bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractDespite 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

AbstractAs 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

AbstractDuring 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

AbstractHOPS/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

AbstractMitochondria 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

AbstractVariation 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

AbstractFear 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.
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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractAcute 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

AbstractEpidemiological 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

AbstractOral 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.