 h exposure. KEGG pathway analysis of eukaryotic homologous genes revealed the differentially expressed genes (DEGs) were involved in diverse pathway; amongst, the genes involved in the translation, spliceosome, and/or signal transduction genes were highly regulated. Most of photosystem related genes were down-regulated and most of mitochondria related genes were up-regulated. In addition, the genes involved in the copper ion binding or transporting and antioxidant systems were identified. Measurement of chlorophyll fluorescence showed that photosynthesis was significantly inhibited by CuSO4 exposure. CONCLUSIONS: This study reported the first transcriptome of the C. polykrikoides. The widely differential expressed photosystem genes suggested photosynthetic machinery were severely affected, and may further contribute to the cell death. Furthermore, gene translation and transcription processes may be disrupted, inhibiting cell growth and proliferation, and possibly accelerating cell death. However, antioxidant systems resistant to CuSO4 caused stress; mitochondrion may compensate for photosynthesis efficiency decreasing caused energy deficiency. In addition, various signal transduction pathways may be involved in the CuSO4 induced regulation network in the C. polykrikoides. These data provide the potential transcriptomic mechanism to explain the algicide CuSO4 effect on the harmful dinoflagellate C. polykrikoides.

Genome-wide analysis of transcription and photosynthesis inhibition in the harmful dinoflagellate Prorocentrum minimum in response to the biocide copper sulfate.

Copper is an essential trace metal for organisms; however, excess copper may damage cellular processes. Their efficiency and physiological effects of biocides have been well documented; however, molecular transcriptome responses to biocides are insufficiently studied. In the present study, a 6.0K oligonucleotide chip was developed to investigate the molecular responses of the harmful dinoflagellate Prorocentrum minimum to copper sulfate (CuSO4) treatment. The results revealed that 515 genes (approximately 8.6%) responded to CuSO4, defined as being within a 2-fold change. Further, KEGG pathway analysis showed that differentially expressed genes (DEGs) were involved in ribosomal function, RNA transport, carbon metabolism, biosynthesis of amino acids, photosystem maintenance, and other cellular processes. Among the DEGs, 49 genes were related to chloroplasts and mitochondria. Furthermore, the genes involved in the RAS signaling pathway, MAPK signaling pathway, and transport pathways were identified. An additional experiment showed that the photosynthesis efficiency decreased considerably, and reactive oxygen species (ROS) production increased in P. minimum after CuSO4 exposure. These results suggest that CuSO4 caused cellular oxidative stress in P. minimum, affecting the ribosome and mitochondria, and severely damaged the photosystem. These effects may potentially lead to cell death, although the dinoflagellate has developed a complex signal transduction process to combat copper toxicity.

Corrigendum to "Heat Shock Protein 70 and 90 Genes in the Harmful Dinoflagellate Cochlodinium polykrikoides: Genomic Structures and Transcriptional Responses to Environmental Stresses".

[This corrects the article DOI: 10.1155/2015/484626.].

A novel cyclophilin gene from the dinoflagellate Prorocentrum minimum and its possible role in the environmental stress response.

Cyclophilins (CYPs) are a family of proteins that bind to cyclosporine and are thought to be involved in the stress response. In dinoflagellate algae, CYPs may function as a survival strategy in cells exposed to environmental stressors. Here, we identified a novel cyclophilin gene (referred to as PmCYP, comprising a 516-bp open reading frame, encoding a 171-aa protein with a molecular mass of 17.5kDa) from the dinoflagellate Prorocentrum minimum, and evaluated the role of dinoflagellate CYP in cells exposed to environmental pollutants copper and polychlorinated biphenyl. In addition, we assessed the cytoprotective role of nitric oxide in relation to the expression of PmCYP. These stressors strongly affected the physiology of the cells, as judged by cell counting, reactive oxygen species (ROS) imaging, and photosynthetic parameters (Fv/Fm and PIABS). PmCYP expression was significantly (P<0.05) induced upon exposure of the cells to all the test pollutants used in this study. These clearly indicate that PmCYP plays a vital role in the oxidative stress response in dinoflagellate survival, although the gene was initially known only for its housekeeping function.

Heat Shock Protein 70 and 90 Genes in the Harmful Dinoflagellate Cochlodinium polykrikoides: Genomic Structures and Transcriptional Responses to Environmental Stresses.

The marine dinoflagellate Cochlodinium polykrikoides is responsible for harmful algal blooms in aquatic environments and has spread into the world's oceans. As a microeukaryote, it seems to have distinct genomic characteristics, like gene structure and regulation. In the present study, we characterized heat shock protein (HSP) 70/90 of C. polykrikoides and evaluated their transcriptional responses to environmental stresses. Both HSPs contained the conserved motif patterns, showing the highest homology with those of other dinoflagellates. Genomic analysis showed that the CpHSP70 had no intron but was encoded by tandem arrangement manner with separation of intergenic spacers. However, CpHSP90 had one intron in the coding genomic regions, and no intergenic region was found. Phylogenetic analyses of separate HSPs showed that CpHSP70 was closely related with the dinoflagellate Crypthecodinium cohnii and CpHSP90 with other Gymnodiniales in dinoflagellates. Gene expression analyses showed that both HSP genes were upregulated by the treatments of separate algicides CuSO4 and NaOCl; however, they displayed downregulation pattern with PCB treatment. The transcription of CpHSP90 and CpHSP70 showed similar expression patterns under the same toxicant treatment, suggesting that both genes might have cooperative functions for the toxicant induced gene regulation in the dinoflagellate.