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Androgen deprivation therapy is a common treatment method for metastatic prostate cancer through lowering androgen levels; however, this therapy frequently leads to the development of castration-resistant prostate cancer (CRPC). This is attributed to the activation of the androgen receptor (AR) signaling pathway. Current treatments targeting AR are often ineffective mostly due to AR gene overexpression and mutations, as well as the presence of splice variants that accelerate CRPC progression. Thus there is a critical need for more specific medication to treat CRPC. Small interfering RNAs have shown great potential as a targeted therapy. This review discusses prostate cancer progression and the role of AR signaling in CRPC, and proposes siRNA-based targeted therapy as a promising strategy for CRPC.
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Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/terapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Androgênios , Antagonistas de Androgênios/uso terapêutico , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Transdução de SinaisRESUMO
Whereas much of the developmental literature has focused on the difficulties of young children in regulating their behavior, an increasing base of evidence suggests that children may be capable of surprisingly flexible engagement of cognitive control when based on implicit experience with the situation. One of the most fine-grained examples of implicit cognitive control in adults is the context-specific proportion congruency (CSPC) effect-the finding that interference in a conflict task is reduced for stimuli that are presented in a context (e.g., a spatial location) where stimuli are generally incongruent. Can such a subtle modulation of control be observed in children? In Experiment 1 (N = 180), we showed that this effect exists in preschoolers for two different types of context manipulation and that its magnitude is at least as large as in older children. In Experiment 2 (N = 40), we confirmed that the effect transfers to unbiased stimuli, indicating that it is not attributable to contingency learning of stimulus-response associations and can be taken to actually reflect cognitive control. These results support the possibility that implicit cognitive control (implemented without explicit intentions and without requiring subject awareness) can be functionally distinct from explicit control and that even very young children can implement fine-grained cognitive control when it is based on implicit cues.
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Atenção , Sinais (Psicologia) , Adulto , Criança , Pré-Escolar , Cognição , Humanos , Tempo de ReaçãoRESUMO
Clostridium perfringens SM101 genome encodes three serine proteases (CspA, CspB, and CspC), and genetic evidence indicates that CspB is required for processing of pro-SleC into active SleC, an enzyme essential for degradation of the peptidoglycan cortex during spore germination. In this study, the expression of cspA and cspC, as well as the germination and colony formation by spores of cspAC and cspC mutants of strain SM101, were assessed. We demonstrated that 1) the cspA and cspC genes were expressed as a bicistronic operon only during sporulation in the mother cell compartment of SM101; 2) both cspAC and cspC mutant spores were unable to germinate significantly with either KCl, l-glutamine, brain heart infusion (BHI) broth, or a 1:1 chelate of Ca2+ and dipicolinic acid (DPA); 3) consistent with germination results, both cspAC and cspC mutant spores were defective in normal DPA release; 4) the colony formation by cspAC and cspC mutant spores was ~106-fold lower than that of wild-type spores, although decoated mutant spores yielded wild-type level colony formation on plates containing lysozyme; 5) no processing of inactive pro-SleC into active SleC was observed in cspAC and cspC mutant spores during germination; and finally, 6) the defects in germination, DPA release, colony formation and SleC processing in cspAC and cspC mutant spores were complemented by the wild-type cspA-cspC operon. Collectively, these results indicate that both CspA and CspC are essential for C. perfringens spore germination through activating SleC and inducing cortex hydrolysis.
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Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Clostridium perfringens/enzimologia , Esporos Bacterianos/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Clostridium perfringens/efeitos dos fármacos , Clostridium perfringens/genética , Clostridium perfringens/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Hidrólise , Óperon , Ácidos Picolínicos/farmacologia , Processamento de Proteína Pós-Traducional , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/enzimologia , Esporos Bacterianos/genéticaRESUMO
Traumatic injuries of the knee joint result in a wide variety of pathomechanisms, which contribute to the development of so-called posttraumatic osteoarthritis (PTOA). These pathogenetic processes include oxidative stress, excessive expression of catabolic enzymes, release of damage-associated molecular patterns (DAMPs), and synovial inflammation. The present review focuses on the underlying pathomechanisms of PTOA and in particular the behavior and fate of the surviving chondrocytes, comprising chondrocyte metabolism, regulated cell death, and phenotypical changes comprising hypertrophy and senescence. Moreover, possible therapeutic strategies, such as chondroanabolic stimulation, anti-oxidative and anti-inflammatory treatment, as well as novel therapeutic targets are discussed.
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Condrócitos/metabolismo , Traumatismos do Joelho/complicações , Osteoartrite do Joelho/metabolismo , Animais , Morte Celular , Condrócitos/patologia , Humanos , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Estresse OxidativoRESUMO
Clostridium botulinum is a notable food pathogen and responsible for botulism due to production of botulinum neurotoxin. Strains of C. botulinum can adapt to and survive in stress conditions and food processing. The cold shock protein coding genes (csp) are involved in growth at low temperature, but they may also possess other functions. In this mutational analysis we show that cspB and cspC, but not cspA, are important for NaCl, pH and ethanol stress responses and for motility of C. botulinum ATCC 3502. In all NaCl concentrations tested, the cspB mutant had lower maximum growth rate and, together with the cspC mutant, a longer lag phase compared to the wild-type strain. At low pH, the cspB and cspC mutants showed either lower maximum growth rates or longer lag phases compared to the wild type. In all ethanol concentrations tested, the cspB mutant had lower maximum growth rates and the cspC mutant had a longer lag phase than the wild-type strain. Motility was reduced in cspA and cspC mutants, and flagella formation was affected. The results suggest that cspB plays a universal role in stress response and cspC aids C. botulinum in NaCl, pH and ethanol stress in C. botulinum ATCC 3502.
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Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Clostridium botulinum/citologia , Clostridium botulinum/fisiologia , Etanol/metabolismo , Proteínas de Choque Térmico/metabolismo , Cloreto de Sódio/metabolismo , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Clostridium botulinum/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Choque Térmico/genética , Concentração de Íons de Hidrogênio , Estresse FisiológicoRESUMO
INTRODUCTION: In the United States, a total of 268,490 men were found to have prostate cancer in 2022, thus making it the most common cancer in men, accounting for 27% of all cancers in the male population. Among all cancers in men, it was the fifth leading cause of death, with 34,500 deaths and a mortality rate of 11%. In 2019, the total number of cases was 94,748, making it the leading cancer in males, accounting for 11% of all male cancers. In terms of mortality, it ranked seventh, with 13,217 deaths and a mortality rate of 1.6%. However, new treatment options for metastatic castration-sensitive prostate cancer (mCSPC) have emerged. Docetaxel has been shown to be effective for both mCSPC and castration-resistant prostate cancer (CRPC). Upfront docetaxel has not been approved in Japan, nor has it been validated in large-scale studies. Furthermore, several agents can be used after docetaxel treatment, but it is unclear which is the most effective. We used a large Japanese health insurance database to determine which agent would be the most effective as a next-line therapy in patients who had received docetaxel. MATERIALS AND METHODS: We used data from medical institutions using the Diagnosis Procedure Combination (DPC), which provides a comprehensive evaluation of medical classifications. The Medical Data Vision database covers approximately 23% of DPC hospitals in Japan. This study analyzed 2938 patients with mCSPC who received docetaxel, followed by CRPC, between April 2008 and December 2021. The study focused on three agents: enzalutamide, abiraterone acetate, and cabazitaxel. Other agents were excluded due to the small number of patients. The following data were analyzed: age, date of CRPC diagnosis, presence of bone metastasis, drug type, and prognosis. RESULTS: This study included 1997 patients with CRPC after upfront docetaxel therapy for mCSPC (enzalutamide [ENZ] group, n = 998; abiraterone acetate [ABI] group, n = 617; and cabazitaxel [CBZ] group, n = 382). The overall survival (OS) time from drug initiation was 456 days in the enzalutamide group, which was significantly longer than that in the cabazitaxel group (p = 0.017, HR 0.94) (ENZ: ABI p = 0.54, HR 0.94; ABI: CBZ p = 0.14, HR 0.75). OS was also compared for the third-line drug in the group that received enzalutamide as the second-line drug, the group that used abiraterone acetate as the third-line drug (ENZ-ABI group), and the group that used abiraterone acetate as the second-line drug. OS from the start of the third-line drug was compared between the ENZ-ABI group and the ABI-ENZ group, which received enzalutamide as the third-line drug, but showed no significant difference (269 vs. 281 days, p = 0.85; HR 1.03). CONCLUSION: ENZ was shown to prolong OS relative to cabazitaxel after the cessation of docetaxel. ENZ was associated with a longer duration of drug use than ABI and CBZ.
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Background: The cartilage stem/progenitor cells (CSPC) play a critical role in maintaining cartilage homeostasis. However, the effects of phenotypic fluctuations of CSPC on cartilage degeneration and the role of CSPC in the pathogenesis of OA is largely unknown. Methods: The cartilage samples of 3 non-OA and 10 OA patients were collected. Human CSPC (hCSPC) derived from these patients were isolated, identified, and evaluated for cellular functions. Additionally, chondrocytes derived from OA patients were isolated. The effect of Yes-associated protein (YAP) expression on hCSPC was investigated in vitro. The OA rat model was established by Hulth's method. Lentivirus-mediated YAP (Lv-YAP) or lentivirus-mediated YAP RNAi (Lv-YAP-RNAi) was injected intra-articularly to modulate YAP expression in rat joints. In addition, allogeneic rat CSPC (rCSPC) overexpressing or silencing YAP were transplanted by intra-articularly injection. We also evaluated the functions of rCSPC and the OA-related cartilage phenotype in the rat model. Finally, the transcriptome of OA rCSPC overexpressing YAP was examined to explore the potential downstream targets of YAP in rCSPC. Results: hCSPC derived from OA patients exhibited differential chondrogenesis capacity. Among them, a subset of hCSPC showed pronounced dysfunction, including impaired chondrogenic differentiation, inhibition of proliferation and migration, and downregulation of lubricin. Additionally, YAP was lowly expressed in quiescent non-OA hCSPC, upregulated in activated OA hCSPC, but significantly downregulated in dysfunctional OA hCSPC. Notably, the overexpression of YAP in OA hCSPC improved the proliferation, lubricin production, cell migration, and senescence, while silencing YAP had the opposite effect. In vivo, upregulation of YAP in the joint delayed OA progression and improved the cartilage regeneration capacity of rCSPC. Using transcriptomic analysis, we found that YAP may regulate rCSPC function by upregulating Baculoviral IAP repeat-containing 2 (BIRC2). Importantly, the knockdown of BIRC2 partly blocked the regulation of YAP on the CSPC function. Conclusion: Dysfunction of CSPC compromises the intrinsic repair capacity of cartilage and impairs cartilage homeostasis in OA. Notably, the transcriptional co-activator YAP plays a critical role in maintaining CSPC function through potential target gene BIRC2. The Translational Potential of this Article: In this study, we observed targeting the YAP-BIRC2 axis improved the CSPC function and restored the cartilage homeostasis in OA. This study provides a potential stem cell-modifying OA therapy.
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Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening human infections. Bacteriophage-encoded endolysins degrade the cell walls of Gram-positive bacteria by selectively hydrolyzing the peptidoglycan layer and thus are promising candidates to combat bacterial infections. PlyGRCS, the S. aureus-specific bacteriophage endolysin, contains a catalytic CHAP domain and a cell-wall binding SH3_5 domain connected by a linker. Here, we show the crystal structure of full-length PlyGRCS refined to 2.1 Å resolution. In addition, a serendipitous finding revealed that PlyGRCS binds to cold-shock protein C (CspC) by interacting with its CHAP and SH3_5 domains. CspC is an RNA chaperone that plays regulatory roles by conferring bacterial adaptability to various stress conditions. PlyGRCS has substantial lytic activity against S. aureus and showed only minimal change in its lytic activity in the presence of CspC. Whereas the PlyGRCS-CspC complex greatly reduced CspC-nucleic acid binding, the aforesaid complex may downregulate the CspC function during bacterial infection. Overall, the crystal structure and biochemical results of PlyGRCS provide a molecular basis for the bacteriolytic activity of PlyGRCS against S. aureus.
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Proteínas de Bactérias , Proteínas e Peptídeos de Choque Frio , Endopeptidases , Proteínas de Choque Térmico , Staphylococcus aureus Resistente à Meticilina , Fagos de Staphylococcus , Humanos , Proteínas e Peptídeos de Choque Frio/química , Endopeptidases/química , Endopeptidases/genética , Endopeptidases/metabolismo , Staphylococcus aureus Resistente à Meticilina/virologia , Proteínas de Bactérias/química , Proteínas de Choque Térmico/química , Fagos de Staphylococcus/enzimologiaRESUMO
Pseudomonas aeruginosa is a ubiquitous pathogenic bacterium that can adapt to a variety environments. The ability to effectively sense and respond to host local nutrients is critical for the infection of P. aeruginosa. However, the mechanisms employed by the bacterium to respond to nutrients remain to be explored. CspA family proteins are RNA binding proteins that are involved in gene regulation. We previously demonstrated that the P. aeruginosa CspA family protein CspC regulates the type III secretion system in response to temperature shift. In this study, we found that CspC regulates the quorum-sensing (QS) systems by repressing the translation of a QS negative regulatory gene, rsaL. Through RNA immunoprecipitation coupled with real-time quantitative reverse transcription-PCR (RIP-qRT-PCR) and electrophoretic mobility shift assays (EMSAs), we found that CspC binds to the 5' untranslated region of the rsaL mRNA. Unlike glucose, itaconate (a metabolite generated by macrophages during infection) reduces the acetylation of CspC, which increases the affinity between CspC and the rsaL mRNA, leading to upregulation of the QS systems. Our results revealed a novel regulatory mechanism of the QS systems in response to a host-generated metabolite. IMPORTANCE Bacterial infectious diseases impose a severe threat to human health. The ability to orchestrate virulence determinant in response to the host environment is critical for the pathogenesis of bacterial pathogens. Pseudomonas aeruginosa is a leading pathogen that causes various infections in humans. In P. aeruginosa, the quorum-sensing (QS) systems play an important role in regulating the production of virulence factors. In this study, we find that a small RNA binding protein, CspC, regulates the QS systems by repressing the expression of a QS negative regulator. We further demonstrate that CspC is acetylated in response to a host-derived metabolite, itaconate, which alters the function of CspC in regulating the QS system. The importance of this work is in elucidation of a novel regulatory pathway that regulates virulence determinants in P. aeruginosa in response to a host signal.
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Regulação Bacteriana da Expressão Gênica , Pseudomonas aeruginosa , Acetilação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum/genética , RNA Mensageiro/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
Introduction: To survive in various hostile environments, two-component system is an adaptive mechanism for diverse bacteria. Activity of the CpxA/CpxR two-component system contributes to coping with different stimuli, such as pH, osmotic and heat stress. Methods: However, the role of the CpxA/CpxR system in cold resistance is little-known. In this study, we showed that CpxA/CpxRwas critical for A. pleuropneumoniae growth under cold stress. Results: ß-Galactosidaseanalysis showed that CpxA/CpxR positively regulated the predicted cold stress gene cspC. The mutant for cold stress gene cspC was impaired in the optimal growth of A. pleuropneumoniae under cold stress. Furthermore, electrophoretic mobility shift assays demonstrated that CpxR-P could directly regulate the transcription of the cold stress gene cspC. Discussion: These results presented in this study illustrated that the CpxA/CpxR system plays an important role in cold resistance by upregulating expression of CspC. The data give new insights into how A. pleuropneumoniae survives in cold stress.
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The RNA chaperones, cold shock proteins CspC and CspE, are important in stress response and adaptation. We studied their role in the pathogenesis of a virulent Escherichia coli, representative of extraintestinal pathogenic E. coli (ExPEC) which are serum resistant and septicemic. We performed a global analysis to identify transcripts that interact with these cold shock proteins (CSPs), focusing on virulence-related genes. We used CLIP-seq, which combines UV cross-linking, immunoprecipitation and RNA sequencing. A large number of transcripts bound to the CSPs were identified, and many bind both CspC and CspE. Many transcripts were of genes involved in protein synthesis, transcription and energy metabolism. In addition, there were virulence-related genes, (i.e., fur and ryhB), essential for iron homeostasis. The CLIP-seq results were validated on two transcripts, clpX and tdcA, reported as virulence-associated. Deletion of either CspC or CspE significantly decreased their transcript levels and in a double deletion mutant cspC/cspE, the transcript stability of tdcA and clpX was reduced by 32-fold and 10-fold, respectively. We showed that these two genes are important for virulence, as deleting either of them resulted in loss of serum resistance, a requirement for sepsis. As several virulence-related transcripts interact with CspC or CspE, we determined the importance of these proteins for growth in serum and showed that deletion of either gene significantly reduced serum survival. This phenotype could be partially complemented by cspE and fully complemented by cspC. These results indicate that the two RNA chaperones are essential for virulence, and that CspC particularly critical. IMPORTANCE Virulent Escherichia coli strains that cause infections outside the intestinal tract-extraintestinal pathogenic E. coli (ExPEC)-constitute a major clinical problem worldwide. They are involved in several distinct conditions, including urinary tract infections, newborn meningitis, and sepsis. Due to increasing antibiotic resistance, these strains are a main factor in hospital and community-acquired infections. Because many strains, which do not cross-react immunologically are involved, developing a simple vaccine is not possible. Therefore, it is essential to understand the pathogenesis of these bacteria to identify potential targets for developing drugs or vaccines. One of the least investigated systems involves RNA binding proteins, important for stability of transcripts and global gene regulation. Two such proteins are CspC and CspE ("cold shock proteins"), RNA chaperones involved in stress adaptation. Here we performed a global analysis to identify the transcripts which are affected by these two chaperones, with focus on virulence-associated transcripts.
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Proteínas de Escherichia coli , Sepse , Humanos , Escherichia coli/genética , Proteínas e Peptídeos de Choque Frio/genética , Proteínas de Escherichia coli/genética , Resposta ao Choque Frio/genética , Proteínas de Choque Térmico/genética , RNA Bacteriano/genética , Sepse/genéticaRESUMO
Patients who receive a diagnosis of metastatic castration-sensitive prostate cancer (CSPC) have different phenotypes of disease. Some of them have de novo CSPC, but others receive a late diagnosis, and still others underwent prostatectomy several years before the diagnosis of metastases. We analyze the presence of these differences in recent clinical trials in CSPC and assess the possible impact on their results.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Prostatectomia , Neoplasias de Próstata Resistentes à Castração/terapia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/secundário , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Quimioterapia Adjuvante/métodos , Ensaios Clínicos como Assunto , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Seleção de Pacientes , Neoplasias de Próstata Resistentes à Castração/patologia , Tomografia Computadorizada por Raios XRESUMO
Since the late 1990s, the American College of Surgeons (ACS) has increasingly recognized and advocated palliative care for patients and their families with serious, critical, and terminal illness under surgical care. The college has been the primary catalyst for the recognition of palliative care in the field of surgery in the U.S. and abroad, primarily through educational efforts directed at practicing surgeons and surgeons in training. Roughly 15 years ago a group of surgeons from the fellowship of the college coalesced and then spearheaded these initiatives with invaluable support and advice from leading non-surgeon pioneers of palliative care. This group is now titled, the Committee on Surgical Palliative Care (CSPC). The CSPC's mission is to incorporate the precepts and techniques of palliative care into surgical clinical practice, education, research, and advocacy. This report chronicles the contributions the ACS has made to the evolution of surgical palliative care and details the formation of its CSPC and its role in shaping surgical palliative care today.
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Cirurgia Geral/organização & administração , Cuidados Paliativos/organização & administração , Sociedades Médicas/organização & administração , Humanos , Estados UnidosRESUMO
The heat shock response is one of the main global regulatory networks in all organisms and involves an increased cellular level of chaperones and proteases to enable correct protein folding and balanced growth. One of the major heat shock chaperones in Escherichia coli is GroESL, composed of GroES and GroEL (the bacterial Hsp10 and Hsp60 homologues), which is essential for refolding of misfolded proteins. GroESL was previously shown to play a role in the regulation of the heat shock response by promoting the proteolysis of the regulatory protein--sigma32 (RpoH), the heat shock transcription activator. Here we show the involvement of GroESL in another proteolytic process, this of the major RNA chaperone--CspC--that specifically stabilizes the transcripts of several stress-related genes. Evidence is provided for an interaction between GroESL and CspC that results in enhanced, temperature-dependent proteolysis of the latter. This interaction is of regulatory importance, as reduction in the cellular levels of CspC leads to a decrease in stability of the major heat shock gene transcripts.
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Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteínas de Choque Térmico/metabolismo , Mapeamento de Interação de Proteínas , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Ligação Proteica , Estabilidade Proteica , ProteóliseRESUMO
A key feature of the human cognitive system is its ability to deal with an ever-changing environment. One prototypical example is the observation that we adjust our information processing depending on the conflict-likelihood of a context (context-specific proportion congruency effect, CSPC, Crump etal., 2006). Recently, empirical studies started to question the role of consciousness in these strategic adaptation processes (for reviews, see Desender and Van den Bussche, 2012; Kunde etal., 2012). However, these studies have not yielded unequivocal results (e.g., Kunde, 2003; Heinemann etal., 2009; Van Gaal etal., 2010a; Desender etal., 2013; Reuss etal., 2014). In the present study, we aim at replicating the experiment of Heinemann etal. (2009) in which the proportion of congruent and incongruent trials between different contexts was varied in a masked priming task. Their results showed a reduction of the congruency effect for the context with more incongruent trials. However, this CSPC effect was only observed when the prime-target conflict was conscious, rather than unconscious, suggesting that context-specific control operates within the boundaries of awareness. Our replication attempt however contrasts these findings. In the first experiment we found no evidence for a CSPC effect in reaction times (RTs), neither in the conscious nor in the unconscious condition. The error rate analysis did show a CSPC effect, albeit not one modulated by consciousness. In the second experiment we found an overall CSPC effect in RTs, independent of consciousness. The error rates did not display a CSPC pattern. These mixed results seem to nuance the findings of Heinemann etal. (2009) and highlight the need for replication studies in psychology research.
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The stress resistance of bacteria is affected by the physiological status of the bacterial cell and environmental factors such as pH, salts and temperature. In this study, we report on the stress response of Lactobacillus plantarum L67 after four consecutive freeze-thaw cycles. The cold stress response of the cold-shock protein genes (cspC, cspL and cspP) and ATPase activities were then evaluated. The cold stress was adjusted to 5 °C when the bacteria were growing at the mid-exponential phase. A comparative proteomic analysis was performed with two-dimensional gel electrophoresis (2D SDS-PAGE) and a matrix assisted laser desorption/ionization-mass spectrometer. Only 56% of the L. plantarum L67 cells without prior exposure to cold stress survived after four consecutive freeze-thaw cycles. However, 78% of the L. plantarum L67 cells that were treated with cold stress at 5 °C for 6 h survived after freeze-thaw conditions. After applying cold stress to the culture for 6h, the cells were then stored for 60 days at 5 °C, 25 °C and 35 °C separately. The cold-stressed culture of L. plantarum L67 showed an 8% higher viability than the control culture. After applying cold stress for 6h, the transcript levels of two genes (cspP and cspL) were up-regulated 1.4 (cspP) and 1.2 (cspL) times compared to the control. However, cspC was not up-regulated. A proteomic analysis showed that the proteins increased after a reduction of the incubation temperature to 5 °C. The importance of the expression of 13 other relevant proteins was also determined through the study. The exposure of L. plantarum cells to low temperatures aids their ability to survive through subsequent freeze-thaw processes and lyophilization.
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Temperatura Baixa , Congelamento , Regulação Bacteriana da Expressão Gênica/fisiologia , Lactobacillus plantarum/fisiologia , Estresse Fisiológico/fisiologia , Proteínas de Bactérias/genética , Proteínas de Choque Térmico/genética , Lactobacillus plantarum/genética , Lactobacillus plantarum/crescimento & desenvolvimento , Viabilidade Microbiana , Proteômica , RNA Mensageiro/metabolismo , TempoRESUMO
Significant cytotoxic effects of procynadins from chestnut (Castanea mollissima Bl.) shell (CSPC) on human hepatoma G2 (HepG2) cells were found in vitro. CSPC could inbibit HepG2 proliferation in a dose-dependent manner (100-400 µg/mL), arrest cell cycle in the G0/G1 phase, induce apoptosis and trigger necrosis of HepG2. Proapoptotic effect of CSPC was evidenced by nuclear condensation, internucleosomal DNA fragmentation. Treatment of HepG2 cells with CSPC caused a loss of mitochondrial membrane potential and stimulated reactive oxidative species (ROS) generation. These results suggested CSPC could trigger apoptosis and necrotic cell death in HepG2 cell, which might be associated with ROS generation through the mitochondria-dependent signaling way.
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Fagaceae/química , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Cromatografia Líquida , DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Necrose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Se describen los escenarios ambientales y los patrones de variabilidad observados en el mar peruano a partir del análisis de información obtenida por el Instituto del Mar del Perú entre los años 1960 - 2011. Se examinan datos de cruceros de investigación oceanográfica, de evaluación de recursos pesqueros y bío-oceanográficos, además de información de diversas publicaciones sobre el mar peruano y sus recursos. Los datos de temperatura, salinidad y contenido de oxígeno, fueron interpolados para obtener promedios mensuales y construir series espaciales y temporales. En la superficie, las Aguas Costeras Frías (ACF) y Aguas Subtropicales Superficiales (ASS) crean condiciones ambientales diferentes a las de la parte subsuperficial donde predomina la intromisión de las aguas ecuatoriales a través de la Corriente Subsuperficial Perú-Chile (CSPC). En el norte, durante el verano y otoño, predominan en la capa superficial aguas cálidas de origen ecuatorial. En el centro, aguas de origen ecuatorial interactúan con las ACF del afloramiento costero. El sur está influenciado por las ASS y el afloramiento costero con mayor intensidad, indicando una mayor actividad en el Sistema de la Corriente del Perú (SCP)
Environmental scenarios and variability patterns observed in the Peruvian waters are described based on the analysis of information obtained by the Instituto del Mar del Peru between 1960 and 2011. This information includes data from oceanographic, stock assessment and bio-oceanographic scientific research surveys, published information was also used to complete this study. Sea temperature, salinity and oxygen content data was interpolated to obtain monthly averages and build temporal and spatial series. Surface Cold Coastal Waters (ACF) and Subtropical Surface Water (SSW) create environmental conditions that are different from those in the subsurface, where the intrusion of equatorial waters dominates through the Peru-Chile Subsurface Current (CSPC). In the north, during the summer and fall, there is predominance in the surface layer of waters from the equatorial system. In the central zone the equatorial waters interact with ACF from coastal upwelling. The south is more strongly influenced by the coastal upwelling and the ASS, which is an indicator of increased activity in the Current System of Peru (SCP)