bluuebunny/crossref_metadata_2025 huggingface dataset:
Das Inzidentalom der Nebenniere
Authors: Meienberg Fabian
Published: October 2020

Zusammenfassung. Dieser Artikel diskutiert anhand eines Fallbeispiels die diagnostische Aufarbeitung beim inzidentellen Nachweis einer Raumforderung der Nebenniere. In dieser Situation geht es primär darum, einen malignen oder hormonaktiven Tumor auszuschliessen. Zur Beurteilung der Dignität werden spezifische bildgebende Kriterien hinzugezogen (’imaging phenotype’). Die Evaluation hinsichtlich hormoneller Aktivität basiert neben der klinischen Beurteilung auf dem Einsatz von ausgewählten Laboruntersuchungen. Die meisten Nebennieren-Inzidentalome können schlussendlich als gutartige, Hormon-inaktive Adenome identifiziert werden. In unklaren Situation ist eine fachärztliche Beurteilung angezeigt.
Kompetenzentwicklung im bildungswissenschaftlichen Studium: Der Einfluss individueller Voraussetzungen auf die Entwicklung des bildungswissenschaftlichen Wissens angehender Lehrkräfte
Authors: Watson Christina , Stender Jana , Schaper Niclas
Published: October 2020

Zusammenfassung. Längsschnittstudien, die das bildungswissenschaftliche Wissen als Teil der professionellen Kompetenz angehender Lehrkräfte über mehr als zwei Messzeitpunkte erfassen und den Einfluss individueller Eingangsvoraussetzungen auf die Wissensentwicklung untersuchen, stellen nach wie vor ein Forschungsdesiderat dar. Bisherige Studien liefern erste Hinweise darauf, dass individuelle Eingangsvoraussetzungen wie die Abiturnote, pädagogische Vorerfahrungen und Berufswahlmotive im Zusammenhang mit der Wissensentwicklung stehen und günstige Eingangsvoraussetzungen den Entwicklungsverlauf fördern können. Bislang ist unklar, wie sich das Wissen über den gesamten Studienverlauf in den Bachelor-/Master-Strukturen entwickelt. Des Weiteren ist auch unklar, inwieweit bestimmte Eingangsvoraussetzungen langfristige Entwicklungsverläufe erklären können. In der vorliegenden Studie wurden die Daten von 276 Studierenden, dessen Wissen zu fünf Messzeitpunkten erhoben wurde, mit Hilfe latenter Wachstumskurvenmodelle ausgewertet. Die Ergebnisse bestätigten einen Zuwachs des bildungswissenschaftlichen Wissens über den gesamten Studienverlauf. Den größten Wissenszuwachs erfuhren die Studierenden in den ersten zwei Semestern ihres Bachelorstudiums und beim Übergang in das Masterstudium. Des Weiteren konnte der Einfluss von individuellen kognitiven und motivationalen Eingangsvoraussetzungen auf den Leistungszuwachs bestätigt werden. So zeigte sich, dass Studierende, die eine bessere Abiturnote aufwiesen und bereits über eine unterrichtsnahe pädagogische Vorerfahrung verfügten, höhere Wissenszuwächse im Vergleich zu ihren Kommilitoninnen und Kommilitonen erfuhren, die einen schlechteren Abiturnotendurchschnitt hatten. Ebenfalls begünstigte das Motiv „mit Kindern und Jugendlichen arbeiten zu wollen“ die Wissensentwicklung. Die Ergebnisse können insbesondere für die Beratung genutzt werden, um die Motivlagen von Studierenden zu erfassen und sie dafür sensibel zu machen, welche Motivkonstellationen für einen erfolgreichen Studienverlauf günstig erscheinen.
Sediment Layers Pinpoint Periods of Climatic Change
Authors: Kornei Katherine
Published: October 2020

Researchers studying sediment cores from the Gulf of Alaska have pinpointed when the Cordilleran Ice Sheet, now extinct, disgorged icebergs into the Pacific Ocean.
Linking Critical Zone Water Storage and Ecosystems
Authors: Bales Roger , Dietrich William
Published: October 2020

The geology and the structure of Earth’s critical zone control subsurface moisture storage potential and determine the resilience of forest and river ecosystems to drought.
Dual‐Lobe Reconnection and Horse‐Collar Auroras
Authors: Milan S. E. , Carter J. A. , Bower G. E. , Imber S. M. , Paxton L. J. , Anderson B. J. , Hairston M. R. , Hubert B.
Published: October 2020

We propose a mechanism for the formation of the horse‐collar auroral configuration during periods of strongly northward interplanetary magnetic field (IMF), invoking the action of dual‐lobe reconnection (DLR). Auroral observations are provided by the Imager for Magnetopause‐to‐Aurora Global Exploration (IMAGE) satellite and spacecraft of the Defense Meteorological Satellite Program (DMSP). We also use ionospheric flow measurements from DMSP and polar maps of field‐aligned currents (FACs) derived from the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE). Sunward convection is observed within the dark polar cap, with antisunward flows within the horse‐collar auroral region, together with the NBZ FAC distribution expected to be associated with DLR. We suggest that newly closed flux is transported antisunward and to dawn and dusk within the reverse lobe cell convection pattern associated with DLR, causing the polar cap to acquire a teardrop shape and weak auroras to form at high latitudes. Horse‐collar auroras are a common feature of the quiet magnetosphere, and this model provides a first understanding of their formation, resolving several outstanding questions regarding the nature of DLR and the magnetospheric structure and dynamics during northward IMF. The model can also provide insights into the trapping of solar wind plasma by the magnetosphere and the formation of a low‐latitude boundary layer and cold, dense plasma sheet. We speculate that prolonged DLR could lead to a fully closed magnetosphere, with the formation of horse‐collar auroras being an intermediate step.
Influence of Effective Stress and Pore Fluid Pressure on Fault Strength and Slip Localization in Carbonate Slip Zones
Authors: Rempe Marieke , Di Toro Giulio , Mitchell Thomas M. , Smith Steven A. F. , Hirose Takehiro , Renner Joerg
Published: October 2020

The presence of pressurized fluids influences the mechanical behavior of faults. To test the roles of normal stress and fluid pressure on shear strength and localization behavior of calcite gouges, we conducted a series of rotary‐shear experiments with pore fluid pressures up to 10.5 MPa and difference between normal stress and fluid pressure up to 11.2 MPa. Calcite gouges were sheared for displacements of 0.3 m to several meters at slip rates of 1 mm/s and 1 m/s. Drainage conditions in experiments were constrained from estimates of the hydraulic diffusivity. Gouges were found to be drained at 1 mm/s, but possibly partially undrained during sliding at 1 m/s. Shear strength obeys an effective‐stress law with an effective‐stress coefficient close to unity with a friction coefficient of ~0.7 that decreases to 0.19 due to dynamic weakening. The degree of comminution and slip localization constrained from experimental microstructures depends on the effective normal stress. Slip localization in calcite gouges does not occur at low effective normal stress. The presence of pore fluids lowers the shear strength of gouges sheared at 1 mm/s and causes an accelerated weakening at 1 m/s compared to dry gouges, possibly due to enhanced subcritical crack growth and intergranular lubrication. Thermal pressurization occurs only after dynamic weakening when friction is generally low and relatively independent of normal stress and therefore unaffected by thermal pressurization. The experimental results are consistent with the view that the presence of pressurized fluid in carbonate‐bearing faults can facilitate earthquake nucleation.
Data‐Driven Optimization of Seismicity Models Using Diverse Data Sets: Generation, Evaluation, and Ranking Using Inlabru
Authors: Bayliss Kirsty , Naylor Mark , Illian Janine , Main Ian G.
Published: October 2020

Recent developments in earthquake forecasting models have demonstrated the need for a robust method for identifying which model components are most beneficial to understanding spatial patterns of seismicity. Borrowing from ecology, we use Log‐Gaussian Cox process models to describe the spatially varying intensity of earthquake locations. These models are constructed using elements which may influence earthquake locations, including the underlying fault map and past seismicity models, and a random field to account for any excess spatial variation that cannot be explained by deterministic model components. Comparing the alternative models allows the assessment of the performance of models of varying complexity composed of different components and therefore identifies which elements are most useful for describing the distribution of earthquake locations. We demonstrate the effectiveness of this approach using synthetic data and by making use of the earthquake and fault information available for California, including an application to the 2019 Ridgecrest sequence. We show the flexibility of this modeling approach and how it might be applied in areas where we do not have the same abundance of detailed information. We find results consistent with existing literature on the performance of past seismicity models that slip rates are beneficial for describing the spatial locations of larger magnitude events and that strain rate maps can constrain the spatial limits of seismicity in California. We also demonstrate that maps of distance to the nearest fault can benefit spatial models of seismicity, even those that also include the primary fault geometry used to construct them.
Flow Separation and Increased Drag Coefficient in Estuarine Channels With Curvature
Authors: Bo Tong , Ralston David K.
Published: October 2020

Flow separation has been observed and studied in sinuous laboratory channels and natural meanders, but the effects of flow separation on along‐channel drag are not well understood. Motivated by observations of large drag coefficients from a shallow, sinuous estuary, we built idealized numerical models representative of that system. We found that flow separation in tidal channels with curvature can create form drag that increases the total drag to more than twice that from bottom friction alone. In the momentum budget, the pressure gradient is balanced by the combined effects of bottom friction and form drag, which is calculated directly. The effective increase in total drag coefficient depends on two geometric parameters: dimensionless water depth and bend sharpness, quantified as the bend radius of curvature to channel width ratio. We introduce a theoretical boundary layer separation model to explain this parameter dependence and to predict flow separation and the increased drag. The drag coefficient can increase by a factor of 2–7 in “sharp” and “deep” sinuous channels where flow separation is most likely. Flow separation also enhances energy dissipation due to increased velocities in bends, resulting in greater loss of tidal energy and weakened stratification. Flow separation and the associated drag increase are expected to be more common in meanders of tidal channels than rivers where point bars that inhibit flow separation are more commonly found. The increased drag due to flow separation reduces tidal amplitude and affects velocity phasing along the estuary and could result in morphological feedbacks.
Shipboard Acoustic Observations of Flow Rate From a Seafloor‐Sourced Oil Spill
Authors: Loranger Scott , Weber Thomas C.
Published: October 2020

In 2004 a debris flow generated by Hurricane Ivan toppled an oil production platform in Mississippi Canyon lease block 20 (MC20). Between 2004 and the installation of a containment system in 2019 MC20 became an in situ laboratory for a wide range of hydrocarbon in the sea‐related research, including different methods of assessing the volumetric flow rate of hydrocarbons spanning different temporal scales. In 2017 a shipboard acoustic Doppler current profiler (ADCP) and high‐frequency (90 to 154 kHz) broadband echosounder were deployed to assess the flow rate of liquid and gas phase hydrocarbons. Measurements of horizontal currents were combined with acoustic mapping to determine the rise velocity of the seep as it moved downstream. Models of the rise velocity for fluid particles were used to predict the size of oil droplets and gas bubbles in the seep. The amplitude and shape of the broadband acoustic backscatter were then used to differentiate between, and determine the flow rate of, hydrocarbons. Oil flow rate in the seep was estimated to be 56 to 86 barrels/day (mean barrels/day) while the flow rate of gaseous hydrocarbons was estimated to be 98 to 359 m3/day (mean m3/day).
Medium Energy Electron Flux in Earth's Outer Radiation Belt (MERLIN): A Machine Learning Model
Authors: Smirnov A. G. , Berrendorf M. , Shprits Y. Y. , Kronberg E. A. , Allison H. J. , Aseev N. A. , Zhelavskaya I. S. , Morley S. K. , Reeves G. D. , Carver M. R. , Effenberger F.
Published: October 2020

The radiation belts of the Earth, filled with energetic electrons, comprise complex and dynamic systems that pose a significant threat to satellite operation. While various models of electron flux both for low and relativistic energies have been developed, the behavior of medium energy (120–600 keV) electrons, especially in the MEO region, remains poorly quantified. At these energies, electrons are driven by both convective and diffusive transport, and their prediction usually requires sophisticated 4D modeling codes. In this paper, we present an alternative approach using the Light Gradient Boosting (LightGBM) machine learning algorithm. The Medium Energy electRon fLux In Earth's outer radiatioN belt (MERLIN) model takes as input the satellite position, a combination of geomagnetic indices and solar wind parameters including the time history of velocity, and does not use persistence. MERLIN is trained on >15 years of the GPS electron flux data and tested on more than 1.5 years of measurements. Tenfold cross validation yields that the model predicts the MEO radiation environment well, both in terms of dynamics and amplitudes o f flux. Evaluation on the test set shows high correlation between the predicted and observed electron flux (0.8) and low values of absolute error. The MERLIN model can have wide space weather applications, providing information for the scientific community in the form of radiation belts reconstructions, as well as industry for satellite mission design, nowcast of the MEO environment, and surface charging analysis.
Suspended Sediment‐Induced Stratification Inferred From Concentration and Velocity Profile Measurements in the Lower Yellow River, China
Authors: Moodie Andrew J. , Nittrouer Jeffrey A. , Ma Hongbo , Carlson Brandee N. , Wang Yuanjian , Lamb Michael P. , Parker Gary
Published: October 2020

Despite a multitude of models predicting sediment transport dynamics in open‐channel flow, self‐organized vertical density stratification that dampens flow turbulence due to the interaction between fluid and sediment has not been robustly validated with field observations from natural rivers. Turbulence‐suppressing density stratification can develop in channels with low channel‐bed slope and high sediment concentration. As the Yellow River, China, maintains one of the highest sediment loads in the world for a low sloping system, this location is ideal for documenting particle and fluid interactions that give rise to density stratification. Herein, we present analyses from a study conducted over a range of discharge conditions (e.g., low flow, rising limb, and flood peak) from a lower reach of the Yellow River, whereby water samples were collected at targeted depths to measure sediment concentration and, simultaneously, velocity measurements were collected throughout the flow depth. Importantly, sediment concentration varied by an order of magnitude between base and flood flows. By comparing measured concentration and velocity profiles to predictive models, we show that the magnitude of density stratification increases with sediment concentration. Furthermore, a steady‐state calculation of sediment suspension is used to determine that sediment diffusivity increases with grain size. Finally, we calculate concentration and velocity profiles, showing that steady‐state sediment suspensions are reliably predicted over a range of stratification conditions larger than had been previously documented in natural river flows. We determine that the magnitude of density stratification can be predicted by a function considering an entrainment parameter, sediment concentration, and bed slope.
Elevated DHODH expression promotes cell proliferation via stabilizing β-catenin in esophageal squamous cell carcinoma
Authors: Qian Yu , Liang Xiao , Kong Pengzhou , Cheng Yikun , Cui Heyang , Yan Ting , Wang Jinghao , Zhang Ling , Liu Yiqian , Guo Shiping , Cheng Xiaolong , Cui Yongping
Published: October 2020

As a key enzyme in de novo pyrimidine biosynthesis, the expression level of dihydroorotate dehydrogenase (DHODH) has been reported to be elevated in various types of malignant tumors and its tumor-promoting effect was considered to relate to its pyrimidine synthesis function. Here, we revealed one intriguing potential mechanism that DHODH modulated β-catenin signaling in esophageal squamous cell carcinoma (ESCC). We demonstrated that DHODH directly bound to the NH2 terminal of β-catenin, thereby, interrupting the interaction of GSK3β with β-catenin and leading to the abrogation of β-catenin degradation and accumulation of β-catenin in the nucleus, which in turn, resulted in the activation of β-catenin downstream genes, including CCND1, E2F3, Nanog, and OCT4. We further demonstrated that the regulation of β-catenin by DHODH was independent of DHODH catalyzing activity. Univariate and multivariate analyses suggested that DHODH expression might be an independent prognostic factor for ESCC patients. Collectively, our study highlights the pivotal role of DHODH mediated β-catenin signaling and indicates that DHODH may act as a multi-functional switcher from catalyzing pyrimidine metabolism to regulating tumor-related signaling pathways in ESCC.
Restoring BMP4 expression in vascular endothelial progenitors ameliorates maternal diabetes-induced apoptosis and neural tube defects
Authors: Cao Songying , Reece E. Albert , Shen Wei-Bin , Yang Peixin
Published: October 2020

During mouse embryonic development, vasculogenesis initially occurs in the yolk sac, preceding neurulation. Our previous studies have demonstrated that maternal diabetes induces embryonic vasculopathy at early embryonic developmental stage by suppressing the expression of vascular growth factors including BMP4 (bone morphogenetic protein 4). This study aimed to determine whether restoring diabetes-inhibited BMP4 expression in Flk-1+ progenitors effectively prevented maternal diabetes-induced embryonic vasculopathy and NTDs. Transgenic (Tg) BMP4 expression in the vascular endothelial growth factor receptor 2 (Flk-1)-positive (Flk-1+) progenitors was achieved by crossing a Floxed BMP4 Tg mouse line with the Flk-1-Cre mouse line. Non-BMP4 Tg and BMP4 Tg embryos were harvested at E8.5 to assess the expression of BMP4, markers of endoplasmic reticulum stress, and expression of the Id genes, direct targets of BMP4; and the presence of cleaved caspase 3 and 8, apoptosis, and Smad signaling. BMP4 Tg overexpression neutralized its down-regulation by maternal diabetes in E8.5 embryos. Maternal diabetes-induced Flk-1+ progenitor apoptosis, impairment of blood island formation, and reduction of Flk-1+ progenitor number and blood vessel density, which were reversed by BMP4 Tg expression. BMP4 Tg expression in Flk-1+ progenitors blocked maternal diabetes-induced vasculopathy in early stage embryos (E7.5-E8.5) and consequently led to amelioration of maternal diabetes-induced neural tube defects (NTDs) at E10.5. BMP4 Tg expression inhibited maternal diabetes-induced endoplasmic reticulum stress and caspase cascade activation in the developing neuroepithelium, and reduced neuroepithelial cell apoptosis. BMP4 Tg expression re-activated Smad1/5/8 phosphorylation and reversed maternal diabetes-suppressed Smad4 expression. BMP4 Tg expression restored Id1 and Smad6 expression inhibited by maternal diabetes. In vitro, recombinant BMP4 protein blocked high glucose-induced Flk-1+ progenitor apoptosis and NTDs. These data demonstrate that BMP4 down-regulation in Flk-1+ progenitors are responsible for diabetes-induced yolk sac vasculopathy, and that restoring BMP4 expression prevents vasculopathy and rescues neuroepithelial cells from cellular organelle stress, leading to NTD reduction.
HOPS/Tmub1 involvement in the NF-kB-mediated inflammatory response through the modulation of TRAF6
Authors: Bellet Marina Maria , Pieroni Stefania , Castelli Marilena , Piobbico Danilo , Fallarino Francesca , Romani Luigina , Della-Fazia Maria Agnese , Servillo Giuseppe
Published: October 2020

HOPS/Tmub1 is a ubiquitously expressed transmembrane ubiquitin-like protein that shuttles between nucleus and cytoplasm during cell cycle progression. HOPS causes cell cycle arrest in G0/G1 phase, an event associated to stabilization of p19Arf, an important tumor suppressor protein. Moreover, HOPS plays an important role in driving centrosomal assembly and maintenance, mitotic spindle proper organization, and ultimately a correct cell division. Recently, HOPS has been described as an important regulator of p53, which acts as modifier, stabilizing p53 half-life and playing a key role in p53 mediating apoptosis after DNA damage. NF-κB is a transcription factor with a central role in many cellular events, including inflammation and apoptosis. Our experiments demonstrate that the transcriptional activity of the p65/RelA NF-κB subunit is regulated by HOPS. Importantly, Hops−/− cells have remarkable alterations of pro-inflammatory responses. Specifically, we found that HOPS enhances NF-κB activation leading to increase transcription of inflammatory mediators, through the reduction of IκBα stability. Notably, this effect is mediated by a direct HOPS binding to the E3 ubiquitin ligase TRAF6, which lessens TRAF6 stability ultimately leading increased IKK complex activation. These findings uncover a previously unidentified function of HOPS/Tmub1 as a novel modulator of TRAF6, regulating inflammatory responses driven by activation of the NF-κB signaling pathway. The comprehension on how HOPS/Tmub1 takes part to the inflammatory processes in vivo and whether this function is important in the control of proliferation and tumorigenesis could establish the basis for the development of novel pharmacological strategies.
Specific features and assembly of the plant mitochondrial complex I revealed by cryo-EM
Authors: Soufari Heddy , Parrot Camila , Kuhn Lauriane , Waltz Florent , Hashem Yaser
Published: October 2020

Mitochondria are the powerhouses of eukaryotic cells and the site of essential metabolic reactions. Complex I or NADH:ubiquinone oxidoreductase is the main entry site for electrons into the mitochondrial respiratory chain and constitutes the largest of the respiratory complexes. Its structure and composition vary across eukaryote species. However, high resolution structures are available only for one group of eukaryotes, opisthokonts. In plants, only biochemical studies were carried out, already hinting at the peculiar composition of complex I in the green lineage. Here, we report several cryo-electron microscopy structures of the plant mitochondrial complex I. We describe the structure and composition of the plant respiratory complex I, including the ancestral mitochondrial domain composed of the carbonic anhydrase. We show that the carbonic anhydrase is a heterotrimeric complex with only one conserved active site. This domain is crucial for the overall stability of complex I as well as a peculiar lipid complex composed of cardiolipin and phosphatidylinositols. Moreover, we also describe the structure of one of the plant-specific complex I assembly intermediates, lacking the whole PD module, in presence of the maturation factor GLDH. GLDH prevents the binding of the plant specific P1 protein, responsible for the linkage of the PP to the PD module.
Health and disease markers correlate with gut microbiome composition across thousands of people
Authors: Manor Ohad , Dai Chengzhen L. , Kornilov Sergey A. , Smith Brett , Price Nathan D. , Lovejoy Jennifer C. , Gibbons Sean M. , Magis Andrew T.
Published: October 2020

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities for targeted interventions that alter the composition of the microbiome to improve host health. By uncovering the interrelationships between host diet and lifestyle factors, clinical blood markers, and the human gut microbiome at the population-scale, our results serve as a roadmap for future studies on host-microbe interactions and interventions.
Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey
Authors: Frontera Jimena Laura , Baba Aissa Hind , Sala Romain William , Mailhes-Hamon Caroline , Georgescu Ioana Antoaneta , Léna Clément , Popa Daniela
Published: October 2020

Fear conditioning is a form of associative learning that is known to involve different brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memories, indicating an important role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. Moreover, FN-vlPAG projections also modulate extinction learning. We also found a FN-parafascicular thalamus pathway, which may relay cerebellar influence to the amygdala and modulates anxiety behaviors. Overall, our results reveal multiple contributions of the cerebellum to the emotional system.
Author Correction: Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis
Authors: Tu Lichan , Su Ping , Zhang Zhongren , Gao Linhui , Wang Jiadian , Hu Tianyuan , Zhou Jiawei , Zhang Yifeng , Zhao Yujun , Liu Yuan , Song Yadi , Tong Yuru , Lu Yun , Yang Jian , Xu Cao , Jia Meirong , Peters Reuben J. , Huang Luqi , Gao Wei
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Achieving fast start-up of anammox process by promoting the growth of anammox bacteria with FeS addition
Authors: Zou Chunzhen , Guo Beibei , Zhuang Xuming , Ren Liying , Ni Shou-Qing , Ahmad Shakeel , Qiao Zhuangming , Cui Zhaojie , Hong Jinglan
Published: October 2020

The effects of FeS on nitrogen removal performance and microbial community of anammox process were studied. During the start-up period, the removal efficiencies of nitrite and total nitrogen were significantly improved by FeS. The addition of FeS increased the content of iron ions in the reactor and promoted the synthesis of heme c, which was involved in the formation of various enzymes. Compared with the control, the abundance of anammox bacteria in the FeS reactor was increased by 29%, and the expression level of the nirS gene (encoding cd1 type nitrite reductase containing heme) was nearly doubled. The content of nitrite reductase (ammonia-forming) in the community was increased by 26.4%. The difference in functional bacteria and enzyme contents in the microbial community resulted in a difference in nitrogen removal rate (NRR) between the two reactors. High-throughput results indicated that FeS increased the richness and diversity of microbial community and enhanced the metabolic function of the microbial community. The addition of FeS did not change the dominant position of Ca. Kuenenia in both reactors. But the relative abundance of heterotrophic denitrifying bacteria was reduced with FeS, which may be related to the inhibition effect of S2− produced by FeS.
Systematic analysis of infectious disease outcomes by age shows lowest severity in school-age children
Authors: Glynn Judith R. , Moss Paul A. H
Published: October 2020

The COVID-19 pandemic has ignited interest in age-specific manifestations of infection but surprisingly little is known about relative severity of infectious disease between the extremes of age. In a systematic analysis we identified 142 datasets with information on severity of disease by age for 32 different infectious diseases, 19 viral and 13 bacterial. For almost all infections, school-age children have the least severe disease, and severity starts to rise long before old age. Indeed, for many infections even young adults have more severe disease than children, and dengue was the only infection that was most severe in school-age children. Together with data on vaccine response in children and young adults, the findings suggest peak immune function is reached around 5–14 years of age. Relative immune senescence may begin much earlier than assumed, before accelerating in older age groups. This has major implications for understanding resilience to infection, optimal vaccine scheduling, and appropriate health protection policies across the life course.
Isolation, characterisation and detection of breath-derived extracellular vesicles
Authors: Dobhal Garima , Datta Amrita , Ayupova Deanna , Teesdale-Spittle Paul , Goreham Renee V.
Published: October 2020

The physical characterisation, capture and detection of extracellular vesicles (EVs) and exosomes derived from breath condensate is reported. Breath-derived EVs were isolated from breath condensate and captured on a gold substrate using two complimentary methods. The characterised and isolated EVs were detected using surface plasmon resonance (SPR) and electrochemical impedance spectroscopy (EIS). EIS was done using aptamers as a targeting moiety and showed a larger change in resistance between dilute concentrations of EVs (less than 7 μg/mL).This is the first report of EVs and exosomes isolated and characterised from breath. In addition, EVs from a non-invasive and easily available source such as breath opens up further avenues in the detection of pulmonary diseases.
Diagnosis of common pulmonary diseases in children by X-ray images and deep learning
Authors: Chen Kai-Chi , Yu Hong-Ren , Chen Wei-Shiang , Lin Wei-Che , Lee Yi-Chen , Chen Hung-Hsun , Jiang Jyun-Hong , Su Ting-Yi , Tsai Chang-Ku , Tsai Ti-An , Tsai Chih-Min , Lu Henry Horng-Shing
Published: October 2020

Acute lower respiratory infection is the leading cause of child death in developing countries. Current strategies to reduce this problem include early detection and appropriate treatment. Better diagnostic and therapeutic strategies are still needed in poor countries. Artificial-intelligence chest X-ray scheme has the potential to become a screening tool for lower respiratory infection in child. Artificial-intelligence chest X-ray schemes for children are rare and limited to a single lung disease. We need a powerful system as a diagnostic tool for most common lung diseases in children. To address this, we present a computer-aided diagnostic scheme for the chest X-ray images of several common pulmonary diseases of children, including bronchiolitis/bronchitis, bronchopneumonia/interstitial pneumonitis, lobar pneumonia, and pneumothorax. The study consists of two main approaches: first, we trained a model based on YOLOv3 architecture for cropping the appropriate location of the lung field automatically. Second, we compared three different methods for multi-classification, included the one-versus-one scheme, the one-versus-all scheme and training a classifier model based on convolutional neural network. Our model demonstrated a good distinguishing ability for these common lung problems in children. Among the three methods, the one-versus-one scheme has the best performance. We could detect whether a chest X-ray image is abnormal with 92.47% accuracy and bronchiolitis/bronchitis, bronchopneumonia, lobar pneumonia, pneumothorax, or normal with 71.94%, 72.19%, 85.42%, 85.71%, and 80.00% accuracy, respectively. In conclusion, we provide a computer-aided diagnostic scheme by deep learning for common pulmonary diseases in children. This scheme is mostly useful as a screening for normal versus most of lower respiratory problems in children. It can also help review the chest X-ray images interpreted by clinicians and may remind possible negligence. This system can be a good diagnostic assistance under limited medical resources.
Repeated sampling facilitates within- and between-subject modeling of the human sperm transcriptome to identify dynamic and stress-responsive sncRNAs
Authors: Morgan Christopher P. , Shetty Amol C. , Chan Jennifer C. , Berger Dara S. , Ament Seth A. , Epperson C. Neill , Bale Tracy L.
Published: October 2020

Epidemiological studies from the last century have drawn strong associations between paternal life experiences and offspring health and disease outcomes. Recent studies have demonstrated sperm small non-coding RNA (sncRNA) populations vary in response to diverse paternal insults. However, for studies in retrospective or prospective human cohorts to identify changes in paternal germ cell epigenetics in association with offspring disease risk, a framework must first be built with insight into the expected biological variation inherent in human populations. In other words, how will we know what to look for if we don’t first know what is stable and what is dynamic, and what is consistent within and between men over time? From sperm samples from a ‘normative’ cohort of healthy human subjects collected repeatedly from each subject over 6 months, 17 healthy male participants met inclusion criteria and completed donations and psychological evaluations of perceived stress monthly. sncRNAs (including miRNA, piRNA, and tRNA) isolated from mature sperm from these samples were subjected to Illumina small RNA sequencing, aligned to subtype-specific reference transcriptomes, and quantified. The repeated measures design allowed us to define both within- and between-subject variation in the expression of 254 miRNA, 194 tRNA, and 937 piRNA in sperm over time. We developed screening criteria to identify a subset of potential environmentally responsive ‘dynamic’ sperm sncRNA. Implementing complex modeling of the relationships between individual dynamic sncRNA and perceived stress states in these data, we identified 5 miRNA (including let-7f-5p and miR-181a-5p) and 4 tRNA that are responsive to the dynamics of prior stress experience and fit our established mouse model. In the current study, we aligned repeated sampling of human sperm sncRNA expression data with concurrent measures of perceived stress as a novel framework that can now be applied across a range of studies focused on diverse environmental factors able to influence germ cell programming and potentially impact offspring development.
Locally administered heparin-binding epidermal growth factor-like growth factor reduces radiation-induced oral mucositis in mice
Authors: Chen Jing , Bekale Laurent A. , Khomtchouk Kelly M. , Xia Anping , Cao Zhixin , Ning Shoucheng , Knox Susan J. , Santa Maria Peter L.
Published: October 2020

Oral mucositis refers to lesions of the oral mucosa observed in patients with cancer being treated with radiation with or without chemotherapy, and can significantly affect quality of life. There is a large unmet medical need to prevent oral mucositis that can occur with radiation either alone or in combination with chemotherapy. We investigated the efficacy of locally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent epithelial proliferation and migration stimulator of the oral mucosa as a potential therapy to prevent radiation induced oral mucositis. Using a single dose (20 Gy) of radiation to the oral cavity of female C57BL/6 J mice, we evaluated the efficacy of HB-EGF treatment (5 µl of 10 µg/ml) solution. The results show that HB-EGF delivered post radiation, significantly increased the area of epithelial thickness on the tongue (dorsal tongue (42,106 vs 53,493 µm2, p < 0.01), ventral tongue (30,793 vs 39,095 µm2, *p < 0.05)) compared to vehicle control, enhanced new epithelial cell division, and increased the quality and quantity of desmosomes in the oral mucosa measured in the tongue and buccal mucosa. This data provides the proof of concept that local administration of HB-EGF has the potential to be developed as a topical treatment to mitigate oral mucositis following radiation.
Immortalization of human hepatocytes from biliary atresia with CDK4R24C, cyclin D1, and TERT for cytochrome P450 induction testing
Authors: Nishiwaki Manami , Toyoda Masashi , Oishi Yoshie , Ishida Seiichi , Horiuchi Shin-ichiro , Makino-Itou Hatsune , Kimura Tohru , Ohno Shin-ichi , Ohkura Takashi , Enosawa Shin , Akutsu Hidenori , Nakazawa Atsuko , Kasahara Mureo , Kiyono Tohru , Umezawa Akihiro
Published: October 2020

Hepatocytes are an important tool for in vitro toxicology testing. In addition to primary cultures, a limited number of immortalized cell lines have been developed. We here describe a new cell line, designated as HepaMN, which has been established from a liver associated with biliary atresia. Hepatocytes were isolated from a liver of 4-year-old girl with biliary atresia and immortalized by inoculation with CSII-CMV-TERT, CSII-CMV-Tet-Off, CSII-TRE-Tight-cyclin D1 and CSII-TRE-Tight-CDK4R24C (mutant CDK4: an INK4a-resistant form of CDK4) lentiviruses at the multiplicity of infection of 3 to 10. HepaMN cells exhibited morphological homogeneity, displaying hepatocyte-like phenotypes. Phenotypic studies in vivo and in vitro revealed that HepaMN cells showed polarized and functional hepatocyte features along with a canalicular cell phenotype under defined conditions, and constitutively expressed albumin and carbamoyl phosphate synthetase I in addition to epithelial markers. Since HepaMN cells are immortal and subcloned, kinetics and expression profiles were independent of population doublings. HepaMN cells showed increased CYP3A4 expression after exposure to rifampicin, implying that their close resemblance to normal human hepatocytes makes them suitable for research applications including drug metabolism studies.
Genomic identification and expression analysis of nuclear pore proteins in Malus domestica
Authors: Zhang Chenguang , An Na , Jia Peng , Zhang Wei , Liang Jiayan , Zhang Xu , Zhou Hua , Ma Wenchun , Han Mingyu , Xing Libo , Ren Xiaolin
Published: October 2020

The nuclear pore complex (NPC), comprised of individual nucleoporin (Nup) proteins, controls nucleo-cytoplasmic transport of RNA and protein, and is important for regulating plant growth and development. However, there are no reports on this complex in fruit tree species. In this study, we identified 38 apple Nups and named them based on the known Arabidopsis thaliana homologs. We also completed bioinformatics analyses of the intron and exon structural data for apple Nups. The proteins encoded by the apple Nups lacked a universally conserved domain. Moreover, a phylogenetic analysis separated the apple and A. thaliana Nups into three groups. The phylogenetic tree indicated that MdNup54 and MdNup62 are most closely related to genes in other Rosaceae species. To characterize the 38 candidate Malus domestica Nups, we measured their stage-specific expression levels. Our tests revealed these proteins were differentially expressed among diverse tissues. We analyzed the expression levels of seven apple Nups in response to an indole-3-acetic acid (IAA) treatment. The phytohormone treatment significantly inhibited apple flowering. A qRT-PCR analysis proved that an IAA treatment significantly inhibited the expression of these seven genes. A preliminary study regarding two members of the Nup62 subcomplex, MdNup54 and MdNup62, confirmed these two proteins can interact with each other. A yeast two-hybrid assay verified that MdNup54 can interact with MdKNAT4 and MdKNAT6. On the basis of the study results, we identified apple NPC and predicted its structure and function. The data generated in this investigation provide important reference material for follow-up research.
Different types of agricultural land use drive distinct soil bacterial communities
Authors: Lee Shin Ae , Kim Jeong Myeong , Kim Yiseul , Joa Jae-Ho , Kang Seong-Soo , Ahn Jae-Hyung , Kim Mincheol , Song Jaekyeong , Weon Hang-Yeon
Published: October 2020

Biogeographic patterns in soil bacterial communities and their responses to environmental variables are well established, yet little is known about how different types of agricultural land use affect bacterial communities at large spatial scales. We report the variation in bacterial community structures in greenhouse, orchard, paddy, and upland soils collected from 853 sites across the Republic of Korea using 16S rRNA gene pyrosequencing analysis. Bacterial diversities and community structures were significantly differentiated by agricultural land-use types. Paddy soils, which are intentionally flooded for several months during rice cultivation, had the highest bacterial richness and diversity, with low community variation. Soil chemical properties were dependent on agricultural management practices and correlated with variation in bacterial communities in different types of agricultural land use, while the effects of spatial components were little.Firmicutes,Chloroflexi, andAcidobacteriawere enriched in greenhouse, paddy, and orchard soils, respectively. Members of these bacterial phyla are indicator taxa that are relatively abundant in specific agricultural land-use types. A relatively large number of taxa were associated with the microbial network of paddy soils with multiple modules, while the microbial network of orchard and upland soils had fewer taxa with close mutual interactions. These results suggest that anthropogenic agricultural management can create soil disturbances that determine bacterial community structures, specific bacterial taxa, and their relationships with soil chemical parameters. These quantitative changes can be used as potential biological indicators for monitoring the impact of agricultural management on the soil environment.
Coexisting with sharks: a novel, socially acceptable and non-lethal shark mitigation approach
Authors: Adams Kye R. , Gibbs Leah , Knott Nathan A. , Broad Allison , Hing Martin , Taylor Matthew D. , Davis Andrew R.
Published: October 2020

Conflict between humans and large predators is a longstanding challenge that can present negative consequences for humans and wildlife. Sharks have a global distribution and are considered to pose a potential threat to humans; concurrently many shark species are themselves threatened. Developing strategies for coexistence between humans and this keystone group is imperative. We assess blimp surveillance as a technique to simply and effectively reduce shark encounters at ocean beaches and determine the social acceptance of this technique as compared to an established mitigation strategy—shark meshing. We demonstrate the suitability of blimps for risk mitigation, with detection probabilities of shark analogues by professional lifeguards of 0.93 in ideal swimming conditions. Social surveys indicate strong social acceptance of blimps and preference for non-lethal shark mitigation. We show that continuous aerial surveillance can provide a measurable reduction in risk from sharks, improving beach safety and facilitating coexistence between people and wildlife.
Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy
Authors: Ando Shiori , Suzuki Shunya , Okubo Shoichi , Ohuchi Kazuki , Takahashi Kei , Nakamura Shinsuke , Shimazawa Masamitsu , Fuji Koji , Hara Hideaki
Published: October 2020

Spinal muscular atrophy (SMA) is a motor neuron disease, typically resulting from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Nusinersen/SPINRAZA, a splice-switching oligonucleotide that modulates SMN2 (a paralog of SMN1) splicing and consequently increases SMN protein levels, has a therapeutic effect for SMA. Previously reported small-molecule SMN2 splicing modulators such as risdiplam/EVRYSDI and its analog SMN-C3 modulate not only the splicing of SMN2 but also that of secondary splice targets, including forkhead box protein M1 (FOXM1). Through screening SMA patient-derived fibroblasts, a novel small molecule, designated TEC-1, was identified that selectively modulates SMN2 splicing over three secondary splice targets. TEC-1 did not strongly affect the splicing of FOXM1, and unlike risdiplam, did not induce micronucleus formation. In addition, TEC-1 showed higher selectively on galactosylceramidase and huntingtin gene expression compared to previously reported compounds (e.g., SMN-C3) due to off-target effects on cryptic exon inclusion and nonsense-mediated mRNA decay. Moreover, TEC-1 significantly ameliorated the disease phenotype in an SMA murine model in vivo. Thus, TEC-1 may have promising therapeutic potential for SMA, and our study demonstrates the feasibility of RNA-targeting small-molecule drug development with an improved tolerability profile.
Dyke apertures record stress accumulation during sustained volcanism
Authors: Thiele Samuel T. , Cruden Alexander R. , Micklethwaite Steven , Bunger Andrew P. , Köpping Jonas
Published: October 2020

The feedback between dyke and sill intrusions and the evolution of stresses within volcanic systems is poorly understood, despite its importance for magma transport and volcano instability. Long-lived ocean island volcanoes are crosscut by thousands of dykes, which must be accommodated through a combination of flank slip and visco-elastic deformation. Flank slip is dominant in some volcanoes (e.g., Kilauea), but how intrusions are accommodated in other volcanic systems remains unknown. Here we apply digital mapping techniques to collect > 400,000 orientation and aperture measurements from 519 sheet intrusions within Volcán Taburiente (La Palma, Canary Islands, Spain) and investigate their emplacement and accommodation. We show that vertically ascending dykes were deflected to propagate laterally as they approached the surface of the volcano, forming a radial dyke swarm, and propose a visco-elastic model for their accommodation. Our model reproduces the measured dyke-aperture distribution and predicts that stress accumulates within densely intruded regions of the volcano, blocking subsequent dykes and causing eruptive activity to migrate. These results have significant implications for the organisation of magma transport within volcanic edifices, and the evolution and stability of long-lived volcanic systems.