bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palliative and end-of-life care in the masters of social work curriculum
Authors: Berkman Cathy , Stein Gary L. 
Published: March 2017

ABSTRACTObjective:There is a shortage of social workers who have palliative care expertise. The aging U.S. population and advances in extending life for seriously ill persons require social workers in a wide range of health care and other settings with specialized palliative care expertise, as well as those with basic competence in palliative care. The objective of the present study was to document course content on palliative care in MSW programs in the United States and Canada.Method:A cross-sectional design with an online questionnaire was used. All 248 accredited MSW programs in the United States and 32 programs in Canada were invited to participate. The measures included the characteristics of the courses on palliative care.Results:Of the 105 participating programs, only 10 had courses dedicated to palliative care, 9 of which were part of a specialization/certificate program. Few programs had plans to develop a dedicated course. There were 106 courses in 63 MSW programs with some content on palliative care. The majority of these had <25%, and few had at least 50%, of palliative care content.Significance of Results:Curricula are needed for preparing MSW graduates for specialty hospice and palliative care practice and non-specialty practice. While there are practice competencies for specialty practitioners, consensus on a core curriculum for all MSW students would be beneficial. Consensus on basic palliative care knowledge and skills for non-specialty social workers in health care and other settings and subsequent curriculum development are also needed. Innovative ways in which to introduce basic and more specialized content on palliative care into the already-crowded MSW curricula will be needed.
Situational and Dispositional Factors that Predict Motivation: a Multilevel Study
Authors: Pineda-Espejel Heriberto Antonio , López-Walle Jeanette , Tomás Inés 
Published: March 2017

AbstractThis study aimed to test a multilevel mediation model which examined the relationship between the perceived motivational climate created by coaches at team level and motivational regulations towards sport at individual level, as mediated by individual goal orientations. 211 university athletes from 20 teams training in different types of sport completed a battery of instruments that measured the variables included in the model. The statistics significance level was .05. Results of the multilevel mediation model revealed that the task-involving climate at team level positively predicted individual task orientation (γ01 = .77, p < .001) and autonomous motivation for sport practice (γ01 = .68, p = .03). Task orientation positively predicts the autonomous motivation (γ10 =.51, p < .01), and inversely the non motivation (γ10 = –.76, p < .001). Also task orientation partially mediated the relationship between task-involving climate and autonomous motivation (b1b2 = .39; 95% CI = [.11, .68]; τ = .68, p < .05), and fully mediated the relationship between task-involving climate and amotivation (b1b2 = –.58; 95% CI = [–.92, –.25]; τ = –.62, p >.05). The results are in line with previous research that have focused in the study of motivational climate at individual level, but the present study make a novel contribution by providing the perspective of a multilevel mediation model and thereby clarifying the phenomenon at team level.
miR-491-5p, mediated by Foxi1, functions as a tumor suppressor by targeting Wnt3a/β-catenin signaling in the development of gastric cancer
Authors: Sun Ruifang , Liu Zhigang , Tong Dongdong , Yang Yang , Guo Bo , Wang Xiaofei , Zhao Lingyu , Huang Chen 
Published: March 2017

AbstractAccumulated evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse signaling pathways. However, the precise role of miRNAs in gastric cancer (GC) has not been elucidated. In this study, we describe the function and regulation network of miR-491-5p in GC. miR-491-5p is frequently downregulated in GC tissues compared with adjacent non-cancerous tissues. Forced expression of miR-491-5p significantly inhibits proliferation and colony formation, and promotes apoptosis in GC cells. Through bioinformatic analysis and luciferase assays, we confirm that miR-491-5p targets Wnt3a. Silencing Wnt3a inhibits cell proliferation and induces apoptosis. Similarly, restoration of Wnt3a counteracts the effects of miR-491-5p expression. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-491-5p is regulated by Foxi1, which binds to its promoter and activates miR-491-5p expression. In conclusion, to the best of our knowledge, our findings are the first to demonstrate that Foxi1 is a key player in the transcriptional control of miR-491-5p and that miR-491-5p acts as an anti-oncogene by targeting Wnt3a/β-catenin signaling in GC. Our study reveals that Foxi1/miR-491-5p/Wnt3a/β-catenin signaling is critical in the progression of GC. Targeting the pathway described in this study may open up new prospects to restrict the progression of GC.
Overexpression of EphB2 in hippocampus rescues impaired NMDA receptors trafficking and cognitive dysfunction in Alzheimer model
Authors: Hu Rui , Wei Pan , Jin Lu , Zheng Teng , Chen Wen-Yu , Liu Xiao-Ya , Shi Xiao-Dong , Hao Jing-Ru , Sun Nan , Gao Can 
Published: March 2017

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease, which affects more and more people. But there is still no effective treatment for preventing or reversing the progression of the disease. Soluble amyloid-beta (Aβ) oligomers, also known as Aβ-derived diffusible ligands (ADDLs) play an important role in AD. Synaptic activity and cognition critically depend on the function of glutamate receptors. Targeting N-methyl-D-aspartic acid (NMDA) receptors trafficking and its regulation is a new strategy for AD early treatment. EphB2 is a key regulator of synaptic localization of NMDA receptors. Aβ oligomers could bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation in the proteasome. Here we identified that overexpression of EphB2 with lentiviral vectors in dorsal hippocampus improved impaired memory deficits and anxiety or depression-like behaviors in APPswe/PS1-dE9 (APP/PS1) transgenic mice. Phosphorylation and surface expression of GluN2B-containing NMDA receptors were also improved. Overexpression of EphB2 also rescued the ADDLs-induced depletion of the expression of EphB2 and GluN2B-containing NMDA receptors trafficking in cultured hippocampal neurons. These results suggest that improving the decreased expression of EphB2 and subsequent GluN2B-containing NMDA receptors trafficking in hippocampus may be a promising strategy for AD treatment.
Novel prosurvival function of Yip1A in human cervical cancer cells: constitutive activation of the IRE1 and PERK pathways of the unfolded protein response
Authors: Taguchi Yuki , Horiuchi Yuta , Kano Fumi , Murata Masayuki 
Published: March 2017

AbstractCancer cells are under chronic endoplasmic reticulum (ER) stress due to hypoxia, low levels of nutrients, and a high metabolic demand for proliferation. To survive, they constitutively activate the unfolded protein response (UPR). The inositol-requiring protein 1 (IRE1) and protein kinase RNA-like ER kinase (PERK) signaling branches of the UPR have been shown to have cytoprotective roles in cancer cells. UPR-induced autophagy is another prosurvival strategy of cancer cells, possibly to remove misfolded proteins and supply nutrients. However, the mechanisms by which cancer cells exploit the UPR and autophagy machinery to promote survival and the molecules that are essential for these processes remain to be elucidated. Recently, a multipass membrane protein, Yip1A, was shown to function in the activation of IRE1 and in UPR-induced autophagy. In the present study, we explored the possible role of Yip1A in activation of the UPR by cancer cells for their survival, and found that depletion of Yip1A by RNA interference (RNAi) induced apoptotic cell death in HeLa and CaSki cervical cancer cells. Intriguingly, Yip1A was found to activate the IRE1 and PERK pathways of the UPR constitutively in HeLa and CaSki cells. Yip1A mediated the phosphorylation of IRE1 and also engaged in the transcription of PERK. The activation of these signaling pathways upregulated the expression of anti-apoptotic proteins and autophagy-related proteins. These events might enhance resistance to apoptosis and promote cytoprotective autophagy in HeLa and CaSki cells. The present study is the first to uncover a key prosurvival modulator, Yip1A, which coordinates IRE1 signaling with PERK signaling to support the survival of HeLa and CaSki cervical cancer cells.
Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathway
Authors: Xu Xiaotian , Wang Yuhui , Wei Zhifeng , Wei Wenhui , Zhao Peng , Tong Bei , Xia Yufeng , Dai Yue 
Published: March 2017

AbstractThe imbalance between Th17 and Treg cells substantially contributes to the intestinal immune disturbance and subsequent tissue injury in ulcerative colitis. The triterpenoid-rich fraction of Centella asiatica was able to ameliorate dextran sulfate sodium-induced colitis in mice. Here we explored its active ingredient and underlying mechanism with a focus on restoring the Th17/Treg balance. The four main triterpenoids occurring in C. asiatica were shown to attenuate colitis in mice by oral administration. The most effective ingredient madecassoside lost anti-colitis effect when applied topically in the colon, and madecassic acid was recognized to be the active form of madecassoside. Oral administration of madecassic acid decreased the percentage of Th17 cells and downregulated the expression of RORγt, IL-17A, IL-17F, IL-21 and IL-22 and increased the percentage of Treg cells and the expression of Foxp3 and IL-10 in the colons of mice with colitis, but it did not affect Th1 and Th2 cells. Under Th17-polarizing conditions, madecassic acid downregulated ACC1 expression and enhanced the shift of Th17 cells toward Treg cells, but it did not affect the differentiation of Treg cells under Treg-polarizing conditions. Both compound C and AMPK siRNA inhibited the madecassic acid-mediated downregulation of ACC1 expression and shift of Th17 cells to Treg cells under Th17-polarizing conditions. GW9662, T0070907 and PPARγ siRNA blocked the effect of madecassic acid on AMPK activation, ACC1 expression and shift of Th17 cells to Treg cells. Furthermore, madecassic acid was identified as a PPARγ agonist, as it promoted PPARγ transactivation. The correlation between activation of PPARγ and AMPK, downregulation of ACC1 expression, restoration of Th17/Treg balance and attenuation of colitis by madecassic acid was validated in mice with DSS-induced colitis. In conclusion, madecassic acid was the active form of madecassoside in ameliorating colitis by restoring the Th17/Treg balance via regulating the PPARγ/AMPK/ACC1 pathway.
Sequence-selective encapsulation and protection of long peptides by a self-assembled FeII8L6 cubic cage
Authors: Mosquera Jesús , Szyszko Bartosz , Ho Sarah K. Y. , Nitschke Jonathan R. 
Published: March 2017

AbstractSelf-assembly offers a general strategy for the preparation of large, hollow high-symmetry structures. Although biological capsules, such as virus capsids, are capable of selectively recognizing complex cargoes, synthetic encapsulants have lacked the capability to specifically bind large and complex biomolecules. Here we describe a cubic host obtained from the self-assembly of FeII and a zinc-porphyrin-containing ligand. This cubic cage is flexible and compatible with aqueous media. Its selectivity of encapsulation is driven by the coordination of guest functional groups to the zinc porphyrins. This new host thus specifically encapsulates guests incorporating imidazole and thiazole moieties, including drugs and peptides. Once encapsulated, the reactivity of a peptide is dramatically altered: encapsulated peptides are protected from trypsin hydrolysis, whereas physicochemically similar peptides that do not bind are cleaved.
Detection of dietetically absorbed maize-derived microRNAs in pigs
Authors: Luo Yi , Wang Pengjun , Wang Xun , Wang Yuhao , Mu Zhiping , Li Qingzhi , Fu Yuhua , Xiao Juan , Li Guojun , Ma Yao , Gu Yiren , Jin Long , Ma Jideng , Tang Qianzi , Jiang Anan , Li Xuewei , Li Mingzhou 
Published: March 2017

AbstractMicroRNAs are a class of small RNAs that are important in post-transcriptional gene regulation in animals and plants. These single-stranded molecules are widely distributed in organisms and influence fundamental biological processes. Interestingly, recent studies have reported that diet-derived plant miRNAs could regulate mammalian gene expression, and these studies have broadened our view of cross-kingdom communication. In the present study, we evaluated miRNA levels in cooked maize-containing chow diets, and found that plant miRNAs were resistant to the harsh cooking conditions to a certain extent. After feeding fresh maize to pigs (7 days), maize-derived miRNAs could be detected in porcine tissues and serum, and the authenticity of these plant miRNAs was confirmed by using oxidization reactions. Furthermore, in vivo and in vitro experiments demonstrated that dietary maize miRNAs could cross the gastrointestinal tract and enter the porcine bloodstream. In the porcine cells, we found that plant miRNAs are very likely to specifically target their endogenous porcine mRNAs and influence gene expression in a fashion similar to that of mammalian miRNAs. Our results indicate that maize-derived miRNAs can cross the gastrointestinal tract and present in pigs, and these exogenous miRNAs have the potential to regulate mammalian gene expression.
Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content
Authors: Farag Mohamed A. , Al-Mahdy Dalia A. , Meyer Achim , Westphal Hildegard , Wessjohann Ludger A. 
Published: March 2017

AbstractThe effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl2, glutathione andβ-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coralSarcophyton ehrenbergiwere assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggesting the absence of a remarkable stress on primary production. Chemometric analyses of UPLC-MS data showed clear segregation of SA and ZnCl2elicited samples at 24 and 48 h post elicitation. Levels of acetylated diterpene and sterolviz., sarcophytonolide I and cholesteryl acetate, was increased in ZnCl2and SA groups, respectively, suggesting an activation of specific acetyl transferases. Post elicitation, sarcophytonolide I level increased 132 and 17-folds at 48 h in 0.1 mM SA and 1 mM ZnCl2groups, respectively. Interestingly, decrease in sarcophine, a major diterpene was observed only in response to ZnCl2, whereas no change was observed in sesquiterpene content following treatments. To the best of our knowledge, this study provides the first documentation for elicitation effects on a soft corals secondary metabolome and suggests that SA could be applied to increase diterpenoid levels in corals.
Suppression of FOXM1 Transcriptional Activities via a Single-Stranded DNA Aptamer Generated by SELEX
Authors: Xiang Qin , Tan Guixiang , Jiang Xia , Wu Kuangpei , Tan Weihong , Tan Yongjun 
Published: March 2017

AbstractThe transcription factor FOXM1 binds to its consensus sequence at promoters through its DNA binding domain (DBD) and activates proliferation-associated genes. The aberrant overexpression of FOXM1 correlates with tumorigenesis and progression of many cancers. Inhibiting FOXM1 transcriptional activities is proposed as a potential therapeutic strategy for cancer treatment. In this study, we obtained a FOXM1-specific single stranded DNA aptamer (FOXM1 Apt) by SELEX with a recombinant FOXM1 DBD protein as the target of selection. The binding of FOXM1 Apt to FOXM1 proteins were confirmed with electrophoretic mobility shift assays (EMSAs) and fluorescence polarization (FP) assays. Phosphorthioate-modified FOXM1 Apt (M-FOXM1 Apt) bound to FOXM1 as wild type FOXM1 Apt, and co-localized with FOXM1 in nucleus. M-FOXM1-Apt abolished the binding of FOXM1 on its consensus binding sites and suppressed FOXM1 transcriptional activities. Compared with the RNA interference of FOXM1 in cancer cells, M-FOXM1 Apt repressed cell proliferation and the expression of FOXM1 target genes without changing FOXM1 levels. Our results suggest that the obtained FOXM1 Apt could be used as a probe for FOXM1 detection and an inhibitor of FOXM1 transcriptional functions in cancer cells at the same time, providing a potential reagent for cancer diagnosis and treatment in the future.
Electron tomographic analysis reveals ultrastructural features of mitochondrial cristae architecture which reflect energetic state and aging
Authors: Jiang Yi-fan , Lin Shao-syuan , Chen Jing-min , Tsai Han-zen , Hsieh Tao-shih , Fu Chi-yu 
Published: March 2017

AbstractWithin mitochondria, the ability to produce energy relies upon the architectural hallmarks of double membranes and cristae invaginations. Herein, we describe novel features of mitochondrial cristae structure, which correspond to the energetic state of the organelle. In concordance with high-energy demand, mitochondria of Drosophila indirect flight muscle exhibited extensive intra-mitochondrial membrane switches between densely packed lamellar cristae that resulted in a spiral-like cristae network and allowed for bidirectional matrix confluency. This highly interconnected architecture is expected to allow rapid equilibration of membrane potential and biomolecules across integrated regions. In addition, mutant flies with mtDNA replication defect and an accelerated aging phenotype accumulated mitochondria that contained subsections of swirling membrane alongside normal cristae. The swirling membrane had impaired energy production capacity as measured by protein composition and function. Furthermore, mitochondrial fusion and fission dynamics were affected in the prematurely aged flies. Interestingly, the normal cristae that remained in the mitochondria with swirling membranes maintained acceptable function that camouflaged them from quality control elimination. Overall, structural features of mitochondrial cristae were described in three-dimension from serial section electron tomographic analysis which reflect energetic state and mtDNA-mediated aging.
Domain-specific interactions between MLN8237 and human serum albumin estimated by STD and WaterLOGSY NMR, ITC, spectroscopic, and docking techniques
Authors: Yang Hongqin , Liu Jiuyang , Huang Yanmei , Gao Rui , Tang Bin , Li Shanshan , He Jiawei , Li Hui 
Published: March 2017

AbstractAlisertib (MLN8237) is an orally administered inhibitor of Aurora A kinase. This small-molecule inhibitor is under clinical or pre-clinical phase for the treatment of advanced malignancies. The present study provides a detailed characterization of the interaction of MLN8237 with a drug transport protein called human serum albumin (HSA). STD and WaterLOGSY nuclear magnetic resonance (NMR)-binding studies were conducted first to confirm the binding of MLN8237 to HSA. In the ligand orientation assay, the binding sites of MLN8237 were validated through two site-specific spy molecules (warfarin sodium and ibuprofen, which are two known site-selective probes) by using STD and WaterLOGSY NMR competition techniques. These competition experiments demonstrate that both spy molecules do not compete with MLN8237 for the specific binding site. The AutoDock-based blind docking study recognizes the hydrophobic subdomain IB of the protein as the probable binding site for MLN8237. Thermodynamic investigations by isothermal titration calorimetry (ITC) reveal that the non-covalent interaction between MLN8237 and HSA (binding constant was approximately 105 M−1) is driven mainly by favorable entropy and unfavorable enthalpy. In addition, synchronous fluorescence, circular dichroism (CD), and 3D fluorescence spectroscopy suggest that MLN8237 may induce conformational changes in HSA.
NMDA receptor antagonism with novel indolyl, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, reduces seizures duration in a rat model of epilepsy
Authors: Rothan Hussin A. , Amini Elham , Faraj Fadihl L. , Golpich Mojtaba , Teoh Teow Chong , Gholami Khadijeh , Yusof Rohana 
Published: March 2017

AbstractN-methyl-D-aspartate receptors (NMDAR) play a central role in epileptogensis and NMDAR antagonists have been shown to have antiepileptic effects in animals and humans. Despite significant progress in the development of antiepileptic therapies over the previous 3 decades, a need still exists for novel therapies. We screened an in-house library of small molecules targeting the NMDA receptor. A novel indolyl compound, 2-(1,1-Dimethyl-1,3-dihydro-benzo[e]indol-2-ylidene)-malonaldehyde, (DDBM) showed the best binding with the NMDA receptor and computational docking data showed that DDBM antagonised the binding sites of the NMDA receptor at lower docking energies compared to other molecules. Using a rat electroconvulsive shock (ECS) model of epilepsy we showed that DDBM decreased seizure duration and improved the histological outcomes. Our data show for the first time that indolyls like DDBM have robust anticonvulsive activity and have the potential to be developed as novel anticonvulsants.
Hot-Volumes as Uniform and Reproducible SERS-Detection Enhancers in Weakly-Coupled Metallic Nanohelices
Authors: Caridad José M. , Winters Sinéad , McCloskey David , Duesberg Georg S. , Donegan John F. , Krstić Vojislav 
Published: March 2017

AbstractReproducible and enhanced optical detection of molecules in low concentrations demands simultaneously intense and homogeneous electric fields acting as robust signal amplifiers. To generate such sophisticated optical near-fields, different plasmonic nanostructures were investigated in recent years. These, however, exhibit either high enhancement factor (EF) or spatial homogeneity but not both. Small interparticle gaps or sharp nanostructures show enormous EFs but no near-field homogeneity. Meanwhile, approaches using rounded and separated monomers create uniform near-fields with moderate EFs. Here, guided by numerical simulations, we show how arrays of weakly-coupled Ag nanohelices achieve both homogeneous and strong near-field enhancements, reaching even the limit forreproducible detection of individual molecules. The unique near-field distribution of a single nanohelix consists of broad hot-spots, merging with those from neighbouring nanohelices in specific array configurations and generating a wide and uniform detection zone (“hot-volume”). We experimentally assessed these nanostructures via surface-enhanced Raman spectroscopy, obtaining a corresponding EF of ~107 and a relative standard deviation <10%. These values demonstrate arrays of nanohelices as state-of-the-art substrates for reproducible optical detection as well as compelling nanostructures for related fields such as near-field imaging.