bluuebunny/crossref_metadata_2025 huggingface dataset:
Sub‐ion‐scale Dynamics of the Ion Diffusion Region in the Magnetotail: MMS Observations
Authors: Zhou M. , Man H. Y. , Zhong Z. H. , Deng X. H. , Pang Y. , Huang S. Y. , Khotyaintsev Y. , Russell C. T. , Giles B.
Published: October 2019

This paper reports magnetospheric multiscale (MMS) observations of the sub‐ion‐scale dynamics within the ion diffusion region (IDR) in the Earth's magnetotail. MMS crossed the IDR from the southern to the northern hemisphere, at about two ion inertial length earthward of the X line with a small guide field. Electrons were anisotropic in the inflow region of the IDR and turned into isotropic within the IDR. The isotropization of the electrons was probably due to the pitch angle scattering in highly curved magnetic field lines. We suggest that the thickness of the electron isotropic region strongly depends on the horizontal distance to the X line. The out‐of‐plane current bifurcated in the IDR. It peaked at the boundaries between the inflow and outflow electrons around the separatrices. Magnetic energy conversion and dissipation predominantly occurred at the peak of the out‐of‐plane current instead of at the neutral sheet center where BL = 0. Both the energy dissipation and normal electric field EN exhibited evident asymmetry with respect to the neutral sheet. The energy dissipation was larger around the northern separatrix than around the southern separatrix. The electric field EN showed a tripolar variation across the neutral sheet, that is, a unipolar EN around the southern separatrix and a bipolar EN around the northern separatrix. The reasons and implications of these asymmetries are discussed.
On the Acceleration Mechanism of Ultrarelativistic Electrons in the Center of the Outer Radiation Belt: A Statistical Study
Authors: Zhao H. , Baker D.N. , Li X. , Malaspina D.M. , Jaynes A.N. , Kanekal S.G.
Published: October 2019

Using energetic particle and wave measurements from the Van Allen Probes, Polar Orbiting Environmental Satellites (POES), and Geostationary Operational Environmental Satellite (GOES), the acceleration mechanism of ultrarelativistic electrons (>3 MeV) in the center of the outer radiation belt is investigated statistically. A superposed epoch analysis is conducted using 19 storms, which caused flux enhancements of 1.8–7.7 MeV electrons. The evolution of electron phase space density radial profile suggests an energy‐dependent acceleration of ultrarelativistic electrons in the outer belt. Especially, for electrons with very high energies (~7 MeV), prevalent positive phase space density radial gradients support inward radial diffusion being responsible for electron acceleration in the center of the outer belt (L*~3–5) during most enhancement events in the Van Allen Probes era. We propose a two‐step acceleration process to explain the acceleration of ~7 MeV electrons in the outer belt: intense and sustained chorus waves locally energize core electron populations to ultrarelativistic energies at high L region beyond the Van Allen Probes' apogee, followed by inward radial diffusion which further energizes these populations to even higher energies. Statistical results of chorus wave activity inferred from POES precipitating electron measurements as well as core electron populations observed by the Van Allen Probes and GOES support this hypothesis.
Subtidal Water Level and Current Variability in a Bar‐Built Estuary During Cold Front Season: Barataria Bay, Gulf of Mexico
Authors: Payandeh A.R. , Justic D. , Mariotti G. , Huang H. , Sorourian S.
Published: October 2019

Subtidal water level and current variability in Barataria Bay—a microtidal bar‐built estuary within the Mississippi Delta—and its relation to local and remote wind forcings were analyzed using three different methods: (1) statistical analysis of in situ observations, (2) an analytical model with idealized wind field, and (3) a barotropic numerical model. Remote wind effects (i.e., the coastal water levels imposed by Ekman transport) are dominant at forcing currents at the bay mouth and thus control estuary‐shelf exchanges. In contrast, subtidal water level variability, which ranges from 0.35 m at the bay mouth to 0.55 m at the bay head, is mainly associated with local wind effects, especially at the head of the bay. This occurs because the local wind‐induced water level tilting within the bay is larger than the coastal sea level pumping, i.e., the spatially uniform variations in water levels forced by remote winds. This result contrasts with (1) most coastal plain, fjord, and tectonic estuaries and (2) with other bar‐built estuaries in the region, in which remote wind effects dominate water level variability within the estuary. These differences are due to geomorphological features unique to Barataria Bay, such as its limited estuarine‐shelf connectivity and its orientation relative to local shoreline.
Methane Production Pathway Regulated Proximally by Substrate Availability and Distally by Temperature in a High‐Latitude Mire Complex
Authors: Chang Kuang‐Yu , Riley William J. , Brodie Eoin L. , McCalley Carmody K. , Crill Patrick M. , Grant Robert F.
Published: October 2019

Projected 21st century changes in high‐latitude climate are expected to have significant impacts on permafrost thaw, which could cause substantial increases in emissions to the atmosphere of carbon dioxide (CO2) and methane (CH4, which has a global warming potential 28 times larger than CO2 over a 100‐year horizon). However, predicted CH4 emission rates are very uncertain due to difficulties in modeling complex interactions among hydrological, thermal, biogeochemical, and plant processes. Methanogenic production pathways (i.e., acetoclastic [AM] and hydrogenotrophic [HM]) and the magnitude of CH4 emissions may both change as permafrost thaws, but a mechanistic analysis of controls on such shifts in CH4 dynamics is lacking. In this study, we reproduced observed shifts in CH4 emissions and production pathways with a comprehensive biogeochemical model (ecosys) at the Stordalen Mire in subarctic Sweden. Our results demonstrate that soil temperature changes differently affect AM and HM substrate availability, which regulates magnitudes of AM, HM, and thereby net CH4 emissions. We predict very large landscape‐scale, vertical, and temporal variations in the modeled HM fraction, highlighting that measurement strategies for metrics that compare CH4 production pathways could benefit from model informed scale of temporal and spatial variance. Finally, our findings suggest that the warming and wetting trends projected in northern peatlands could enhance peatland AM fraction and CH4 emissions even without further permafrost degradation.
Detecting Changes in River Flow Caused by Wildfires, Storms, Urbanization, Regulation, and Climate Across Sweden
Authors: Arheimer Berit , Lindström Göran
Published: October 2019

Changes in river flow may appear from shifts in land cover, constructions in the river channel, and climatic change, but currently there is a lack of understanding of the relative importance of these drivers. Therefore, we collected gauged river flow time series from 1961 to 2018 from across Sweden for 34 disturbed catchments to quantify how the various types of disturbances have affected river flow. We used trend analysis and the differences in observations versus hydrological modeling to explore the effects on river flow from (1) land cover changes from wildfires, storms, and urbanization; (2) dam constructions with regulations for hydropower production; and (3) climate‐change impact in otherwise undisturbed catchments. A mini model ensemble, consisting of three versions of the S‐HYPE model, was used, and the three models gave similar results. We searched for changes in annual and daily stream flow, seasonal flow regime, and flow duration curves. The results show that regulation of river flow has the largest impact, reducing spring floods with up to 100% and increasing winter flow by several orders of magnitude, with substantial effects transmitted far downstream. Climate changed the total river flow up to 20%. Tree removal by wildfires and storms has minor impacts at medium and large scales. Urbanization, on the contrary, showed a 20% increase in high flows also at medium scales. This study emphasizes the benefits of combining observed time series with numerical modeling to exclude the effect of varying weather conditions, when quantifying the effects of various drivers on long‐term streamflow shifts.
Landscape Water Storage and Subsurface Correlation From Satellite Surface Soil Moisture and Precipitation Observations
Authors: Short Gianotti Daniel J. , Salvucci Guido D. , Akbar Ruzbeh , McColl Kaighin A. , Cuenca Richard , Entekhabi Dara
Published: October 2019

Surface soil moisture measurements are typically correlated to some degree with changes in subsurface soil moisture. We calculate a hydrologic length scale, λ, which represents (1) the mean‐state estimator of total column water changes from surface observations, (2) an e‐folding length scale for subsurface soil moisture profile covariance fall‐off, and (3) the best second‐moment mass‐conserving surface layer thickness for a simple bucket model, defined by the data streams of satellite soil moisture and precipitation retrievals. Calculations are simple, based on three variables: the autocorrelation and variance of surface soil moisture and the variance of the net flux into the column (precipitation minus estimated losses), which can be estimated directly from the soil moisture and precipitation time series. We develop a method to calculate the lag‐one autocorrelation for irregularly observed time series and show global surface soil moisture autocorrelation. λ is driven in part by local hydroclimate conditions and is generally larger than the 50‐mm nominal radiometric length scale for the soil moisture retrievals, suggesting broad subsurface correlation due to moisture drainage. In all but the most arid regions, radiometric soil moisture retrievals provide more information about ecosystem‐relevant water fluxes than satellite radiometers can explicitly “see”; lower‐frequency radiometers are expected to provide still more statistical information about subsurface water dynamics.
River Water‐Quality Concentration and Flux Estimation Can be Improved by Accounting for Serial Correlation Through an Autoregressive Model
Authors: Zhang Qian , Hirsch Robert M.
Published: October 2019

Accurate quantification of riverine water‐quality concentration and flux is challenging because monitoring programs typically collect concentration data at lower frequencies than discharge data. Statistical methods are often used to estimate concentration and flux on days without observations. One recently developed approach is the Weighted Regressions on Time, Discharge, and Season (WRTDS), which has been shown to provide among the most accurate estimates compared to other common methods. The main objective of this work was to improve WRTDS estimation by accounting for the autocorrelation structure of model residuals using the first‐order autoregressive model (AR1). This modified approach, called WRTDS‐Kalman Filter (WRTDS‐K), was compared with WRTDS for six constituents including nitrate‐plus‐nitrite (NOx), total phosphorus, total Kjeldahl nitrogen, soluble reactive phosphorus, suspended sediment, and chloride. Near‐daily concentration records at nine sites were used to generate subsets through Monte Carlo sampling for five different sampling scenarios. Results show that WRTDS‐K provided generally better daily estimates of concentration and flux than WRTDS under these sampling scenarios for all constituents, especially NOx. The degree of improvement is strongly affected by the underlying sampling scenario, with WRTDS‐K gaining more advantage when more samples are available, and hence more residuals can be exploited. The performance of WRTDS‐K depends on the AR1 coefficient (ρ) and that relationship varies with constituents and sampling scenarios. These results provided recommendations on the optimal ρ for each constituent and sampling scenario. Overall, WRTDS‐K has the potential for broad applications to monitoring records elsewhere, as demonstrated by a pilot application to Chesapeake Bay tributaries.
A Framework for Global Multicategory and Multiscalar Drought Characterization Accounting for Snow Processes
Authors: Zhang Baoqing , Xia Youlong , Huning Laurie S. , Wei Jiahua , Wang Guangqian , AghaKouchak Amir
Published: October 2019

Drought indices do not always provide the most relevant information for water resources management as most of them neglect the role of snow in the land surface water balance. In this study, a physically based drought index, the Standardized Moisture Anomaly Index (SZI), was modified and improved by incorporating the effects of snow dynamics for drought characterization at multiple time scales. The new version of the SZI, called SZIsnow, includes snow in both the water supply and demand in drought characterization by using the water‐energy budgets from the Global Land Data Assimilation Systems product. We compared and evaluated the performance of SZIsnow and SZI in drought identification globally across various time scales using observed multicategory drought evidences from several sources. Results show that the SZIsnow agrees better with the observed changes in hydrological and agricultural droughts than the SZI, particularly over basins with high snow accumulation. Furthermore, the SZIsnow is more consistent with the residual water‐energy ratio than the SZI over snow‐influenced regions. Overall, the SZIsnow can be either a complement or an improvement over the SZI for identifying, monitoring, and characterizing hydrological and agricultural droughts at various scales (e.g., 1–48 months) over high‐latitude and high‐elevation regions that receive snow.
Effects of Pore‐Scale Heterogeneity on Macroscopic NAPL Dissolution Efficiency: A Two‐Scale Numerical Simulation Study
Authors: Aminnaji Morteza , Rabbani Arash , J. Niasar Vahid , Babaei Masoud
Published: October 2019

Interphase mass transfer or dissolution coefficient of nonaqueous phase liquids (NAPL) is an important parameter in predicting the transport of contaminant species in porous media. While the literature offers valuable insights into the dependence of this coefficient on different parameters at the continuum scale (e.g., contaminant saturation and Darcy velocity), effects of pore‐scale heterogeneity on macroscopic dissolution coefficient have received little attention. In this work a three‐dimensional pore‐scale model is developed to simulate interphase mass transfer over different synthetic pore network structures with various pore radii correlation lengths. The pore network modeling simulates dissolution of immobile NAPL into water (single phase) through diffusive throats for the water‐NAPL interface. The impacts of pore network spatially correlated heterogeneities, NAPL saturation/distribution, and aqueous phase velocity on NAPL mass transfer coefficient and water‐NAPL interfacial surface area are studied. These macroscopic properties are then employed in two‐dimensional continuum‐scale domains formed by concatenating 20 by 20 pore networks in x and y directions. The results highlight the impact of pore‐scale heterogeneity on the distribution of NAPL and subsequently on the dissolution rate (i.e., dissolution coefficient). An uncorrelated distribution of pore radii consistently leads to higher NAPL dissolution coefficient than spatially correlated heterogeneity. The results of continuum modeling show that NAPL dissolution rates are only different between domains formed by correlated and uncorrelated pore networks at very high flow rates and Darcy velocities. However, for typical values of Darcy velocity in groundwater systems, variation in mass transfer coefficient due to pore‐scale heterogeneity is minimal for efficient mass removal.
Methylation determines the extracellular calcium sensitivity of the leak channel NALCN in hippocampal dentate granule cells
Authors: Lee Seul-Yi , Vuong Tuan Anh , Wen Xianlan , Jeong Hyeon-Ju , So Hyun-Kyung , Kwon Ilmin , Kang Jong-Sun , Cho Hana
Published: October 2019

The sodium leak channel NALCN is a key player in establishing the resting membrane potential (RMP) in neurons and transduces changes in extracellular Ca2+concentration ([Ca2+]e) into increased neuronal excitability as the downstream effector of calcium-sensing receptor (CaSR). Gain-of-function mutations in the human NALCN gene cause encephalopathy and severe intellectual disability. Thus, understanding the regulatory mechanisms of NALCN is important for both basic and translational research. This study reveals a novel mechanism for NALCN regulation by arginine methylation. Hippocampal dentate granule cells in protein arginine methyltransferase 7 (PRMT7)-deficient mice display a depolarization of the RMP, decreased threshold currents, and increased excitability compared to wild-type neurons. Electrophysiological studies combined with molecular analysis indicate that enhanced NALCN activities contribute to hyperexcitability in PRMT7−/− neurons. PRMT7 depletion in HEK293T cells increases NALCN activity by shifting the dose-response curve of NALCN inhibition by [Ca2+]ewithout affecting NALCN protein levels. In vitro methylation studies show that PRMT7 methylates a highly conserved Arg1653 of the NALCN gene located in the carboxy-terminal region that is implicated in CaSR-mediated regulation. A kinase-specific phosphorylation site prediction program shows that the adjacent Ser1652 is a potential phosphorylation site. Consistently, our data from site-specific mutants and PKC inhibitors suggest that Arg1653 methylation might modulate Ser1652 phosphorylation mediated by CaSR/PKC-delta, leading to [Ca2+]e-mediated NALCN suppression. Collectively, these data suggest that PRMT7 deficiency decreases NALCN methylation at Arg1653, which, in turn, decreases CaSR/PKC-mediated Ser1652 phosphorylation, lifting NALCN inhibition, thereby enhancing neuronal excitability. Thus, PRMT7-mediated NALCN inhibition provides a potential target for the development of therapeutic tools for neurological diseases.
Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma
Authors: Song Hang , Ma Ji , Bian Zhixuan , Chen Shuhua , Zhu Jiabei , Wang Jing , Huang Nan , Yin Minzhi , Sun Fenyong , Xu Min , Pan Qiuhui
Published: October 2019

O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors. However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed. Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues. Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins. Interestingly, 41 proteins were modified by both O-GlcNAcylation and phosphorylation. These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization. In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1. Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro. Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.
YAP integrates the regulatory Snail/HNF4α circuitry controlling epithelial/hepatocyte differentiation
Authors: Noce Valeria , Battistelli Cecilia , Cozzolino Angela Maria , Consalvi Veronica , Cicchini Carla , Strippoli Raffaele , Tripodi Marco , Marchetti Alessandra , Amicone Laura
Published: October 2019

Yes-associated protein (YAP) is a transcriptional co-factor involved in many cell processes, including development, proliferation, stemness, differentiation, and tumorigenesis. It has been described as a sensor of mechanical and biochemical stimuli that enables cells to integrate environmental signals. Although in the liver the correlation between extracellular matrix elasticity (greatly increased in the most of chronic hepatic diseases), differentiation/functional state of parenchymal cells and subcellular localization/activation of YAP has been previously reported, its role as regulator of the hepatocyte differentiation remains to be clarified. The aim of this study was to evaluate the role of YAP in the regulation of epithelial/hepatocyte differentiation and to clarify how a transducer of general stimuli can integrate tissue-specific molecular mechanisms determining specific cell outcomes. By means of YAP silencing and overexpression we demonstrated that YAP has a functional role in the repression of epithelial/hepatocyte differentiation by inversely modulating the expression of Snail (master regulator of the epithelial-to-mesenchymal transition and liver stemness) and HNF4α (master regulator of hepatocyte differentiation) at transcriptional level, through the direct occupancy of their promoters. Furthermore, we found that Snail, in turn, is able to positively control YAP expression influencing protein level and subcellular localization and that HNF4α stably represses YAP transcription in differentiated hepatocytes both in cell culture and in adult liver. Overall, our data indicate YAP as a new member of the HNF4/Snail epistatic molecular circuitry previously demonstrated to control liver cell state. In this model, the dynamic balance between three main transcriptional regulators, that are able to control reciprocally their expression/activity, is responsible for the induction/maintenance of different liver cell differentiation states and its modulation could be the aim of therapeutic protocols for several chronic liver diseases.
The crosstalk between autophagy and apoptosis was mediated by phosphorylation of Bcl-2 and beclin1 in benzene-induced hematotoxicity
Authors: Chen Yujiao , Zhang Wei , Guo Xiaoli , Ren Jing , Gao Ai
Published: October 2019

Increasing evidence suggested that benzene exposure resulted in different types of hematological cancer. Both autophagy and apoptosis were reported to play vital roles in benzene toxicity, but the relationship between autophagy and apoptosis remain unclear in benzene-induced hematotoxicity. In this study, the toxic effect of benzene on autophagy and apoptosis in benzene-exposed workers and in vitro were verified. Results showed that benzene metabolite (1, 4-benzoquinone, 1, 4-BQ) dose-dependently induced autophagy and apoptosis via enhancing phosphorylation of Bcl-2 and beclin1. Finally, we also found that the elevated ROS was in line with enhancing the phosphorylation of Bcl-2 and beclin1 which contributed to 1, 4-BQ-induced autophagy and apoptosis. Taken together, this study for the first time found that the effect of 1, 4-BQ on the crosstalk between autophagy and apoptosis were modulated by the ROS generation via enhancing phosphorylation of Bcl-2(Ser70) and phosphorylation of beclin1(Thr119), which offered a novel insight into underlying molecular mechanisms of benzene-induced hematotoxicity, and specifically how the crosstalk between autophagy and apoptosis was involved in benzene toxicity. This work provided novel evidence for the toxic effects and risk assessment of benzene.
A new family with a homozygous nonsense variant in NTHL1 further delineated the clinical phenotype of NTHL1-associated polyposis
Authors: Altaraihi Mays , Gerdes Anne-Marie , Wadt Karin
Published: October 2019

A new family with NTHL1-associated polyposis (NAP) is described, involving a 58-year-old male affected with >100 colorectal polyps and a 55-year-old female sibling with nine colorectal polyps. The female was also diagnosed with a thyroid adenoma at age 40. Significantly, no malignant neoplasms have been detected in this family, which is important to further delineate the clinical phenotype related to NAP. A review of previously reported obligate heterozygous carriers of NTHL1 variants showed two patients affected with neoplasms at <55 years of age, generating a study to outline the phenotypic spectrum in patients with heterozygous pathogenic NTHL1 variants relevant.
Publisher Correction: Ecological control of nitrite in the upper ocean
Authors: Zakem Emily J. , Al-Haj Alia , Church Matthew J. , van Dijken Gert L. , Dutkiewicz Stephanie , Foster Sarah Q. , Fulweiler Robinson W. , Mills Matthew M. , Follows Michael J.
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
N6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis
Authors: Kuppers Daniel A. , Arora Sonali , Lim Yiting , Lim Andrea R. , Carter Lucas M. , Corrin Philip D. , Plaisier Christopher L. , Basom Ryan , Delrow Jeffrey J. , Wang Shiyan , Hansen He Housheng , Torok-Storb Beverly , Hsieh Andrew C. , Paddison Patrick J.
Published: October 2019

Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators of erythropoiesis, we utilize a functional genomic screen for genes affecting expression of the erythroid marker CD235a/GYPA. Among validating hits are genes coding for the N6-methyladenosine (m6A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m6A MTase activity promotes erythroid gene expression programs through selective translation of ~300 m6A marked mRNAs, including those coding for SETD histone methyltransferases, ribosomal components, and polyA RNA binding proteins. Remarkably, loss of m6A marks results in dramatic loss of H3K4me3 marks across key erythroid-specific KLF1 transcriptional targets (e.g., Heme biosynthesis genes). Further, each m6A MTase subunit and a subset of their mRNAs targets are required for human erythroid specification in primary bone-marrow derived progenitors. Thus, m6A mRNA marks promote the translation of a network of genes required for human erythropoiesis.
Spontaneous ssDNA stretching on graphene and hexagonal boron nitride in plane heterostructures
Authors: Luan Binquan , Zhou Ruhong
Published: October 2019

Single-stranded DNA (ssDNA) molecules in solution typically form coiled structures, therefore stretching ssDNA is extremely crucial before applying any nanotechnology for ssDNA analysis. Recent advances in material fabrication enable the deployment of nanochannels to manipulate, stretch, sort and map double-stranded DNA (dsDNA) molecules, however nanochannels fail to stretch ssDNA molecules due to the ultra-short persistence length and the potential nonspecific-interaction-induced clogging. Given the significance of ssDNA stretching in genome analysis, here we report an ssDNA stretching platform: two dimensional in-plane heterostructure comprising graphene and hexagonal boron nitride (h-BN), and show that ssDNA can be stretched on a h-BN nanostripe sandwiched between two adjacent graphene domains (“nanochannel”). We further show that with a biasing voltage the stretched ssDNA can be electrophoretically transported along the “nanochannel”, allowing easy controls/manipulations. When being conveniently integrated with existing atomic resolution sensors, the heterostructure platform paves the way for sequencing DNA on a planar surface.
Allosteric activation of an ion channel triggered by modification of mechanosensitive nano-pockets
Authors: Kapsalis Charalampos , Wang Bolin , El Mkami Hassane , Pitt Samantha J. , Schnell Jason R. , Smith Terry K. , Lippiat Jonathan D. , Bode Bela E. , Pliotas Christos
Published: October 2019

Lipid availability within transmembrane nano-pockets of ion channels is linked with mechanosensation. However, the effect of hindering lipid-chain penetration into nano-pockets on channel structure has not been demonstrated. Here we identify nano-pockets on the large conductance mechanosensitive channel MscL, the high-pressure threshold channel. We restrict lipid-chain access to the nano-pockets by mutagenesis and sulfhydryl modification, and monitor channel conformation by PELDOR/DEER spectroscopy. For a single site located at the entrance of the nano-pockets and distal to the channel pore we generate an allosteric response in the absence of tension. Single-channel recordings reveal a significant decrease in the pressure activation threshold of the modified channel and a sub-conducting state in the absence of applied tension. Threshold is restored to wild-type levels upon reduction of the sulfhydryl modification. The modification associated with the conformational change restricts lipid access to the nano-pocket, interrupting the contact between the membrane and the channel that mediates mechanosensitivity.
Meiotic crossovers characterized by haplotype-specific chromosome painting in maize
Authors: do Vale Martins Lívia , Yu Fan , Zhao Hainan , Dennison Tesia , Lauter Nick , Wang Haiyan , Deng Zuhu , Thompson Addie , Semrau Kassandra , Rouillard Jean-Marie , Birchler James A. , Jiang Jiming
Published: October 2019

Meiotic crossovers (COs) play a critical role in generating genetic variation and maintaining faithful segregation of homologous chromosomes during meiosis. We develop a haplotype-specific fluorescence in situ hybridization (FISH) technique that allows visualization of COs directly on metaphase chromosomes. Oligonucleotides (oligos) specific to chromosome 10 of maize inbreds B73 and Mo17, respectively, are synthesized and labeled as FISH probes. The parental and recombinant chromosome 10 in B73 x Mo17 F1 hybrids and F2 progenies can be unambiguously identified by haplotype-specific FISH. Analysis of 58 F2 plants reveals lack of COs in the entire proximal half of chromosome 10. However, we detect COs located in regions very close to the centromere in recombinant inbred lines from an intermated B73 x Mo17 population, suggesting effective accumulation of COs in recombination-suppressed chromosomal regions through intermating and the potential to generate favorable allelic combinations of genes residing in these regions.
Oligomeric state of the ZIKV E protein defines protective immune responses
Authors: Metz Stefan W. , Thomas Ashlie , Brackbill Alex , Forsberg John , Miley Michael J. , Lopez Cesar A. , Lazear Helen M. , Tian Shaomin , de Silva Aravinda M.
Published: October 2019

The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines.
Upper limb activity of twenty myoelectric prosthesis users and twenty healthy anatomically intact adults
Authors: Chadwell Alix , Kenney Laurence , Granat Malcolm , Thies Sibylle , Galpin Adam , Head John
Published: October 2019

The upper limb activity of twenty unilateral upper limb myoelectric prosthesis users and twenty anatomically intact adults were recorded over a 7-day period using two wrist worn accelerometers (Actigraph, LLC). This dataset reflects the real-world activities of the participants during their normal day-to-day routines. Participants included students, working adults, and retirees recruited from across the United Kingdom. This dataset offers a potential wealth of knowledge into a poorly understood cohort. The raw unprocessed data files and the activity count data exported from the Actilife software are provided. We also provide a non-wear algorithm developed for the removal of prosthesis non-wear periods and resulting activity count data corresponding to prothesis wear periods. Finally, we have included the transposed activity diaries provided by the participants. Analysis to date has primarily involved assessment of the symmetry of upper limb activity, however, there is potential to undertake additional analysis such as understanding the differences in the way a prosthesis is used compared to an anatomical arm.
Characterization of coral-associated microbial aggregates (CAMAs) within tissues of the coral Acropora hyacinthus
Authors: Wada Naohisa , Ishimochi Mizuki , Matsui Taeko , Pollock F. Joseph , Tang Sen-Lin , Ainsworth Tracy D. , Willis Bette L. , Mano Nobuhiro , Bourne David G.
Published: October 2019

Bacterial diversity associated with corals has been studied extensively, however, localization of bacterial associations within the holobiont is still poorly resolved. Here we provide novel insight into the localization of coral-associated microbial aggregates (CAMAs) within tissues of the coralAcropora hyacinthus.In total, 318 and 308 CAMAs were characterized via histological and fluorescentin situhybridization (FISH) approaches respectively, and shown to be distributed extensively throughout coral tissues collected from five sites in Japan and Australia. The densities of CAMAs within the tissues were negatively correlated with the distance from the coastline (i.e. lowest densities at offshore sites). CAMAs were randomly distributed across the six coral tissue regions investigated. Within each CAMA, bacterial cells had similar morphological characteristics, but bacterial morphologies varied among CAMAs, with at least five distinct types identified. Identifying the location of microorganisms associated with the coral host is a prerequisite for understanding their contributions to fitness. Localization of tissue-specific communities housed within CAMAs is particularly important, as these communities are potentially important contributors to vital metabolic functions of the holobiont.
Induced pluripotent stem cells-derived neurons from patients with Friedreich ataxia exhibit differential sensitivity to resveratrol and nicotinamide
Authors: Georges Pauline , Boza-Moran Maria-Gabriela , Gide Jacqueline , Pêche Georges Arielle , Forêt Benjamin , Bayot Aurélien , Rustin Pierre , Peschanski Marc , Martinat Cécile , Aubry Laetitia
Published: October 2019

Translation of pharmacological results from in vitro cell testing to clinical trials is challenging. One of the causes that may underlie these discrepant results is the lack of the phenotypic or species-specific relevance of the tested cells; today, this lack of relevance may be reduced by relying on cells differentiated from human pluripotent stem cells. To analyse the benefits provided by this approach, we chose to focus on Friedreich ataxia, a neurodegenerative condition for which the recent clinical testing of two compounds was not successful. These compounds, namely, resveratrol and nicotinamide, were selected because they had been shown to stimulate the expression of frataxin in fibroblasts and lymphoblastoid cells. Our results indicated that these compounds failed to do so in iPSC-derived neurons generated from two patients with Friedreich ataxia. By comparing the effects of both molecules on different cell types that may be considered to be non-relevant for the disease, such as fibroblasts, or more relevant to the disease, such as neurons differentiated from iPSCs, a differential response was observed; this response suggests the importance of developing more predictive in vitro systems for drug discovery. Our results demonstrate the value of utilizing human iPSCs early in drug discovery to improve translational predictability.
Quantitative biparametric analysis of hybrid 18F-FET PET/MR-neuroimaging for differentiation between treatment response and recurrent glioma
Authors: Lohmeier Johannes , Bohner Georg , Siebert Eberhard , Brenner Winfried , Hamm Bernd , Makowski Marcus R.
Published: October 2019

We investigated the diagnostic potential of simultaneous 18F-FET PET/MR-imaging for differentiation between recurrent glioma and post-treatment related effects (PTRE) using quantitative volumetric (3D-VOI) lesion analysis. In this retrospective study, a total of 42 patients including 32 patients with histologically proven glioma relapse and 10 patients with PTRE (histopathologic follow-up, n = 4, serial imaging follow-up, n = 6) were evaluated regarding recurrence. PET/MR-imaging was semi-automatically analysed based on FET tracer uptake using conservative SUV thresholding (isocontour 80%) with emphasis on the metabolically most active regions. Mean (relative) apparent diffusion coefficient (ADCmean, rADCmean), standardised-uptake-value (SUV) including target-to-background (TBR) ratio were determined. Glioma relapse presented higher ADCmean (MD ± SE, 284 ± 91, p = 0.003) and TBRmax (MD ± SE, 1.10 ± 0.45, p = 0.02) values than treatment-related changes. Both ADCmean (AUC ± SE = 0.82 ± 0.07, p-value < 0.001) and TBRmax (AUC ± SE = 0.81 ± 0.08, p-value < 0.001) achieved reliable diagnostic performance in differentiating glioma recurrence from PTRE. Bivariate analysis based on a combination of ADCmean and TBRmax demonstrated highest diagnostic accuracy (AUC ± SE = 0.90 ± 0.05, p-value < 0.001), improving clinical (false negative and false positive) classification. In conclusion, biparametric analysis using DWI and FET PET, both providing distinct information regarding the underlying pathophysiology, presented best diagnostic accuracy and clinical benefit in differentiating recurrent glioma from treatment-related changes.
Skew informations from an operational view via resource theory of asymmetry
Authors: Takagi Ryuji
Published: October 2019

The Wigner-Yanase skew information was proposed to quantify the information contained in quantum states with respect to a conserved additive quantity, and it was later extended to the Wigner-Yanase-Dyson skew informations. Recently, the Wigner-Yanase-Dyson skew informations have been recognized as valid resource measures for the resource theory of asymmetry, and their properties have been investigated from a resource-theoretic perspective. The Wigner-Yanse-Dyson skew informations have been further generalized to a class called metric-adjusted skew informations, and this general family of skew informations have also been found to be valid asymmetry monotones. Here, we analyze this general family of the skew informations from an operational point of view by utilizing the fact that they are valid asymmetry resource monotones. We show that such an approach allows for clear physical meanings as well as simple proofs of some of the basic properties of the skew informations. Notably, we constructively prove that any type of skew information cannot be superadditive, where the violation of the superadditivity had been only known for a specific class of skew informations with numerical counterexamples. We further show a weaker version of superadditivity relation applicable to the general class of the skew informations, which proves a conjecture made for the Wigner-Yanase skew information as a special case. We finally discuss an application of our results for a situation where quantum clocks are distributed to multiple parties.
Simulated microgravity with floating environment promotes migration of non-small cell lung cancers
Authors: Ahn Chi Bum , Lee Ji-Hyun , Han Dae Geun , Kang Hyun-Wook , Lee Sung-Ho , Lee Jae-Ik , Son Kuk Hui , Lee Jin Woo
Published: October 2019

A migration of cancer is one of the most important factors affecting cancer therapy. Particularly, a cancer migration study in a microgravity environment has gained attention as a tool for developing cancer therapy. In this study, we evaluated the proliferation and migration of two types (adenocarcinoma A549, squamous cell carcinoma H1703) of non-small cell lung cancers (NSCLC) in a floating environment with microgravity. When we measured proliferation of two NSCLCs in the microgravity (MG) and ground-gravity (CONT), although initial cell adhesion in MG was low, a normalized proliferation rate of A549 in MG was higher than that in CONT. Wound healing results of A549 and H1703 showed rapid recovery in MG; particularly, the migration rate of A549 was faster than that of H1703 both the normal and low proliferating conditions. Gene expression results showed that the microgravity accelerated the migration of NSCLC. Both A549 and H1703 in MG highly expressed the migration-related genes MMP-2, MMP-9, TIMP-1, and TIMP-2 compared to CONT at 24 h. Furthermore, analysis of MMP-2 protein synthesis revealed weaker metastatic performance of H1703 than that of A549. Therefore, the simulated microgravity based cancer culture environment will be a potential for migration and metastasis studies of lung cancers.
Ricinus communis L. fruit extract inhibits migration/invasion, induces apoptosis in breast cancer cells and arrests tumor progression in vivo
Authors: Majumder Munmi , Debnath Shibjyoti , Gajbhiye Rahul L. , Saikia Rimpi , Gogoi Bhaskarjyoti , Samanta Suman Kumar , Das Deepjyoti K. , Biswas Kaushik , Jaisankar Parasuraman , Mukhopadhyay Rupak
Published: October 2019

Medicinal plant-based therapies can be important for treatment of cancer owing to high efficiency, low cost and minimal side effects. Here, we report the anti-cancer efficacy of Ricinus communis L. fruit extract (RCFE) using estrogen positive MCF-7 and highly aggressive, triple negative MDA-MB-231 breast cancer cells. RCFE induced cytotoxicity in these cells in dose and time-dependent manner. It also demonstrated robust anti-metastatic activity as it significantly inhibited migration, adhesion, invasion and expression of matrix metalloproteinases (MMPs) 2 and 9 in both cell lines. Further, flow cytometry analysis suggested RCFE-mediated induction of apoptosis in these cells. This was supported by attenuation of anti-apoptotic Bcl-2, induction of pro-apoptotic Bax and caspase-7 expressions as well as PARP cleavage upon RCFE treatment. RCFE (0.5 mg/Kg body weight) treatment led to significant reduction in tumor volume in 4T1 syngeneic mouse model. HPLC and ESI-MS analysis of active ethyl acetate fraction of RCFE detected four compounds, Ricinine, p-Coumaric acid, Epigallocatechin and Ricinoleic acid. Individually these compounds showed cytotoxic and migration-inhibitory activities. Overall, this study for the first time demonstrates the anti-cancer efficacy of the fruit extract of common castor plant which can be proposed as a potent candidate for the treatment of breast cancer.
Nondestructive real-space imaging of energy dissipation distributions in randomly networked conductive nanomaterials
Authors: Morimoto Takahiro , Ata Seisuke , Yamada Takeo , Okazaki Toshiya
Published: October 2019

For realization the new functional materials and devices by conductive nanomaterials, how to control and realize the optimum network structures are import point for fundamental, applied and industrial science. In this manuscript, the nondestructive real-space imaging technique has been studied with the lock-in thermal scope via Joule heating caused by ac bias conditions. By this dynamical method, a few micrometer scale energy dissipations originating from local current density and resistance distributions are visualized in a few tens of minutes due to the frequency-space separation and the strong temperature damping of conductive heat components. Moreover, in the tensile test, the sample broken points were completely corresponding to the intensity images of lock-in thermography. These results indicated that the lock-in thermography is a powerful tool for inspecting the intrinsic network structures, which are difficult to observe by conventional imaging methods.
Characterisation of aptamer-anchored poly(EDMA-co-GMA) monolith for high throughput affinity binding
Authors: Acquah Caleb , Chan Yi Wei , Pan Sharadwata , Yon Lau Sie , Ongkudon Clarence M. , Guo Haobo , Danquah Michael K.
Published: October 2019

Immobilisation of aptameric ligands on solid stationary supports for effective binding of target molecules requires understanding of the relationship between aptamer-polymer interactions and the conditions governing the mass transfer of the binding process. Herein, key process parameters affecting the molecular anchoring of a thrombin-binding aptamer (TBA) onto polymethacrylate monolith pore surface, and the binding characteristics of the resulting macroporous aptasensor were investigated. Molecular dynamics (MD) simulations of the TBA-thrombin binding indicated enhanced Guanine 4 (G4) structural stability of TBA upon interaction with thrombin in an ionic environment. Fourier-transform infrared spectroscopy and thermogravimetric analyses were used to characterise the available functional groups and thermo-molecular stability of the immobilised polymer generated with Schiff-base activation and immobilisation scheme. The initial degradation temperature of the polymethacrylate stationary support increased with each step of the Schiff-base process: poly(Ethylene glycol Dimethacrylate-co-Glycidyl methacrylate) or poly(EDMA-co-GMA) [196.0 °C (±1.8)]; poly(EDMA-co-GMA)-Ethylenediamine [235.9 °C (±6.1)]; poly(EDMA-co-GMA)-Ethylenediamine-Glutaraldehyde [255.4 °C (±2.7)]; and aptamer-modified monolith [273.7 °C (±2.5)]. These initial temperature increments reflected in the associated endothermic energies were determined with differential scanning calorimetry. The aptameric ligand density obtained after immobilisation was 480 pmol/μL. Increase in pH and ionic concentration affected the surface charge distribution and the binding characteristics of the aptamer-modified disk-monoliths, resulting in the optimum binding pH and ionic concentration of 8.0 and 5 mM Mg2+, respectively. These results are critical in understanding and setting parametric constraints indispensable to develop and enhance the performance of aptasensors.
Overexpression of BZW1 is an independent poor prognosis marker and its down-regulation suppresses lung adenocarcinoma metastasis
Authors: Chiou Jean , Chang Yu-Chan , Jan Yi-Hua , Tsai Hsing-Fang , Yang Chih-Jen , Huang Ming-Shyan , Yu Yung-Luen , Hsiao Michael
Published: October 2019

The basic leucine zipper and the W2 domain-containing protein 1 (BZW1) plays a key role in the cell cycle and transcriptionally control the histone H4 gene during G1/S phase. Since cellular proliferation rates are frequently dysregulated in human cancers, we identified the characteristics of BZW1 in cancer cells and analyzed its prognostic value in lung cancer patients. By searching public databases, we found that high BZW1 expression was significantly correlated with poor survival rate in non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma. Similar trends were also shown in an array comprising NSCLC patient tissue. Knockdown of BZW1 inhibited cell metastatic ability, but did not affect the cell proliferation rate of NSCLC cells. From transcriptomics data mining, we found that coordination between BZW1 and EGFR overexpression was correlated with a worse outcome for lung cancer patients. In summary, BZW1 expression serves as an independent prognostic factor of NSCLC, especially in lung adenocarcinoma. Overexpression of BZW1 in lung cancer cells revealed a novel pathway underlying the induction of lung cancer metastasis.