Miracle-dz/UniFAR-FTUs huggingface dataset:
Mouse Sphingosine Kinase 1a Is Negatively Regulated through Conventional PKC-Dependent Phosphorylation at S373 Residue

Sphingosine kinase is a lipid kinase that converts sphingosine into sphingosine-1-phosphate, an important signaling molecule with intracellular and extracellular functions. Although diverse extracellular stimuli influence cellular sphingosine kinase activity, the molecular mechanisms underlying its regulation remain to be clarified. In this study, we investigated the phosphorylation-dependent regulation of mouse sphingosine kinase (mSK) isoforms 1 and 2. mSK1a was robustly phosphorylated in response to extracellular stimuli such as phorbol ester, whereas mSK2 exhibited a high basal level of phosphorylation in quiescent cells regardless of agonist stimulation. Interestingly, phorbol ester-induced phosphorylation of mSK1a correlated with suppression of its activity. Chemical inhibition of conventional PKCs (cPKCs) abolished mSK1a phosphorylation, while overexpression of PKCα, a cPKC isoform, potentiated the phosphorylation, in response to phorbol ester. Furthermore, an in vitro kinase assay showed that PKCα directly phosphorylated mSK1a. In addition, phosphopeptide mapping analysis determined that the S373 residue of mSK1a was the only site phosphorylated by cPKC. Interestingly, alanine substitution of S373 made mSK1a refractory to the inhibitory effect of phorbol esters, whereas glutamate substitution of the same residue resulted in a significant reduction in mSK1a activity, suggesting the significant role of this phosphorylation event. Taken together, we propose that mSK1a is negatively regulated through cPKC-dependent phosphorylation at S373 residue.
Significant associations of stearoyl-CoA desaturase (SCD1) gene with fat deposition and composition in skeletal muscle

Gene expression studies in humans and animals have shown that elevated stearoyl-CoA desaturase (SCD1) activity is associated with increased fat accumulation and monounsaturation of saturated fatty acids in skeletal muscle. However, results of the two reported association studies in humans are inconsistent. In the present study, we annotated the bovine SCD1 gene and identified 3 single nucleotide polymorphisms (SNPs) in its 3'untranslated region (UTR). Genotyping these SNPs on a Wagyu x Limousin reference population revealed that the SCD1 gene was significantly associated with six fat deposition and fatty acid composition traits in skeletal muscle, but not with subcutaneous fat depth and percent kidney-pelvic-heart fat. In particular, we confirmed that the high stearoyl-CoA desaturase activities/alleles were positively correlated with beef marbling score, amount of monounsaturated fatty acids and conjugated linoleic acid content, but negatively with amount of saturated fatty acids. The inconsistent associations between human studies might be caused by using different sets of markers because we observed that most associated markers are located near the end of 3'UTR. We found that the proximity of the polyadenylation signal site is highly conserved among human, cattle and pig, indicating that the region might contain functional elements involved in posttranscriptional control of SCD1 activity. In conclusion, our cross species study provided solid evidence to support SCD1 gene as a critical player in skeletal muscle fat metabolism.
Quercetin Suppresses Drug-Resistant Spheres via the p38 MAPK–Hsp27 Apoptotic Pathway in Oral Cancer Cells

Background Treatment failure in oral squamous cell carcinoma (OSCC) leading to local recurrence(s) and metastases is mainly due to drug resistance. Cancer stem cells (CSCs) are thought be responsible for the development of drug resistance. However, the correlations between CSCs, drug resistance, and new strategy against drug resistance in OSCC remain elusive. Methods A drug-resistant sphere (DRSP) model was generated by using a nonadhesive culture system to induce drug-resistant cells from SCC25 oral cancer cells. A comparative analysis was performed between the parent control cells and DRSPs with a related treatment strategy focusing on the expression of epithelial–mesenchymal transition (EMT)-associated markers, drug-resistance-related genes, and CSC properties in vitro, as well as tumorigenicity and the regimen for tumor regression in vivo. Results Our data show the presence of a phenomenon of EMT with gradual cellular transition from an epithelioid to mesenchymal-like spheroid morphology during induction of drug resistance. The characterization of DRSPs revealed the upregulation of the drug-resistance-related genes ABCG2 and MDR-1 and of CSC-representative markers, suggesting that DRSPs have greater resistance to cisplatin (Cis) and stronger CSC properties compared with the control. Moreover, overexpression of phosphorylated heat-shock protein 27 (p-Hsp27) via the activation of p38 MAPK signaling was observed in DRSPs. Knockdown of Hsp27 decreased Cis resistance and induced apoptosis in DRSPs. Furthermore, an inhibitor of Hsp27, quercetin (Qu), suppressed p-Hsp27 expression, with alterations of the EMT signature, leading to the promotion of apoptosis in DRSPs. A xenographic study also confirmed the increase of tumorigenicity in DRSPs. The combination of Qu and Cis can reduce tumor growth and decrease drug resistance in OSCC. Conclusions The p38 MAPK–Hsp27 axis plays an important role in CSCs-mediated drug resistance in OSCC. Targeting this axis using Qu combined with Cis may be a treatment strategy to improve prognosis in patients with OSCC.
VICTIM PARTICIPATORY RIGHTS IN PAROLE: THEIR ROLE AND THE DYNAMICS OF VICTIM INFLUENCE AS SEEN BY BOARD MEMBERS

The last decade has seen as escalating demand from victims to be given a voice in the parole phase of the criminal justice system. Both the Canadian and American governments have responded to this demand by significantly expanding victims' participatory rights in parole. This study examines victim participation in parole from the perspective of individual parole board members. Specifically, this study provides an in-depth exploration of the opinions of individual board members on victim participatory rights in parole and examines how the victim fits into and effects parole board decision-making processes, practices, and outcomes. Particular attention is paid to the analysis of individual, contextual, and environmental variables as they relate to the weighting and integration of victim information. Results obtained suggest that victim participatory rights in a parole context are not fully understood or welcomed by some board members. Most noticeably, significant disparity was evident in how victim information was used and incorporated into parole practices and outcomes by individual board members. Further, the level of support for victim involvement in parole and the extent and method by which victim information is incorporated into parole decision making is influenced by individual board member differences such as gender. These findings and others are discussed in the context of policy implications for the future of victim participatory rights in parole.
Prenatal Stress and Peripubertal Stimulation of the Endocannabinoid System Differentially Regulate Emotional Responses and Brain Metabolism in Mice

The central endocannabinoid system (ECS) and the hypothalamic-pituitary-adrenal-axis mediate individual responses to emotionally salient stimuli. Their altered developmental adjustment may relate to the emergence of emotional disturbances. Although environmental influences regulate the individual phenotype throughout the entire lifespan, their effects may result particularly persistent during plastic developmental stages (e.g. prenatal life and adolescence). Here, we investigated whether prenatal stress – in the form of gestational exposure to corticosterone supplemented in the maternal drinking water (100 mg/l) during the last week of pregnancy – combined with a pharmacological stimulation of the ECS during adolescence (daily fatty acid amide hydrolase URB597 i.p. administration - 0.4 mg/kg - between postnatal days 29–38), influenced adult mouse emotional behaviour and brain metabolism measured through in vivo quantitative magnetic resonance spectroscopy. Compared to control mice, URB597-treated subjects showed, in the short-term, reduced locomotion and, in the long term, reduced motivation to execute operant responses to obtain palatable rewards paralleled by reduced levels of inositol and taurine in the prefrontal cortex. Adult mice exposed to prenatal corticosterone showed increased behavioural anxiety and reduced locomotion in the elevated zero maze, and altered brain metabolism (increased glutamate and reduced taurine in the hippocampus; reduced inositol and N-Acetyl-Aspartate in the hypothalamus). Present data further corroborate the view that prenatal stress and pharmacological ECS stimulation during adolescence persistently regulate emotional responses in adulthood. Yet, whilst we hypothesized these factors to be interactive in nature, we observed that the consequences of prenatal corticosterone administration were independent from those of ECS drug-induced stimulation during adolescence.
New learning in semantic dementia: Implications for cognitive and neuroanatomical models of long-term memory

Les recherches effectuees sur des patients atteints du syndrome de demence semantique ont permis, d'un point de vue theorique, de mettre en evidence certains principes d'organisation de la membire semantique et de la memoire episodique. Dans cet article nous presentons un ensemble d'etudes recentes qui suggere que la memoire utilisee lors de la reconnaissance de stimuli picturaux (objets, visages, etc.) est preservee, du moins durant les premiers temps de la maladie. Cette hypothese est ensuite discutee dans le cadre des theories concernant l'interaction entre la memoire semantique et la memoire episodique, ainsi que dans le cadre des theories concernant les contributions des differentes structures du lobe medio-temporal.
Potential Risk of Dengue and Chikungunya Outbreaks in Northern Italy Based on a Population Model of Aedes albopictus (Diptera: Culicidae)

The rapid invasion and spread of Aedes albopictus (Skuse, 1894) within new continents and climatic ranges has created favorable conditions for the emergence of tropical arboviral diseases in the invaded areas. We used mosquito abundance data from 2014 collected across ten sites in northern Italy to calibrate a population model for Aedes albopictus and estimate the potential of imported human cases of chikungunya or dengue to generate the condition for their autochthonous transmission in the absence of control interventions. The model captured intra-year seasonality and heterogeneity across sites in mosquito abundance, based on local temperature patterns and the estimated site-specific mosquito habitat suitability. A robust negative correlation was found between the latter and local late spring precipitations, indicating a possible washout effect on larval breeding sites. The model predicts a significant risk of chikungunya outbreaks in most sites if a case is imported between the beginning of summer and up to mid-November, with an average outbreak probability between 4.9% and 25%, depending on the site. A lower risk is predicted for dengue, with an average probability between 4.2% and 10.8% for cases imported between mid-July and mid-September. This study shows the importance of an integrated entomological and medical surveillance for the evaluation of arboviral disease risk, which is a precondition for designing cost-effective vector control programs.
The Effects of Systemic, Topical, and Intralesional Steroid Treatments on Apoptosis Level of Nasal Polyps

Objective The purpose of this study was to compare the apoptotic responses to systemic, topical, and intrapolyp injection of glucocorticoid with no treatment in nasal polyps. Study Design Prospective, randomized controlled study. Setting Tertiary training hospital. Subjects and Methods The study was performed on 48 patients with nasal polyposis in the Department of Otorhinolaryngology between 2008 and 2009. Patients were assigned to 1 of 4 groups of 12 patients. Group A was treated with oral methylprednisolone 1 mg/kg/d, and the dose was tapered gradually. Group B received 0.3 mL triamcinolone acetonide (40 mg/mL), which was injected into polyp tissue. Group C was treated with topical 55 µg triamcinolone acetonide 2 times daily for 1 month. Group D received no medication. Samples were collected endoscopically after the seventh day for groups A and B, the first month for group C, and the first visit for group D. Apoptotic indexes were determined using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Results Statistically significant differences in apoptotic index were found between each steroid-medicated group and the control group (PD-A = .0001; PD-B = .003; PD-C = .026) and between groups A and C (PA-C = .012). Group B did not differ significantly from either group A or C (PA-B = .11; PB-C = .75). Conclusions The apoptotic index in nasal polyps treated with systemic, topical, and intrapolyp injection forms of glucocorticoids was higher than that in the control group. Systemic steroid treatment induced the most apoptosis.
Antioxidant Effect of a Marine Oligopeptide Preparation from Chum Salmon (Oncorhynchus keta) by Enzymatic Hydrolysis in Radiation Injured Mice

Marine oligopeptide preparation (MOP) obtained from Chum Salmon (Oncorhynchus keta) by the method of enzymatic hydrolysis, has been found to possess a radioprotective property through stimulation of the radiation-induced immunosuppression. The current study aimed to further investigate the free radicals scavenging and antioxidant effects of MOP in radiation injured mice. Female ICR mice (6–8 weeks old) were randomly divided into 5 groups, i.e., blank control, irradiation control and MOP (0.225, 0.450 and 1.350 g/kg body weight) plus an irradiation-treated group. The result revealed that MOP significantly increased the white blood cell counts after irradiation, and lessened the radiation-induced oxidative damage. These effects may be caused by augmentation of the activities of antioxidant enzymes, such as SOD and GSH-Px, reduction of the lipid peroxidation (MDA level) in liver, and protection against radiation-induced apoptosis. Therefore, we propose that MOP be used as an ideal antioxidant to alleviate radiation-induced oxidation damage in cancer patients.
Measuring Aedes & Breteau Indices in Determining Dengue Outbreak; A Study in Kota Tinggi.

ABSTRACT Introduction Dengue fever, the most known vector-borne disease in the tropical and subtropical regions has become major public health concern worldwide. Rapid urbanization, increased population movement and poor public hygienic lifestyle contributed to the proliferated of high incidence of dengue fever in urban and semi urban areas. With the increasing trend of dengue cases and deaths, methods of dengue surveillance should be reevaluated in predicting dengue outbreak. Objective This study aimed to determine association between Aedes Index and Breteau Index with dengue outbreak in the district of Kota Tinggi, Johor. Result Total of 593 dengue cases in 2015 collected from Kota Tinggi Health Office. The study found that although there were significant association between Aedes Index and Breteau Index with localities (p< 0.001), the Aedes Index sensitivity level of 29.3% , specificity level of 44.2% and Breteau Index of 12% sensitivity and 81.5% specificity showed that the indices were not the most accurate and sensitive as the tools of dengue surveillance in determining dengue outbreak. Conclusion As dengue disease remains a major endemic in Malaysia, better surveillance index should be reconsider as the main surveillance for dengue disease.
The Term Structure of Credit Spreads in Project Finance

This paper finds that the term structure of credit spreads in project finance is hump-shaped. This contrasts with other types of debt, where credit risk is shown instead to increase monotonically with maturity ceteris paribus. We emphasize a number of peculiar features of project finance structures that might underlie this finding, such as high leverage decreasing over time, long-term political risk guarantees and the sequential resolution of uncertainty along project advancement stages. Our result is particularly relevant given the importance of project finance as a source of long-term capital for infrastructure especially in developing countries and has implications for risk management in the framework of Basel II. Copyright © 2007 John Wiley & Sons, Ltd.
Quality of Learning With an Active Versus Passive Motivational Set

This study tested whether students who learned with an active orientation would be more intrinsically motivated to learn and would learn more than students who learned with a passive orientation. The active orientation was created by having subjects learn material with the expectation of teaching it to another student; the passive orientation was created by having subjects learn the same material with the expectation of being tested on it. The results indicate that subjects who learned in order to teach were more intrinsically motivated, had higher conceptual learning scores, and perceived themselves to be more actively engaged with the environment than subjects who learned in order to be examined. The two groups were equal, however, in their rote learning scores. The effects of exposure to the material were ruled out as an explanation because the two groups reported spending equal time with the material. The results are discussed in terms of intrinsic motivation theory.
Aging with a long-term physical impairment: An ever-changing process

The experience of people aging with long-term physical impairments is a relatively new area of research which requires further attention. There will be more people who reach old age who have lived with a long-term physical impairment as the population ages and life expectancy continues to increase. There is a gap in the research that explores life course theory while a person ages with a physical impairment. Using a life course perspective, this thesis examines the aging experiences of eight people between the ages of 50 and 68 who have lived with their physical impairment for more than 10 years. Data were gathered through in-depth, semistructured interviews. My participants experienced problems in their life as a result of their physical impairment and the stereotypes and barriers constructed by mainstream society. Their impairments have led to physical, emotional and financial problems throughout their lives. They have learned to develop coping mechanisms, mostly on their own, to adjust to these problems and continue participating in society despite initial limitations. My thesis concludes by offering suggestions to improve policies to meet the needs of a large population of people aging with long-term physical impairments.
The Effect of Learning on Bursting

We have studied the effect that learning a new stimulus-response (SR) relationship had within a neuronal network cultured on a multielectrode array. For training, we applied repetitive focal electrical stimulation delivered at a low rate (Lt1/s). Stimulation was withdrawn when a desired SR success ratio was achieved. It has been shown elsewhere, and we verified that this training algorithm, named conditional repetitive stimulation (CRS), can be used to strengthen an initially weak SR. So far, it remained unclear what the role of the rest of the network during learning was. We therefore studied the effect of CRS on spontaneously occurring network bursts. To this end, we made profiles of the firing rates within network bursts. We have earlier shown that these profiles change shape on a time base of several hours during spontaneous development. We show here that profiles of summed activity, called burst profiles, changed shape at an increased rate during CRS. This suggests that the whole network was involved in making the changes necessary to incorporate the desired SR relationship. However, a local (path-specific) component to learning was also found by analyzing profiles of single-electrode-activity phase profiles. Phase profiles that were not part of the SR relationship changed far less during CRS than the phase profiles of the electrodes that were part of the SR relationship. Finally, the manner in which phase profiles changed shape varied and could not be linked to the SR relationship.
β1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance

The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of β1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of β1 integrin expression in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin α2 chain. Expression levels of lamininα 2 are reduced in the postnatal CNS, but a population of cells expressing high levels of β1 remains. Using neurospheres – aggregate cultures, derived from single stem cells, that have a three-dimensional architecture that results in the localisation of the stem cell population around the edge of the sphere – we show directly thatβ 1 integrins are expressed at high levels on neural stem cells and can be used for their selection. MAPK, but not PI3K, signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of β1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control neural stem cell behaviour in specific areas of the CNS.
Clinical Ophthalmology Dovepress Dovepress Folate Status in Type 2 Diabetic Patients with and without Retinopathy

Background: Folate deficiency is associated with cardiovascular disease, megaloblastic anemia, and with hyperhomocysteinemia. This study has been undertaken to investigate the role of folate status during the progression of the diabetic retinopathy. Methods: We measured the plasma levels of homocysteine, folic acid, and red cell folate in 70 diabetic type 2 patients with nonproliferative diabetic retinopathy (NPDR), 65 with prolif-erative diabetic retinopathy (PDR), 96 without diabetic retinopathy, and 80 healthy subjects used as a control group. Results: We found higher plasma levels of homocysteine in the NPDR group compared to the control group (P,0.001) and in the PDR group compared to control group (P,0.001) and NPDR group (P,0.01). The severity of diabetic retinopathy was associated with lower folic acid and red cell folate levels, and a significant difference was observed between PDR and NPDR groups (P,0.05). Conclusion: The folate status could play a role in the development and progression of diabetic retinopathy.