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Prostate cancer is a leading cause of cancer death in men. Inflammation and overexpression of inducible nitric oxide synthase (NOS2) have been implicated in prostate carcinogenesis. We aimed to explore the hypothesis that nitric oxide NO exerts pro-tumorigenic effects on prostate cells at physiologically relevant levels contributing to carcinogenesis. We investigated the impact of acute exposure of normal immortalised prostate cells (RWPE-1) to NO on cell proliferation and activation of DNA damage repair pathways. Furthermore we investigated the long term effects of chronic NO exposure on RWPE-1 cell migration and invasion potential and hallmarks of transformation. Our results demonstrate that NO induces DNA damage as indicated by γH2AX foci and p53 activation resulting in a G1/S phase block and activation of 53BP1 DNA damage repair protein. Long term adaption to NO results in increased migration and invasion potential, acquisition of anchorage independent growth and increased resistance to chemotherapy. This was recapitulated in PC3 and DU145 prostate cancer cells which upon chronic exposure to NO displayed increased cell migration, colony formation and increased resistance to chemotherapeutics. These findings indicate that NO may play a key role in the development of prostate cancer and the acquisition of an aggressive metastatic phenotype.
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Próstata , Neoplasias da Próstata , Carcinogênese , Linhagem Celular Tumoral , Humanos , Masculino , Óxido Nítrico/metabolismo , Fenótipo , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismoRESUMO
Biological invasions represent one of the main threats to marine biodiversity. From a conservation perspective, especially in the context of increasing sea warming, it is critical to examine the suitability potential of geographical areas for the arrival of Range-Expanding Introduced and Native Species (REINS), and hence anticipate the risk of such species to become invasive in their new distribution areas. Here, we developed an empirical index, based on functional and bio-ecological traits, that estimates the Invasive Potential (IP; i.e. the potential success in transport, introduction and population establishment) for a set of 13 fishes that are expanding their distributional range into the Mediterranean Sea, the most invaded sea in the world. The IP index showed significant correlation with the observed spreading of REINS. For the six species characterized by the highest IP, we calculated contemporary and future projections of their Environmental Suitability Index (ESI). By using an ensemble modelling approach, we estimated the geographical areas that are likely to be the most impacted by REINS spreading under climate change. Our results demonstrated the importance of functional traits related to reproduction for determining high invasion potential. For most species, we found high contemporary ESI values in the South-eastern Mediterranean Sea and low to intermediate contemporary ESI values in the Adriatic Sea and North-western Mediterranean sector. Moreover, we highlighted a major potential future expansion of high ESI values, and thus REINS IP, towards the northern Mediterranean, especially in the northern Adriatic Sea. This potential future northward expansion highlights the risk associated with climate-induced impacts on ecosystem conservation and fish stock management throughout the entire Mediterranean Sea.
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Mudança Climática , Espécies Introduzidas , Animais , Ecossistema , Peixes , Mar MediterrâneoRESUMO
Predicting tumor metastatic potential remains a challenge in cancer research and in clinical diagnosis. Cancer invasion to neighboring tissues is a significant event in cancer progression to metastasis. Optical redox imaging (ORI) is based on detecting the endogenous fluorescence signals of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD). Previously, we found that ORI can discriminate between cancer and normal tissue specimens from clinical breast cancer patients and can differentiate the relative invasiveness of melanoma and breast tumors. In this study, we aimed to identify ORI biomarkers to differentiate the invasiveness of four triple-negative breast cancer cell lines (TNBC). Using a fluorescence microscope, we acquired NADH and FAD fluorescent signals from cultured MDA-MB-231, MDA-MB-436, HCC1806, and MDA-MB-468 cells. We found that (1) the redox ratio, FAD/(NADH+FAD), differentiated the four TNBC lines; (2) there was a significant difference of invasive potential between MDA-MB-231 and the other three TNBC lines measured by the transwell invasion assay; and (3) there was a positive logarithmic correlation between the redox ratio and the invasive potential, where the most invasive MDA-MB-231 cells had the highest redox ratio and the least invasive MDA-MB-468 cells had the lowest redox ratio. These results suggest that the redox ratio can potentially be used as a biomarker for TNBC invasiveness and prognosis.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Biomarcadores , Linhagem Celular Tumoral , Humanos , NAD/metabolismo , Invasividade Neoplásica , Imagem Óptica , Oxirredução , Neoplasias de Mama Triplo Negativas/diagnóstico por imagemRESUMO
The receptor-interacting protein kinase 4 (RIPK4) plays an important role in the development and maintenance of various tissues including skin, but its role in melanoma has not been reported. Using patient-derived cell lines and clinical samples, we show that RIPK4 is expressed in melanomas at different levels. This heterogenous expression, together with very low level of RIPK4 in melanocytes, indicates that the role of this kinase in melanoma is context-dependent. While the analysis of microarray data has revealed no straightforward correlation between the stage of melanoma progression and RIPK4 expression in vivo, relatively high levels of RIPK4 are in metastatic melanoma cell lines. RIPK4 down-regulation by siRNA resulted in the attenuation of invasive potential as assessed by time-lapse video microscopy, wound-healing and transmigration assays. These effects were accompanied by reduced level of pro-invasive proteins such as MMP9, MMP2, and N-cadherin. Incubation of melanoma cells with phorbol ester (PMA) increased PKC-1ß level and hyperphosphorylation of RIPK4 resulting in degradation of RIPK4. Interestingly, incubation of cells with PMA for short and long durations revealed that cell migration is controlled by the NF-κB signaling in a RIPK4-dependent (RIPK4high) or independent (RIPK4low) manner depending on cell origin (distant or lymph node metastasis) or phenotype (mesenchymal or epithelial).
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Proliferação de Células/genética , Melanócitos/metabolismo , Melanoma/patologia , Proteína Quinase C beta/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Antígenos CD/análise , Apoptose/fisiologia , Caderinas/análise , Movimento Celular/fisiologia , Células Cultivadas , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Quinase I-kappa B/metabolismo , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 9 da Matriz/análise , Melanoma/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Fosforilação , Proteína Quinase C beta/análise , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/genética , Interferência de RNA , RNA Interferente Pequeno/genética , Fator de Transcrição RelA/metabolismo , Transplante HeterólogoRESUMO
After a long pause, the accumulation of data on the involvement of tumor-specific DNA and extracellular DNA in metastasis has again placed enzymes with deoxyribonuclease activity in the focus of the search for antitumor and antimetastatic drugs. In this work, the ability of bovine pancreatic DNase I to reduce the invasive potential of B16 melanoma has been investigated in vitro and in vivo. It was found that DNase I had a cytotoxic effect on B16 melanoma cells (IC50 ≈ 10^(4) U/mL). At the same time, significantly lower doses of DNase I (10^(2)-10^(3) U/mL) inhibited the migratory activity of melanoma cells in vitro, causing a decrease in the distance of cell front migration and in the area of scratch healing 48 h after the enzyme addition, as well as reducing the rate of cell migration. In mice with B16 metastatic melanoma, intramuscular administration of DNase I in the dose range of 0.12-1.20 mg/kg resulted in a two- to threefold decrease in the number of surface lung metastases and caused nonspecific antigenic immune stimulation.
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Antineoplásicos/farmacologia , Desoxirribonuclease I/farmacologia , Imunidade Inata/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos/isolamento & purificação , Bovinos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desoxirribonuclease I/isolamento & purificação , Feminino , Injeções Intramusculares , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Melanoma Experimental/imunologia , Melanoma Experimental/secundário , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Pâncreas/química , Pâncreas/enzimologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
The invasive/metastatic potential of cancer cells is an important factor in tumor progression. The redox ratios obtained from ratios of the endogenous fluorescent signals of NADH and FAD, can effectively respond to the alteration of cancer cells in its mitochondrial energy metabolism. It has been shown previously that the redox ratios may predict the metastatic potential of cancer mouse xenografts. In this report, we aimed to investigate the metabolic state represented by the redox ratios of cancer cells in vitro. Fluorescence microscopic imaging technology was used to observe the changes of the endogenous fluorescence signals of NADH and FAD in the energy metabolism pathways. We measured the redox ratios (FAD/NADH) of breast cancer cell lines MDA-MB-231, MDA-MB-468, MCF-7, and SKBR3. We found that the more invasive cancer cells have higher FAD/NADH ratios, largely consistent with previous studies on breast cancer xenografts. Furthermore, by comparing the fluorescence signals of the breast cancer cells under different nutritional environments including starvation and addition of glutamine, pyruvate and lactate, we found that the redox ratios still effectively distinguished the highly invasive MDA-MB-231 cells from less invasive MCF-7 cells. These preliminary data suggest that the redox ratio may potentially provide a new index to stratefy breast cancer with different degrees of aggressiveness, which could have significance for the diagnosis and treatment of breast cancer.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Movimento Celular , Metabolismo Energético , Mitocôndrias/metabolismo , Neoplasias da Mama/patologia , Metabolismo Energético/efeitos dos fármacos , Feminino , Flavina-Adenina Dinucleotídeo/metabolismo , Humanos , Células MCF-7 , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , NAD/metabolismo , Invasividade Neoplásica , Oxirredução , Rotenona/farmacologia , Microambiente Tumoral , Desacopladores/farmacologiaRESUMO
Natural phenolic compounds have antioxidant properties owing to their free radical-scavenging capability. The combined effect of a mixture of phenolic compounds has been studied; however, the detailed investigation for finding a correlation between single phenolic molecules and antioxidant activity has not been explored. Herein, we revealed that the number of phenolic hydroxyl groups in phenolics played a central role in their antioxidant capacity. Based on the finding, tannic acid showed the most effective antioxidant potential, e.g., 76% in tannic acid versus 22% in vitamin C as a standard antioxidant component. Because cancer progression is closely related to oxidative processes at the cellular level, we further applied the surface treatment of tannic acid drug-delivery nanocarriers. Tannic acid-loaded nanocarriers reduced reactive oxygen species of cancer cells as much as 41% of vehicle treatment and remodeled cytoskeletal network. By a gelatin degradation study, TA-loaded nanocarrier-treated cells induced 44.6% reduction of degraded area than vehicle-treated cells, implying a potential of blocking invasiveness of cancer cells.
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Antioxidantes , Neoplasias , Antioxidantes/farmacologia , Fenóis/farmacologia , Oxirredução , Taninos/farmacologia , Espécies Reativas de OxigênioRESUMO
Ornamental plant species introduced into new environments can exhibit an invasive potential and adaptability to abiotic stress factors. In this study, the drought stress responses of four potentially invasive ornamental grass species (Cymbopogon citratus, Cortaderia selloana, Pennisetum alopecuroides and P. setaceum) were analysed. Several seed germination parameters were determined under increasing polyethylene glycol (PEG 6000) concentrations. Additionally, plants in the vegetative stage were subjected to intermediate and severe water stress treatments for four weeks. All species registered high germination rates in control conditions (no stress treatment), even at high PEG concentrations, except C. citratus, which did not germinate at -1 MPa osmotic potential. Upon applying the water stress treatments, P. alopecuroides plants showed the highest tolerance, and C. citratus appeared the most susceptible to drought. Stress-induced changes in several biochemical markers (photosynthetic pigments, osmolytes, antioxidant compounds, root and shoot Na+ and K+ contents), highlighted different responses depending on the species and the stress treatments. Basically, drought tolerance seems to depend to a large extent on the active transport of Na+ and K+ cations to the aerial part of the plants, contributing to osmotic adjustment in all four species and, in the case of the most tolerant P. alopecuroides, on the increasing root K+ concentration under water deficit conditions. The study shows the invasive potential of all species, except C. citratus, in dry areas such as the Mediterranean region, especially in the current climate change scenario. Particular attention should be given to P. alopecuroides, which is widely commercialised in Europe as ornamental.
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Increased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, a major cause of mortality, is not yet understood. It is previously identified that the composition and stiffness of alginate-based hydrogels mimicking normal (1-2 kPa) and cancerous (6-10 kPa) breast tissue govern phenotype of breast cancer cells (including MDA-MB-231) in vitro. Here, to understand the causal effect of primary tumor stiffness on metastatic potential, a new breast-to-bone in vitro model is described. Together with alginate-gelatin hydrogels to mimic breast tissue, 3D printed biohybrid poly-caprolactone (PCL)-composite scaffolds, decellularized following bone-ECM deposition through Saos-2 engraftment, are used to mimic the bone tissue. It is reported that higher hydrogel stiffness results in the increased migration and invasion capacity of MDA-MB 231 cells. Interestingly, increased expression of osteolytic factors PTHrP and IL-6 is observed when MDA-MB-231 cells pre-conditioned in stiffer hydrogels (10 kPa, 3% w/v gelatin) colonize the bone/PCL scaffolds. The new breast-to-bone in vitro models herein described are designed with relevant tissue microenvironmental factors and could emerge as future non-animal technological platforms for monitoring metastatic processes and therapeutic efficacy.
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Neoplasias Ósseas , Gelatina , Humanos , Osso e Ossos , Hidrogéis , Alginatos , Alicerces TeciduaisRESUMO
The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor mediating the clearance of various molecules from the extracellular matrix. LRP1 also regulates cell surface expression of matrix receptors by modulating both extracellular and intracellular signals, though current knowledge of the underlying mechanisms remains partial in the frame of cancer cells interaction with matricellular substrates. In this study we identified that LRP1 downregulates calpain activity and calpain 2 transcriptional expression in an invasive thyroid carcinoma cell model. LRP1-dependent alleviation of calpain activity limits cell-matrix attachment strength and contributes to FTC133 cells invasive abilities in a modified Boyden chamber assays. In addition, using enzymatic assays and co-immunoprecipitation experiments, we demonstrated that LRP1 exerts post-translational inhibition of calpain activity through PKA-dependent phosphorylation of calpain-2. This LRP-1 dual mode of control of calpain activity fine-tunes carcinoma cell spreading. We showed that LRP1-mediated calpain inhibition participates in talin-positive focal adhesions dissolution and limits ß1-integrin expression at carcinoma cell surface. In conclusion, we identified an additional and innovative intracellular mechanism which demonstrates LRP-1 pro-motile action in thyroid cancer cells. LRP-1 ability to specifically control calpain-2 expression and activity highlights a novel facet of its de-adhesion receptor status.
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BACKGROUND: The SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany. METHODS: Between March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically ill patients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS). RESULTS: Major clinical neurological features of hospitalized COVID-19 patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR. CONCLUSIONS: In line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.
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The presence of the oligochaete species Quistadrilus multisetosus (Smith, 1900) originating from North America has been mentioned for several decades in Europe, the Middle East and Russia. Its distribution and abundance in Europe is still unknown but it can be considered as potentially invasive. This species was recently discovered in Lake Geneva (Switzerland/France) and three other Swiss lakes. The aims of the present work are to report its repartition and abundance in Lake Geneva, to study its ecology and to determine its invasive potential in this lake. We also provide an identification key for correctly differentiating Q. multisetosus from the closely related species Spirosperma ferox Eisen, 1879 and Embolocephalus velutinus (Grube, 1879), and study the phylogenetic position of Q. multisetosus within several Tubificinae lineages based on the cytochrome c oxidase (COI) marker. Twenty-eight sites have been monitored since 2009 in Lake Geneva. In several sites, the COI sequence corresponding to this species was also searched for in sediment samples using high-throughput sequencing. In addition, we examined specimens collected in this lake before 2009 likely to belong to Q. multisetosus and to have been misidentified. We found that Q. multisetosus was only present in the lake downstream of a wastewater treatment plant and a combined sewer overflow in the Vidy Bay (near Lausanne) and at a site located nearby. These results confirmed the high tolerance of this species to organic matter pollution. Q. multisetosus was already present in this location in 1974 (misidentified as Spirosperma ferox), which suggests that Q. multisetosus has a limited capacity to disseminate in this lake. However, we recommend continuing monitoring its presence in Lake Geneva in the future, especially in the context of warming of waters that could contribute to the expansion of this species.
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AIMS AND OBJECTIVES: The aim of this study was to evaluate the effectiveness of three different caries excavation methods using micro-computed tomography (micro-CT). MATERIALS AND METHODS: Fifteen freshly extracted human molar teeth with occlusal dentinal caries were selected. The teeth were sectioned longitudinally into two halves and were randomly divided into three groups (n = 10) depending on the caries removal technique: Group 1: tungsten carbide (TC) bur, Group 2: cerabur (CB), and Group 3: Excavus (EX) tipEX). A preoperative micro-CT scan of all the samples was taken. The caries excavation procedures were carried out followed by postoperative micro-CT scan. The preoperative and postoperative scans of each tooth were analyzed for caries removal effectiveness (CRE), mineral density (MD), and minimal invasiveness potential (MIP) using Avizo 9.4 software (Thermo Fisher Scientific, Germany). Statistical analysis was conducted by applying three-way analysis of variance and independent sample t-test using the Statistical Package for the Social Sciences software, version 20.0 (IBM Corporation, USA). RESULTS: Among the three groups, the TC group had the smallest RC/IC (residual caries/initial caries) ratio, highest mean MD at the cavity floor, and highest MIP. The EX group significantly had the highest RC/IC, lowest mean MD, and lowest MIP. Both the CRE and MIP parameters of CB group were acceptable (RC/IC = 0.08, mean MD = 1.09g/cm3, and MIP = 1.09). CONCLUSION: As compared with the three excavation methods, CBs can be considered as an alternative to TC burs because of its MIP and complete removal of infected carious dentin.
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Black soldier flies, Hermetia illucens (L.), consume decaying organic materials at the larval stage and can be used for recycling a variety of biogenic wastes into value-added products. Black soldier flies are normally found in subtropical and warm temperate regions. Cold temperatures may prevent their establishment in colder areas, thus alleviating a concern of their becoming an invasive species. Potentially, cold temperatures can also be used to manipulate the rate of black soldier fly development, which may be needed for timing certain life stages for mass-production needs. In the present study, immature black soldier flies were highly susceptible to freezing. Their survivorship decreased as time spent at -12°C increased from 10 to 60 min. Only ca. 2% of eggs, <1% of larvae, and no pupae survived after 60 min of exposure. Chilling at 4°C also had a significant negative effect that became more pronounced as duration of exposure increased from 24 to 72 h. Only ca. 2% of eggs and second instars and ca. 23% of pupae survived after 72 h. In the same time, >80% of third instars and >90% of fifth instars were still alive following 72 h of exposure. Chilling fifth instars resulted in smaller adults but freezing them for 48 h resulted in bigger adults. Based on these results, black soldier fly is unlikely to establish in areas with long periods of subfreezing winter temperatures. Low temperatures may be used to manipulate development of the late instars, but at a cost of higher mortality.
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Dípteros , Simuliidae , Animais , Temperatura Baixa , Congelamento , Larva , PupaRESUMO
Plant deaths had been observed in the sub-alpine and alpine areas of Australia. Although no detailed aetiology was established, patches of dying vegetation and progressive thinning of canopy suggested the involvement of root pathogens. Baiting of roots and associated rhizosphere soil from surveys conducted in mountainous regions New South Wales and Tasmania resulted in the isolation of eight Phytophthora species; Phytophthora cactorum, Phytophthora cryptogea, Phytophthora fallax, Phytophthora gonapodyides, Phytophthora gregata, Phytophthora pseudocryptogea, and two new species, Phytophthora cacuminis sp. nov and Phytophthora oreophila sp. nov, described here. P. cacuminis sp. nov is closely related to P. fallax, and was isolated from asymptomatic Eucalyptus coccifera and species from the family Proteaceae in Mount Field NP in Tasmania. P. oreophila sp. nov, was isolated from a disturbed alpine herbfield in Kosciuzsko National Park. The low cardinal temperature for growth of the new species suggest they are well adapted to survive under these conditions, and should be regarded as potential threats to the diverse flora of sub-alpine/alpine ecosystems. P. gregata and P. cryptogea have already been implicated in poor plant health. Tests on a range of alpine/subalpine plant species are now needed to determine their pathogenicity, host range and invasive potential.
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Phytophthora/classificação , Phytophthora/isolamento & purificação , Rizosfera , Microbiologia do Solo , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Eucalyptus/crescimento & desenvolvimento , Técnicas de Tipagem Micológica , New South Wales , Filogenia , Phytophthora/genética , Phytophthora/fisiologia , Doenças das Plantas/microbiologia , Proteaceae/crescimento & desenvolvimento , Análise de Sequência de DNA , TasmâniaRESUMO
PURPOSE: Optical redox imaging (ORI), based on collecting the endogenous fluorescence of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) containing a redox cofactor flavin adenine dinucleotide (FAD), provides sensitive indicators of cellular metabolism and redox status. ORI indices (such as NADH, FAD, and their ratio) have been under investigation as potential progression/prognosis biomarkers for cancer. Higher FAD redox ratio (i.e., FAD/(FAD + NADH)) has been associated with higher invasive/metastatic potential in tumor xenografts and cultured cells. This study is to examine whether ORI indices can respond to the modulation of oncogene DEK activities that change cancer cell invasive/metastatic potential. PROCEDURES: Using lentiviral shRNA, DEK gene expression was efficiently knocked down in MDA-MB-231 breast cancer cells (DEKsh). These DEKsh cells, along with scrambled shRNA-transduced control cells (NTsh), were imaged with a fluorescence microscope. In vitro invasive potential of the DEKsh cells and NTsh cells was also measured in parallel using the transwell assay. RESULTS: FAD and FAD redox ratios in polyclonal cells with DEKsh were significantly lower than that in NTsh control cells. Consistently, the DEKsh cells demonstrated decreased invasive potential than their non-knockdown counterparts NTsh cells. CONCLUSIONS: This study provides direct evidence that oncogene activities could mediate ORI-detected cellular redox state.
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Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Proteínas Cromossômicas não Histona/genética , Técnicas de Silenciamento de Genes , Proteínas Oncogênicas/genética , Oncogenes , Imagem Óptica , Proteínas de Ligação a Poli-ADP-Ribose/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Invasividade Neoplásica , OxirreduçãoRESUMO
INTRODUCTION: In human cancers, podoplanin expression and its correlation with tumour invasive potential raise its possible role as a diagnostic and prognostic marker for cancer. AIM: To investigate the immunohistochemical expression of podoplanin in laryngeal Squamous Cell Carcinoma (SCC) and dysplasia. MATERIALS AND METHODS: This study included a total of 60 archived, formalin fixed, paraffin embedded tissue blocks of 40 cases of laryngeal SCC and 20 cases of dysplastic lesions. The samples were immunohistochemically analysed for podoplanin expression. RESULTS: Podoplanin expression was significantly higher in laryngeal SCC (90%) than laryngeal dysplastic lesions (55%) (p-value=0.002). The expression of podoplanin was significantly increased with the higher grades of dysplasia (p-value=0.016). A significant positive correlation was detected between podoplanin expression in laryngeal SCC and depth of tumour invasion (p-value=0.035), and stage (p-value=0.026). CONCLUSION: The high expression of podoplanin in laryngeal SCC and its significant correlation with poor prognostic parameters recommends podoplanin as a prognostic marker in laryngeal SCC. In addition, increased podoplanin expression with higher grades of dysplasia, supports its role in malignant transformation and allows us to recommend its evaluation in premalignant lesions.
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Salinity (5-30) effects on golden alga growth were determined at a standard laboratory temperature (22°C) and one associated with natural blooms (13°C). Inoculum-size effects were determined over a wide size range (100-100,000cellsml-1). A strain widely distributed in the USA, UTEX-2797 was the primary study subject but another of limited distribution, UTEX-995 was used to evaluate growth responses in relation to genetic background. Variables examined were exponential growth rate (r), maximum cell density (max-D) and, when inoculum size was held constant (100cellsml-1), density at onset of exponential growth (early-D). In UTEX-2797, max-D increased as salinity increased from 5 to â¼10-15 and declined thereafter regardless of temperature but r remained generally stable and only declined at salinity of 25-30. In addition, max-D correlated positively with r and early-D, the latter also being numerically highest at salinity of 15. In UTEX-995, max-D and r responded similarly to changes in salinity - they remained stable at salinity of 5-10 and 5-15, respectively, and declined at higher salinity. Also, max-D correlated with r but not early-D. Inoculum size positively and negatively influenced max-D and r, respectively, in both strains and these effects were significant even when the absolute size difference was small (100 versus 1000 cells ml-1). When cultured under similar conditions, UTEX-2797 grew faster and to much higher density than UTEX-995. In conclusion, (1) UTEX-2797's superior growth performance may explain its relatively wide distribution in the USA, (2) the biphasic growth response of UTEX-2797 to salinity variation, with peak abundance at salinity of 10-15, generally mirrors golden alga abundance-salinity associations in US inland waters, and (3) early cell density - whether artificially manipulated or naturally attained - can influence UTEX-2797 bloom potential.
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Eutrofização , Patrimônio Genético , Haptófitas/fisiologia , Salinidade , Haptófitas/genética , Haptófitas/crescimento & desenvolvimento , Dinâmica PopulacionalRESUMO
Exotic species invasions are serious ecological problems. Leaf construction cost (CC) and growth traits of two Sonneratia (Sonneratia caseolaris and S. apetala) and four native species (Bruguiera gymnorrhiza, Kandelia obovata, Aegiceras corniculatum and Avicennia marina) in Hainan and Shenzhen mangrove wetlands were compared to evaluate invasive potentials of Sonneratia after introduced to Shenzhen, their new habitat. There were no significant differences in CC and growth traits between two wetlands, suggesting Sonneratia did not lose any advantage in the new habitat and were competitive in both wetlands. CC per unit mass (CCM), CC per unit area (CCA) and caloric values of Sonneratia were significantly lower than those of native mangrove species while specific leaf area (SLA) was just the opposite. CCM of S. caseolaris and S. apetala were 6.1% and 11.9% lower than those of natives, respectively. These findings indicated the invasive potential of Sonneratia in Shenzhen after their introduction.
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Lythraceae/metabolismo , Folhas de Planta/metabolismo , Primulaceae/metabolismo , Rhizophoraceae/metabolismo , Áreas Alagadas , Avicennia/metabolismo , China , Ecossistema , Metabolismo Energético , Espécies Introduzidas , Folhas de Planta/crescimento & desenvolvimento , Rhizophoraceae/crescimento & desenvolvimentoRESUMO
Although of crucial importance for invasion biology and impact assessments of climate change, it remains widely unknown how species cope with and adapt to environmental conditions beyond their currently realized climatic niches (i.e., those climatic conditions existing populations are exposed to). The African clawed frog Xenopus laevis, native to southern Africa, has established numerous invasive populations on multiple continents making it a pertinent model organism to study environmental niche dynamics. In this study, we assess whether the realized niches of the invasive populations in Europe, South, and North America represent subsets of the species' realized niche in its native distributional range or if niche shifts are traceable. If shifts are traceable, we ask whether the realized niches of invasive populations still contain signatures of the niche of source populations what could indicate local adaptations. Univariate comparisons among bioclimatic conditions at native and invaded ranges revealed the invasive populations to be nested within the variable range of the native population. However, at the same time, invasive populations are well differentiated in multidimensional niche space as quantified via n-dimensional hypervolumes. The most deviant invasive population are those from Europe. Our results suggest varying degrees of realized niche shifts, which are mainly driven by temperature related variables. The crosswise projection of the hypervolumes that were trained in invaded ranges revealed the south-western Cape region as likely area of origin for all invasive populations, which is largely congruent with DNA sequence data and suggests a gradual exploration of novel climate space in invasive populations.