bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between recognition and help-seeking preferences and stigma towards people with mental illness
Authors: Picco L. , Abdin E. , Pang S. , Vaingankar J. A. , Jeyagurunathan A. , Chong S. A. , Subramaniam M. 
Published: December 2016

Aims.The ability to recognise a mental illness has important implications as it can aid in timely and appropriate help-seeking, and ultimately improve outcomes for people with mental illness. This study aims to explore the association between recognition and help-seeking preferences and stigmatising attitudes, for alcohol abuse, dementia, depression, obsessive-compulsive disorder (OCD) and schizophrenia, using a vignette-based approach.Methods.This was a population-based, cross-sectional survey conducted among Singapore Residents (n = 3006) aged 18–65 years. All respondents were asked what they think is wrong with the person in the vignette and who they should seek help from. Respondents were also administered the Personal and Perceived sub scales of the Depression Stigma Scale and the Social Distance Scale. Weighted frequencies and percentages were calculated for categorical variables. A series of multiple logistic and linear regression models were performed separately by vignette to generate odd ratios and 95% confidence intervals for the relationship between help-seeking preference, and recognition and beta coefficients and 95% confidence intervals for the relationship between stigma and recognition.Results.Correct recognition was associated with less preference to seek help from family and friends for depression and schizophrenia. Recognition was also associated with increased odds of endorsing seeking help from a psychiatric hospital for dementia, depression and schizophrenia, while there was also an increased preference to seek help from a psychologist and psychiatrist for depression. Recognition was associated with less personal and perceived stigma for OCD and less personal stigma for schizophrenia, however, increased odds of social distancing for dementia.Conclusion.The ability to correctly recognise a mental illness was associated with less preference to seek help from informal sources, whilst increased preference to seek help from mental health professionals and services and less personal and perceived stigma. These findings re-emphasise the need to improve mental health literacy and reinforce the potential benefits recognition can have to individuals and the wider community in Singapore.
Dual targeting of glutaminase 1 and thymidylate synthase elicits death synergistically in NSCLC
Authors: Lee Jae-Seon , Kang Joon H , Lee Seon-Hyeong , Hong Dongwan , Son Jaekyoung , Hong Kyeong M , Song Jaewhan , Kim Soo-Youl 
Published: December 2016

AbstractGlutaminase 1 (GLS1) expression is increased in non-small cell lung cancer (NSCLC). GLS1 knockdown using siRNA or inhibition using bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) induced cell cycle arrest with significant reduction of ATP level while levels of reactive oxygen species or glutathione were not affected in NSCLC cell lines. Recently we found that NSCLC significantly depends on cytosol NADH for ATP production. GLS1 remarkably contributes to ATP production through transferring cytosolic NADH into mitochondria via malate-aspartate shuttle by supply of glutamate in NSCLC. Regulation of malate-aspartate shuttle by knockdown or inhibition of glutamic-oxaloacetic transaminase 2 or malate dehydrogenase 2 mimicked GLS1 knockdown, which induced cell death with ATP reduction in NSCLC. Therefore, GLS1 inhibition induced cell cycle arrest with ATP depletion by glutamate reduction. Dual inhibition with BPTES and thymidylate synthase inhibitor, 5-fluorouracil (5-FU), elicits cell death synergistically through cell cycle arrest in NSCLC. A preclinical xenograft model of NSCLC showed remarkable anti-tumour effect synergistically in the BPTES and 5-FU dual therapy group.
Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation
Authors: Marsman Gerben , Zeerleder Sacha , Luken Brenda M 
Published: December 2016

AbstractIn inflammation, extensive cell death may occur, which results in the release of chromatin components into the extracellular environment. Individually, the purified chromatin components double stranded (ds)DNA and histones have been demonstrated, both in vitro and in vivo, to display various immunostimulatory effects, for example, histones induce cytotoxicity and proinflammatory signaling through toll-like receptor (TLR)2 and 4, while DNA induces signaling through TLR9 and intracellular nucleic acid sensing mechanisms. However, DNA and histones are organized in nucleosomes in the nucleus, and evidence suggests that nucleosomes are released as such in inflammation. The cytotoxicity and proinflammatory signaling induced by nucleosomes have not been studied as extensively as the separate effects brought about by histones and dsDNA, and there appear to be some marked differences. Remarkably, little distinction between the different forms in which histones circulate has been made throughout literature. This is partly due to the limitations of existing techniques to differentiate between histones in their free or DNA-bound form. Here we review the current understanding of immunostimulation induced by extracellular histones, dsDNA and nucleosomes, and discuss the importance of techniques that in their detection differentiate between these different chromatin components.
Upregulation of MiR-205 under hypoxia promotes epithelial–mesenchymal transition by targeting ASPP2
Authors: Wang Xingwen , Yu Miao , Zhao Kunming , He Mengmeng , Ge Wenjie , Sun Yuhui , Wang Yihua , Sun Haizhu , Hu Ying 
Published: December 2016

AbstractThe epithelial–mesenchymal transition (EMT) is one of the crucial procedures for cancer invasion and distal metastasis. Despite undergoing intensive studies, the mechanisms underlying EMT remain to be completely elucidated. Here, we identified that apoptosis-stimulating protein of p53-2 (ASPP2) is a novel target of MiR-205 in various cancers. Interestingly, the binding site of MiR-205 at the 3′-untranslated region of ASPP2 was highly conserved among different species. An inverse correlation between MiR-205 and ASPP2 was further observed in vivo in cervical cancers, suggesting MiR-205 may be an important physiological inhibitor of ASPP2. Hypoxia is a hallmark of solid tumor microenvironment and one of such conditions to induce EMT. Notably, MiR-205 was remarkably induced by hypoxia in cervical and lung cancer cells. A marked suppression of ASPP2 was observed simultaneously. Further studies confirmed that hypoxia-induced ASPP2 suppression was mainly attributed to the elevated MiR-205. Interestingly, the alteration of MiR-205/ASPP2 under hypoxia was accompanied with the decreased epithelial marker E-cadherin and increased mesenchymal marker Vimentin, as well as a morphological transition from the typical cobblestone-like appearance to the mesenchymal-like structure. More importantly, MiR-205 mimics or ASPP2 silencing similarly promoted EMT process. By contrast, ASPP2 recovery or MiR-205 inhibitor reversed MiR-205-dependent EMT. Further studies demonstrated that the newly revealed MiR-205/ASPP2 axis promoted cell migration and also increased cell proliferation both in vivo and in vitro. These data together implicated a critical impact of MiR-205/ASPP2 on promoting EMT. MiR-205/ASPP2 may be potential diagnostic and therapeutic biomarkers in cervical and lung cancers.
Autophagy and epithelial–mesenchymal transition: an intricate interplay in cancer
Authors: Gugnoni Mila , Sancisi Valentina , Manzotti Gloria , Gandolfi Greta , Ciarrocchi Alessia 
Published: December 2016

AbstractAutophagy and epithelial to mesenchymal transition (EMT) are major biological processes in cancer. Autophagy is a catabolic pathway that aids cancer cells to overcome intracellular or environmental stress, including nutrient deprivation, hypoxia and drugs effect. EMT is a complex transdifferentiation through which cancer cells acquire mesenchymal features, including motility and metastatic potential. Recent observations indicate that these two processes are linked in a complex relationship. On the one side, cells that underwent EMT require autophagy activation to survive during the metastatic spreading. On the other side, autophagy, acting as oncosuppressive signal, tends to inhibit the early phases of metastasization, contrasting the activation of the EMT mainly by selectively destabilizing crucial mediators of this process. Currently, still limited information is available regarding the molecular hubs at the interplay between autophagy and EMT. However, a growing number of evidence points to the functional interaction between cytoskeleton and mitochondria as one of the crucial regulatory center at the crossroad between these two biological processes. Cytoskeleton and mitochondria are linked in a tight functional relationship. Controlling mitochondria dynamics, the cytoskeleton cooperates to dictate mitochondria availability for the cell. Vice versa, the number and structure of mitochondria, which are primarily affected by autophagy-related processes, define the energy supply that cancer cells use to reorganize the cytoskeleton and to sustain cell movement during EMT. In this review, we aim to revise the evidence on the functional crosstalk between autophagy and EMT in cancer and to summarize the data supporting a parallel regulation of these two processes through shared signaling pathways. Furthermore, we intend to highlight the relevance of cytoskeleton and mitochondria in mediating the interaction between autophagy and EMT in cancer.
Interrogation of bimetallic particle oxidation in three dimensions at the nanoscale
Authors: Han Lili , Meng Qingping , Wang Deli , Zhu Yimei , Wang Jie , Du Xiwen , Stach Eric A. , Xin Huolin L. 
Published: December 2016

AbstractAn understanding of bimetallic alloy oxidation is key to the design of hollow-structured binary oxides and the optimization of their catalytic performance. However, one roadblock encountered in studying these binary oxide systems is the difficulty in describing the heterogeneities that occur in both structure and chemistry as a function of reaction coordinate. This is due to the complexity of the three-dimensional mosaic patterns that occur in these heterogeneous binary systems. By combining real-time imaging and chemical-sensitive electron tomography, we show that it is possible to characterize these systems with simultaneous nanoscale and chemical detail. We find that there is oxidation-induced chemical segregation occurring on both external and internal surfaces. Additionally, there is another layer of complexity that occurs during the oxidation, namely that the morphology of the initial oxide surface can change the oxidation modality. This work characterizes the pathways that can control the morphology in binary oxide materials.
A room-temperature magnetic semiconductor from a ferromagnetic metallic glass
Authors: Liu Wenjian , Zhang Hongxia , Shi Jin-an , Wang Zhongchang , Song Cheng , Wang Xiangrong , Lu Siyuan , Zhou Xiangjun , Gu Lin , Louzguine-Luzgin Dmitri V. , Chen Mingwei , Yao Kefu , Chen Na 
Published: December 2016

AbstractEmerging for future spintronic/electronic applications, magnetic semiconductors have stimulated intense interest due to their promises for new functionalities and device concepts. So far, the so-called diluted magnetic semiconductors attract many attentions, yet it remains challenging to increase their Curie temperatures above room temperature, particularly those based on III–V semiconductors. In contrast to the concept of doping magnetic elements into conventional semiconductors to make diluted magnetic semiconductors, here we propose to oxidize originally ferromagnetic metals/alloys to form new species of magnetic semiconductors. We introduce oxygen into a ferromagnetic metallic glass to form a Co28.6Fe12.4Ta4.3B8.7O46 magnetic semiconductor with a Curie temperature above 600 K. The demonstration of p–n heterojunctions and electric field control of the room-temperature ferromagnetism in this material reflects its p-type semiconducting character, with a mobility of 0.1 cm2 V−1 s−1. Our findings may pave a new way to realize high Curie temperature magnetic semiconductors with unusual multifunctionalities.
Structural basis for Epstein–Barr virus host cell tropism mediated by gp42 and gHgL entry glycoproteins
Authors: Sathiyamoorthy Karthik , Hu Yao Xiong , Möhl Britta S. , Chen Jia , Longnecker Richard , Jardetzky Theodore S. 
Published: December 2016

AbstractHerpesvirus entry into host cells is mediated by multiple virally encoded receptor binding and membrane fusion glycoproteins. Despite their importance in host cell tropism and associated disease pathology, the underlying and essential interactions between these viral glycoproteins remain poorly understood. For Epstein–Barr virus (EBV), gHgL/gp42 complexes bind HLA class II to activate membrane fusion with B cells, but gp42 inhibits fusion and entry into epithelial cells. To clarify the mechanism by which gp42 controls the cell specificity of EBV infection, here we determined the structure of gHgL/gp42 complex bound to an anti-gHgL antibody (E1D1). The critical regulator of EBV tropism is the gp42 N-terminal domain, which tethers the HLA-binding domain to gHgL by wrapping around the exterior of three gH domains. Both the gp42 N-terminal domain and E1D1 selectively inhibit epithelial-cell fusion; however, they engage distinct surfaces of gHgL. These observations clarify key determinants of EBV host cell tropism.
Tectal-derived interneurons contribute to phasic and tonic inhibition in the visual thalamus
Authors: Jager Polona , Ye Zhiwen , Yu Xiao , Zagoraiou Laskaro , Prekop Hong-Ting , Partanen Juha , Jessell Thomas M. , Wisden William , Brickley Stephen G. , Delogu Alessio 
Published: December 2016

AbstractThe release of GABA from local interneurons in the dorsal lateral geniculate nucleus (dLGN-INs) provides inhibitory control during visual processing within the thalamus. It is commonly assumed that this important class of interneurons originates from within the thalamic complex, but we now show that during early postnatal development Sox14/Otx2-expressing precursor cells migrate from the dorsal midbrain to generate dLGN-INs. The unexpected extra-diencephalic origin of dLGN-INs sets them apart from GABAergic neurons of the reticular thalamic nucleus. Using optogenetics we show that at increased firing rates tectal-derived dLGN-INs generate a powerful form of tonic inhibition that regulates the gain of thalamic relay neurons through recruitment of extrasynaptic high-affinity GABAA receptors. Therefore, by revising the conventional view of thalamic interneuron ontogeny we demonstrate how a previously unappreciated mesencephalic population controls thalamic relay neuron excitability.
An oxygen-sensitive toxin–antitoxin system
Authors: Marimon Oriol , Teixeira João M. C. , Cordeiro Tiago N. , Soo Valerie W. C. , Wood Thammajun L. , Mayzel Maxim , Amata Irene , García Jesús , Morera Ainara , Gay Marina , Vilaseca Marta , Orekhov Vladislav Yu , Wood Thomas K. , Pons Miquel 
Published: December 2016

AbstractThe Hha and TomB proteins from Escherichia coli form an oxygen-dependent toxin–antitoxin (TA) system. Here we show that YmoB, the Yersinia orthologue of TomB, and its single cysteine variant [C117S]YmoB can replace TomB as antitoxins in E. coli. In contrast to other TA systems, [C117S]YmoB transiently interacts with Hha (rather than forming a stable complex) and enhances the spontaneous oxidation of the Hha conserved cysteine residue to a -SOxH-containing species (sulfenic, sulfinic or sulfonic acid), which destabilizes the toxin. The nuclear magnetic resonance structure of [C117S]YmoB and the homology model of TomB show that the two proteins form a four-helix bundle with a conserved buried cysteine connected to the exterior by a channel with a diameter comparable to that of an oxygen molecule. The Hha interaction site is located on the opposite side of the helix bundle.
Thioredoxin-interacting protein regulates haematopoietic stem cell ageing and rejuvenation by inhibiting p38 kinase activity
Authors: Jung Haiyoung , Kim Dong Oh , Byun Jae-Eun , Kim Won Sam , Kim Mi Jeong , Song Hae Young , Kim Young Kwan , Kang Du-Kyeong , Park Young-Jun , Kim Tae-Don , Yoon Suk Ran , Lee Hee Gu , Choi Eun-Ji , Min Sang-Hyun , Choi Inpyo 
Published: December 2016

AbstractAgeing is a natural process in living organisms throughout their lifetime, and most elderly people suffer from ageing-associated diseases. One suggested way to tackle such diseases is to rejuvenate stem cells, which also undergo ageing. Here we report that the thioredoxin-interacting protein (TXNIP)-p38 mitogen-activated protein kinase (p38) axis regulates the ageing of haematopoietic stem cells (HSCs), by causing a higher frequency of long-term HSCs, lineage skewing, a decrease in engraftment, an increase in reactive oxygen species and loss of Cdc42 polarity. TXNIP inhibits p38 activity via direct interaction in HSCs. Furthermore, cell-penetrating peptide (CPP)-conjugated peptide derived from the TXNIP-p38 interaction motif inhibits p38 activity via this docking interaction. This peptide dramatically rejuvenates aged HSCs in vitro and in vivo. Our findings suggest that the TXNIP-p38 axis acts as a regulatory mechanism in HSC ageing and indicate the potent therapeutic potential of using CPP-conjugated peptide to rejuvenate aged HSCs.
The STIM1-binding site nexus remotely controls Orai1 channel gating
Authors: Zhou Yandong , Cai Xiangyu , Loktionova Natalia A. , Wang Xianming , Nwokonko Robert M. , Wang Xizhuo , Wang Youjun , Rothberg Brad S. , Trebak Mohamed , Gill Donald L. 
Published: December 2016

AbstractThe ubiquitously expressed Orai Ca2+ channels are gated through a unique process of intermembrane coupling with the Ca2+-sensing STIM proteins. Despite the significance of Orai1-mediated Ca2+ signals, how gating of Orai1 is triggered by STIM1 remains unknown. A widely held gating model invokes STIM1 binding directly to Orai1 pore-forming helix. Here we report that an Orai1 C-terminal STIM1-binding site, situated far from the N-terminal pore helix, alone provides the trigger that is necessary and sufficient for channel gating. We identify a critical ‘nexus’ within Orai1 connecting the peripheral C-terminal STIM1-binding site to the Orai1 core helices. Mutation of the nexus transforms Orai1 into a persistently open state exactly mimicking the action of STIM1. We suggest that the Orai1 nexus transduces the STIM1-binding signal through a conformational change in the inner core helices, and that STIM1 remotely gates the Orai1 channel without the necessity for direct STIM1 contact with the pore-forming helix.
Tracking the coherent generation of polaron pairs in conjugated polymers
Authors: De Sio Antonietta , Troiani Filippo , Maiuri Margherita , Réhault Julien , Sommer Ephraim , Lim James , Huelga Susana F. , Plenio Martin B. , Rozzi Carlo Andrea , Cerullo Giulio , Molinari Elisa , Lienau Christoph 
Published: December 2016

AbstractThe optical excitation of organic semiconductors not only generates charge-neutral electron-hole pairs (excitons), but also charge-separated polaron pairs with high yield. The microscopic mechanisms underlying this charge separation have been debated for many years. Here we use ultrafast two-dimensional electronic spectroscopy to study the dynamics of polaron pair formation in a prototypical polymer thin film on a sub-20-fs time scale. We observe multi-period peak oscillations persisting for up to about 1 ps as distinct signatures of vibronic quantum coherence at room temperature. The measured two-dimensional spectra show pronounced peak splittings revealing that the elementary optical excitations of this polymer are hybridized exciton-polaron-pairs, strongly coupled to a dominant underdamped vibrational mode. Coherent vibronic coupling induces ultrafast polaron pair formation, accelerates the charge separation dynamics and makes it insensitive to disorder. These findings open up new perspectives for tailoring light-to-current conversion in organic materials.
Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish
Authors: Xiao Chenglu , Gao Lu , Hou Yu , Xu Congfei , Chang Nannan , Wang Fang , Hu Keping , He Aibin , Luo Ying , Wang Jun , Peng Jinrong , Tang Fuchou , Zhu Xiaojun , Xiong Jing-Wei 
Published: December 2016

AbstractThe zebrafish possesses a remarkable capacity of adult heart regeneration, but the underlying mechanisms are not well understood. Here we report that chromatin remodelling factor Brg1 is essential for adult heart regeneration. Brg1 mRNA and protein are induced during heart regeneration. Transgenic over-expression of dominant-negative Xenopus Brg1 inhibits the formation of BrdU+/Mef2C+ and Tg(gata4:EGFP) cardiomyocytes, leading to severe cardiac fibrosis and compromised myocardial regeneration. RNA-seq and RNAscope analyses reveal that inhibition of Brg1 increases the expression of cyclin-dependent kinase inhibitors such as cdkn1a and cdkn1c in the myocardium after ventricular resection; and accordingly, myocardial-specific expression of dn-xBrg1 blunts myocardial proliferation and regeneration. Mechanistically, injury-induced Brg1, via its interaction with Dnmt3ab, suppresses the expression of cdkn1c by increasing the methylation level of CpG sites at the cdkn1c promoter. Taken together, our results suggest that Brg1 promotes heart regeneration by repressing cyclin-dependent kinase inhibitors partly through Dnmt3ab-dependent DNA methylation.
A diverse intrinsic antibiotic resistome from a cave bacterium
Authors: Pawlowski Andrew C. , Wang Wenliang , Koteva Kalinka , Barton Hazel A. , McArthur Andrew G. , Wright Gerard D. 
Published: December 2016

AbstractAntibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus.