bluuebunny/crossref_metadata_2025 huggingface dataset:
Fossil flower ofStaphyleaL. from the Miocene amber of Mexico: New evidence of the Boreotropical Flora in low-latitude North America
Authors: Hernández-Damián Ana L. , Cevallos-Ferriz Sergio R. S. , Huerta-Vergara Alma R.
Published: October 2018

A new flower preserved in amber in sediments of Simojovel de Allende, México, is identified as an extinct member of Staphyleaceae, a family of angiosperms consisting of only three genera (Staphylea,TurpiniaandEuscaphis), which has a large and abundant fossil record and is today distributed over the Northern Hemisphere.Staphylea ochoterenaesp. nov. is the first record of a flower for this group, which is small, pedicelled, pentamer, bisexual, with sepals and petals with similar size, dorsifixed anthers and superior ovary. Furthermore, the presence of stamens with pubescent filaments allows close comparison with extant flowers ofStaphylea bulmadaandS. forresti, species currently growing in Asia. However, their different number of style (one vs. three) and the apparent lack of a floral disc distinguish them fromS. ochoterenae.The presence of Staphyleaceae in southern Mexico ca. 23 to 15My ago is evidence of the long history of integration of vegetation in low-latitude North America, in which some lineages, such asStaphylea, could move southwards from high latitudes of the Northern Hemisphere, as part of the Boreotropical Flora. In Mexico it grew in association with tropical elements, as suggested by the fossil record of the area.
Arrival Angle and Travel Time Measurements of HF Transequatorial Propagation for Plasma Bubble Monitoring
Authors: Saito Susumu , Yamamoto Mamoru , Maruyama Takashi
Published: October 2018

A system to measure travel times of high‐frequency (HF) radio waves was developed based on a digital receiver technique. Travel times of HF transequatorial propagation (HF‐TEP) of signals of Radio Australia from Shepparton (36.2°S, 145.3°E), Australia to Oarai (36.3°N, 140.6°E), Japan, were measured by the system. Directions of arrival of the signals were simultaneously observed by a HF Direction Finder located at Oarai (Oarai Direction Finder: ODF). When the ODF observed signals arriving from great circle direction, constant multiple discrete values of propagation times were observed. After sunset, propagation times longer than those expected from the great circle propagation were observed and the ODF observed corresponding signals from off‐great‐circle directions (off‐great‐circle propagation). The observed maximum azimuth angle deviation (∼50°) was much larger than the angle that would have been obtained when a single side reflection in HF‐TEP was assumed. This result supports the multireflection model of off‐great‐circle propagation of HF‐TEP proposed by Tsunoda et al. (2016a, https://doi.org/10.1002/2015JA021695). The propagation time measurements are useful to determine the propagation paths, when they are used with HF‐TEP observations by a HF Direction Finder system. Ray tracing analysis with the propagation times and arrival angles will contribute to monitoring locations of plasma bubbles as well as understanding their structures and the physics behind them. The technique can also be applied to determine the propagation paths in the normal great circle propagations and other geophysical phenomena, such as midlatitude trough, deep traveling ionospheric disturbance modulation of the ionospheric height due to Perkins instability and sporadic E layer irregularities.
Timing of Orogenic Exhumation Processes of the Qinling Orogen: Evidence From40Ar/39Ar Dating
Authors: Dong Yunpeng , Neubauer Franz , Genser Johann , Sun Shengsi , Yang Zhao , Zhang Feifei , Cheng Bin , Liu Xiaoming , Zhang Guowei
Published: October 2018

The Qinling Orogenic Belt was formed by long‐lived subduction and collision between the North and South China blocks. Our40Ar/39Ar geochronological data of amphibole, white mica, and biotite reveal different exhumation and cooling histories of the major units in the North Qinling Belt and South Qinling Belt (SQB), constraining the multiple orogenic processes. The exhumation of the Qinling Group in the North Qinling Belt started before 432 Ma, through about 500 °C during 432.3–405 Ma, followed by rapid cooling below 425 °C at 388.9 ± 1.1 Ma and slow cooling through about 300 °C during 333.3–329.5 Ma. A similar exhumation history of the Kuanping Group started from about 383 Ma, cooled below 425 °C at 364.9 ± 1.2 Ma and 300 °C at 341.8 ± 1.3 Ma. The metamorphic fore‐arc sedimentary wedge cooled below 500 °C during 322–311.2 Ma, below 425 °C at 306.3 ± 2.8 Ma, and 300 °C at 249 ± 2.8 Ma. However, the white mica40Ar/39Ar ages of 349.4 ± 5.1 and 363.2 ± 2.5 Ma constrain the syntectonic metamorphic crystallization age of the Devonian Liuling Group in the northern SQB, whereas 228.2 ± 0.7 Ma indicates either a delayed cooling of the Wudang Group in the southern SQB or a second stage of low‐temperature thermal overprint. Together with previous cooling ages and regional geology, our new data support a tectonic model of Early Paleozoic Andean‐type orogeny with subsequent Late Paleozoic continental subduction in the Qinling Orogenic Belt.
Variability in Atmospheric Methane From Fossil Fuel and Microbial Sources Over the Last Three Decades
Authors: Thompson R. L. , Nisbet E. G. , Pisso I. , Stohl A. , Blake D. , Dlugokencky E. J. , Helmig D. , White J. W. C.
Published: October 2018

Atmospheric measurements show an increase in CH4 from the 1980s to 1998 followed by a period of near‐zero growth until 2007. However, from 2007, CH4 has increased again. Understanding the variability in CH4 is critical for climate prediction and climate change mitigation. We examine the role of CH4 sources and the dominant CH4 sink, oxidation by the hydroxyl radical (OH), in atmospheric CH4 variability over the past three decades using observations of CH4, C2H6, and δ13CCH4 in an inversion. From 2006 to 2014, microbial and fossil fuel emissions increased by 36 ± 12 and 15 ± 8 Tg y−1, respectively. Emission increases were partially offset by a decrease in biomass burning of 3 ± 2 Tg y−1 and increase in soil oxidation of 5 ± 6 Tg y−1. A change in the atmospheric sink did not appear to be a significant factor in the recent growth of CH4.
Examining the Origins of Ocean Heat Content Variability in the Eastern North Atlantic Subpolar Gyre
Authors: Foukal Nicholas P. , Lozier M. Susan
Published: October 2018

We analyze sources of ocean heat content (OHC) variability in the eastern North Atlantic subpolar gyre from both Eulerian and Lagrangian perspectives within two ocean simulations from 1990 to 2015. Heat budgets reveal that while the OHC seasonal cycle is driven by air‐sea fluxes, interannual OHC variability is driven by both air‐sea fluxes and the divergence of ocean heat transport, the latter of which is dominated by the oceanic flux through the southern face of the study area. Lagrangian trajectories initialized along the southern face and run backward in time indicate that interannual variability in the subtropical‐origin volume flux (i.e., the upper limb of the overturning circulation) drives variability in the temperature flux through the southern face. As such, the heat carried by the imported subtropical waters is an important component of the eastern subpolar gyre heat budget on interannual time scales.
Revisiting Pan Evaporation Trends in Australia a Decade on
Authors: Stephens Clare M. , McVicar Tim R. , Johnson Fiona M. , Marshall Lucy A.
Published: October 2018

Decreases in pan evaporation (Epan) have been reported around the world despite increasing air temperatures; this was attributed to reductions in wind speed and solar radiation. Using 42 years (1975–2016) of Australian Epan data, we reexamined Epan trends, adding over a decade of observations to previous analyses. Flexible local linear regression models showed that many previously reported decreasing Epan trends have plateaued or reversed. Attribution analysis confirmed that 1975–1994 Epan decreases in southern/western Australia were chiefly driven by decreasing wind speeds. Increasing vapor pressure deficit subsequently became dominant, resulting in 1994–2016 Epan increases. Climate trend analyses should consider applying flexible statistical models to qualitatively understand temporal dynamics, complementing linear models that are able to provide quantitative assessments, especially when multiple drivers are involved.
Ash Particles Detected in the Tropical Lower Stratosphere
Authors: Jensen Eric J. , Woods Sarah , Lawson R. Paul , Bui T. Paul , Pfister Leonhard , Thornberry Troy Dean , Rollins Andrew W. , Vernier Jean‐Paul , Pan Laura L. , Honomichl Shawn , Toon Owen Brian
Published: October 2018

We report here on measurements of relatively large (up to ≃5‐μm maximum dimension) particles detected in the tropical western Pacific lower stratosphere. The particles were observed at low relative humidities and contain no detectable ice mass. We conclude that these particles are silicate ash injected by the Mount Kelud eruption in Indonesia a few weeks prior to the aircraft observations. The Kelud ash particles were detected by cloud probes on the National Aeronautics and Space Administration Global Hawk between the lapse rate tropopause (≃16.5 km) and the aircraft ceiling (18.5 km). The ash particles detected in the lowermost stratosphere by the aircraft extended well into the northern subtropics. The concentration of ash particles dropped off rapidly below the lapse rate tropopause, presumably because of rapid removal by ice nucleation scavenging. Although ash particles are very effective ice nuclei, the low particle concentrations detected in the upper troposphere precludes a significant impact on cirrus clouds.
Determining the Shortwave Radiative Flux From Earth Polychromatic Imaging Camera
Authors: Su Wenying , Liang Lusheng , Doelling David R. , Minnis Patrick , Duda David P. , Khlopenkov Konstantin , Thieman Mandana M. , Loeb Norman G. , Kato Seiji , Valero Francisco P. J. , Wang Hailan , Rose Fred G.
Published: October 2018

The Earth Polychromatic Imaging Camera (EPIC) onboard Deep Space Climate Observatory provides 10 narrowband spectral images of the sunlit side of the Earth. The blue (443 nm), green (551 nm), and red (680 nm) channels are used to derive EPIC broadband radiances based upon narrowband‐to‐broadband regressions developed using collocated MODIS equivalent channels and Clouds and the Earth's Radiant Energy System (CERES) broadband measurements. The pixel‐level EPIC broadband radiances are averaged to provide global daytime means at all applicable EPIC times. They are converted to global daytime mean shortwave (SW) fluxes by accounting for the anisotropy characteristics using a cloud property composite based on lower Earth orbiting satellite imager retrievals and the CERES angular distribution models (ADMs). Global daytime mean SW fluxes show strong diurnal variations with daily maximum‐minimum differences as great as 20 W/m2 depending on the conditions of the sunlit portion of the Earth. The EPIC SW fluxes are compared against the CERES SYN1deg hourly SW fluxes. The global monthly mean differences (EPIC‐SYN) between them range from 0.1 W/m2 in July to −4.1 W/m2 in January, and the RMS errors range from 3.2 to 5.2 W/m2. Daily mean EPIC and SYN fluxes calculated using concurrent hours agree with each other to within 2% and both show a strong annual cycle. The SW flux agreement is within the calibration and algorithm uncertainties, which indicates that the method developed to calculate the global anisotropic factors from the CERES ADMs is robust and that the CERES ADMs accurately account for the Earth's anisotropy in the near‐backscatter direction.
The Impact of Magnetic Field Temporal Sampling on Modeled Surface Electric Fields
Authors: Grawe Matthew A. , Makela Jonathan J. , Butala Mark D. , Kamalabadi Farzad
Published: October 2018

Descriptions of the surface magnetic‐to‐electric field relationship, using magnetotelluric impedance tensors, have seen refinement in recent years. Correspondingly, models of geomagnetically induced currents flowing in power line conductors using input from more fundamental observables (e.g., the surface magnetic field or solar wind drivers) have become more sophisticated. Magnetometer data used for purposes of surface electric field modeling typically have cadences between 1 s and 1 min. Using 1‐D and 3‐D magnetotelluric impedance tensors, we quantify the effect of magnetometer cadence on modeled peak surface electric fields during the 22 June 2015, 17 March 2015, and 2 October 2013 geomagnetic storms. It is shown that 1‐min magnetometer data sampling leads to median biases in the peak electric field of 10–20% magnitude attenuation and 2–17° in direction (depending on the storm) across the United States using the Fernberg 1‐D conductivity models and 11–26% (0.9–8° ) using the 3‐D impedance tensors derived from the USArray magnetotelluric survey. The largest 10% of attenuations almost entirely occur near low‐resistivity subsurface structures in the western and eastern United States, reaching a 50% median attenuation during the 17 March 2015 event. It is concluded that cadence, local geology, and the spectral content of the geomagnetic field all play a significant role in the bias.
The Ground‐Level Enhancement Event of September 2017 and Other Large Solar Energetic Particle Events of Cycle 24
Authors: Cohen C. M. S. , Mewaldt R. A.
Published: October 2018

The 10 September 2017 solar energetic particle (SEP) event was the largest since June 2015 and one of only two ground‐level enhancement (GLE) events of solar cycle 24. GLE events are subset of large SEP events (~15% of events identified by Space Weather Prediction Center) with particularly hard spectra, making them a substantial space weather hazard to space‐based instrumentation and exposed astronauts. We present analysis of the 10 September 2017 event and compare it to the other cycle 24 GLE events, to those of cycle 23, and also to two extreme SEP events observed by Solar Terrestrial Relations Observatory (STEREO). We find the 10 September 2017 event had a broken power law spectrum typical of GLE events but was softer than average at high energies. However, it was hard at low energies with a relatively high break energy, which led to 100‐MeV proton fluences within a factor of 4.5 of the largest cycle 23 GLE events. The composition was nominal, except for a low Fe/O ratio, which has also been seen in large SEP events this cycle, but is somewhat atypical of the cycle 23 GLE events. The extreme events seen by STEREO exhibited very hard high‐energy spectra, with one event producing ~80‐MeV proton fluences larger than the largest cycle 23 GLE event. However, even including STEREO events, the top 10 largest cycle 24 events are, on average, 2.4 times smaller than the top 10 of cycle 23 based on >10‐MeV proton fluences.
Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice
Authors: Wolters-Eisfeld Gerrit , Mercanoglu Baris , Hofmann Bianca T. , Wolpers Thomas , Schnabel Claudia , Harder Sönke , Steffen Pascal , Bachmann Kai , Steglich Babett , Schrader Jörg , Gagliani Nicola , Schlüter Hartmut , Güngör Cenap , Izbicki Jakob R. , Wagener Christoph , Bockhorn Maximilian
Published: October 2018

Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase. Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins. Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes. To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis. Interestingly, a variety of proteins were identified, of which bile salt-activated lipase (also denoted carboxyl-ester lipase, Cel) was the most abundant. In humans, frameshift mutations in CEL cause maturity-onset diabetes of the young type 8 (MODY8), a monogenic syndrome of diabetes and pancreatic exocrine dysfunction. Here, we provide data suggesting that differentially O-glycosylated Cel could negatively affect beta cell function. Taken together, our findings demonstrate the importance of correct O-glycan formation for normal exocrine and endocrine pancreatic function, implying that aberrant O-glycans might be relevant for pathogenic mechanisms of the pancreas.
Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis
Authors: Zhang Kui , Fu Gang , Pan Guangzhao , Li Chongyang , Shen Li , Hu Renjian , Zhu Shunqin , Chen Yibiao , Cui Hongjuan
Published: October 2018

Glioma is the most common and malignant form of primary brain tumour, and is characterised by high proliferation and extensive invasion and neurological destruction. Demethylzeylasteral (T-96), which is extracted from Tripterygium wilfordii, is considered to have immunosuppressive, anti-inflammatory and anti-angiogenic effects. Here, the anti-tumour effect of T-96 on glioma was evaluated. Our results demonstrated that T-96 significantly inhibited glioma cell growth and induced cell cycle arrest in G1 phase but did not induce apoptosis. Cell invasion and migration were dramatically suppressed after treatment with T-96. Almost all genes related to cell cycle and DNA replication were downregulated after treatment with T-96. Our results showed that miR-30e-5p was noticeably upregulated after T-96 treatment, and MYBL2, which is involved in cell cycle progression and is a target gene of miR-30e-5p, was significantly reduced in synchrony. Overexpression of MYBL2 partially rescued the T-96-induced inhibition of cell growth and proliferation. Moreover, a miR-30e-5p antagomir significantly reduced the upregulation of miR-30e-5p expression induced by T-96, leading to recovery of MYBL2 expression, and partially rescued the T-96-induced inhibition of cell growth and proliferation. More important, T-96 effectively upregulated miR-30e-5p expression and downregulated MYBL2 expression, thus inhibiting LN-229 cell tumour growth in a mouse model. These results indicated that T-96 might inhibit glioma cell growth by regulating the miR-30e-5p/MYBL2 axis. Our study demonstrated that T-96 might act as a promising agent for malignant glioma therapy.
Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression
Authors: Lv Yi-pin , Peng Liu-sheng , Wang Qi-hong , Chen Na , Teng Yong-sheng , Wang Ting-ting , Mao Fang-yuan , Zhang Jin-yu , Cheng Ping , Liu Yu-gang , Kong Hui , Wu Xiao-long , Hao Chuan-jie , Chen Weisan , Zhu Jiang , Han Bin , Ma Qiang , Li Ke , Zou Quanming , Zhuang Yuan
Published: October 2018

Mast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, their precise mechanism of communication in gastric cancer remains largely unclear. Here, we found that patients with GC showed a significantly higher mast cell infiltration in tumors. Mast cell levels increased with tumor progression and independently predicted reduced overall survival. Tumor-derived adrenomedullin (ADM) induced mast cell degranulation via PI3K-AKT signaling pathway, which effectively promoted the proliferation and inhibited the apoptosis of GC cells in vitro and contributed to the growth and progression of GC tumors in vivo, and the effect could be reversed by blocking interleukin (IL)-17A production from these mast cells. Our results illuminate a novel protumorigenic role and associated mechanism of mast cells in GC, and also provide functional evidence for these mast cells to prevent, and to treat this immunopathogenesis feature of GC.
DNA-methylation-mediated silencing of miR-486-5p promotes colorectal cancer proliferation and migration through activation of PLAGL2/IGF2/β-catenin signal pathways
Authors: Liu Xiangxiang , Chen Xiaoxiang , Zeng Kaixuan , Xu Mu , He Bangshun , Pan Yuqin , Sun Huiling , Pan Bei , Xu Xueni , Xu Tao , Hu Xiuxiu , Wang Shukui
Published: October 2018

As one of the most common cancers worldwide, colorectal cancer (CRC) causes a large number of mortality annually. Aberrant expression of microRNAs (miRNAs) is significantly associated with the initiation and development of CRC. Further investigations regarding the regulatory mechanism of miRNAs is warranted. In this study, we discovered that miR-486-5p was remarkably downregulated in CRC, which partially results from higher DNA methylation in the promoter region detected by using methylation-specific PCR, bisulfite sequencing PCR, and DNA demethylation treatment. Besides, decreased miR-486-5p was obviously associated with advanced TNM stage, larger tumor size, lymphatic metastasis, and poor prognosis in CRC. Upregulated miR-486-5p inhibited the proliferation and migration of CRC through targeting PLAGL2 expression and subsequent repressing IGF/β-catenin signal pathways both in vitro and in vivo. Notably, plasma miR-486-5p expression was significantly upregulated in CRC patients and we identified plasma miR-486-5p as a novel diagnostic biomarker of CRC using receiver operating characteristic (ROC) curve analysis. Moreover, exploration in GEO dataset revealed that circulating miR-486-5p is tumor derived through being packaged into secretory exosomes. Taken together, our data demonstrated that miR-486-5p promotes colorectal cancer proliferation and migration through activation of PLAGL2/IGF2/β-catenin signal pathway, which is a promising therapeutic target of CRC treatment.
More complete polarization of renal tubular epithelial cells by artificial urine
Authors: Vinaiphat Arada , Charngkaew Komgrid , Thongboonkerd Visith
Published: October 2018

Cell polarization using Transwell is a common method employed to study renal tubular epithelial cells. However, this conventional protocol does not precisely recapitulate renal tubular epithelial cell phenotypes. In this study, we simulated renal physiological microenvironment by replacing serum-containing culture medium in upper chamber of the Transwell with physiologic artificial urine (AU) (to mimic renal tubular fluid), whereas the lower chamber still contained serum-containing medium (to mimic plasma-enriched renal interstitium). Comparing to the conventional protocol (control), the AU-assisted protocol offered more complete polarization of MDCK renal tubular cells as indicated by higher transepithelial electrical resistance (TER) and greater levels of tight junction (TJ) proteins (ZO-1 and occludin). Transmission electron microscopy (TEM) showed greater densities of TJ and desmosome, narrower intercellular spaces, greater cell height, and longer microvilli in the AU-treated cells. Secretome analysis revealed that the AU-treated cells secreted greater proportion of the proteins matched to normal human urinary proteome via both classical and non-classical secretory pathways. Finally, modifying/omitting each component of AU (one at a time) followed by validation revealed that urea was responsible for such property of AU to improve cell polarization. These data indicate that replacing AU on the upper chamber of Transwell can improve or optimize renal cell polarization for more precise investigations of renal physiology and cell biology in vitro.
Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice
Authors: Courchet Virginie , Roberts Amanda J. , Meyer-Dilhet Géraldine , Del Carmine Peggy , Lewis Tommy L. , Polleux Franck , Courchet Julien
Published: October 2018

Recently, numerous rare de novo mutations have been identified in patients diagnosed with autism spectrum disorders (ASD). However, despite the predicted loss-of-function nature of some of these de novo mutations, the affected individuals are heterozygous carriers, which would suggest that most of these candidate genes are haploinsufficient and/or lead to expression of dominant-negative forms of the protein. Here, we tested this hypothesis with the candidate ASD gene Nuak1 that we previously identified for its role in the development of cortical connectivity. We report that Nuak1 is haploinsufficient in mice with regard to its function in cortical development. Furthermore Nuak1+/− mice show a combination of abnormal behavioral traits ranging from defective spatial memory consolidation, defects in social novelty (but not social preference) and abnormal sensorimotor gating. Overall, our results demonstrate that Nuak1 haploinsufficiency leads to defects in the development of cortical connectivity and a complex array of behavorial deficits.
Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation
Authors: Liang Huiyi , Peng Bo , Dong Cong , Liu Lixin , Mao Jiaji , Wei Song , Wang Xinlu , Xu Hanshi , Shen Jun , Mao Hai-Quan , Gao Xiaohu , Leong Kam W. , Chen Yongming
Published: October 2018

Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.
Cancer exosomes induce tumor innervation
Authors: Madeo Marianna , Colbert Paul L. , Vermeer Daniel W. , Lucido Christopher T. , Cain Jacob T. , Vichaya Elisabeth G. , Grossberg Aaron J. , Muirhead DesiRae , Rickel Alex P. , Hong Zhongkui , Zhao Jing , Weimer Jill M. , Spanos William C. , Lee John H. , Dantzer Robert , Vermeer Paola D.
Published: October 2018

Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth. Using a cancer mouse model, we show that tumors compromised in exosome release are less innervated than controls. Moreover, in vivo pharmacological blockade of exosome release similarly attenuates tumor innervation. We characterize these nerves as sensory in nature and demonstrate that axonogenesis is potentiated by the exosome-packaged axonal guidance molecule, EphrinB1. These findings indicate that tumor released exosomes induce tumor innervation and exosomes containing EphrinB1 potentiate this activity.
Human breast tumor-infiltrating CD8+ T cells retain polyfunctionality despite PD-1 expression
Authors: Egelston Colt A. , Avalos Christian , Tu Travis Y. , Simons Diana L. , Jimenez Grecia , Jung Jae Y. , Melstrom Laleh , Margolin Kim , Yim John H. , Kruper Laura , Mortimer Joanne , Lee Peter P.
Published: October 2018

Functional CD8+T cells in human tumors play a clear role in clinical prognosis and response to immunotherapeutic interventions. PD-1 expression in T cells involved in chronic infections and tumors such as melanoma often correlates with a state of T-cell exhaustion. Here we interrogate CD8+tumor-infiltrating lymphocytes (TILs) from human breast and melanoma tumors to explore their functional state. Despite expression of exhaustion hallmarks, such as PD-1 expression, human breast tumor CD8+TILs retain robust capacity for production of effector cytokines and degranulation capacity. In contrast, melanoma CD8+TILs display dramatic reduction of cytokine production and degranulation capacity. We show that CD8+TILs from human breast tumors can potently kill cancer cells via bi-specific antibodies. Our data demonstrate that CD8+TILs in human breast tumors retain polyfunctionality, despite PD-1 expression, and suggest that they may be harnessed for effective immunotherapies.
Shaping the topology of folding pathways in mechanical systems
Authors: Stern Menachem , Jayaram Viraaj , Murugan Arvind
Published: October 2018

Disordered mechanical systems, when strongly deformed, have complex configuration spaces with multiple stable states and pathways connecting them. The topology of such pathways determines which states are smoothly accessible from any part of configuration space. Controlling this topology would allow us to limit access to undesired states and select desired behaviors in metamaterials. Here, we show that the topology of such pathways, as captured by bifurcation diagrams, can be tuned using imperfections such as stiff hinges in elastic networks and creased thin sheets. We derive Linear Programming-like equations for designing desirable pathway topologies. These ideas are applied to eliminate the exponentially many ways of misfolding self-folding sheets by making some creases stiffer than others. Our approach allows robust folding by entire classes of external folding forces. Finally, we find that the bifurcation diagram makes pathways accessible only at specific folding speeds, enabling speed-dependent selection of different folded states.
Action sharpens sensory representations of expected outcomes
Authors: Yon Daniel , Gilbert Sam J. , de Lange Floris P. , Press Clare
Published: October 2018

When we produce actions we predict their likely consequences. Dominant models of action control suggest that these predictions are used to ‘cancel’ perceptual processing of expected outcomes. However, normative Bayesian models of sensory cognition developed outside of action propose that rather than being cancelled, expected sensory signals are represented with greater fidelity (sharpened). Here, we distinguished between these models in an fMRI experiment where participants executed hand actions (index vs little finger movement) while observing movements of an avatar hand. Consistent with the sharpening account, visual representations of hand movements (index vs little finger) could be read out more accurately when they were congruent with action and these decoding enhancements were accompanied by suppressed activity in voxels tuned away from, not towards, the expected stimulus. Therefore, inconsistent with dominant action control models, these data show that sensorimotor prediction sharpens expected sensory representations, facilitating veridical perception of action outcomes.
A selenium-catalysed para-amination of phenols
Authors: Yan Dingyuan , Wang Guoqiang , Xiong Feng , Sun Wei-Yin , Shi Zhuangzhi , Lu Yi , Li Shuhua , Zhao Jing
Published: October 2018

Antioxidant enzyme glutathione peroxidase (GPx) decomposes hydroperoxides by utilizing the different redox chemistry of the selenium and sulfur. Here, we report a Se-catalysed para-amination of phenols while, in contrast, the reactions with sulfur donors are stoichiometric. A catalytic amount of phenylselenyl bromide smoothly converts N-aryloxyacetamides to N-acetyl p-aminophenols. When the para position was substituted (for example, with tyrosine), the dearomatization 4,4-disubstituted cyclodienone products were obtained. A combination of experimental and computational studies was conducted and suggested the weaker Se−N bond plays a key role in the completion of the catalytic cycle. Our method extends the selenium-catalysed processes to the functionalisation of aromatic compounds. Finally, we demonstrated the mild nature of the para-amination reaction by generating an AIEgen 2-(2′-hydroxyphenyl)benzothiazole (HBT) product in a fluorogenic fashion in a PBS buffer.
Narrow bandgap oxide nanoparticles coupled with graphene for high performance mid-infrared photodetection
Authors: Yu Xuechao , Li Yangyang , Hu Xiaonan , Zhang Daliang , Tao Ye , Liu Zhixiong , He Yongmin , Haque Md. Azimul , Liu Zheng , Wu Tom , Wang Qi Jie
Published: October 2018

The pursuit of optoelectronic devices operating in the mid-infrared regime is driven by both fundamental interests and envisioned applications ranging from imaging, sensing to communications. Despite continued achievements in traditional semiconductors, notorious obstacles such as the complicated growth processes and cryogenic operation preclude the usage of infrared detectors. As an alternative path towards high-performance photodetectors, hybrid semiconductor/graphene structures have been intensively explored. However, the operation bandwidth of such photodetectors has been limited to visible and near-infrared regimes. Here we demonstrate a mid-infrared hybrid photodetector enabled by coupling graphene with a narrow bandgap semiconductor, Ti2O3 (Eg = 0.09 eV), which achieves a high responsivity of 300 A W−1 in a broadband wavelength range up to 10 µm. The obtained responsivity is about two orders of magnitude higher than that of the commercial mid-infrared photodetectors. Our work opens a route towards achieving high-performance optoelectronics operating in the mid-infrared regime.
Dopamine-dependent prefrontal reactivations explain long-term benefit of fear extinction
Authors: Gerlicher A. M. V. , Tüscher O. , Kalisch R.
Published: October 2018

Fear extinction does not prevent post-traumatic stress or have long-term therapeutic benefits in fear-related disorders unless extinction memories are easily retrieved at later encounters with the once-threatening stimulus. Previous research in rodents has pointed towards a role for spontaneous prefrontal activity occurring after extinction learning in stabilizing and consolidating extinction memories. In other memory domains spontaneous post-learning activity has been linked to dopamine. Here, we show that a neural activation pattern — evoked in the ventromedial prefrontal cortex (vmPFC) by the unexpected omission of the feared outcome during extinction learning — spontaneously reappears during postextinction rest. The number of spontaneous vmPFC pattern reactivations predicts extinction memory retrieval and vmPFC activation at test 24 h later. Critically, pharmacologically enhancing dopaminergic activity during extinction consolidation amplifies spontaneous vmPFC reactivations and correspondingly improves extinction memory retrieval at test. Hence, a spontaneous dopamine-dependent memory consolidation-based mechanism may underlie the long-term behavioral effects of fear extinction.
Tailoring near-field thermal radiation between metallo-dielectric multilayers using coupled surface plasmon polaritons
Authors: Lim Mikyung , Song Jaeman , Lee Seung S. , Lee Bong Jae
Published: October 2018

Several experiments have shown a huge enhancement in thermal radiation over the blackbody limit when two objects are separated by nanoscale gaps. Although those measurements only demonstrated enhanced radiation between homogeneous materials, theoretical studies now focus on controlling the near-field radiation by tuning surface polaritons supported in nanomaterials. Here, we experimentally demonstrate near-field thermal radiation between metallo-dielectric multilayers at nanoscale gaps. Significant enhancement in heat transfer is achieved due to the coupling of surface plasmon polaritons (SPPs) supported at multiple metal-dielectric interfaces. This enables the metallo-dielectric multilayers at a 160-nm vacuum gap to have the same heat transfer rate as that between semi-infinite metal surfaces separated by only 75 nm. We also demonstrate that near-field thermal radiation can be readily tuned by modifying the resonance condition of coupled SPPs. This study will provide a new direction for exploiting surface-polariton-mediated near-field thermal radiation between planar structures.
MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy
Authors: Liu Feng , Chen Jianxia , Wang Peng , Li Haohao , Zhou Yilong , Liu Haipeng , Liu Zhonghua , Zheng Ruijuan , Wang Lin , Yang Hua , Cui Zhenling , Wang Fei , Huang Xiaochen , Wang Jie , Sha Wei , Xiao Heping , Ge Baoxue
Published: October 2018

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches.
PEDOT:PSS-based Multilayer Bacterial-Composite Films for Bioelectronics
Authors: Zajdel Tom J. , Baruch Moshe , Méhes Gábor , Stavrinidou Eleni , Berggren Magnus , Maharbiz Michel M. , Simon Daniel T. , Ajo-Franklin Caroline M.
Published: October 2018

Microbial electrochemical systems provide an environmentally-friendly means of energy conversion between chemical and electrical forms, with applications in wastewater treatment, bioelectronics, and biosensing. However, a major challenge to further development, miniaturization, and deployment of bioelectronics and biosensors is the limited thickness of biofilms, necessitating large anodes to achieve sufficient signal-to-noise ratios. Here we demonstrate a method for embedding an electroactive bacterium, Shewanella oneidensis MR-1, inside a conductive three-dimensional poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) matrix electropolymerized on a carbon felt substrate, which we call a multilayer conductive bacterial-composite film (MCBF). By mixing the bacteria with the PEDOT:PSS precursor in a flow-through method, we maintain over 90% viability of S. oneidensis during encapsulation. Microscopic analysis of the MCBFs reveal a tightly interleaved structure of bacteria and conductive PEDOT:PSS up to 80 µm thick. Electrochemical experiments indicate S. oneidensis in MCBFs can perform both direct and riboflavin-mediated electron transfer to PEDOT:PSS. When used in bioelectrochemical reactors, the MCBFs produce 20 times more steady-state current than native biofilms grown on unmodified carbon felt. This versatile approach to control the thickness of bacterial composite films and increase their current output has immediate applications in microbial electrochemical systems, including field-deployable environmental sensing and direct integration of microorganisms into miniaturized organic electronics.
High-Ranking Geladas Protect and Comfort Others After Conflicts
Authors: Palagi Elisabetta , Leone Alessia , Demuru Elisa , Ferrari Pier Francesco
Published: October 2018

Post-conflict affiliation is a mechanism favored by natural selection to manage conflicts in animal groups thus avoiding group disruption. Triadic affiliation towards the victim can reduce the likelihood of redirection (benefits to third-parties) and protect and provide comfort to the victim by reducing its post-conflict anxiety (benefits to victims). Here, we test specific hypotheses on the potential functions of triadic affiliation inTheropithecus gelada, a primate species living in complex multi-level societies. Our results show that higher-ranking geladas provided more spontaneous triadic affiliation than lower-ranking subjects and that these contacts significantly reduced the likelihood of further aggression on the victim. Spontaneous triadic affiliation significantly reduced the victim’s anxiety (measured by scratching), although it was not biased towards kin or friends. In conclusion, triadic affiliation in geladas seems to be a strategy available to high-ranking subjects to reduce the social tension generated by a conflict. Although this interpretation is the most parsimonious one, it cannot be totally excluded that third parties could also be affected by the negative emotional state of the victim thus increasing a third party’s motivation to provide comfort. Therefore, the debate on the linkage between third-party affiliation and emotional contagion in monkeys remains to be resolved.
An interspecies barrier to tetraploid complementation and chimera formation
Authors: Yamaguchi Tomoyuki , Sato Hideyuki , Kobayashi Toshihiro , Kato-itoh Megumi , Goto Teppei , Hara Hiromasa , Mizuno Naoaki , Yanagida Ayaka , Umino Ayumi , Hamanaka Sanae , Suchy Fabian , Masaki Hideki , Ota Yasunori , Hirabayashi Masumi , Nakauchi Hiromitsu
Published: October 2018

To study development of the conceptus in xenogeneic environments, we assessed interspecies chimera formation as well as tetraploid complementation between mouse and rat. Overall contribution of donor PSC-derived cells was lower in interspecies chimeras than in intraspecies chimeras, and high donor chimerism was associated with anomalies or embryonic death. Organ to organ variation in donor chimerism was greater in interspecies chimeras than in intraspecies chimeras, suggesting species-specific affinity differences among interacting molecules necessary for organogenesis. In interspecies tetraploid complementation, embryo development was near normal until the stage of placental formation, after which no embryos survived.
Metal-Organic Frameworks as advanced moisture sorbents for energy-efficient high temperature cooling
Authors: Cui Shuqing , Qin Menghao , Marandi Afsaneh , Steggles Victoria , Wang Sujing , Feng Xiaoxiao , Nouar Farid , Serre Christian
Published: October 2018

Latent cooling load accounts for 30% of the total load of air-conditioning, and its proportion is even higher in many tropical and subtropical climates. Traditional vapour-compression air-conditioning (VCAC) has a low coefficient of performance (COP) due to the refrigeration dehumidification process, which often makes necessary a great deal of subsequent re-heating. Technologies using conventional desiccants or sorbents for indoor moisture control are even less competitive than VCAC due to their high regeneration temperature, long cycling time and bulky components. Here, we report a novel high temperature cooling system that uses porous metal-organic frameworks (MOFs) as advanced sorbents for humidity control. We directly coat MOFs on the surface of evaporator and condenser. The system has no additional components compared to a traditional VCAC. The evaporator can simultaneously remove both the sensible and latent loads of the incoming air without reducing the temperature below its dew point. The regeneration of wet MOFs is completely driven by the residual heat from the condenser. The MOF-coated heat exchangers can achieve a cooling power density of 82 W·L−1. We demonstrate that the system has a high COP, up to 7.9, and can save 36.1% of the energy required, compared to the traditional VCAC system with reheating. The amphiphilic MOFs used in the research have high water uptake, are made of low-cost raw materials and have high hydrothermal stability. They thus have the potential for being scaled up for large-scale applications in air conditioning.
ClpAP protease is a universal factor that activates the parDE toxin-antitoxin system from a broad host range RK2 plasmid
Authors: Dubiel Andrzej , Wegrzyn Katarzyna , Kupinski Adam P. , Konieczny Igor
Published: October 2018

The activity of type II toxin-antitoxin systems (TA), which are responsible for many important features of bacterial cells, is based on the differences between toxin and antitoxin stabilities. The antitoxin lability results from bacterial protease activity. Here, we investigated how particular Escherichia coli cytosolic proteases, namely, Lon, ClpAP, ClpXP, and ClpYQ, affect the stability of both the toxin and antitoxin components of the parDE system from the broad host range plasmid RK2. The results of our in vivo and in vitro experiments show that the ParD antitoxin is degraded by the ClpAP protease, and dsDNA stimulates this process. The ParE toxin is not degraded by any of these proteases and can therefore cause growth inhibition of plasmid-free cells after an unequal plasmid distribution during cell division. We also demonstrate that the ParE toxin interaction with ParD prevents antitoxin proteolysis by ClpAP; however, this interaction does not prevent the ClpAP interaction with ParD. We show that ClpAP protease homologs affect plasmid stability in other bacterial species, indicating that ClpAP is a universal activator of the parDE system and that ParD is a universal substrate for ClpAP.
Fabrication and evaluation of molecularly imprinted magnetic nanoparticles for selective recognition and magnetic separation of lysozyme in human urine
Authors: Zhang Zulei , Wang Hongmei , Wang Hailong , Wu Cuichen , Li Mengli , Li Lei
Published: October 2018

The Lyz-MMIPs displayed a uniform core–shell structure, favorable magnetic properties, good accessibility, and good stability and had a good affinity and excellent binding selectivity to Lyz.
An octanuclear Cu(ii) cluster with a bio-inspired Cu4O4 cubic fragment for efficient photocatalytic water oxidation
Authors: Lin Junqi , Liang Xiangming , Cao Xiaohu , Wei Nannan , Ding Yong
Published: October 2018

An octanuclear Cu(ii) cluster [Cu8(dpk·OH)8(OAc)4](ClO4)4 was found to be an efficient homogeneous catalyst for photocatalytic water oxidation with an oxygen yield, TON and TOF of 35.6%, 178 and 3.6 s−1, respectively.
Probing the combined additions of Ca2+ and PO43− in the stabilized ZrO2 polymorph: structural, morphological and mechanical analysis
Authors: Kalaivani S. , Anamiga V. , Kannan S.
Published: October 2018

Selective uptake of Ca2+ at c-ZrO2 lattice: additions beyond critical limit lead to β-Ca3(PO4)2 crystallization in the presence of PO43−.
Massive replica exchange Monte Carlo algorithm: a tool to access high pressure thermodynamics of hard systems
Authors: Basurto Eduardo , Haro-Pérez Catalina , Vargas Carlos A. , Odriozola Gerardo
Published: October 2018

Pressure increases with the replica index, so that the size of the circular cavity decreases. Hence, the system is ordered by the replica index. At high pressures an optimal packing is produced.
Size, dimensionality and composition effects on the Debye temperature of nanocrystals
Authors: Ma Yan-Li , Zhu Ke , Li Ming
Published: October 2018

Comparisons of model predictions with experimental results and other theoretical calculations for ΘD(D) of Au nanoparticles
The effect of electrostatic interactions on the formation of pharmaceutical eutectics
Authors: Wojnarowska Z. , Smolka W. , Zotova J. , Knapik-Kowalczuk J. , Sherif A. , Tajber L. , Paluch M.
Published: October 2018

We have investigated two anesthetic agents, lidocaine hydrochloride (LD-HCl) and prilocaine hydrochloride (PRL-HCl), as well as their unionized counterparts, to explore the effect of intermolecular interactions on the formation and thermodynamic properties of eutectic mixtures.
Carboxyl-modified colloidal crystal templates for the synthesis of three-dimensionally ordered macroporous SMMN2O5 mullite and its application in NOx-assisted soot combustion
Authors: Chen Yongjie , Du Chun , Lang Yun , Jia Liwei , Chen Rong , Shan Bin
Published: October 2018

Schematic illustration of NOx-assisted soot combustion.