Exercise induction at expression immediate early gene (c-Fos, ARC, EGR-1) in the hippocampus: a systematic review.

The immediate early gene exhibits activation markers in the nervous system consisting of ARC, EGR-1, and c-Fos and is related to synaptic plasticity, especially in the hippocampus. Immediate early gene expression is affected by physical exercise, which induces direct ARC, EGR-1, and c-Fos expression. Objective: To assess the impact of exercise, we conducted a literature study to determine the expression levels of immediate early genes (ARC, c-Fos, and EGR-1). Methods: The databases accessed for online literature included PubMed-Medline, Scopus, and ScienceDirect. The original English articles were selected using the following keywords in the title: (Exercise OR physical activity) AND (c-Fos) AND (Hippocampus), (Exercise OR physical activity) AND (ARC) AND (Hippocampus), (Exercise OR physical activity) AND (EGR-1 OR zif268) AND (Hippocampus). Results: Physical exercise can affect the expression of EGR-1, c-Fos, and ARC in the hippocampus, an important part of the brain involved in learning and memory. High-intensity physical exercise can increase c-Fos expression, indicating neural activation. Furthermore, the expression of the ARC gene also increases due to physical exercise. ARC is a gene that plays a role in synaptic plasticity and regulation of learning and memory, changes in synaptic structure and increased synaptic connections, while EGR-1 also plays a role in synaptic plasticity, a genetic change that affects learning and memory. Overall, exercise or regular physical exercise can increase the expression of ARC, c-Fos, and EGR-1 in the hippocampus. This reflects the changes in neuroplasticity and synaptic plasticity that occur in response to physical activity. These changes can improve cognitive function, learning, and memory. Conclusion: c-Fos, EGR-1, and ARC expression increases in hippocampal neurons after exercise, enhancing synaptic plasticity and neurogenesis associated with learning and memory.

O gene precoce imediato (GPI) exibe marcadores de ativação no sistema nervoso constituídos por ARC, EGR-1 e c-Fos e está relacionado à plasticidade sináptica, especialmente no hipocampo. A expressão do GPI é afetada pelo exercício físico, que induz a expressão direta de ARC, EGR-1 e c-Fos. Objetivo: Para avaliar o impacto do exercício físico, realizamos um estudo de literatura para determinar os níveis de expressão dos GPIs (ARC, c-Fos e EGR-1). Métodos: A base de dados utiliza literatura on-line, PubMed-Medline, Scopus e ScienceDirect. O artigo original em inglês usa as seguintes palavras-chave em seu título: (Exercise) AND (c-Fos) AND (Hippocampus), (Exercise) AND (ARC) AND (Hippocampus), (Exercise) AND (EGR-1) AND (Hippocampus). Resultados: O exercício físico pode afetar a expressão de EGR-1, c-fos e ARC no hipocampo, uma parte importante do cérebro envolvida na aprendizagem e na memória. O exercício físico aumenta a expressão do gene c-Fos; sua alta intensidade pode aumentar a expressão de c-Fos, indicando ativação neural. Além disso, a expressão do gene ARC aumentou devido ao exercício físico, onde ARC é um gene que desempenha um papel na plasticidade sináptica e na regulação da aprendizagem e da memória, nas mudanças na estrutura sináptica e no aumento das conexões sinápticas, enquanto o EGR-1 também desempenha um papel na plasticidade sináptica, uma mudança genética que afeta o aprendizado e a memória. De maneira geral, o exercício físico regular pode aumentar a expressão de ARC, c-fos e EGR-1 no hipocampo. Isso reflete as mudanças na neuroplasticidade e na plasticidade sináptica que ocorrem em resposta à atividade física. Essas mudanças podem melhorar a função cognitiva, o aprendizado e a memória. Conclusão: A expressão de c-Fos, EGR-1 e ARC aumenta após o exercício físico nos neurônios do hipocampo, para aumentar a plasticidade sináptica, a neurogênese associada ao aprendizado e à memória.

New hybrid radio-fluorescent probes [131I]-BPF-01 and [131I]-BPF-02 for visualisation of cancer cells: Synthesis and preliminary in vitro and ex vivo evaluations.

We synthesised and biologically evaluated two new hybrid probes [131I]BPF-01 and [131I]BPF-02 which were built from three structural entities: benzothiazole-phenyl, fluorescein isothiocyanate (FITC), and iodine-131. These probes were designed for potential applications in assisting surgical procedures of solid cancers. The cytotoxicity study demonstrated that fluorescent probes BPF-01 (31.23 µg/mL) and BPF-02 (250 µg/mL) were relatively not toxic to normal immortalized human keratinocytes (HaCaT) cells, as indicated by the percentage of cell survival above 50 %. Furthermore, both probes displayed low to moderate anticancer activity against the breast cancer cells (MDA-MB-231) and prostate cancer cells (LNCaP and DU-145). The probe BPF-01 apparently showed an accumulation in the tumour tissues, as suggested by ex vivo fluorescence examinations. In addition, the cellular uptake study suggests that hybrid probe [131I]-BPF-01 was potentially accumulated in the MCF-7 cell line with the highest uptake of 16.11 ± 1.52 % after 2 h of incubation, approximately 50-fold higher than the accumulation of iodine-131 (control). The magnetic bead assay suggests that [131I]-BPF-02 and [131I]-BPF-02 showed a promising capability to interact with translocator protein 18 kDa (TSPO). Moreover, the computational data showed that the binding scores for ligands 7-8, BPF-01 and BPF-02, and [131I]-BPF-01 and [131I]-BPF-02 in the TSPO were considerably high. Accordingly, fluorescent probes BPF-01 and BPF-02, and hybrid probes [131I]BPF-01 and [131I]BPF-02 can be further developed for targeting cancer cells during intraoperative tumour surgery.

Calcitriol potentially alters HeLa cell viability via inhibition of autophagy.

Objective: This study was conducted to evaluate the effect of Calcitriol on cellular death in HeLa cells via autophagy and turn over due to mitochondria homeostasis. Methods: HeLa cell lines were grown in 24-well plates and treated with Calcitriol at varying doses (0.013 µM-0.325 µM) for varying time periods (2, 6, 12, and 18 h). Cell proteins were extracted with scrapers and lysed using RIPA buffer. Western blots were performed for proteins involved with autophagy (Lc3, p62), signaling (mTOR, PI3K, HIF1α), mitochondria (PGC1α, COX4, and Tom 20), and apoptosis (Caspase 3, Caspase 9, and PARP). Protein carbonyl levels were determined by measuring the indirect ROS level. An inhibition study using L-mimosine was performed to analyze the significance of HIF1α. Results: Calcitriol treatment induced cytotoxicity in a dose- and time-dependent manner and caused growth arrest in HeLa cells. The PI3K-AKT-mTOR pathway was activated, leading to inhibition of autophagy and alterations in mitochondria biogenesis homeostasis. Treatment with Calcitriol produced protein carbonyl levels similar to those in the cisplatin-treated and control groups. Increased ROS levels may cause toxicity and induce cell death specifically in cancer cells but not in normal cells. The inhibition of HIF1α partially rescued the HeLa cells from the toxic effects of Calcitriol treatment. Conclusion: We suggest that Calcitriol may shut down mitochondrial homeostasis in HeLa cells by inducing the PI3K-AKT-mTOR pathway and inhibiting autophagy, which leads to cell death.

Correlation between Prognostic Factors and the Histopathological Response to Neoadjuvant Chemotherapy in Osteosarcoma: A Retrospective Study.

BACKGROUND: Multimodality treatment, incorporating neoadjuvant chemotherapy and adjuvant chemotherapy, is the standard management plan for osteosarcoma that increases the overall survival (OS) rate. However, data regarding prognostic factors affecting the histopathological response following neoadjuvant chemotherapy is limited. Patients and Methods. We retrospectively reviewed patients diagnosed with osteosarcoma in our center between 2008 and 2018. We classified patient characteristics according to gender, age, tumor size, site and stage at diagnosis, site of metastasis, type of surgery, necrosis rate based on the Huvos grading system, and the number of neoadjuvant chemotherapy cycles. We divided response to neoadjuvant chemotherapy into poor responder for patients with Huvos grades 1 and 2 and good responder for patients with Huvos grades 3 and 4. We also documented patients' survival and follow-up information. RESULTS: We reviewed 64 patients within 5-65 years of age, dominated by men (62.5%). The distal femur (53.1%) was the most common site of osteosarcoma. Fifteen (23.4%) patients had a good response while 49 (76.6%) patients were poor responders to neoadjuvant chemotherapy based on the Huvos grading system. Based on multivariate analysis, gender (p = 0.012), age (p = 0.029), symptom duration (p = 0.004), and tumor enlargement after neoadjuvant chemotherapy (p < 0.001) were significantly associated with histopathological response. A scoring system was proposed integrating these significant variables (age > 20 years = 1 point, female gender = 1 point, symptom duration > 12 weeks = 1 point, and increased tumor size after neoadjuvant chemotherapy = 2 points). This scoring system divides patients into two groups with a total score of more than two predicting a poor responder to neoadjuvant chemotherapy. CONCLUSIONS: Age, gender, symptoms duration, and tumor size after neoadjuvant chemotherapy are the prognostic features that affect the histopathological response to neoadjuvant chemotherapy in patients with osteosarcoma.

Elaborating the Physiological Role of YAP as a Glucose Metabolism Regulator:A Systematic Review.

Yes-associated protein (YAP) is one of the Hippo pathway's two effectors, a pathway associated with organ size control. Research on YAP has focused on its oncogenic potential. However, in cancer cells, aside from inducing growth, YAP was also found to regulate glucose metabolism. The present review explores YAP's control of glucose metabolism and whether these findings are translatable to physiological conditions. According to current literature, YAP induces the transcriptional activity of most genes associated with glucose metabolism from enzymes to transport proteins. In glycolysis and gluconeogenesis, YAP upregulates all enzymes except for enolase and pyruvate kinase. Multiple research has also shown YAP's ability to regulate the expression of glucose transporter of the GLUT family. Additionally, glucose concentration, hypoxia, and hormones such as insulin and glucagon regulate YAP activity and depend on YAP to exert their biological activity. YAP is thus a central regulator of glucose metabolism, controlling both enzymes and proteins involved in glucose transport. YAP is also situated strategically in several pathways controlling glucose and was found to mediate their effects. If these results were consistent in physiological conditions and across glucose-associated metabolic disturbances, then YAP may become a prospective therapeutic target.

Hippo pathway effectors YAP and TAZ and their association with skeletal muscle ageing.

Skeletal muscle atrophy commonly occurs during ageing, thus pathways that regulate muscle mass may represent a potential therapeutic avenue for interventions. In this review, we explored the Hippo signalling pathway which plays an essential role in human oncogenesis and the pathway's influence on myogenesis and satellite cell functions, on supporting cells such as fibroblasts, and autophagy. YAP/TAZ was found to regulate both myoblast proliferation and differentiation, albeit with unique roles. Additionally, YAP/TAZ has different functions depending on the expressing cell type, making simple inference of their effects difficult. Studies in cancers have shown that the Hippo pathway influenced the autophagy pathway, although with mixed results. Most of the present researches on YAP/TAZ are focused on its oncogenicity and further studies are needed to translate these findings to physiological ageing. Taken together, the modulation of YAP/TAZ or the Hippo pathway in general may offer potential new strategies for the prevention or treatment of ageing.

Nurses' roles in palliative care: An Islamic perspective.

Palliative care is an important approach for nurses to improve the quality of life of patients holistically and mitigate suffering among the patients in critical condition and near to death. This article provides an Islamic perspective about nurses' roles in palliative care, which can be applied worldwide, especially in Muslim-majority countries. Understanding Islamic beliefs will help nurses provide professional and culturally sensitive nursing care. In its principle, Islam always respects the process of life until death comes. So, the application of Islamic values in palliative care will make the patients accept their ill condition completely, keep being close to Allah SWT (God), and die peacefully. The concepts of illness, death, early action on the dead, and palliative care application in nursing are explained in this article to open up new ideas rather than provide definitive answers. We hope that this perspective will highlight healthcare policymakers the need to integrate Islamic values in nursing practice.

Effect of Differents Cowmilk and Soymilk (soy yogurt) Formulation on Blood Glucose Level and Glut4 Gene Expression in Rats Soleus Muscle.

BACKGROUND AND OBJECTIVE: Soy yogurt is fermented soy milk and its nutrient-rich with isoflavones. Soy yogurt decreases blood glucose levels by utilizing the conversion of isoflavones. This study aimed to analyze the effect of soy yogurt on blood glucose level and Glut4 gene expression on rats' soleus muscle. MATERIALS AND METHODS: Twenty-five rats (eighteen-weeks old) were divided into 5 groups, e.g., the control (P0), positive control (P1, 100% yogurt) and three treatment groups (P2, 50% soy yogurt+50% yogurt; P3, 75% yogurt+25% soy yogurt and P4, 75% soy yogurt+25% yogurt). All treatment groups were treated with different soy yogurt formula and administered for 12 weeks by gavaging. Under anesthetized, rats were sacrificed, then blood samples and soleus muscle were collected and stored at -80°C until use. RNA was extracted from soleus muscle and run for Glut4 mRNA expression using (RT)-PCR. Data were analyzed using one way ANOVA and followed by post hoc test LSD (Least Significant Differences test). RESULTS: There is no difference in rat body weight among groups after 12 weeks of soy yogurt consumption. Blood glucose levels were decreased at least 25% lower level compared to the control baseline by the various formulation of soy yogurt. Interestingly, there is a distinct pattern of Glut4 mRNA expression level in the soleus muscle, P1 increased the expression but not with other formulations decreased the expression (P2, P3 and P4). CONCLUSION: Taken together, a different formulation of soymilk and cowmilk effectively reduces blood glucose level and modulates Glut4 mRNA expression. In addition, a specific combination of bacteria type for fermenting soy yogurt could be a key to effectiveness for modulating blood glucose levels.

Different training intensities induced autophagy and histopathology appearances potentially associated with lipid metabolism in wistar rat liver.

INTRODUCTION: Aerobic training has a beneficial effect on enhancing liver functions. Autophagy might potentially play a role in preventing excessive lipid accumulation, regulating oxidative stress, and inflammation in the liver. OBJECTIVE: To investigate the potential linking role of autophagy-related gene expressions and protein levels with histopathology changes in Wistar rat livers after treadmill training under different intensities. METHODS: 20 rats were divided into 4 groups (control, low intensity, moderate intensity, and high intensity). 8 weeks of treadmill training was conducted with a frequency of 5 days per week, for a duration of 30 min per day. Liver histopathology was studied using hematoxylin-eosin, and oil red O staining. RNA and protein from the liver tissues were extracted to examine the autophagy-related gene (LC3, p62) and protein levels (Beclin, ATG5, LC3, p62). The gene expressions of CPT1a, CD36, FATP 2,3,5, GLUT2, and FGF21 were also studied. RESULTS: Different intensities of training might potentially modulate autophagy-related gene expressions in rat livers. LC3 and p62 mRNA expressions in moderate and high intensities decreased compared to control. Beclin, ATG5, and LC3 protein level increased compared to control, while p62 protein level decreased compared to control. Whereas for the other genes, we found an increase in CPT1a, but we did not observed any changes in the expression of the other genes. Interestingly, autophagy-related gene expressions might be correlated with the changes of sinusoidal dilatation, cloudy swelling, inflammation, and lipid droplets of the liver tissues. CONCLUSION: Moderate and high intensities of training induce autophagy activity, combined with a shift in metabolic zonation in liver that might be potentially correlated with lipophagy. Our results showed the potential interplay role between autophagy and liver histopathology appearances as a part of the adaptation process to training.

Adaptation of aerobic training essentially involved autophagy, mitochondrial marker and muscle fibre genetic modulation in rat cardiac muscles.

Information about the role of moderate acute treadmill training in modulating autophagy and mitochondrial markers that might be correlated with alteration of muscle fibre gene expression in rat cardiac muscles is very limited. In this present study, the researchers divided twenty male Wistar rats into four groups: sedentary control, 3, 6 and 15 days and subjected them to treadmill training with moderate intensity (20 m/min), 30 min each day. RNA was extracted from cardiac muscles and stored in temperature of -80°C. Specific primers were utilized for semi-quantitative PCR. Treadmill training decreased autophagy-related gene expression (LC3, p62) and upper stream signalling of autophagy (PIK3CA, Akt and mTOR) in 3 and 6 d, but stimulated gene expression of mitochondrial markers (PGC1α, Cox1, Cox2 and Cox4) in 15 days. αMHC gene expression increased while ßMHC gene expression decreased in 15 days. In line with this, autophagy-related genes increased in 3 and 6 days and returned to baseline in 15 days. The increment in mitochondrial gene expression might be correlated with shifting gene expression of αMHC and ßMHC in 15 days. Taken together, acute adaptation in cardiac muscles is stimulated by genetic modulation of autophagy, mitochondrial marker and muscle fibre that may explain physiological cardiac adaptation after training. This study can be used as a reference for optimizing performance in period of cardiac muscle adaptation stimulated by treadmill training.

Cardiac hypertrophy is stimulated by altered training intensity and correlates with autophagy modulation in male Wistar rats.

BACKGROUND: The mechanism for cardiac hypertrophy process that would be a benefit for improvement of cardiovascular endurance needed to be investigated throughly. Specific intensity of training may play a role for homeostasis process in cardiac during training. In the present study, we examine the effect of different intensity of treadmill training on cardiac hypertrophy process and autophagy related gene expression in male wistar rats. METHODS: Three different intensities of treadmill training were conducted on 15 male wistar rats (Low Intensity: 10 m/minute, Moderate Intensity: 20 m/minute, and High Intensity: 30 m/minute) compared to 5 sedentary rats as control. Training duration was 30 min per day, frequency was 5 days per week, during 8 weeks period. Heart weight and heart weight/body weight ratio were measured after the experiments. Left ventricle myocardium was taken for microscopic analysis with HE staining. mRNA was extracted from left ventricle myocardium for examining αMHC and autophagy related gene expression (PIK3CA, mTOR, LC3, p62) using semi quantitative PCR. RESULTS: We observed that altered training intensity might stimulate cardiac hypertrophy process. MI and HI training increased heart weight and heart weight/body weight ratio. This finding is supported by microscopic result in which cardiac hypertrophy was found in MI and HI, with focal fibrosis in HI, and increased αMHC gene expression in MI (p < 0.05) and HI (p = 0.076). We also observed decreased PIK3CA (LI 0.8 fold, MI 0.9 fold), mTOR (LI 0.9 fold, MI 0.9 fold), LC3 (LI 0.9 fold, MI 0.8 fold, HI 0.8 fold), and p62 (LI 0.8 fold, MI 0.9 fold) compared to control. Interestingly, we found increased mTOR (HI 1.1 fold) and p62 (HI 1.1 fold) compared to control. CONCLUSION: Training with different intensity creates different cardiac hypertrophy process based on heart weight and heart weight/body weight ratio, microscopic examination and autophagy related gene expression.

Nutmeg Extract Increases Skeletal Muscle Mass in Aging Rats Partly via IGF1-AKT-mTOR Pathway and Inhibition of Autophagy.

The sarcopenic phenotype is characterized by a reduction of muscle mass, a shift in fiber-type distribution, and reduced satellite cell regeneration. Sarcopenia is still a major challenge to healthy aging. Traditional Indonesian societies in Sulawesi island have been using nutmeg for maintaining health condition during aging. Interestingly, nutmeg has been known to stimulate peroxisome proliferator activated receptors γ (PPARγ) which may contribute to myogenesis process in cardiac muscle. There is limited information about the role of nutmeg extract into physiological health benefit during aging especially myogenesis process in skeletal muscle. In the present study, we want to explore the potential effect of nutmeg in preserving skeletal muscle mass of aging rats. Aging rats, 80 weeks old, were divided into two groups (control and nutmeg). Nutmeg extract was administered for 12 weeks by gavaging. After treatment, rats were anaesthesized, then soleus and gastrocnemius muscles were collected, weighted, frozen using liquid nitrogen, and stored at -80°C until use. We observed phenomenon that nutmeg increased a little but significant food consumption on week 12, but significant decrease in body weight on weeks 10 and 12 unexpectedly increased significantly in soleus muscle weight (p<0.05). Nutmeg extract increased significantly gene expression of myogenic differentiation (MyoD), paired box 7 (Pax7), myogenin, myosin heavy chain I (MHC I), and insulin-like growth factor I (p<0.01) in soleus muscle. Furthermore, nutmeg increased serine/threonine kinase (AKT) protein levels and activation of mammalian target of rapamycin (mTOR), inhibited autophagy activity, and stimulated or at least preserved muscle mass during aging. Taken together, nutmeg extract may increase muscle mass or prevent decrease of muscle wasting in soleus muscle by partly stimulating myogenesis, regeneration process, and preserving muscle mass via IGF-AKT-mTOR pathway leading to inhibition of autophagy activity during aging. This finding may reveal the potential nutmeg benefits as alternative supplement for preserving skeletal muscle mass and preventing sarcopenia in elderly.

Pancreatic effect of andrographolide isolated from Andrographis paniculata (Burm. f.) Nees.

Andrographis paniculata (Burm. f.) Nees is a plant that originates from India and grows widely to Southeast which used for several purposes mainly as treatment of diabetes mellitus so the aim of this study was evaluate andrographolide for its pancreatic effect in neonatal streptozotocin (STZ)-induced diabetic rats, a model of type 2 diabetic rats. Diabetic condition was induced with an intraperitoneal injection of 90 mg kg(-1) streptozotocin in two-day-old rats. After three months, the neonatal STZ-induced diabetic rats were treated with andrographolide or andrographolide-enriched extract of A. paniculata (AEEAP) for 8 consecutive days. Pancreatic effect was evaluated by estimating mainly the preprandial and postprandial blood glucose levels and other parameters such as morphology of pancreatic islet, beta cells density and morphology and immunohistochemically pancreatic insulin. Andrographolide significantly (p < 0.05) decreased the levels of blood glucose and improved diabetic rat islet and beta cells. However, AEEAP exhibited moderate hypoglycaemic effects on the blood glucose levels. Moderate changes in beta cells were observed after AEEAP treatment. They could restore decreasing of pancreatic insulin contents. Based on these results andrographolide and AEEAP exhibited pancreatic actions in neonatal STZ-induced diabetic rats. The activity of andrographolide was more effective than this of AEEAP.

Structural disruption of phospholipid bilayers over a range of length scales by n-butanol.

We report on the exposure of planar multicomponent lipid bilayers supported on mica to n-butanol. The bilayer contains 49 mol % 1,2-dioleoyl-sn-phosphatidylcholine (DOPC), 10 mol % cholesterol, 40 mol % sphingomyelin, and 1 mol % sulforhodamine-tagged 1,2-dioleoyl-sn-phosphatidylethanolamine (SR-DOPE). Phase separation of the cholesterol domains is seen within the bilayer structure, and exposure of this supported bilayer to controlled amounts of n-butanol in the aqueous overlayer produces morphological changes over a range of length scales. We report steady state fluorescence imaging, fluorescence lifetime imaging, and fluorescence anisotropy decay imaging for these bilayers. These data are consistent with literature reports on the interactions of lipid bilayers with n-butanol and provide molecular-scale insight relative to bilayer organization that has not been available to date. The exposure of these bilayers to n-butanol leads to more extensive disruption of the bilayer than is seen for their exposure to ethanol.

Ethanol-induced perturbations to planar lipid bilayer structures.

We report on the formation of planar lipid bilayer structures on mica where the bilayer contains the phosphocholine 1,2-dioleoyl-sn-phosphatidylcholine (DOPC), cholesterol, sphingomyelin and sulforhodamine-tagged-1,2-dioleoyl-sn-phosphatidylethanolamine (SR-DOPE). Phase separation is seen for the cholesterol domains within the bilayer structure, and exposure of this supported bilayer to controlled concentrations of ethanol reveals organizational changes on both the micrometer- and molecular-length scales. We report steady state fluorescence imaging, fluorescence lifetime imaging, and fluorescence anisotropy decay imaging for these bilayers. These data are complementary to existing information on the interactions of lipid bilayers with ethanol and point to subtle but important changes in the molecular-scale organization of these structures.

Interactions of doxorubicin with organized interfacial assemblies. 2. Spectroscopic characterization.

Doxorubicin is an anthracycline that has found wide use as a chemotherapeutic agent, with the primary limitation to its use being cardiotoxicity. Depending on the identity and location of pendent side groups, the anthracyclines exhibit varying degrees of chemotherapeutic activity and toxicity, and a key area of research activity lies in understanding how the structure of the anthracycline influences its interactions with amphiphilic interfaces. We have studied interactions between doxorubicin and interfacial adlayers of octadecylamine (C18NH2), dihexadecylphosphate (DHP), and both monolayers and bilayers of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) on mica using time- and frequency-resolved spectroscopic measurements. We report surface-enhanced resonance Raman data and fluorescence lifetime and anisotropy imaging data for doxorubicin at these interfaces. For all monolayers, there is a substantial interaction between doxorubicin and the interface. For DMPC bilayers, the extent of the interaction between doxorubicin and the interface depends on how the interface was formed.

Characterization of polychlorinated biphenyls and brominated flame retardants in sludge, sediment and fish from municipal dumpsite at Surabaya, Indonesia.

We investigated the PCBs, PBDEs and HBCDs contamination in sludge, sediments and fish from various locations including raw leachate pond, leachate treatment plans (LTPs), control wells and reference site at open landfill of municipal dumpsite, Surabaya City, Indonesia. 62 PCBs and 14 PBDEs congeners, and 3 HBCDs isomers were identified and quantified using GC-MS and LC-MS/MS, respectively. Concentration ranges and median (value in parentheses) of PCBs, PBDEs and HBCDs were from not detected (ND) to 60 (3.9) ng g(-1) dw, 0.0075 to 45 (4.5) ng g(-1) dw and ND to 2.8 (0.052) ng g(-1) dw in sludge and sediments, respectively. While in two polled of fish samples were 30-55 ng g(-1) lw, 6.6-11 ng g(-1) lw and 1.6-3.3 ng g(-1) lw, respectively. Among the sampling sites, the highest level of PCBs and PBDEs were detected in sludge from raw leachate pond. However, PCBs and PBDEs levels were showing decreased in LTP-1 that could be due to the bacterial degradation but not in LTP-2, HBCDs were more stable in both LTPs. Levels of PCBs and BFRs in sludge at the present study were lower than those reported in sewage sludge reported from some other countries. PCBs profiles were mainly composed in that order by CB-138, -153, -180, -101, -118 and -28, while by BDE-47, -99, -100, -153, -154 and -28 for PBDEs in sludge, sediments and fish. Profiles of HBCDs were predominantly composed by γ- and α-isomers in sludge and fish, respectively. Debromination, dechlorination, commercial formulations used and congener-specific accumulation of those contaminants are the factors influenced the profiles.

Up-regulation of the inwardly rectifying K⁺ channel Kir2.1 (KCNJ2) by protein kinase B (PKB/Akt) and PIKfyve.

The inward rectifier K⁺ channel Kir2.1 contributes to the maintenance of the resting cell membrane potential in excitable cells. Loss of function mutations of KCNJ2 encoding Kir2.1 result in Andersen-Tawil syndrome, a disorder characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. The ubiquitously expressed protein kinase B (PKB/Akt) activates the phosphatidylinositol-3-phosphate-5-kinase PIKfyve, which in turn regulates a variety of carriers and channels. The present study explored whether PKB/PIKfve contributes to the regulation of Kir2.1. To this end, cRNA encoding Kir2.1 was injected into Xenopus oocytes with and without additional injection of cRNA encoding wild type PKB (PKB), constitutively active (T308D,S473D)PKB or inactive (T308A,S473A)PKB. Kir2.1 activity was determined by two-electrode voltage-clamp. As a result, PKB and (T308D,S473D)PKB, but not (T308A,S473A)PKB, significantly increased Kir2.1-mediated currents. The effect of PKB was mimicked by coexpression of PIKfyve but not of (S318A)Pikfyve lacking the PKB phosphorylation site. The decay of Kir2.1-mediated currents after inhibition of channel insertion into the cell membrane by brefeldin A (5 µM) was similar in oocytes expressing Kir2.1 + PKB or Kir2.1 + PIKfyve to those expressing Kir2.1 alone, suggesting that PKB and PIKfyve influence channel insertion into rather than channel retrieval from the cell membrane. In conclusion, PKB and PIKfyve are novel regulators of Kir2.1.

Evaluating the sensitivity of lipid headgroup-bound chromophores to their local environment.

We report on the steady state and time-resolved fluorescence behavior of the chromophore 1,2-dimiryristoyl-sn-glycero-3-phosphoethanolamine-N-lissamine rhodamine B sulfonyl ammonium salt (SR-DMPE) in a series of solution phase and lipid bilayer environments. The issue of interest is whether or not the lipid headgroup-bound chromophore is sensitive to its local environment under conditions where vesicles have not been formed in lipid-containing mixtures and where unilamellar vesicles have been formed by extrusion. Our data point to the strong interaction of SR-DMPE with 1,2-dimirystoyl-sn-glycero-phosphocholine (DMPC) in solution whether or not the solution has undergone extrusion. The amount of SR-DMPE in the lipid-containing systems affects both the steady state and time-resolved spectroscopic response. Excitation of the chromophore to the S(2) state deposits sufficient excess energy into the system to influence its rotational diffusion dynamics, demonstrating significant interactions between SR-DMPE and DMPC. Comparison of SR-DMPE reorientation dynamics in DMPC-containing solutions with corresponding data on SR-DMPE in aqueous solution indicates that the lipids impose a restrictive local environment on the chromophore that is a factor of ca. 10 more viscous than an aqueous environment. The similarity of the reorientation data in all DMPC-containing solutions suggests that SR-DMPE is a local probe that is not sensitive to longer range organization.

Characterization of polychlorinated biphenyls and brominated flame retardants in surface soils from Surabaya, Indonesia.

In this study, soil contamination by PCBs, PBDEs, HBCDs and two novel BFRs such as 1,2-bis-(2,4,6-tribromopenoxy) ethane (BTBPE) and decabromodiphenyl ethane (DBDPE) in various locations such as industrial, urban, rural, dumping site and agricultural areas of Surabaya, Indonesia has been characterized in order to evaluate their contamination status, profiles, potential sources, fate and behavior. Range and median concentrations of PCBs, PBDEs, HBCDs, BTBPE and DBDPE were ND - 9.6 (1.2), 0.069 - 24 (7.4), ND - 1.8 (0.48), ND - 1.7 (0.14) and ND - 7.6 (2.2) ng g(-1)dw, respectively. Industrial, urban and dumping areas were inventoried as the main sources of these pollutants. Decreasing gradient levels were observed for these contaminants from industrial district, urban, dumping site, rural and agricultural areas, in that order. Furthermore, organic carbon contents and proximity to the point sources were found as the major controlling factors. Contaminant profiles were characterized by the predominance of hexa-, hepta- and penta-homologues for PCBs; deca-, nona- and octa- for PBDEs and α-isomer for HBCDs. Product mixtures such as Ar1260/KC600 and Ar1254/KC500 for PCBs, deca- and octa-BDEs for PBDEs were the possible common formulations used in study area. To our knowledge, this is a first comprehensive study on characterization of soil contamination by PCBs, PBDEs and HBCDs together with two novel BFRs in a highly industrialized city located in tropical region. This study provides baseline information for establishing national monitoring programs in Indonesia.