bluuebunny/crossref_metadata_2025_split huggingface dataset:
A concept analysis in relation to the cultural competency of the palliative care workforce in meeting the needs of young people from South Asian cultures
Authors: Brown Erica , Franklin Anita , Coad Jane 
Published: April 2017

ABSTRACTObjective:Our aims were to report an analysis of the concept of cultural competency and to explore how the cultural competency of the palliative care workforce impacts the holistic care of young people with palliative care needs from South Asian cultures.Method:Using keywords, we searched the online databases MEDLINE, CINAHL, ScienceDirect, and PubMed from January of 1990 through to December of 2016. Some 1543 articles were retrieved, and inclusion and exclusion criteria were applied. A total of 38 papers were included in the concept analysis. The data were analyzed using Coad's (2002) adapted framework based on Rodgers's (1989) evolutionary concept analysis, focusing on the attributes, antecedents, consequences, and related terms in relation to culturally competent care. A model case of culturally competent care was also constructed.Results:The literature provides evidence that the concept of culturally competent care is a complex one, which is often expressed ambiguously. In addition, there is a paucity of research that involves service users as experts in defining their own needs and assessing their experiences related to cultural care.Significance of Results:Cultural care should be integral to holistic patient care, irrespective of a person's race or ethnicity. There is an urgent need to involve young BAME patients with palliative care needs and their families in the development of a robust tool to assess cultural competency in clinical practice.
Association between burnout and cortisol secretion, perceived stress, and psychopathology in palliative care unit health professionals
Authors: Fernández-Sánchez José Carlos , Pérez-Mármol José Manuel , Blásquez Antonia , Santos-Ruiz Ana María , Peralta-Ramírez María Isabel 
Published: April 2017

ABSTRACTObjective:A high incidence of burnout has been reported in health professionals working in palliative care units. Our present study aims to determine whether there are differences in the secretion of salivary cortisol between palliative care unit health professionals with and without burnout, and to elucidate whether there is a relationship between burnout syndrome and perceived stress and psychopathological status in this population.Method:A total of 69 health professionals who met the inclusion criteria participated in our study, including physicians, nurses, and nursing assistants. Some 58 were women (M = 29.65 years, SD = 8.64) and 11 men (M = 35.67 years, SD = 11.90). The level of daily cortisol was registered in six measurements taken over the course of a workday. Burnout syndrome was evaluated with the Maslach Burnout Inventory–Human Services Survey (MBI–HSS), the level of perceived stress was measured using the Perceived Stress Scale, and psychopathological status was gauged using the SCL–90–R Symptoms Inventory.Results:There were statistically significant differences in secretion of cortisol in professionals with high scores on a single subscale of the MBI–HSS [F(3.5) = 2.48, p < 0.03]. This effect was observed 15–30 minutes after waking up (p < 0.01) and at bedtime (p < 0.06). Moreover, the professionals with burnout showed higher scores on the psychopathology and stress subscales than professionals without it.Significance of results:A higher score in any dimension of the burnout syndrome in palliative care unit health professionals seems to be related to several physiological and psychological parameters. These findings may be relevant for further development of our understanding of the relationship between levels of burnout and cortisol secretion in the health workers in these units.
Flavored little cigar smoke induces cytotoxicity and apoptosis in airway epithelia
Authors: Ghosh Arunava , Nethery Rachel C , Herring Amy H , Tarran Robert 
Published: April 2017

AbstractAddition of flavors reduces the harsh taste of tobacco, facilitating the initiation and maintenance of addiction among youths. Flavored cigarettes (except menthol) are now banned. However, the legislation on little cigars remains unclear and flavored little cigars are currently available for purchase. Since inhaled tobacco smoke directly exerts toxic effects on the lungs, we tested whether non-flavored and flavored little cigar smoke exposure had the potential for harm in cultured pulmonary epithelia. We cultured Calu-3 lung epithelia on both 96-well plates and at the air–liquid interface and exposed them to smoke from non-flavored Swisher Sweets and flavored (sweet cherry, grape, menthol, peach and strawberry) Swisher Sweets little cigars. Irrespective of flavor, acute little cigar smoke exposure (10×35 ml puffs) significantly increased cell death and decreased the percentage of live cells. Chronic exposure (10×35 ml puffs per day for 4 days) of smoke to Calu-3 cultures significantly increased lactate dehydrogenase release, further indicating toxicity. To determine whether this exposure was associated with increased cell death/apoptosis, a protein array was used. Chronic exposure to smoke from all types of little cigars induced the activation of the two major apoptosis pathways, namely the intrinsic (mitochondrial-mediated) and the extrinsic (death receptor-mediated) pathways. Both flavored and non-flavored little cigar smoke caused similar levels of toxicity and activation of apoptosis, suggesting that flavored and non-flavored little cigars are equally harmful. Hence, the manufacture, advertisement, sale and use of both non-flavored and flavored little cigars should be strictly controlled.
DNA single-strand break-induced DNA damage response causes heart failure
Authors: Higo Tomoaki , Naito Atsuhiko T. , Sumida Tomokazu , Shibamoto Masato , Okada Katsuki , Nomura Seitaro , Nakagawa Akito , Yamaguchi Toshihiro , Sakai Taku , Hashimoto Akihito , Kuramoto Yuki , Ito Masamichi , Hikoso Shungo , Akazawa Hiroshi , Lee Jong-Kook , Shiojima Ichiro , McKinnon Peter J. , Sakata Yasushi , Komuro Issei 
Published: April 2017

AbstractThe DNA damage response (DDR) plays a pivotal role in maintaining genome integrity. DNA damage and DDR activation are observed in the failing heart, however, the type of DNA damage and its role in the pathogenesis of heart failure remain elusive. Here we show the critical role of DNA single-strand break (SSB) in the pathogenesis of pressure overload-induced heart failure. Accumulation of unrepaired SSB is observed in cardiomyocytes of the failing heart. Unrepaired SSB activates DDR and increases the expression of inflammatory cytokines through NF-κB signalling. Pressure overload-induced heart failure is more severe in the mice lacking XRCC1, an essential protein for SSB repair, which is rescued by blocking DDR activation through genetic deletion of ATM, suggesting the causative role of SSB accumulation and DDR activation in the pathogenesis of heart failure. Prevention of SSB accumulation or persistent DDR activation may become a new therapeutic strategy against heart failure.
Photostriction of strontium ruthenate
Authors: Wei Tzu-Chiao , Wang Hsin-Ping , Liu Heng-Jui , Tsai Dung-Sheng , Ke Jr-Jian , Wu Chung-Lun , Yin Yu-Peng , Zhan Qian , Lin Gong-Ru , Chu Ying-Hao , He Jr-Hau 
Published: April 2017

AbstractTransition metal oxides with a perovskite crystal structure exhibit a variety of physical properties associated with the lattice. Among these materials, strontium ruthenate (SrRuO3) displays unusually strong coupling of charge, spin and lattice degrees of freedom that can give rise to the photostriction, that is, changes in the dimensions of material due to the absorption of light. In this study, we observe a photon-induced strain as high as 1.12% in single domain SrRuO3, which we attribute to a nonequilibrium of phonons that are a result of the strong interaction between the crystalline lattice and electrons excited by light. In addition, these light-induced changes in the SrRuO3 lattice affect its electrical resistance. The observation of both photostriction and photoresistance in SrRuO3 suggests the possibility of utilizing the mechanical and optical functionalities of the material for next-generation optoelectronics, such as remote switches, light-controlled elastic micromotors, microactuators and other optomechanical systems.
TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1
Authors: Wang C , Liu H , Qiu Q , Zhang Z , Gu Y , He Z 
Published: April 2017

AbstractTongue cancer resistance-related protein 1 (TCRP1) gene was first cloned from the multidrug resistance tongue cancer cell (Tca8113/pingyangmycin) in our lab. Our precious studies demonstrated that TCRP1 was involving in chemotherapy and radiotherapy resistance of tongue cancer cells, lung cancer cells and ovarian cancer cells. In this study, we showed that TCRP1 overexpression promotes cell transformation and tumorigenesis through hyperphosphorylation of the oncogenic kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT1, whereas inhibition of PDK1 by OSU-03012 or PDK1 small interfering RNA reversed TCRP1-mediated cell transformation. Importantly, TCRP1 was able to directly interact with PDK1, and 93–107 amino-acid and 109–124 amino-acid sites of TCRP1 were the common binding domain of PDK1. Moreover, in line with its oncogenic activity, we found that TCRP1 is often overexpressed in human in lung cancer, glioma, ovarian cancer, thyroid cancer, nasopharyngeal carcinoma, pancreatic cancer, stomach cancer and tongue carcinoma tissues. Spearman correlation analysis showed that the expression of TCRP1 has a positive correlation with p-PDK1, as well as p-AKT1 in lung cancer and gliomas tissues. Thus, TCRP1 may be a candidate as human oncoprotein that promotes cancer development by activation of PDK1/AKT1 signaling.
Gravireceptors in eukaryotes—a comparison of case studies on the cellular level
Authors: Häder Donat-P. , Braun Markus , Grimm Daniela , Hemmersbach Ruth 
Published: April 2017

AbstractWe have selected five evolutionary very different biological systems ranging from unicellular protists via algae and higher plants to human cells showing responses to the gravity vector of the Earth in order to compare their graviperception mechanisms. All these systems use a mass, which may either by a heavy statolith or the whole content of the cell heavier than the surrounding medium to operate on a gravireceptor either by exerting pressure or by pulling on a cytoskeletal element. In many cases the receptor seems to be a mechanosensitive ion channel activated by the gravitational force which allows a gated ion flux across the membrane when activated. This has been identified in many systems to be a calcium current, which in turn activates subsequent elements of the sensory transduction chain, such as calmodulin, which in turn results in the activation of ubiquitous enzymes, gene expression activation or silencing. Naturally, the subsequent responses to the gravity stimulus differ widely between the systems ranging from orientational movement and directed growth to physiological reactions and adaptation to the environmental conditions.
Role of activating transcription factor 4 in the hepatic response to amino acid depletion by asparaginase
Authors: Al-Baghdadi Rana J. T. , Nikonorova Inna A. , Mirek Emily T. , Wang Yongping , Park Jinhee , Belden William J. , Wek Ronald C. , Anthony Tracy G. 
Published: April 2017

AbstractThe anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2−/−, and Atf4−/− mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4+/− mice. Here, we show that ATF4 controls a hepatic gene expression profile that overlaps with GCN2 but is not required for downregulation of mTORC1 during asparaginase. Ingenuity pathway analysis indicates GCN2 independently influences inflammation-mediated hepatic processes whereas ATF4 uniquely associates with cholesterol metabolism and endoplasmic reticulum (ER) stress. Livers from Atf4−/− or Atf4+/− mice displayed an amplification of the amino acid response and ER stress response transcriptional signatures. In contrast, reduction in hepatic mTORC1 signaling was retained in Atf4−/− mice treated with asparaginase. Conclusions: GCN2 and ATF4 serve complementary roles in the hepatic response to asparaginase. GCN2 functions to limit inflammation and mTORC1 signaling whereas ATF4 serves to limit the amino acid response and prevent ER stress during amino acid depletion by asparaginase.
Genome-wide fitness analyses of the foodborne pathogen Campylobacter jejuni in in vitro and in vivo models
Authors: de Vries Stefan P. , Gupta Srishti , Baig Abiyad , Wright Elli , Wedley Amy , Jensen Annette Nygaard , Lora Lizeth LaCharme , Humphrey Suzanne , Skovgård Henrik , Macleod Kareen , Pont Elsa , Wolanska Dominika P. , L’Heureux Joanna , Mobegi Fredrick M. , Smith David G. E. , Everest Paul , Zomer Aldert , Williams Nicola , Wigley Paul , Humphrey Thomas , Maskell Duncan J. , Grant Andrew J. 
Published: April 2017

AbstractCampylobacter is the most common cause of foodborne bacterial illness worldwide. Faecal contamination of meat, especially chicken, during processing represents a key route of transmission to humans. There is a lack of insight into the mechanisms driving C. jejuni growth and survival within hosts and the environment. Here, we report a detailed analysis of C. jejuni fitness across models reflecting stages in its life cycle. Transposon (Tn) gene-inactivation libraries were generated in three C. jejuni strains and the impact on fitness during chicken colonisation, survival in houseflies and under nutrient-rich and –poor conditions at 4 °C and infection of human gut epithelial cells was assessed by Tn-insertion site sequencing (Tn-seq). A total of 331 homologous gene clusters were essential for fitness during in vitro growth in three C. jejuni strains, revealing that a large part of its genome is dedicated to growth. We report novel C. jejuni factors essential throughout its life cycle. Importantly, we identified genes that fulfil important roles across multiple conditions. Our comprehensive screens showed which flagella elements are essential for growth and which are vital to the interaction with host organisms. Future efforts should focus on how to exploit this knowledge to effectively control infections caused by C. jejuni.
Calcium-Sensing Receptor Antagonist NPS 2143 Restores Amyloid Precursor Protein Physiological Non-Amyloidogenic Processing in Aβ-Exposed Adult Human Astrocytes
Authors: Chiarini Anna , Armato Ubaldo , Liu Daisong , Dal Prà Ilaria 
Published: April 2017

AbstractPhysiological non-amyloidogenic processing (NAP) of amyloid precursor holoprotein (hAPP) by α-secretases (e.g., ADAM10) extracellularly sheds neurotrophic/neuroprotective soluble (s)APPα and precludes amyloid-β peptides (Aβs) production via β-secretase amyloidogenic processing (AP). Evidence exists that Aβs interact with calcium-sensing receptors (CaSRs) in human astrocytes and neurons, driving the overrelease of toxic Aβ42/Aβ42-os (oligomers), which is completely blocked by CaSR antagonist (calcilytic) NPS 2143. Here, we investigated the mechanisms underlying NPS 2143 beneficial effects in human astrocytes. Moreover, because Alzheimer’s disease (AD) involves neuroinflammation, we examined whether NPS 2143 remained beneficial when both fibrillary (f)Aβ25–35 and a microglial cytokine mixture (CMT) were present. Thus, hAPP NAP prevailed over AP in untreated astrocytes, which extracellularly shed all synthesized sAPPα while secreting basal Aβ40/42 amounts. Conversely, fAβ25–35 alone dramatically reduced sAPPα extracellular shedding while driving Aβ42/Aβ42-os oversecretion that CMT accelerated but not increased, despite a concurring hAPP overexpression. NPS 2143 promoted hAPP and ADAM10 translocation to the plasma membrane, thereby restoring sAPPα extracellular shedding and fully suppressing any Aβ42/Aβ42-os oversecretion, but left hAPP expression unaffected. Therefore, as anti-AD therapeutics calcilytics support neuronal viability by safeguarding astrocytes neurotrophic/neuroprotective sAPPα shedding, suppressing neurons and astrocytes Aβ42/Aβ42-os build-up/secretion, and remaining effective even under AD-typical neuroinflammatory conditions.
ER retention receptor, MoERR1 is required for fungal development and pathogenicity in the rice blast fungus, Magnaporthe oryzae
Authors: Goh Jaeduk , Jeon Junhyun , Lee Yong-Hwan 
Published: April 2017

AbstractER retention receptor is a seven trans-membrane protein that plays pivotal roles in function and integrity of endoplasmic reticulum (ER). Insertional mutagenesis of Magnaporthe oryzae identified MoERR1 as a pathogenicity gene encoding putative ER retention receptor orthologous to ERD2 in Saccharomyces cerevisiae. Search through the genome identified that M. oryzae possesses another ortholog of ERD2, which is designated as MoERR2. When MoERR1 and MoERR2 were tagged with GFP, both were localized to ER. Targeted disruption of MoERR1 showed pleiotropic effects on phenotypes, while deletion of MoERR2 had no effect on phenotypes we examined. The disruption mutant of MoERR1 showed growth retardation and produced significantly reduced number of conidia with aberrant morphology. Appressoria from the mutant were unable to penetrate into plant tissues presumably due to defect in cell wall integrity, thereby rendering the mutant non-pathogenic. The MoERR1 mutant also appeared to display abnormal ER structure and mis-regulation of genes involved in chaperone function and unfolded protein response under ER stress condition. Taken together, these results suggest that MoERR1 is a ER retention receptor required for function and integrity of ER, and that MoERR1-mediated ER functionalities are essential for fungal development and pathogenesis.
Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways
Authors: Janjetovic Zorica , Jarrett Stuart G. , Lee Elizabeth F. , Duprey Cory , Reiter Russel J. , Slominski Andrzej T. 
Published: April 2017

AbstractUltraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB. Silencing of NRF2 using siRNA diminished the protective effects of melatonin, while the membrane melatonin receptors (MT1 or MT2) did not change the activities of either melatonin or its derivatives. Melatonin and its metabolites enhanced the DNA repair in melanocytes exposed to UVB and stimulated expression of p53 phosphorylated at Ser-15. In conclusion, melatonin and its metabolites protect melanocytes from UVB-induced DNA damage and oxidative stress through activation of NRF2-dependent pathways; these actions are independent of an effect on the classic membrane melatonin receptors. Thus, melatonin and its derivatives can serve as excellent protectors of melanocytes against UVB-induced pathology.
Lamins and nesprin-1 mediate inside-out mechanical coupling in muscle cell precursors through FHOD1
Authors: Schwartz Christine , Fischer Martina , Mamchaoui Kamel , Bigot Anne , Lok Thevy , Verdier Claude , Duperray Alain , Michel Richard , Holt Ian , Voit Thomas , Quijano-Roy Suzanna , Bonne Gisèle , Coirault Catherine 
Published: April 2017

AbstractLINC complexes are crucial for the response of muscle cell precursors to the rigidity of their environment, but the mechanisms explaining this behaviour are not known. Here we show that pathogenic mutations in LMNA or SYNE-1 responsible for severe muscle dystrophies reduced the ability of human muscle cell precursors to adapt to substrates of different stiffness. Plated on muscle-like stiffness matrix, mutant cells exhibited contractile stress fibre accumulation, increased focal adhesions, and higher traction force than controls. Inhibition of Rho-associated kinase (ROCK) prevented cytoskeletal defects, while inhibiting myosin light chain kinase or phosphorylation of focal adhesion kinase was ineffective. Depletion or inactivation of a ROCK-dependent regulator of actin remodelling, the formin FHOD1, largely rescued morphology in mutant cells. The functional integrity of lamin and nesprin-1 is thus required to modulate the FHOD1 activity and the inside-out mechanical coupling that tunes the cell internal stiffness to match that of its soft, physiological-like environment.
Grb2 carboxyl-terminal SH3 domain can bivalently associate with two ligands, in an SH3 dependent manner
Authors: Arya Richa , Dangi Rohit Singh , Makwana Pinakin K. , Kumar Ambrish , Upadhyay Santosh Kumar , Sundd Monica 
Published: April 2017

AbstractSrc homology domain containing leukocyte protein of 65 kDa (SLP65), the growth factor receptor binding protein 2 (Grb2), and the guanine nucleotide exchange factor for the Rho family GTPases (Vav), self associate in unstimulated B cells as components of the preformed B cell receptor transducer module, in an SH3-dependent manner. The complex enables the B cell to promptly respond to BCR aggregation, resulting in signal amplification. It also facilitates Vav translocation to the membrane rafts, for activation. Here we uncover the molecular mechanism by which the complex may be formed in the B cell. The C-terminal SH3 domain (SH3C) of Grb2 bivalently interacts with the atypical non-PxxP proline rich region of SLP65, and the N-terminal SH3 domain (SH3N) of Vav, both the interactions crucial for the proper functioning of the B cell. Most surprisingly, the two ligands bind the same ligand binding site on the surface of Grb2 SH3C. Addition of SLP65 peptide to the Grb2-Vav complex abrogates the interaction completely, displacing Vav. However, the addition of Vav SH3N to the SLP65-Grb2 binary complex, results in a trimeric complex. Extrapolating these results to thein vivoconditions, Grb2 should bind the SLP65 transducer module first, and then Vav should associate.
Elasticity and Stability of Clathrate Hydrate: Role of Guest Molecule Motions
Authors: Jia Jihui , Liang Yunfeng , Tsuji Takeshi , Murata Sumihiko , Matsuoka Toshifumi 
Published: April 2017

AbstractMolecular dynamic simulations were performed to determine the elastic constants of carbon dioxide (CO2) and methane (CH4) hydrates at one hundred pressure–temperature data points, respectively. The conditions represent marine sediments and permafrost zones where gas hydrates occur. The shear modulus and Young’s modulus of the CO2 hydrate increase anomalously with increasing temperature, whereas those of the CH4 hydrate decrease regularly with increase in temperature. We ascribe this anomaly to the kinetic behavior of the linear CO2 molecule, especially those in the small cages. The cavity space of the cage limits free rotational motion of the CO2 molecule at low temperature. With increase in temperature, the CO2 molecule can rotate easily, and enhance the stability and rigidity of the CO2 hydrate. Our work provides a key database for the elastic properties of gas hydrates, and molecular insights into stability changes of CO2 hydrate from high temperature of ~5 °C to low decomposition temperature of ~−150 °C.