bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical Experience with Hole-Free Phase Plates for Cryo Electron Microscopy
Authors: Marko Michael , Hsieh Chyongere , Leith Eric , Mastronarde David , Motoki Sohei
Published: November 2016

Phase plate (PP) imaging has proven to be valuable in transmission cryo electron microscopy of unstained, native-state biological specimens. Many PP types have been described, however until the recent implementation of the “hole-free” phase plate (HFPP), imaging has been challenging. We found the HFPP to be simple to construct and to set up in the transmission electron microscopy, but care in implementing automated data collection is needed. Performance may be variable, both initially and over time, thus it is important to monitor and evaluate image quality by observing the power spectrum. We found that while some HFPPs gave transfer to high resolution without CTF oscillation, most reached high resolution when operated with modest defocus.
Social Security Reform and the Surveillance State: Exploring the Operation of ‘Hidden Conditionality’ in the Reform of Disability Benefits Since 2010
Authors: Manji Kainde
Published: November 2016

The application of formal conditionality to address ‘dependence’ on social security has been an important trend since the 1990s. Reforms between 2010 and 2015 saw a renewed interest in this approach. This article will focus on conditionality in disability benefits in that period. It will present findings from a qualitative study of twenty-three disabled people living in the central-belt of Scotland, exploring the operation of surveillance as a form of ‘hidden conditionality’. It will find that this had a significant impact on participants’ daily lives, affecting who they interacted with, and what activities they felt they could take part in. The implications of this for disabled people's ability to realise equal citizenship will be examined.
Yet more on a stochastic economic model: Part 3C: stochastic bridging for share yields and dividends and interest rates
Authors: Wilkie A. D. , Şahin Şule
Published: November 2016

This is the third and last subpart of a long paper in which we consider stochastic interpolation for the Wilkie asset model, considering both Brownian bridges and Ornstein–Uhlenbeck (OU) bridges. In Part 3A, we developed certain properties for both these types of stochastic bridge, and in Part 3B we investigated retail prices and wages. In this paper, we investigate the remainder of many of our data series, relating to shares and interest rates. We conclude that, regardless of the form of the annual model, the monthly data within each year can be modelled by Brownian bridges, usually on the logarithm of the principal variable. But in no case is a simple Brownian bridge enough, and all series have their own peculiarities. Overall, however, our modelling produces simulations that are realistic in comparison with the known data. Many of our findings would apply to any similar model used for simulation over time. Our results have considerable importance for financial economics. We reconcile the conflict between the long-term mean-reverting modelling of Schiller and the short-term random walk modelling of Fama. This conclusion therefore has very wide significance.
Die Rolle von Fähigkeit, Persönlichkeit und Interesse bei derEntscheidung zwischen Schule und Berufsausbildung
Authors: Dumfart Barbara , Krammer Georg , Neubauer Aljoscha
Published: November 2016

Zusammenfassung. Eine bedeutende Bildungsentscheidung, die von Jugendlichen getroffen werden muss, ist die zwischen dem Übergang in die höhere Bildung oder dem Beginn einer Berufsausbildung. Um herauszufinden, wie Fähigkeiten, Persönlichkeitsmerkmale und Interessen mit dieser Entscheidung zusammenhängen, wurden 358 Jugendliche der 8. Schulstufe untersucht. Pfadanalysen modellierten die direkten und indirekten Zusammenhänge mit der Entscheidung Schule vs. Ausbildung. Ein hoher Zusammenhang wurde mit der Schulleistung gefunden: Je besser die Schulnoten waren, desto eher wurde zugunsten der Schule entschieden. Die Schulleistung wiederum mediierte den Zusammenhang zwischen Intelligenz (mittlerer Effekt) sowie Gewissenhaftigkeit (kleiner Effekt) und der Entscheidung Schule vs. Ausbildung. Außerdem hingen bestimmte berufliche Interessendimensionen direkt und indirekt mit der Entscheidung Schule vs. Ausbildung zusammen – teils unterschiedlich für Mädchen und Jungen. Die Ergebnisse deuten darauf hin, dass auch bei dieser Bildungsentscheidung Fähigkeiten, Persönlichkeitsmerkmale und Interessen berücksichtigt werden sollten.
Differenzielle Effekte von Klassenführung und Unterstützung fürSchülerinnen und Schüler mit Migrationshintergrund
Authors: Seiz Johanna , Decristan Jasmin , Kunter Mareike , Baumert Jürgen
Published: November 2016

Zusammenfassung. Für einen erfolgreichen Umgang mit Heterogenität im Unterricht werden überwiegend Differenzierungsmaßnahmen vorgeschlagen, die eine Veränderung von Sichtstrukturen bedeuten. Verglichen mit Tiefenstrukturen sind Sichtstrukturen jedoch weniger bedeutsam für den Lernerfolg. Bisher wurden kaum differenzielle Wirkungen von Tiefenstrukturen untersucht. Diese Studie überprüft daher sowohl allgemeine Wirkungen von Klassenführung und Unterstützung als auch differenzielle Wirkungen für Schülerinnen und Schüler mit Migrationshintergrund. In einer Längsschnittstudie mit 3483 Schülerinnen und Schülern aus 155 Klassen wurde die Mathematikleistung der 9. sowie der 10. Klasse erhoben; Klassenführung und Unterstützung wurden aus Schüler- sowie teilweise aus Lehrerperspektive erfasst. Klassenführung zeigt positive Effekte auf die Leistung aller Schülerinnen und Schüler. Zusätzlich zeigen Cross-Level-Interaktionen in latenten mehrebenenanalytischen Modellen, dass Schülerinnen und Schüler mit Migrationshintergrund bezogen auf ihre Mathematikleistung stärker von einer effektiven Klassenführung und hohen Unterstützung profitieren als ihre Mitschülerinnen und -schüler ohne Migrationshintergrund (unter Kontrolle der Eingangsleistung). Dies weist auf die kompensatorische Funktion der Tiefenstrukturen des Unterrichts hin.
Stabilität, Bezugsnormorientierung und Auswirkungen derUrteilsgenauigkeit
Authors: Stang Justine , Urhahne Detlef
Published: November 2016

Zusammenfassung. Über die Stabilität, genauigkeitsbeeinflussende Faktoren und differenzielle Wirkungen des Lehrkrafturteils zur Schülerleistung ist noch relativ wenig bekannt. In einer Längsschnittstudie mit zwei Messzeitpunkten wurden diese Aspekte näher analysiert. An der Studie nahmen 294 Schülerinnen und Schüler der Realschule und deren 17 Mathematiklehrkräfte teil. Die Fünftklässler bearbeiteten standardisierte Mathematikleistungstests und Skalen zum wahrgenommenen Lehrkraftverhalten, während die Lehrkräfte die Testleistungen einschätzten und Fragen zur Bezugsnormorientierung beantworteten. Die Rangkomponente, die Übereinstimmung des Lehrkrafturteils mit den Schülerleistungen, verbesserte sich im Zeitraum eines halben Jahres signifikant. Sie korrelierte zudem positiv mit der kriterialen Bezugsnormorientierung. Die Genauigkeit des Lehrkrafturteils war prädiktiv für die Schülerleistung. In der Leistung überschätzte Schülerinnen und Schüler wiesen im Vergleich zu unterschätzten Schülerinnen und Schülern den größeren Leistungszuwachs auf und nahmen das Lehrkraftverhalten anders wahr. Lehrkräfte sollten sich ihrer Leistungsurteile und ihres Verhaltens stärker bewusst werden, um sich selbsterfüllende Prophezeiungen zu vermeiden.
First of Next Generation of U.S. Weather Satellites Hits the Sky
Authors: Wendel JoAnna
Published: November 2016

The novel spacecraft and three sister satellites to follow are expected to vastly improve storm forecasting.
Direct regulation of FOXK1 by C-jun promotes proliferation, invasion and metastasis in gastric cancer cells
Authors: Peng Ying , Zhang Pei , Huang Xiaoting , Yan Qingqing , Wu Meiyan , Xie Ruyi , Wu Yao , Zhang Mengnan , Nan Qingzhen , Zhao Jinjun , Li Aimin , Xiong Jing , Ren Yuexin , Bai Yang , Chen Ye , Liu Side , Wang Jide
Published: November 2016

Forkhead box (FOX) K1 is a member of the FOX transcription factor superfamily. High FOXK1 expression is associated with several cancers. However, whether FOXK1 expression contributes to gastric cancer (GC) development and progression remains unknown. We analyzed the FOXK1 promoter using the Promo software and found several binding sequence transcription factors, including c-jun. However, the molecular mechanism by which FOXK1 affects the c-jun-mediated malignant phenotype is poorly understood. Here, we found that FOXK1 protein expression was higher in 8/10 (80.0%) fresh cancer tissues compared with that in adjacent normal tissues. FOXK1 overexpression enhanced the proliferation, migration and invasion of GC cells. Moreover, FOXK1 expression was stimulated by transforming growth factor-β1 (TGF-β1). FOXK1 acted as a potential epithelial-to-mesenchymal transition (EMT) inducer by stimulating vimentin expression and inducing the loss of E-cadherin in stable FOXK1-transfected cells. The results of promoter reporter and chromatin immunoprecipitation assays demonstrated that c-jun directly binds to and activates the human FOXK1 gene promoter. A positive correlation was observed between the expression patterns of FOXK1 and c-jun in GC cells and tissue. FOXK1 and c-jun expression were correlated with tumor progression and represented significant predictors of overall survival in GC patients. However, the siRNA-mediated repression of c-jun in FOXK1-overexpressing cells reversed EMT, as well as the proliferative and metastatic phenotypes. In vivo, c-jun promoted FOXK1-mediated proliferation and metastasis via orthotopic implantation. The evidence presented here suggests that FOXK1-directed regulation by c-jun promote the development and progression of human GC.
Arginase 2 promotes neurovascular degeneration during ischemia/reperfusion injury
Authors: Shosha Esraa , Xu Zhimin , Yokota Harumasa , Saul Alan , Rojas Modesto , Caldwell R William , Caldwell Ruth B , Narayanan S Priya
Published: November 2016

Retinal ischemia is a major cause of visual impairment and blindness and is involved in various disorders including diabetic retinopathy, glaucoma, optic neuropathies and retinopathy of prematurity. Neurovascular degeneration is a common feature of these pathologies. Our lab has previously reported that the ureahydrolase arginase 2 (A2) is involved in ischemic retinopathies. Here, we are introducing A2 as a therapeutic target to prevent neurovascular injury after retinal ischemia/reperfusion (I/R) insult. Studies were performed with mice lacking both copies of A2 (A2−/−) and wild-type (WT) controls (C57BL6J). I/R insult was conducted on the right eye and the left eye was used as control. Retinas were collected for analysis at different times (3 h–4 week after injury). Neuronal and microvascular degeneration were evaluated using NeuN staining and vascular digests, respectively. Glial activation was evaluated by glial fibrillary acidic protein expression. Necrotic cell death was studied by propidium iodide labeling and western blot for RIP-3. Arginase expression was determined by western blot and quantitative RT-PCR. Retinal function was determined by electroretinography (ERG). A2 mRNA and protein levels were increased in WT I/R. A2 deletion significantly reduced ganglion cell loss and microvascular degeneration and preserved retinal morphology after I/R. Glial activation, reactive oxygen species formation and cell death by necroptosis were significantly reduced by A2 deletion. ERG showed improved positive scotopic threshold response with A2 deletion. This study shows for the first time that neurovascular injury after retinal I/R is mediated through increased expression of A2. Deletion of A2 was found to be beneficial in reducing neurovascular degeneration after I/R.
TGF-β signaling controls FSHR signaling-reduced ovarian granulosa cell apoptosis through the SMAD4/miR-143 axis
Authors: Du Xing , Zhang Lifan , Li Xinyu , Pan Zengxiang , Liu Honglin , Li Qifa
Published: November 2016

Follicle-stimulating hormone receptor (FSHR) and its intracellular signaling control mammalian follicular development and female infertility. Our previous study showed that FSHR is downregulated during follicular atresia of porcine ovaries. However, its role and regulation in follicular atresia remain unclear. Here, we showed that FSHR knockdown induced porcine granulosa cell (pGC) apoptosis and follicular atresia, and attenuated the levels of intracellular signaling molecules such as PKA, AKT and p-AKT. FSHR was identified as a target of miR-143, a microRNA that was upregulated during porcine follicular atresia. miR-143 enhanced pGC apoptosis by targeting FSHR, and reduced the levels of intracellular signaling molecules. SMAD4, the final molecule in transforming growth factor (TGF)-βsignaling, bound to the promoter and induced significant downregulation of miR-143in vitroandin vivo. Activated TGF-βsignaling rescued miR-143-reduced FSHR and intracellular signaling molecules, and miR-143-induced pGC apoptosis. Overall, our findings offer evidence to explain how TGF-βsignaling influences and FSHR signaling for regulation of pGC apoptosis and follicular atresia by a specific microRNA, miR-143.
Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in pancreatic β-cells
Authors: Brereton Melissa F. , Rohm Maria , Shimomura Kenju , Holland Christian , Tornovsky-Babeay Sharona , Dadon Daniela , Iberl Michaela , Chibalina Margarita V. , Lee Sheena , Glaser Benjamin , Dor Yuval , Rorsman Patrik , Clark Anne , Ashcroft Frances M.
Published: November 2016

Insulin secretion from pancreatic β-cells is impaired in all forms of diabetes. The resultant hyperglycaemia has deleterious effects on many tissues, including β-cells. Here we show that chronic hyperglycaemia impairs glucose metabolism and alters expression of metabolic genes in pancreatic islets. In a mouse model of human neonatal diabetes, hyperglycaemia results in marked glycogen accumulation, and increased apoptosis in β-cells. Sulphonylurea therapy rapidly normalizes blood glucose levels, dissipates glycogen stores, increases autophagy and restores β-cell metabolism. Insulin therapy has the same effect but with slower kinetics. Similar changes are observed in mice expressing an activating glucokinase mutation, in in vitro models of hyperglycaemia, and in islets from type-2 diabetic patients. Altered β-cell metabolism may underlie both the progressive impairment of insulin secretion and reduced β-cell mass in diabetes.
The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities
Authors: Wu Chu-Chiao , Lee Sunhee , Malladi Srinivas , Chen Miao-Der , Mastrandrea Nicholas J. , Zhang Zhiwen , Bratton Shawn B.
Published: November 2016

According to dogma, initiator caspases are activated through proximity-induced homodimerization, but some studies infer that during apoptosis caspase-9 may instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical approaches, including a novel site-specific crosslinking technique, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, markedly increasing its avidity for the complex and inducing selective intramolecular cleavage at Asp-315. Remarkably, however, procaspase-9 could also bind via its small subunit to the NOD domain in Apaf-1, resulting in the formation of a heterodimer that more efficiently activated procaspase-3. Following cleavage, the intersubunit linker (and associated conformational changes) in caspase-9-p35/p12 inhibited its ability to form homo- and heterodimers, but feedback cleavage by caspase-3 at Asp-330 removed the linker entirely and partially restored activity to caspase-9-p35/p10. Thus, the apoptosome mediates the formation of caspase-9 homo- and heterodimers, both of which are impacted by cleavage and contribute to its overall function.
First in-flight synchrotron X-ray absorption and photoemission study of carbon soot nanoparticles
Authors: Ouf F.-X. , Parent P. , Laffon C. , Marhaba I. , Ferry D. , Marcillaud B. , Antonsson E. , Benkoula S. , Liu X.-J. , Nicolas C. , Robert E. , Patanen M. , Barreda F.-A. , Sublemontier O. , Coppalle A. , Yon J. , Miserque F. , Mostefaoui T. , Regier T. Z. , Mitchell J.-B. A. , Miron C.
Published: November 2016

Many studies have been conducted on the environmental impacts of combustion generated aerosols. Due to their complex composition and morphology, their chemical reactivity is not well understood and new developments of analysis methods are needed. We report the first demonstration of in-flight X-ray based characterizations of freshly emitted soot particles, which is of paramount importance for understanding the role of one of the main anthropogenic particulate contributors to global climate change. Soot particles, produced by a burner for several air-to-fuel ratios, were injected through an aerodynamic lens, focusing them to a region where they interacted with synchrotron radiation. X-ray photoelectron spectroscopy and carbon K-edge near-edge X-ray absorption spectroscopy were performed and compared to those obtained for supported samples. A good agreement is found between these samples, although slight oxidation is observed for supported samples. Our experiments demonstrate that NEXAFS characterization of supported samples provides relevant information on soot composition, with limited effects of contamination or ageing under ambient storage conditions. The highly surface sensitive XPS experiments of airborne soot indicate that the oxidation is different at the surface as compared to the bulk probed by NEXAFS. We also report changes in soot’s work function obtained at different combustion conditions.
Differential neural encoding of sensorimotor and visual body representations
Authors: Perruchoud David , Michels Lars , Piccirelli Marco , Gassert Roger , Ionta Silvio
Published: November 2016

Sensorimotor processing specifically impacts mental body representations. In particular, deteriorated somatosensory input (as after complete spinal cord injury) increases the relative weight of visual aspects of body parts’ representations, leading to aberrancies in how images of body parts are mentally manipulated (e.g. mental rotation). This suggests that a sensorimotor or visual reference frame, respectively, can be relatively dominant in local (hands) versus global (full-body) bodily representations. On this basis, we hypothesized that the recruitment of a specific reference frame could be reflected in the activation of sensorimotor versus visual brain networks. To this aim, we directly compared the brain activity associated with mental rotation of hands versus full-bodies. Mental rotation of hands recruited more strongly the supplementary motor area, premotor cortex, and secondary somatosensory cortex. Conversely, mental rotation of full-bodies determined stronger activity in temporo-occipital regions, including the functionally-localized extrastriate body area. These results support that (1) sensorimotor and visual frames of reference are used to represent the body, (2) two distinct brain networks encode local or global bodily representations, and (3) the extrastriate body area is a multimodal region involved in body processing both at the perceptual and representational level.
The efficacy of high-throughput sequencing and target enrichment on charred archaeobotanical remains
Authors: Nistelberger H. M. , Smith O. , Wales N. , Star B. , Boessenkool S.
Published: November 2016

The majority of archaeological plant material is preserved in a charred state. Obtaining reliable ancient DNA data from these remains has presented challenges due to high rates of nucleotide damage, short DNA fragment lengths, low endogenous DNA content and the potential for modern contamination. It has been suggested that high-throughput sequencing (HTS) technologies coupled with DNA enrichment techniques may overcome some of these limitations. Here we report the findings of HTS and target enrichment on four important archaeological crops (barley, grape, maize and rice) performed in three different laboratories, presenting the largest HTS assessment of charred archaeobotanical specimens to date. Rigorous analysis of our data – excluding false-positives due to background contamination or incorrect index assignments – indicated a lack of endogenous DNA in nearly all samples, except for one lightly-charred maize cob. Even with target enrichment, this sample failed to yield adequate data required to address fundamental questions in archaeology and biology. We further reanalysed part of an existing dataset on charred plant material, and found all purported endogenous DNA sequences were likely to be spurious. We suggest these technologies are not suitable for use with charred archaeobotanicals and urge great caution when interpreting data obtained by HTS of these remains.
Endothelial cell colony forming units derived from malignant breast diseases are resistant to tumor necrosis factor-α-induced apoptosis
Authors: Chou Chen-Pin , Jiang Shih Sheng , Pan Huay-Ben , Yen Yi-Chen , Tseng Hui-Hwa , Hung Yu-Ting , Wang Ssu-Han , Chen Yu-Lin , Chen Ya-Wen
Published: November 2016

Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be elevated in certain malignant states. Using flow cytometry and a Hill-based colony forming unit (CFU) assay, the present study indicated that higher levels of CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of endothelial cell colony-forming units (EC-CFUs) are associated with benign and malignant breast diseases, providing possible indicators for breast disease detection. Gene expression profiles revealed a genetic difference between CD34+ VEGFR2+ EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor 2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)-induced signalling were demonstrated in EC-CFUs derived from patients with malignant breast disease in comparison with those from healthy controls. Interestingly, our data provided the first evidence that EC-CFUs derived from patients with malignant breast disease were resistant to TNF-α-induced apoptosis, indicating a plausible target for future therapeutic interventions.
Prevalence of overweight and malnutrition among ethnic minority children and adolescents in China, 1991–2010
Authors: Guo Sifan , Zhao Chunhua , Ma Qinghua , Sun Hong-peng , Pan Chen-wei
Published: November 2016

This study aimed to determine the trends in prevalence of childhood overweight and malnutrition in a large Chinese ethnic minority population from 1991 to 2010. In the Chinese National Survey on Students’ Constitution and Health from 1991 to 2010, multistage stratified sampling was conducted in the series of cross-sectional studies. Participants were 7–18-year-old students randomly selected by sex and region, and included Han and 26 ethnic minorities. During the survey period, the overall prevalence of overweight increased from 5.8% to 13.5%, and malnutrition trend increased from 3.6% to 4.1% in ethnic minority children and adolescents. Moreover, Korean and Mongol children were more likely than Han children to be obese (Korean: RR = 1.52; 95% CI: 1.48–1.56; Mongol: RR = 1.24; 95% CI: 1.20–1.28). Among these minorities, the Dongxiang and Li children were more likely to be malnourished (Li: RR = 1.47; 95% CI: 1.37–1.57; Dongxiang: RR = 1.45; 95% CI: 1.34–1.58). Shui, Khalkhas, Lisu, and Monguor children were less likely to be overweight and malnourished compared with the Hans. The prevalence of overweight among ethnicities increased yearly while that for malnutrition has fluctuated over the past few decades.
“Hearing faces and seeing voices”: Amodal coding of person identity in the human brain
Authors: Awwad Shiekh Hasan Bashar , Valdes-Sosa Mitchell , Gross Joachim , Belin Pascal
Published: November 2016

Recognizing familiar individuals is achieved by the brain by combining cues from several sensory modalities, including the face of a person and her voice. Here we used functional magnetic resonance (fMRI) and a whole-brain, searchlight multi-voxel pattern analysis (MVPA) to search for areas in which local fMRI patterns could result in identity classification as a function of sensory modality. We found several areas supporting face or voice stimulus classification based on fMRI responses, consistent with previous reports; the classification maps overlapped across modalities in a single area of right posterior superior temporal sulcus (pSTS). Remarkably, we also found several cortical areas, mostly located along the middle temporal gyrus, in which local fMRI patterns resulted in identity “cross-classification”: vocal identity could be classified based on fMRI responses to the faces, or the reverse, or both. These findings are suggestive of a series of cortical identity representations increasingly abstracted from the input modality.
Wide-Field Detected Fourier Transform CARS Microscopy
Authors: Duarte Alex Soares , Schnedermann Christoph , Kukura Philipp
Published: November 2016

We present a wide-field imaging implementation of Fourier transform coherent anti-Stokes Raman scattering (wide-field detected FT-CARS) microscopy capable of acquiring high-contrast label-free but chemically specific images over the full vibrational ‘fingerprint’ region, suitable for a large field of view. Rapid resonant mechanical scanning of the illumination beam coupled with highly sensitive, camera-based detection of the CARS signal allows for fast and direct hyperspectral wide-field image acquisition, while minimizing sample damage. Intrinsic to FT-CARS microscopy, the ability to control the range of time-delays between pump and probe pulses allows for fine tuning of spectral resolution, bandwidth and imaging speed while maintaining full duty cycle. We outline the basic principles of wide-field detected FT-CARS microscopy and demonstrate how it can be used as a sensitive optical probe for chemically specific Raman imaging.
Netrin-1-Induced Stem Cell Bioactivity Contributes to the Regeneration of Injured Tissues via the Lipid Raft-Dependent Integrin α6β4 Signaling Pathway
Authors: Lee Soo Sang , Lee Sei-Jung , Lee Sang Hun , Ryu Jung Min , Lim Hyeon Su , Kim Jun Sung , Song Eun Ju , Jung Young Hyun , Lee Hyun Jik , Kim Chung Hun , Han Ho Jae
Published: November 2016

Netrin-1 (Ntn-1) is a multifunctional neuronal signaling molecule; however, its physiological significance, which improves the tissue-regeneration capacity of stem cells, has not been characterized. In the present study, we investigate the mechanism by which Ntn-1 promotes the proliferation of hUCB-MSCs with regard to the regeneration of injured tissues. We found that Ntn-1 induces the proliferation of hUCB-MSCs mainly via Inα6β4 coupled with c-Src. Ntn-1 induced the recruitment of NADPH oxidases and Rac1 into membrane lipid rafts to facilitate ROS production. The Inα6β4 signaling of Ntn-1 through ROS production is uniquely mediated by the activation of SP1 for cell cycle progression and the transcriptional occupancy of SP1 on the VEGF promoter. Moreover, Ntn-1 has the ability to induce the F-actin reorganization of hUCB-MSCs via the Inα6β4 signaling pathway. In anin vivomodel, transplantation of hUCB-MSCs pre-treated with Ntn-1 enhanced the skin wound healing process, where relatively more angiogenesis was detected. The potential effect of Ntn-1 on angiogenesis is further verified by the mouse hindlimb ischemia model, where the pre-activation of hUCB-MSCs with Ntn-1 significantly improved vascular regeneration. These results demonstrate that Ntn-1 plays an important role in the tissue regeneration process of hUCB-MSC via the lipid raft-mediated Inα6β4 signaling pathway.
Disturbed phospholipid homeostasis in endoplasmic reticulum initiates tri-o-cresyl phosphate-induced delayed neurotoxicity
Authors: Zhu Li , Wang Pan , Sun Ying-Jian , Xu Ming-Yuan , Wu Yi-Jun
Published: November 2016

Tri-o-cresyl phosphate (TOCP) is a widely used organophosphorus compound, which can cause a neurodegenerative disorder, i.e., organophosphate-induced delayed neurotoxicity (OPIDN). The biochemical events in the initiation of OPIDN were not fully understood except for the essential inhibition of neuropathy target esterase (NTE). NTE, located in endoplasmic reticulum (ER), catalyzes the deacylation of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) to glycerophosphocholine (GPC). The present study aims to study the changes of ER phospholipids profile as well as levels of important intermediates of phospholipid synthesis such as diacylglycerol (DAG) and phosphatidic acid (PA) at the initiation stage of OPIDN. Hens are the most commonly used animal models of OPIDN. The spinal cord phospholipidomic profiles of hens treated by TOCP were studied by using HPLC-MS-MS. The results revealed that TOCP induced an increase of PC, LPC, and sphingomyelin (SM) levels and a decrease of GPC, phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), phosphatidylglycerol (PG), and phosphatidylinositol (PI) levels., Levels of DAG and PA were also decreased. Pretreatment with phenylmethylsulfonyl fluoride (PMSF) 24 h before TOCP administration prevented OPIDN and restored the TOCP-induced changes of phospholipids except GPC. Thus, the disruption of ER phospholipid homeostasis may contribute to the initiation of organophosphate-induced delayed neurotoxicity.
Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis development in LDL-receptor deficient mice
Authors: Kritikou Eva , van Puijvelde Gijs H. M. , van der Heijden Thomas , van Santbrink Peter J. , Swart Maarten , Schaftenaar Frank H. , Kröner Mara J. , Kuiper Johan , Bot Ilze
Published: November 2016

Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425. We show that LPA1/3 inhibition significantly impaired atherosclerosis progression. Treatment with Ki16425 also resulted in reduced CCL2 production and secretion, which led to less monocyte and neutrophil infiltration. Furthermore, we provide evidence that LPA1/3 blockade enhanced the percentage of non-inflammatory, Ly6Clow monocytes and CD4+ CD25+ FoxP3+ T-regulatory cells. Finally, we demonstrate that LPA1/3 antagonism mildly reduced plasma LDL cholesterol levels. Therefore, pharmacological inhibition of LPA1/3 receptors may prove a promising approach to diminish atherosclerosis development.
Detecting and utilizing minority phases in heterogeneous catalysis
Authors: Hartfelder Urs , Singh Jagdeep , Haase Johannes , Nachtegaal Maarten , Grolimund Daniel , van Bokhoven Jeroen A.
Published: November 2016

Highly active phases in carbon monoxide oxidation are known, however they are transient in nature. Here, we determined for the first time the structure of such a highly active phase on platinum nanoparticles in an actual reactor. Unlike generally assumed, the surface of this phase is virtually free of adsorbates and co-exists with carbon-monoxide covered and surface oxidized platinum. Understanding the relation between gas composition and catalyst structure at all times and locations within a reactor enabled the rational design of a reactor concept, which maximizes the amount of the highly active phase and minimizes the amount of platinum needed.
17-oxo-DHA displays additive anti-inflammatory effects with fluticasone propionate and inhibits the NLRP3 inflammasome
Authors: Cipollina Chiara , Di Vincenzo Serena , Siena Liboria , Di Sano Caterina , Gjomarkaj Mark , Pace Elisabetta
Published: November 2016

Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function associated with increased local and systemic inflammatory markers, such as TNFα and IL-1β. Glucocorticoids are used to treat this chronic disease, however their efficacy is low and new drugs are very much required. 17-oxo-DHA is a cyclooxygenase-2-dependent, electrophilic, α,β-unsaturated keto-derivative of docosahexaenoic acid with anti-inflammatory properties. We evaluated the action of 17-oxo-DHA alone or in combination with the steroid fluticasone propionate (FP) in peripheral blood mononuclear cells (PBMCs) from COPD patients and healthy individuals exposed to lipopolysaccharide. We show that PBMCs from COPD patients released higher levels of TNFα and IL-1β compared to controls. 17-oxo-DHA displayed strong anti-inflammatory effects. The addition of 17-oxo-DHA in combination with FP showed enhanced anti-inflammatory effects through the modulation of transcriptional and post-transcriptional mechanisms. 17-oxo-DHA, but not FP, was able to suppress the release of mature IL-1β through inhibition of the NLRP3 inflammasome. Furthermore, 17-oxo-DHA inhibited inflammasome-dependent degradation of the glucocorticoid receptor (GR). Our findings suggest that 17-oxo-DHA in combination with FP or other steroids might achieve higher therapeutic efficacy than steroids alone. Combined treatment might be particularly relevant in those conditions where increased inflammasome activation may lead to GR degradation and steroid-unresponsive inflammation.
A comparison of the performance of molecularly imprinted polymer nanoparticles for small molecule targets and antibodies in the ELISA format
Authors: Smolinska-Kempisty Katarzyna , Guerreiro Antonio , Canfarotta Francesco , Cáceres César , Whitcombe Michael J. , Piletsky Sergey
Published: November 2016

Here we show that molecularly imprinted polymer nanoparticles, prepared in aqueous media by solid phase synthesis with immobilised L-thyroxine, glucosamine, fumonisin B2 or biotin as template, can demonstrate comparable or better performance to commercially produced antibodies in enzyme-linked competitive assays. Imprinted nanoparticles-based assays showed detection limits in the pM range and polymer-coated microplates are stable to storage at room temperature for at least 1 month. No response to analyte was detected in control experiments with nanoparticles imprinted with an unrelated template (trypsin) but prepared with the same polymer composition. The ease of preparation, high affinity of solid-phase synthesised imprinted nanoparticles and the lack of requirement for cold chain logistics make them an attractive alternative to traditional antibodies for use in immunoassays.
Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells In the Absence of a Leader Sequence Through a Pannexin-1 Interactome
Authors: Atanasova Kalina , Lee Jungnam , Roberts JoAnn , Lee Kyulim , Ojcius David M , Yilmaz Özlem
Published: November 2016

Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co-cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation induced NDK recruitment to the cell periphery. Depletion of PNX1 by siRNA or inhibition by probenecid resulted in significant blocking of extracellular NDK activity and secretion using ATPase and ELISA assays. Co-immunoprecipitation-coupled Mass-spectrometry method revealed association of P. gingivalis-NDK to the myosin-9 motor molecule. Interestingly, inhibition of myosin-9, actin, and lipid-rafts, shown to be involved in PNX1-hemichannel function, resulted in marked intracellular accumulation of NDK and decreased NDK secretion from infected GECs. These results elucidate for the first time PNX1-hemichannels as potentially main extracellular translocation pathway for NDKs from an intracellular pathogen, suggesting that PNX1-hemichannels may represent a therapeutic target for chronic opportunistic infections.
Thermodynamic origin of instability in hybrid halide perovskites
Authors: Tenuta E. , Zheng C. , Rubel O.
Published: November 2016

Degradation of hybrid halide perovskites under the influence of environmental factors impairs future prospects of using these materials as absorbers in solar cells. First principle calculations can be used as a guideline in search of new materials, provided we can rely on their predictive capabilities. We show that the instability of perovskites can be captured using ab initio total energy calculations for reactants and products augmented with additional thermodynamic data to account for finite temperature effects. Calculations suggest that the instability of CH3NH3PbI3 in moist environment is linked to the aqueous solubility of the CH3NH3I salt, thus making other perovskite materials with soluble decomposition products prone to degradation. Properties of NH3OHPbI3, NH3NH2PbI3, PH4PbI3, SbH4PbI3, CsPbBr3, and a new hypothetical SF3PbI3 perovskite are studied in the search for alternative solar cell absorber materials with enhanced chemical stability.
Questioning the Mpemba effect: hot water does not cool more quickly than cold
Authors: Burridge Henry C. , Linden Paul F.
Published: November 2016

The Mpemba effect is the name given to the assertion that it is quicker to cool water to a given temperature when the initial temperature is higher. This assertion seems counter-intuitive and yet references to the effect go back at least to the writings of Aristotle. Indeed, at first thought one might consider the effect to breach fundamental thermodynamic laws, but we show that this is not the case. We go on to examine the available evidence for the Mpemba effect and carry out our own experiments by cooling water in carefully controlled conditions. We conclude, somewhat sadly, that there is no evidence to support meaningful observations of the Mpemba effect.
Role of ectonucleotide pyrophosphatase/phosphodiesterase 2 in the midline axis formation of zebrafish
Authors: Frisca Frisca , Colquhoun Daniel , Goldshmit Yona , Änkö Minna-Liisa , Pébay Alice , Kaslin Jan
Published: November 2016

Lysophosphatidic acid (LPA) is a unique bioactive lysophospholipid that induces pleiotropic effects in various cell types and organisms by acting on its specific receptors. LPA is mainly synthetised extracellularly by the ectonucleotide pyrophosphatase/phosphodiesterase 2/autotaxin (enpp2). Altered LPA signalling is associated with embryonic abnormalities, suggesting critical roles for LPA during development. However, the role of LPA signalling during early embryogenesis is not well established. We demonstrate that enpp2/LPA signalling in the early zebrafish embryo results in altered axis and midline formation, defects in left right (L-R) patterning, ciliogenesis of the Kupffer’s vesicle (KV), through the modulation of cell migration during gastrulation in a lpar1–3 Rho/ROCK-dependant manner. Overall, this study demonstrates an essential role of enpp2/LPA signalling during early embryogenesis.
Ground states of a Bose-Einstein Condensate in a one-dimensional laser-assisted optical lattice
Authors: Sun Qing , Hu Jie , Wen Lin , Liu W.-M. , Juzeliūnas G. , Ji An-Chun
Published: November 2016

We study the ground-state behavior of a Bose-Einstein Condensate (BEC) in a Raman-laser-assisted one-dimensional (1D) optical lattice potential forming a multilayer system. We find that, such system can be described by an effective model with spin-orbit coupling (SOC) of pseudospin (N-1)/2, where N is the number of layers. Due to the intricate interplay between atomic interactions, SOC and laser-assisted tunnelings, the ground-state phase diagrams generally consist of three phases–a stripe, a plane wave and a normal phase with zero-momentum, touching at a quantum tricritical point. More important, even though the single-particle states only minimize at zero-momentum for odd N, the many-body ground states may still develop finite momenta. The underlying mechanisms are elucidated. Our results provide an alternative way to realize an effective spin-orbit coupling of Bose gas with the Raman-laser-assisted optical lattice, and would also be beneficial to the studies on SOC effects in spinor Bose systems with large spin.
Alpha band disruption in the AD-continuum starts in the Subjective Cognitive Decline stage: a MEG study
Authors: López-Sanz D. , Bruña R. , Garcés P. , Camara C. , Serrano N. , Rodríguez-Rojo I. C. , Delgado M. L. , Montenegro M. , López-Higes R. , Yus M. , Maestú F.
Published: November 2016

The consideration of Subjective Cognitive Decline (SCD) as a preclinical stage of AD remains still a matter of debate. Alpha band alterations represent one of the most significant changes in the electrophysiological profile of AD. In particular, AD patients exhibit reduced alpha relative power and frequency. We used alpha band activity measured with MEG to study whether SCD and MCI elders present these electrophysiological changes characteristic of AD, and to determine the evolution of the observed alterations across AD spectrum. The total sample consisted of 131 participants: 39 elders without SCD, 41 elders with SCD and 51 MCI patients. All of them underwent MEG and MRI scans and neuropsychological assessment. SCD and MCI patients exhibited a similar reduction in alpha band activity compared with the no SCD group. However, only MCI patients showed a slowing in their alpha peak frequency compared with both SCD and no SCD. These changes in alpha band were related to worse cognition. Our results suggest that AD-related alterations may start in the SCD stage, with a reduction in alpha relative power. It is later, in the MCI stage, where the slowing of the spectral profile takes place, giving rise to objective deficits in cognitive functioning.
Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control
Authors: Luo Shuju , Zhao Jinmin , Fowdur Mitra , Wang Kun , Jiang Tenglong , He Maolin
Published: November 2016

Osteosarcoma has devastating health implications on children and adolescents. However, due to its low incidence and high tumor heterogeneity, it is hard to achieve any further improvements in therapy and overall survival. Ribosomal protein L34 (RPL34) has been increasingly recognized to promote the proliferation of malignant cells, but its role in osteosarcoma has not been investigated. In this study, real-time quantitative PCR (RT-qPCR) and immunohistochemistry revealed that RPL34 was highly expressed in osteosarcoma tissues when compared to adjacent tissues and normal bone tissues. Survival analysis showed that high expression of RPL34 predicted a poor prognosis for osteosarcoma patients. Knockdown of RPL34 in Saos-2 cells via lentivirus-mediated small interfering RNA (siRNA) significantly inhibited cell proliferation, induced cell apoptosis and G2/M phase arrest. Moreover, screening of transcription factors using University of California Santa Cruz (UCSC) Genome Browser, protein-protein interaction (PPI) network analysis, Gene Ontology (GO) and pathway enrichment analysis revealed that MYC participates in the transcriptional regulation of RPL34, which interacts with the subunits of eukaryotic translation initiation factor 3 (eIF3) and probably involves the translational control of growth-promoting proteins. Our findings suggest that RPL34 plays an important role in the proliferation of osteosarcoma cells.
Mycobacterium tuberculosis-triggered Hippo pathway orchestrates CXCL1/2 expression to modulate host immune responses
Authors: Boro Monoranjan , Singh Vikas , Balaji Kithiganahalli Narayanaswamy
Published: November 2016

Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20–like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner. Mtb-triggered Hippo signaling modulates the expression and secretion of chemokines (CXCL1 and CXCL2); as silencing MST1/2 compromised the ability of Mtb to furnish the same. Further insight into the mechanism of Hippo-mediated regulation of chemokines revealed the role for a non-canonical Hippo effector interferon (IFN) regulatory factor (IRF) 3 in the process and marked the effect to be independent of LATS1. Alongside their ability to guide directed recruitment of immune cells, we have uncovered a paracrine role for Hippo-mediated secretion of CXCL1 and CXCL2 in the production of anti-microbial peptides (beta-defensins), iNOS, NOX2 and pro-inflammatory molecules during mycobacterial infection of the host. This study highlights the involvement of TLR2-IRAK1/4-MST1/2-IRF3 axis in Mtb-triggered modulation of chemokines and identifies Hippo signaling as a novel regulator of host-mycobacterial interactions.
The mevalonate pathway regulates primitive streak formation via protein farnesylation
Authors: Okamoto-Uchida Yoshimi , Yu Ruoxing , Miyamura Norio , Arima Norie , Ishigami-Yuasa Mari , Kagechika Hiroyuki , Yoshida Suguru , Hosoya Takamitsu , Nawa Makiko , Kasama Takeshi , Asaoka Yoichi , Alois Reiner Wimmer , Elling Ulrich , Penninger Josef M. , Nishina Sachiko , Azuma Noriyuki , Nishina Hiroshi
Published: November 2016

The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Here we utilised a mouse embryonic stem (ES) cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. We found that statins, which inhibit the mevalonate metabolic pathway, suppressed primitive streak formation in vitro and in vivo. Using metabolomics and pharmacologic approaches we identified the downstream signalling pathway of mevalonate and revealed that primitive streak formation requires protein farnesylation but not cholesterol synthesis. A tagging-via-substrate approach revealed that nuclear lamin B1 and small G proteins were farnesylated in embryoid bodies and important for primitive streak gene expression. In conclusion, protein farnesylation driven by the mevalonate pathway is a metabolic cue essential for primitive streak formation.