bluuebunny/crossref_metadata_2025 huggingface dataset:
Digitalisierung in der deutschen Pflegeausbildung: Potenziale und Herausforderungen des AKOLEP-Projekts
Authors: Trübswetter Angelika , Figueiredo Lina
Published: August 2019

Zusammenfassung. Hintergrund: In der Pflegeausbildung spielt der Erwerb von Handlungssicherheit eine zentrale Rolle. Technologische Systeme können zukünftig unterstützen, dass Pflegeauszubildende durch selbstständiges Üben und unmittelbares Feedback eine größere Handlungssicherheit erlangen. Insbesondere im Bereich des motorischen Lernens sind technologische Lernsysteme erfolgversprechend. Ziel: Im Projekt AKOLEP wurden Potenziale und Herausforderungen technologischer Lernsysteme für die Pflegeausbildung einerseits, sowie die Technikakzeptanz von Pflegeauszubildende andererseits untersucht. Methode: Der Zugang zu den Zielgruppen erfolgte über einen Mixed-Methods-Ansatz, in dem leitfadengestützte Interviews mit 8 Entscheidungsträger/-innen aus Pflegeschulen und -praxis sowie eine quantitative Befragung mit 147 Pflegeauszubildenden durchgeführt wurden. Ergebnisse: Technische Systeme sind in der Pflegeausbildung noch wenig verbreitet. Das größte Potenzial liegt in der Förderung der individuellen Handlungssicherheit der Pflegeauszubildenden. Als zentrale Herausforderungen für Digitalisierungsaktivitäten werden Datensicherheit und Finanzierungswege artikuliert. Die Ergebnisse der quantitativen Befragung zeigen eine hohe Technikakzeptanz der Zielgruppe. Diese wiederum korreliert positiv mit der Akzeptanz des AKOLEP-Systems. Schlussfolgerung: Das größte Potenzial digitaler Lernsysteme wird einstimmig in der Ergänzung zum Unterricht und zur Förderung der Handlungssicherheit gesehen. Gegen den Ersatz von Pflegepädagoginnen und -pädagogen durch technologische Systeme sprechen sich alle Befragten aus.
Tomographic Images of Magma Chambers Beneath the Avacha and Koryaksky Volcanoes in Kamchatka
Authors: Bushenkova Natalia , Koulakov Ivan , Senyukov Sergey , Gordeev Evgeny I. , Huang Hsin‐Hua , El Khrepy Sami , Al Arifi Nassir
Published: August 2019

A new tomographic model (Vp, Vs, and Vp/Vs ratio) was built for two neighboring active volcanoes, Avacha and Koryaksky, which represent a serious hazard to the population and infrastructure of Petropavlovsk‐Kamchatsky, the main city of Kamchatka, Russia. Arrival times of seismic P and S waves from almost 5,000 local events, recorded by a permanent network of seismic stations during 2009–2018, were used for tomography. The resolution of the derived models was carefully tested by a series of synthetic simulations. Prominent anomalies with extremely high Vp/Vs ratios (up to 2.4) were retrieved directly beneath both volcanoes and interpreted as magma reservoirs containing high degrees of partial melt and/or fluids. Beneath Avacha, the upper limit of the anomaly is located at the depth of ~2 km below the surface. The reservoir appears to be connected to the surface by a neck‐shaped anomaly of high Vp/Vs ratio associated with active seismicity, which is interpreted as a magma and fluid conduit. Beneath Koryaksky, the magma related anomaly is deeper: Its upper limit is located at a depth of ~7 km below the surface. This anomaly is connected with the volcanic cone and is associated with a vertical seismicity cluster, which possibly marks the pathway of fluid ascent and degassing. Between the volcanoes, a 2‐ to 3‐km thick layer of very low Vp and Vs is interpreted as deposits of volcanoclastic sediments. Generally low Vp/Vs ratios in the area between the volcanoes show that the magma reservoirs in the upper crust are not interconnected.
Soil Fluid Biogeochemical Response to Climatic Events
Authors: Olshansky Yaniv , Knowles John F. , Barron‐Gafford Greg A. , Rasmussen Craig , Abramson Nate , Chorover Jon
Published: August 2019

Predicting fluid biogeochemistry in the vadose zone is difficult because of time‐dependent variation in multiple controlling factors, such as temperature, moisture, and biological activity. Furthermore, soils are multicomponent, heterogeneous porous media where manifold reactions may be affecting solution chemistry. We postulated that ecosystem‐scale processes, such as carbon fixation and ecohydrologic partitioning, control subsurface biogeochemical reactions, including mineral weathering. To test this hypothesis, we applied a novel “instrumented pedon” research approach. Analysis of the data streams demonstrates the interactions between pulsed wetting events and biogeochemical processes in the soil profile, and along groundwater flow paths. Rapid wetting front propagation into dry soil resulted in a pulsed increase in CO2 partial pressure in deeper soil layers, whereas wetting front propagation into a premoistened soil profile showed the opposite effect. The apparent respiratory quotient (ARQ), calculated from CO2 and O2 fluxes, deviated from expected oxidative ratios particularly during soil wetting events. These deviations were correlated in time with pore water geochemical responses, revealing that a fraction of the respired CO2 was consumed locally in pulsed silicate weathering events that accompanied wetting‐front propagation. However, most of this CO2 was dissolved in the soil pore water and transported downgradient, and along the soil‐bedrock interface, where a portion of it was further consumed in silicate weathering reactions, and another portion was degassed to the atmosphere. These results highlight the tight coupling that exists between physical, biological, and chemical processes, on event time scales, during incremental co‐evolution of the critical zone, particularly in water‐limited systems.
Correction: ERβ promotes Aβ degradation via the modulation of autophagy
Authors: Wei Yong , Zhou Jiawei , Wu Jun , Huang Jian
Published: August 2019

Following the publication of this article, the authors realized there was an error in Figure 6H in which two versions of the figure appear.

This does not impact the conclusions of the article.
Genomic landscape and chronological reconstruction of driver events in multiple myeloma
Authors: Maura Francesco , Bolli Niccoló , Angelopoulos Nicos , Dawson Kevin J. , Leongamornlert Daniel , Martincorena Inigo , Mitchell Thomas J. , Fullam Anthony , Gonzalez Santiago , Szalat Raphael , Abascal Federico , Rodriguez-Martin Bernardo , Samur Mehmet Kemal , Glodzik Dominik , Roncador Marco , Fulciniti Mariateresa , Tai Yu Tzu , Minvielle Stephane , Magrangeas Florence , Moreau Philippe , Corradini Paolo , Anderson Kenneth C. , Tubio Jose M. C. , Wedge David C. , Gerstung Moritz , Avet-Loiseau Hervé , Munshi Nikhil , Campbell Peter J.
Published: August 2019

The multiple myeloma (MM) genome is heterogeneous and evolves through preclinical and post-diagnosis phases. Here we report a catalog and hierarchy of driver lesions using sequences from 67 MM genomes serially collected from 30 patients together with public exome datasets. Bayesian clustering defines at least 7 genomic subgroups with distinct sets of co-operating events. Focusing on whole genome sequencing data, complex structural events emerge as major drivers, including chromothripsis and a novel replication-based mechanism of templated insertions, which typically occur early. Hyperdiploidy also occurs early, with individual trisomies often acquired in different chronological windows during evolution, and with a preferred order of acquisition. Conversely, positively selected point mutations, whole genome duplication and chromoplexy events occur in later disease phases. Thus, initiating driver events, drawn from a limited repertoire of structural and numerical chromosomal changes, shape preferred trajectories of evolution that are biologically relevant but heterogeneous across patients.
Photocatalytic enantioselective α-aminoalkylation of acyclic imine derivatives by a chiral copper catalyst
Authors: Han Bowen , Li Yanjun , Yu Ying , Gong Lei
Published: August 2019

Copper-based asymmetric photocatalysis has great potential in the development of green synthetic approaches to chiral molecules. However, there are several formidable challenges associated with such a conception. These include the relatively weak visible light absorption, short excited-state lifetimes, incompatibility of different catalytic cycles, and the difficulty of the stereocontrol. We report here an effective strategy by means of single-electron-transfer (SET) initiated formation of radicals and photoactive intermediates to address the long-standing problems. Through elaborate selection of well-matched reaction partners, the chiral bisoxazoline copper catalyst is engaged in the SET process, photoredox catalysis, Lewis acid activation and asymmetric induction. Accordingly, a highly enantioselective photocatalytic α-aminoalkylation of acyclic imine derivatives has been accessed. This strategy sheds light on how to make use of diverse functions of a single transition metal catalyst in one reaction, and offers an economic and simplified approach to construction of highly valuable chiral vicinal diamines.
A drop in Sahara dust fluxes records the northern limits of the African Humid Period
Authors: Palchan Daniel , Torfstein Adi
Published: August 2019

Northern and eastern Africa were exposed to significantly wetter conditions relative to present during the early Holocene period known as the African Humid Period (AHP), although the latitudinal extent of the northward expansion of the tropical rain belt remains poorly constrained. New records of 230Thxs-normalized accumulation rates in marine sediment cores from the Red Sea and Gulf of Aden are combined with existing records of western Africa dust and terrestrial records across the Sahara Desert, revealing that fluxes of dust transported east from the Sahara decreased by at least 50% during the AHP, due to the development of wetter conditions as far north as ~22°N. These results provide the first quantitative record of sediment and dust accumulation rates in the Red Sea and the Gulf of Aden over the past 20 kyrs and challenge the paradigm of vast vegetative cover across the north and northeastern Sahara Desert during the AHP.
PKHD1L1 is a coat protein of hair-cell stereocilia and is required for normal hearing
Authors: Wu Xudong , Ivanchenko Maryna V. , Al Jandal Hoor , Cicconet Marcelo , Indzhykulian Artur A. , Corey David P.
Published: August 2019

The bundle of stereocilia on inner ear hair cells responds to subnanometer deflections produced by sound or head movement. Stereocilia are interconnected by a variety of links and also carry an electron-dense surface coat. The coat may contribute to stereocilia adhesion or protect from stereocilia fusion, but its molecular identity remains unknown. From a database of hair-cell-enriched translated proteins, we identify Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1), a large, mostly extracellular protein of 4249 amino acids with a single transmembrane domain. Using serial immunogold scanning electron microscopy, we show that PKHD1L1 is expressed at the tips of stereocilia, especially in the high-frequency regions of the cochlea. PKHD1L1-deficient mice lack the surface coat at the upper but not lower regions of stereocilia, and they develop progressive hearing loss. We conclude that PKHD1L1 is a component of the surface coat and is required for normal hearing in mice.
Glia-neuron interactions underlie state transitions to generalized seizures
Authors: Diaz Verdugo Carmen , Myren-Svelstad Sverre , Aydin Ecem , Van Hoeymissen Evelien , Deneubourg Celine , Vanderhaeghe Silke , Vancraeynest Julie , Pelgrims Robbrecht , Cosacak Mehmet Ilyas , Muto Akira , Kizil Caghan , Kawakami Koichi , Jurisch-Yaksi Nathalie , Yaksi Emre
Published: August 2019

Brain activity and connectivity alter drastically during epileptic seizures. The brain networks shift from a balanced resting state to a hyperactive and hypersynchronous state. It is, however, less clear which mechanisms underlie the state transitions. By studying neural and glial activity in zebrafish models of epileptic seizures, we observe striking differences between these networks. During the preictal period, neurons display a small increase in synchronous activity only locally, while the gap-junction-coupled glial network was highly active and strongly synchronized across large distances. The transition from a preictal state to a generalized seizure leads to an abrupt increase in neural activity and connectivity, which is accompanied by a strong alteration in glia-neuron interactions and a massive increase in extracellular glutamate. Optogenetic activation of glia excites nearby neurons through the action of glutamate and gap junctions, emphasizing a potential role for glia-glia and glia-neuron connections in the generation of epileptic seizures.
Alternative ecological strategies lead to avian brain size bimodality in variable habitats
Authors: Fristoe Trevor S. , Botero Carlos A.
Published: August 2019

The ecological contexts that promote larger brains have received considerable attention, but those that result in smaller-than-expected brains have been largely overlooked. Here, we use a global sample of 2062 species to provide evidence that metabolic and life history tradeoffs govern the evolution of brain size in birds and play an important role in defining the ecological strategies capable of persisting in Earth’s most thermally variable and unpredictable habitats. While some birds cope with extreme winter conditions by investing in large brains (e.g., greater capacity for planning, innovation, and behavioral flexibility), others have small brains and invest instead in traits that allow them to withstand or recover from potentially deadly events. Specifically, these species are restricted to large body sizes, diets consisting of difficult-to-digest but readily available foods, and high reproductive output. Overall, our findings highlight the importance of considering strategic tradeoffs when investigating potential drivers of brain size evolution.
Equivalence and its invalidation between non-Markovian and Markovian spreading dynamics on complex networks
Authors: Feng Mi , Cai Shi-Min , Tang Ming , Lai Ying-Cheng
Published: August 2019

Epidemic spreading processes in the real world depend on human behaviors and, consequently, are typically non-Markovian in that the key events underlying the spreading dynamics cannot be described as a Poisson random process and the corresponding event time is not exponentially distributed. In contrast to Markovian type of spreading dynamics for which mathematical theories have been well developed, we lack a comprehensive framework to analyze and fully understand non-Markovian spreading processes. Here we develop a mean-field theory to address this challenge, and demonstrate that the theory enables accurate prediction of both the transient phase and the steady states of non-Markovian susceptible-infected-susceptible spreading dynamics on synthetic and empirical networks. We further find that the existence of equivalence between non-Markovian and Markovian spreading depends on a specific edge activation mechanism. In particular, when temporal correlations are absent on active edges, the equivalence can be expected; otherwise, an exact equivalence no longer holds.
Left dorsolateral prefrontal cortex supports context-dependent prioritisation of off-task thought
Authors: Turnbull A. , Wang H. T. , Murphy C. , Ho N. S. P. , Wang X. , Sormaz M. , Karapanagiotidis T. , Leech R. M. , Bernhardt B. , Margulies D. S. , Vatansever D. , Jefferies E. , Smallwood J.
Published: August 2019

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when ‘on-task’ under demanding conditions and ‘off-task’ in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC.
Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome
Authors: Faull Sarah V. , Lau Andy M. C. , Martens Chloe , Ahdash Zainab , Hansen Kjetil , Yebenes Hugo , Schmidt Carla , Beuron Fabienne , Cronin Nora B. , Morris Edward P. , Politis Argyris
Published: August 2019

Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members.
Quadruple perovskite ruthenate as a highly efficient catalyst for acidic water oxidation
Authors: Miao Xianbing , Zhang Lifu , Wu Liang , Hu Zhenpeng , Shi Lei , Zhou Shiming
Published: August 2019

Development of highly active and durable oxygen-evolving catalysts in acid media is a major challenge to design proton exchange membrane water electrolysis for producing hydrogen. Here, we report a quadruple perovskite oxide CaCu3Ru4O12 as a superior catalyst for acidic water oxidation. This complex oxide exhibits an ultrasmall overpotential of 171 mV at 10 mA cm−2geo, which is much lower than that of the state-of-the-art RuO2. Moreover, compared to RuO2, CaCu3Ru4O12 shows a significant increase in mass activity by more than two orders of magnitude and much better stability. Density functional theory calculations reveal that the quadruple perovskite catalyst has a lower Ru 4d-band center relative to RuO2, which effectively optimizes the binding energy of oxygen intermediates and thereby enhances the catalytic activity.
hCINAP regulates the DNA-damage response and mediates the resistance of acute myelocytic leukemia cells to therapy
Authors: Xu Ruidan , Yu Shuyu , Zhu Dan , Huang Xinping , Xu Yuqi , Lao Yimin , Tian Yonglu , Zhang Jinfang , Tang Zefang , Zhang Zemin , Yi Jing , Zhu Hong-Hu , Zheng Xiaofeng
Published: August 2019

Acute myeloid leukemia (AML) is a genetically heterogeneous malignant disorder of the hematopoietic system, characterized by the accumulation of DNA-damaged immature myeloid precursors. Here, we find that hCINAP is involved in the repair of double-stranded DNA breaks (DSB) and that its expression correlates with AML prognosis. Following DSB, hCINAP is recruited to damage sites where it promotes SENP3-dependent deSUMOylation of NPM1. This in turn results in the dissociation of RAP80 from the damage site and CTIP-dependent DNA resection and homologous recombination. NPM1 SUMOylation is required for recruitment of DNA repair proteins at the early stage of DNA-damage response (DDR), and SUMOylated NPM1 impacts the assembly of the BRCA1 complex. Knockdown of hCINAP also sensitizes a patient-derived xenograft (PDX) mouse model to chemotherapy. In clinical AML samples, low hCINAP expression is associated with a higher overall survival rate in patients. These results provide mechanistic insight into the function of hCINAP during the DNA-damage response and its role in AML resistance to therapy.
Systemic acquired resistance networks amplify airborne defense cues
Authors: Wenig Marion , Ghirardo Andrea , Sales Jennifer H. , Pabst Elisabeth S. , Breitenbach Heiko H. , Antritter Felix , Weber Baris , Lange Birgit , Lenk Miriam , Cameron Robin K. , Schnitzler Joerg-Peter , Vlot A. Corina
Published: August 2019

Salicylic acid (SA)-mediated innate immune responses are activated in plants perceiving volatile monoterpenes. Here, we show that monoterpene-associated responses are propagated in feed-forward loops involving the systemic acquired resistance (SAR) signaling components pipecolic acid, glycerol-3-phosphate, and LEGUME LECTIN-LIKE PROTEIN1 (LLP1). In this cascade, LLP1 forms a key regulatory unit in both within-plant and between-plant propagation of immunity. The data integrate molecular components of SAR into systemic signaling networks that are separate from conventional, SA-associated innate immune mechanisms. These networks are central to plant-to-plant propagation of immunity, potentially raising SAR to the population level. In this process, monoterpenes act as microbe-inducible plant volatiles, which as part of plant-derived volatile blends have the potential to promote the generation of a wave of innate immune signaling within canopies or plant stands. Hence, plant-to-plant propagation of SAR holds significant potential to fortify future durable crop protection strategies following a single volatile trigger.
TriQuinoline
Authors: Adachi Shinya , Shibasaki Masakatsu , Kumagai Naoya
Published: August 2019

The bottom-up synthesis of structurally well-defined motifs of graphitic materials is crucial to understanding their physicochemical properties and to elicit new functions. Herein, we report the design and synthesis of TriQuinoline (TQ) as a molecular model for pyridinic-nitrogen defects in graphene sheets. TQ is a trimer of quinoline units concatenated at the 2- and 8-positions in a head-to-tail fashion, whose structure leads to unusual aromatisation behaviour at the final stage of the synthesis. The central atomic-sized void endows TQ with high proton affinity, which was confirmed empirically and computationally. TQ•H+ is a two-dimensional cationic molecule that displays both π–π and CH–π contact modes, culminating in the formation of the ternary complex ([12]cycloparaphenylene(CPP) ⊃ (TQ•H+/coronene)) that consists of TQ•H+, coronene (flat), and [12]cycloparaphenylene ([12]CPP) (ring). The water-miscibility of TQ•H+ allows it to serve as an efficient DNA intercalator for e.g. the inhibition of topoisomerase I activity.
Isolated zero field sub-10 nm skyrmions in ultrathin Co films
Authors: Meyer Sebastian , Perini Marco , von Malottki Stephan , Kubetzka André , Wiesendanger Roland , von Bergmann Kirsten , Heinze Stefan
Published: August 2019

Due to their exceptional topological and dynamical properties magnetic skyrmions—localized stable spin structures—show great promise for spintronic applications. To become technologically competitive, isolated skyrmions with diameters below 10 nm stable at zero magnetic field and at room temperature are desired. Despite finding skyrmions in a wide spectrum of materials, the quest for a material with these envisioned properties is ongoing. Here we report zero field isolated skyrmions at T = 4 K with diameters below 5 nm observed in the virgin ferromagnetic state coexisting with 1 nm thin domain walls in Rh/Co atomic bilayers on Ir(111). These spin structures are investigated by spin-polarized scanning tunneling microscopy and can also be detected using non-spin-polarized tips via the noncollinear magnetoresistance. We demonstrate that sub-10 nm skyrmions are stabilized in these ferromagnetic Co films at zero field due to strong frustration of exchange interaction, together with Dzyaloshinskii–Moriya interaction and large magnetocrystalline anisotropy.
Surpassing the single-atom catalytic activity limit through paired Pt-O-Pt ensemble built from isolated Pt1 atoms
Authors: Wang Hui , Liu Jin-Xun , Allard Lawrence F. , Lee Sungsik , Liu Jilei , Li Hang , Wang Jianqiang , Wang Jun , Oh Se H. , Li Wei , Flytzani-Stephanopoulos Maria , Shen Meiqing , Goldsmith Bryan R. , Yang Ming
Published: August 2019

Despite the maximized metal dispersion offered by single-atom catalysts, further improvement of intrinsic activity can be hindered by the lack of neighboring metal atoms in these systems. Here we report the use of isolated Pt1 atoms on ceria as “seeds” to develop a Pt-O-Pt ensemble, which is well-represented by a Pt8O14 model cluster that retains 100% metal dispersion. The Pt atom in the ensemble is 100–1000 times more active than their single-atom Pt1/CeO2 parent in catalyzing the low-temperature CO oxidation under oxygen-rich conditions. Rather than the Pt-O-Ce interfacial catalysis, the stable catalytic unit is the Pt-O-Pt site itself without participation of oxygen from the 10–30 nm-size ceria support. Similar Pt-O-Pt sites can be built on various ceria and even alumina, distinguishable by facile activation of oxygen through the paired Pt-O-Pt atoms. Extending this design to other reaction systems is a likely outcome of the findings reported here.
A co-expressed gene status of adenylate kinase 1/4 reveals prognostic gene signature associated with prognosis and sensitivity to EGFR targeted therapy in lung adenocarcinoma
Authors: Jan Yi-Hua , Lai Tsung-Ching , Yang Chih-Jen , Huang Ming-Shyan , Hsiao Michael
Published: August 2019

Cancer cells utilize altered bioenergetics to fuel uncontrolled proliferation and progression. At the core of bioenergetics, adenine nucleotides are the building blocks for nucleotide synthesis, energy transfer and diverse metabolic processes. Adenylate kinases (AK) are ubiquitous phosphotransferases that catalyze the conversion of adenine nucleotides and regulate the homeostasis of nucleotide ratios within cellular compartments. Recently, different isoforms of AK have been shown to induce metabolic reprograming in cancer and were identified as biomarkers for predicting disease progression. Here we aim to systemically analyze the impact of all AK-associated gene signatures on lung adenocarcinoma patient survival and decipher the value for therapeutic interventions. By analyzing TCGA Lung Adenocarcinoma (LUAD) RNA Seq data, we found gene signatures from AK4 and AK1 have higher percentage of prognostic genes compared to other AK-gene signatures. A 118-gene signature was identified from consensus gene expression in AK1 and AK4 prognostic gene signatures. Immunohistochemistry (IHC) analyses in 140 lung adenocarcinoma patients showed overexpression of AK4 significantly correlated with worse overall survival (P = 0.001) whereas overexpression of AK1 significantly associated with good prognosis (P = 0.009). Furthermore, reduced AK4 expression by shRNA reduced the EGFR protein expression in EGFR mutation cells. The inhibition of AK4-AK1 signal might provide a potential target for synergistic effect in target therapy in lung cancer patients.
An Observed Regime Shift in the Formation of Warm Core Rings from the Gulf Stream
Authors: Gangopadhyay Avijit , Gawarkiewicz Glen , Silva E. Nishchitha S. , Monim M. , Clark Jenifer
Published: August 2019

We present observational evidence that a significant regime change occurred around the year 2000 in the formation of Warm Core Rings (WCRs) from the Gulf Stream (GS) between 75° and 55°W. The dataset for this study is a set of synoptic oceanographic charts available over the thirty-eight-year period of 1980–2017. The upward regime change shows an increase to 33 WCRs per year during 2000–2017 from an average of 18 WCRs during 1980 to 1999. A seasonal analysis confirms May-June-July as the peak time for WCR births in agreement with earlier studies. The westernmost region (75°-70°W) is least ring-productive, while the region from 65°W to 60°W is most productive. This regime shift around 2000 is detected in WCR formation for all of the four 5-degree wide sub-regions and the whole region (75°-55°W). This might be related to a reduction of the deformation radius for ring formation, allowing unstable meanders to shed more frequent rings in recent years. A number of possible factors resulting in such a regime shift related to the possible changes in reduced gravity, instability, transport of the GS, large-scale changes in the wind system and atmospheric fluxes are outlined, which suggest new research directions. The increase in WCRs has likely had an impact on the marine ecosystem since 2000, a topic worthy for future studies.
Agent-based simulations of China inbound tourism network
Authors: Wu Jinfeng , Wang Xingang , Pan Bing
Published: August 2019

Based on the results of a large-scale survey, we construct an agent-based network model for the China independent inbound tourism system and, by the approach of numerical simulation, investigate the responses of the tourist behaviors to perturbations in different scenarios, including the closure of a tourism city, the opening of a new port city in western China, and the increase of the tourism attractiveness of a specific city. Numerical results show that: (1) the closure of a single city in general will affect the tourist visitations of many other cities and, comparing to the non-port cities, the overall visitation volume of the system is more influenced by closing a port city; (2) the opening of a new port city in western China will attract more tourists to the western cities, but has a negligible impact on either the overall visitation volume or the imbalanced tourist distribution; and (3) the increase of the tourism attractiveness of a non-port (port) city normally increases (decreases) the overall visitation volume, yet there are exceptions due to the spillover effect. Furthermore, by increasing the tourism attractiveness of a few cities simultaneously, we investigate also the strategy of multiple-city-upgrade in tourism development. We find that the overall tourist volume is better improved by upgrading important non-port cities that are geographically distant from each other. The study reveals the rich dynamic inherent in complex tourism network, and the findings could be helpful to the development and management of China inbound tourism.
Disruptive effects of repeated stress on basolateral amygdala neurons and fear behavior across the estrous cycle in rats
Authors: Blume Shannon R. , Padival Mallika , Urban Janice H. , Rosenkranz J. Amiel
Published: August 2019

Stress is a precipitating factor in depression and anxiety disorders. Patients with these disorders often show amygdala abnormalities. The basolateral amygdala (BLA) is integral in mood and emotion, and is sensitive to stress. While much is known about effects of stress on BLA neuron activity and morphology in males, less is known in females. We tested whether repeated stress exerts distinct effects on BLA in vivo neuronal activity and morphology of Golgi-stained BLA neurons [lateral (LAT) and basal (BA) nuclei] in adult female rats. Repeated restraint stress increased BLA neuronal firing and caused hypertrophy of BLA neurons in males, while it decreased LAT and BA neuronal firing and caused hypotrophy of neurons in the LAT of females. BLA neuronal activity and function, such as fear conditioning, shifts across the estrous cycle. Repeated stress disrupted this pattern of BLA activity and fear expression over the estrous cycle. The disruptive effects of stress on the pattern of BLA function across estrous may produce behavior that is non-optimal for a specific phase of the estrous cycle. The contrasting effects of stress may contribute to sex differences in the effects of stress on mood and psychiatric disorders.
Deaf readers benefit from lexical feedback during orthographic processing
Authors: Gutierrez-Sigut Eva , Vergara-Martínez Marta , Perea Manuel
Published: August 2019

It has been proposed that poor reading abilities in deaf readers might be related to weak connections between the orthographic and lexical-semantic levels of processing. Here we used event related potentials (ERPs), known for their excellent time resolution, to examine whether lexical feedback modulates early orthographic processing. Twenty congenitally deaf readers made lexical decisions to target words and pseudowords. Each of those target stimuli could be preceded by a briefly presented matched-case or mismatched-case identity prime (e.g., ALTAR-ALTAR vs. altar- ALTAR). Results showed an early effect of case overlap at the N/P150 for all targets. Critically, this effect disappeared for words but not for pseudowords, at the N250—an ERP component sensitive to orthographic processing. This dissociation in the effect of case for word and pseudowords targets provides strong evidence of early automatic lexical-semantic feedback modulating orthographic processing in deaf readers. Interestingly, despite the dissociation found in the ERP data, behavioural responses to words still benefited from the physical overlap between prime and target, particularly in less skilled readers and those with less experience with words. Overall, our results support the idea that skilled deaf readers have a stronger connection between the orthographic and the lexical-semantic levels of processing.
Compact all-fiber source of coherent linearly polarized octave-spanning supercontinuum based on normal dispersion silica fiber
Authors: Tarnowski Karol , Martynkien Tadeusz , Mergo Paweł , Sotor Jarosław , Soboń Grzegorz
Published: August 2019

We report the generation of coherent octave-spanning supercontinuum in an all-fiber system, without any free-space optical components. The setup uses the femtosecond fiber laser as a pump and an all-normal dispersion microstructured fiber as a medium for supercontinuum generation. The generated spectrum is characterized both experimentally and numerically and shows a broad bandwidth (1.1−2.2 μm), a high signal to noise ratio reaching 100 at maximum, a high coherence (closing to 1), linear polarization and average output power up to 57 mW. The source is characterized by exceptional simplicity and does not require any alignment (the nonlinear fiber is spliced to the pump) which finally opens the path to outside-lab applications of supercontinuum radiation.
Sex and age specific reduction in stress resistance and mitochondrial DNA copy number in Drosophila melanogaster
Authors: Kristensen Torsten Nygaard , Loeschcke Volker , Tan Qihua , Pertoldi Cino , Mengel-From Jonas
Published: August 2019

Environmental stresses such as extreme temperatures, dehydration and food deprivation may have distinct consequences for different age-classes and for males and females across species. Here we investigate a natural population of the model organism Drosophila melanogaster. Males and females at ages 3, 19 and 35 days were tested for stress resistance; i.e. the ability of flies to cope with starvation and both cold and hot temperatures. Further, we tested a measure of metabolic efficiency, namely mitochondrial DNA copy number (mtDNA CN) in both sexes at all three age-classes. We hypothesize that stress resistance is reduced at old age and more so in males, and that mtDNA CN is a biomarker for sex- and age-dependent reductions in the ability to cope with harsh environments. We show that: (1) males exhibit reduced starvation tolerance at old age, whereas older females are better in coping with periods without food compared to younger females, (2) heat tolerance decreases with increasing age in males but not in females, (3) cold tolerance is reduced at old age in both sexes, and (4) old males have reduced mtDNA CN whereas mtDNA CN slightly increases with age in females. In conclusion, our data provide strong evidence for trait and sex specific consequences of aging with females generally being better at coping with environmental stress at old age. The reduced mtDNA CN in old males suggests reduced metabolic efficiency and this may partly explain why males are less stress tolerant at old age than females. We suggest that mtDNA CN might be a suitable biomarker for physiological robustness. Our findings likely extend to other taxa than Drosophila and therefore we discuss the observations in relation to aging and sex specific lifespan across species.
Association of MTMR3 rs12537 at miR-181a binding site with rheumatoid arthritis and systemic lupus erythematosus risk in Egyptian patients
Authors: Senousy Mahmoud A. , Helmy Hebatullah S. , Fathy Nevine , Shaker Olfat G. , Ayeldeen Ghada M.
Published: August 2019

Single nucleotide polymorphisms (SNPs) in microRNA-target sites influence an individual’s risk and prognosis for autoimmune diseases. Myotubularin-related protein 3 (MTMR3), an autophagy-related gene, is a direct target of miR-181a. We investigated whether MTMR3 SNP rs12537 in the miR-181a-binding site is associated with the susceptibility and progression of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Overall, 94 patients with RA, 80 patients with SLE, and 104 healthy volunteers were recruited. Genotyping and expression analysis of circulating MTMR3 and miR-181a were performed by qPCR. The autophagic marker MAP1LC3B was measured by ELISA. The rs12537 minor homozygote (TT) genotype was a candidate risk factor of both RA and SLE. rs12537TT was associated with lower serum MTMR3 expression and higher LC3B levels than other genotypes in patients with both diseases. Serum miR-181a expression was higher in rs12537TT carriers than in other genotypes among SLE patients. Serum miR-181a and MTMR3 levels were inversely correlated in SLE but not in RA patients. rs12537TT and serum miR-181a were positively associated with disease severity in both diseases. Our results identify a novel role of rs12537 in the susceptibility and progression of RA and SLE, possibly through impacting the interaction between miR-181a and MTMR3 leading to increased autophagy.
InN superconducting phase transition
Authors: Song Zhi-Yong , Shang Liyan , Hu Zhigao , Chu JunHao , Chen Ping-Ping , Yamamoto Akio , Kang Ting-Ting
Published: August 2019

InN superconductivity is very special among III–V semiconductors, as other III–V semiconductors (such as GaAs, GaN, InP, InAs, etc.) usually lack strong covalent bonding and thus seldom show superconductivity at low temperatures. Here, we probe the different superconducting phase transitions in InN highlighted by its microstructure. Those chemical-unstable phase-separated inclusions, such as metallic indium or In2O3, are intentionally removed by HCl acid etching. The quasi-two-dimensional vortex liquid-glass transition is observed in the sample with a large InN grain size. In contrast, the superconducting properties of InN with a small grain size are sensitive to acid etching, showing a transition into a nonzero resistance state when the temperature approaches zero. Since the value of ξ0 (the zero-temperature-limit superconducting coherence length) is close to the grain size, it is suggested that individual InN grains and intergrain coupling should be responsible for the sample-dependent InN superconducting phase transition. Our work establishes a guideline for engineering superconductivity in III-nitride.
Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
Authors: Karlsson Lars , González-Alvarado María Nazareth , Motalleb Reza , Blomgren Klas , Börjesson Mats , Kuhn Hans Georg
Published: August 2019

Aerobic exercise prevents age-dependent decline in cognition and hippocampal neurogenesis. The transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) mediates many of the exercise-induced benefits in skeletal muscle, including the release of factors into the circulation with neurotrophic effects. We use a transgenic mouse model with muscle-specific overexpression of PGC-1α to study the contribution of chronic muscle activation on exercise-induced effects on hippocampal neurogenesis in aging. Young and old transgenic and wild type animals of both sexes displayed a robust age-related reduction in newborn BrdU+-cells, immature neurons (DCX+-cells) and new mature BrdU+/NeuN+-neurons in the dentate gyrus. No differences were detected between genotypes or sexes. Analysis of serum proteins showed a tendency towards increased levels of myokines and reduced levels of pro-inflammatory cytokines for transgenic animals, but only musclin was found to be significantly up-regulated in transgenic animals. We conclude that constitutive muscular overexpression of PGC-1α, despite potent systemic changes, is insufficient for mimicking exercise-induced effects on hippocampal neurogenesis in aging. Continued studies are required to investigate the complex molecular mechanisms by which circulating signals could mediate exercise-induced effects on the central nervous system in disease and aging, with the aim of discovering new therapeutic possibilities for patients.
+50 Years of Terrestrial Hydroclimatic Variability in Africa’s Transboundary Waters
Authors: Hasan Emad , Tarhule Aondover , Zume Joseph T. , Kirstetter Pierre-Emmanuel
Published: August 2019

GRACE Terrestrial Water Storage (TWS) provides unique and unprecedented perspectives about freshwater availability and change globally. However, GRACE-TWS records are relatively short for long-term hydroclimatic variability studies, dating back to April 2002. In this paper, we made use of Noah Land Surface Model (LSM), and El Niño–Southern Oscillation (ENSO) data in an autoregressive model with exogenous variables (ARX) to reconstruct a 66-year record of TWS for nine major transboundary river basins (TRBs) in Africa. Model performance was evaluated using standard indicators, including the Nash Sutcliffe Efficiency criteria, cumulative density frequency, standardized residuals plots, and model uncertainty bounds. Temporally, the reconstruction results were evaluated for trend, cycles, and mode of variability against ancillary data from the WaterGAP Model (WGHM-TWS) and GPCC-based precipitation anomalies. The temporal pattern reveals good agreement between the reconstructed TWS, WGHM-TWS, and GPCC, (p-value < 0.0001). The reconstructed TWS suggests a significant declining trend across the northern and central TRBs since 1951, while the southern basins show an insignificant trend. The mode of variability analysis indicates short storage periodicity of four to sixteen-month in the northern basins, while strong intra-annual variability in the central and southern basins. The long-term TWS records provide additional support to Africa’s water resources research on hydroclimatic variability and change in shared transboundary water basins.
Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors
Authors: Skrenkova Kristyna , Hemelikova Katarina , Kolcheva Marharyta , Kortus Stepan , Kaniakova Martina , Krausova Barbora , Horak Martin
Published: August 2019

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that play an essential role in mediating excitatory neurotransmission in the mammalian central nervous system (CNS). Functional NMDARs are tetramers composed of GluN1, GluN2A-D, and/or GluN3A-B subunits, giving rise to a wide variety of NMDAR subtypes with unique functional properties. Here, we examined the surface delivery and functional properties of NMDARs containing mutations in the glycine-binding sites in GluN1 and GluN3A subunits expressed in mammalian cell lines and primary rat hippocampal neurons. We found that the structural features of the glycine-binding sites in both GluN1 and GluN3A subunits are correlated with receptor forward trafficking to the cell surface. In addition, we found that a potentially clinically relevant mutation in the glycine-binding site of the human GluN3A subunit significantly reduces surface delivery of NMDARs. Taken together, these findings provide novel insight into how NMDARs are regulated by their glycine-binding sites and may provide important information regarding the role of NMDARs in both physiological and pathophysiological processes in the mammalian CNS.
TLR-2 mediated cytosolic-Ca2+ surge activates ER-stress-superoxide-NO signalosome augmenting TNF-α production leading to apoptosis of Mycobacterium smegmatis-infected fish macrophages
Authors: Hussain Md. Arafat , Datta Debika , Singh Rashmi , Kumar Manmohan , Kumar Jai , Mazumder Shibnath
Published: August 2019

The implications of TLR-2 mediated alterations in cytosolic-Ca2+((Ca2+)c) levels inM.smegmatisinfections is not well known. Using headkidney macrophages (HKM) fromClarias gariepinus, we observed TLR-2 signalling is required in the phagocytosis ofM.smegmatis.M.smegmatisinduced caspase-dependent HKM apoptosis in MOI, time and growth-phase dependent manner. RNAi and inhibitor studies demonstrated critical role of TLR-2 in eliciting (Ca2+)c-surge and c-Src-PI3K-PLC axis playing an intermediary role in the process. The (Ca2+)c-surge triggered downstream ER-stress and superoxide (O2−) generation. The cross-talk between ER-stress and O2−amplified TNF-α production, which led to HKM apoptosis and bacterial clearance. Release of nitric oxide (NO) was also observed and silencing the NOS2-NO axis enhanced intracellular bacterial survival and attenuated caspase activity. Pre-treatment with diphenyleneidonium chloride inhibited NO production implicating O2−–NO axis imperative inM.smegmatis-induced HKM apoptosis. NO positively impacted CHOP expression and TNF-α production in infected HKM. We conclude that, TLR-2 induced (Ca2+)c-surge and ensuing cross-talk between ER-stress and O2−potentiates HKM pathology by amplifying pro-inflammatory TNF-α production. Moreover, the pro-oxidant environment triggers NO release which prolonged ER-stress and TNF-α production, culminating in HKM apoptosis and bacterial clearance. Together, our study suggests HKM an alternate model to study macrophage-mycobacteria interactions.
Synthesis, characterisation and water–gas shift activity of nano-particulate mixed-metal (Al, Ti) cobalt oxides
Authors: Wolf Moritz , Roberts Stephen J. , Marquart Wijnand , Olivier Ezra J. , Luchters Niels T. J. , Gibson Emma K. , Catlow C. Richard A. , Neethling Jan. H. , Fischer Nico , Claeys Michael
Published: August 2019

Mixed-metal cobalt oxide, namely cobalt aluminate and titanate, were shown to be water gas shift inactive.
Complex organic particulate artificial sewage (COPAS) as surrogate wastewater in anaerobic assays
Authors: Prieto Ana L. , Criddle Craig S. , Yeh Daniel H.
Published: August 2019

By mimicking the complex organic matter composition in sewage, COPAS is a readily available and practical alternative in anaerobic lab-scale studies.
The synergistic effect of Lactobacillus plantarum CCFM242 and zinc on ulcerative colitis through modulating intestinal homeostasis
Authors: Zhai Qixiao , Zhang Qingsong , Tian Fengwei , Zhao Jianxin , Zhang Hao , Chen Wei
Published: August 2019

Zn-enriched Lactobacillus plantarum treatment protects intestinal barrier and immune function and alleviates colitis in mice.
Structural modification of azolylacryloyl derivatives yields a novel class of covalent modifiers of hemoglobin as potential antisickling agents
Authors: Omar A. M. , David T. , Pagare P. P. , Ghatge M. S. , Chen Q. , Mehta A. , Zhang Y. , Abdulmalik O. , Naghi A. H. , El-Araby M. E. , Safo M. K.
Published: August 2019

The intracellular polymerization and the concomitant sickling processes, central to the pathology of sickle cell disease, can be mitigated by increasing the oxygen affinity of sickle hemoglobin (HbS).
[MW12O44] clusters: unprecedented central heteroatoms atomically dispersed in the eight coordination state bridging the 1 : 12 polyoxometalate family of Keggin and Silverton
Authors: Chen Yongdong , Tian Shanli , Qin Zhaoxian , Zhang Jiangwei , Cao Youhai , Chu Shengqi , Lu Lanlu , Li Gao
Published: August 2019

A series of [MW12O44] nanoclusters is designed that possesses central heteroatoms atomically dispersed in the eight coordination state; they bridge the 1 : 12 polyoxometalate families of Keggin and Silverton.