bluuebunny/crossref_metadata_2025 huggingface dataset:
The time spent in fresh cow pen influences total lactational performance
Authors: Hoseyni F. , Zahmatkesh D. , Mahjoubi E. , Yazdi M. Hossein , Patton R. A.
Published: July 2020

This research paper addresses the effect of different grouping strategies of fresh cows on total lactational and reproductive performance. Hundred-sixty multiparous Holstein cows were enrolled in a completely randomized design and assigned to one of following treatments: 21 days in fresh pen with 12.5 kg/day concentrate (C21,n= 60), 10 days in fresh pen with 12.5 kg/day concentrate (C10,n= 50) and 10 days in fresh pen with 10 kg/day concentrate (L10,n= 50). Although there were no differences among treatments within the first 10 days in milk (DIM), C10 and L10 cows tended to produce more milk than C21 from 10 to 21 DIM. In addition, greater milk yield was obtained in C10 and L10 cows during 22–28 DIM and 29–70 DIM. Higher production in early lactation resulted in a tendency for greater milk production for C10 and L10 cows throughout a 305 days lactation. There was no difference in productivity between C10 and L10 groups at any time point. No blood metabolites (Ca, P, non-esterified fatty acids andβ-hydroxy butyrate) were affected by treatments. Pregnancy at first, second and third service was 38, 39 and 40%, respectively, which were not influenced by the days in fresh pen or concentrate allowance. Collectively, our results for the first time suggest that fresh cow grouping strategy has a long-term effect on productivity but that adding 2.5 kg/day concentrate has no effect on milk yield in fresh pen.
Inhibitory control of positive and negative information and adolescent depressive symptoms: a population-based cohort study
Authors: Lewis Gemma , Button Katherine S. , Pearson Rebecca M. , Munafò Marcus R. , Lewis Glyn
Published: July 2020

Background

Large population-based cohort studies of neuropsychological factors that characterise or precede depressive symptoms are rare. Most studies use small case-control or cross-sectional designs, which may cause selection bias and cannot test temporality. In a large UK population-based cohort, we investigated cross-sectional and longitudinal associations between inhibitory control of positive and negative information and adolescent depressive symptoms.

Methods

Cohort study of 2328 UK adolescents who completed an affective go/no-go task at age 18. Depressive symptoms were assessed with the Clinical Interview Schedule Revised (CIS-R) and short Mood and Feeling Questionnaire (sMFQ) at age 18, and with the sMFQ 1 year later (age 19). Analyses were multilevel and traditional linear regressions, before and after adjusting for confounders.

Results

Cross-sectionally, we found little evidence that adolescents with more depressive symptoms made more inhibitory control errors [after adjustments, errors increased by 0.04% per 1 s.d. increase in sMFQ score (95% confidence interval 0.02–0.06)], but this association was not observed for the CIS-R. There was no evidence for an influence of valence. Longitudinally, there was no evidence that reduced inhibitory control was associated with future depressive symptoms.

Conclusions

Inhibitory control of positive and negative information does not appear to be a marker of current or future depressive symptoms in adolescents and would not be a useful target in interventions to prevent adolescent depression. Our lack of convincing evidence for associations with depressive symptoms suggests that the affective go/no-go task is not a promising candidate for future neuroimaging studies of adolescent depression.
Relationship between nutrition knowledge, education and other determinants of food intake and lifestyle habits among adolescents from urban and rural secondary schools in Tyrol, Western Austria
Authors: Egg Sabrina , Wakolbinger Maria , Reisser Anna , Schätzer Manuel , Wild Birgit , Rust Petra
Published: July 2020

Objective:

The aim of this study was to investigate the association of the number of hours of nutrition education and teachers’ qualifications with nutrition knowledge and dietary behaviour in students.

Design:

In this representative cross-sectional study, socio-demographic data, anthropometric measurements, socio-economic status (SES), physical fitness, nutrition knowledge and eating habits were assessed. Differences between groups were tested byχ2andttests. Multiple linear and logistic regression modelling was used to examine the relationship between demographic characteristics, lifestyle and dietary behaviours, nutrition knowledge, nutrition-trained teachers and number of nutrition lessons.

Setting:

Sixteen secondary schools in urban (n6) and rural regions (n10) of Tyrol, Western Austria.

Participants:

Students (n513) aged 14·2 (sd0·7) years.

Results:

Higher nutrition knowledge was significantly associated with attending rural school (P= 0·001), having no migration background (P< 0·001), (very) good physical activity behaviour (P= 0·040), non-trained teacher (P= 0·006) but higher number of hours of nutrition education (P= 0·013). Regression models showed that higher nutrition knowledge was independently associated with lower intake of meat and iced tea and higher intake of vegetables and plant-based oils. A higher amount of nutrition education (h/week) was significantly associated with higher intake of dark (wholegrain) bread, lower intake of meat and of energy drinks sweetened with sweeteners.

Conclusions:

Our results suggest that more hours in nutrition education result in higher nutrition knowledge and greater nutrition literacy, which may lead to health-promoting dietary habits. School-based nutrition education can be seen as preventive measure to increase nutritional competences in adolescents independent of their SES.
Prevalence of carotid plaque stenosis after head and neck	radiotherapy – an observational study of 156 survivors
Authors: Valentin Marie-Luise , Barco Stefano , Studer Gabriela , Clemens Robert , Kreuzpointner Robert , Sebastian Tim , Thalhammer Christoph , Kucher Nils
Published: July 2020

Summary: Background: Radiotherapy for head and neck cancer (HNC) represents a well-known predisposing factor for asymptomatic carotid artery lesions and acute cerebrovascular accidents. Our aim is to provide contemporary estimates on the prevalence, severity, and characteristics of carotid artery lesions in HNC survivors. Patients and methods: We prospectively included HNC patients who underwent radiotherapy and were free from the disease at the time of duplex ultrasound evaluation. Patients were re-contacted telephonically and those who agreed to participate were invited for an ambulatory visit when the investigators collected clinical information and performed duplex ultrasound examination based on a predefined protocol. Results: A total of 156 patients were included and underwent duplex ultrasound examination after a mean of 65.2 months from the last session of radiotherapy. A total of 36 patients (23.1%) had normal carotid arteries; mild, non-stenotic lesions were observed in 49.4% (n = 77) of patients; severe stenotic plaques were found in 27.5% (n = 43) of patients. One patient found with an asymptomatic occlusion of the left ICA. The prevalence of major cardiovascular risk factors and high radiation dose increased proportionally with plaque severity. Low echogenicity plaque was found in 59 (37.8%) patients on the right side and 57 (36.5%) on the left side; long segment plaque in 49 (31.4%) patients on the right side and in 47 (30.1%) on the left side; an atypical location of the lesions in 42 (26.9%) patients on the right side and in 48 (30.8%) on the left side. Conclusions: The prevalence of occlusion and severe stenosis after radiotherapy for HNC was very low in our study population. Low echogenicity plaque, long segment plaque, and an atypical location were common findings. Classic cardiovascular risk factors appear to have had a causative role: a routine screening of radiotherapy-treated patients might be necessary only in patients with concomitant cardiovascular risk factors or exposed to high-dose neck radiation.
High‐Sensitivity Moment Magnetometry With the Quantum Diamond Microscope
Authors: Fu Roger R. , Lima Eduardo A. , Volk Michael W. R. , Trubko Raisa
Published: July 2020

Interest in magnetic fields on the ancient Earth and other planetary bodies has motivated the paleomagnetic analysis of complex rocks such as meteorites that carry heterogeneous magnetizations at <<1 mm scales. The net magnetic moment of natural remanent magnetization (NRM) in such small samples is often below the detection threshold of common cryogenic magnetometers. The quantum diamond microscope (QDM) is an emerging magnetic imaging technology with ~1 μm resolution and can, in principle, recover magnetizations as weak as 10−17 Am2. However, the typically 1–100 μm sample‐to‐sensor distance of QDM measurements can result in complex (nondipolar) magnetic field maps, from which the net magnetic moment cannot be determined using a simple algorithm. Here we generate synthetic magnetic field maps to quantify the errors introduced by sample nondipolarity and by map processing procedures such as upward continuation. We find that inversions based on least squares dipole fits of upward continued data can recover the net moment of complex samples with <5% to 10% error for maps with signal‐to‐noise ratio (SNR) in the range typical of current generation QDMs. We validate these error estimates experimentally using comparisons between QDM maps and between QDM and SQUID microscope data, concluding that, within the limitations described here, the QDM is a robust technique for recovering the net magnetic moment of weakly magnetized samples. More sophisticated net moment fitting algorithms in the future can be combined with upward continuation methods described here to improve accuracy.
Influence of a Subducted Oceanic Ridge on the Distribution of Shallow VLFEs in the Nankai Trough as Revealed by Moment Tensor Inversion and Cluster Analysis
Authors: Toh A. , Chen W. J. , Takeuchi N. , Dreger D. S. , Chi W. C. , Ide S.
Published: July 2020

The eastern Nankai Trough is a unique site where many shallow, very low frequency earthquakes (sVLFEs) are recorded by nearby broadband ocean bottom seismometers. Here, we estimated the locations and seismic moment tensors (MTs) of sVLFEs based on the low‐frequency (<0.07 Hz) components of the records. Although some sVLFEs exhibited long‐duration signals (>100 s), indicating a degree of source complexity, the MT inversions were limited to events with impulsive and short durations (20–30 s). Nevertheless, cluster analysis confirmed that the MTs of impulsive sVLFEs reasonably represented the overall deformation for an event group including many longer‐duration events. The distribution of MTs indicates that deformations associated with sVLFEs are influenced by a subducted oceanic ridge in this region, which produces an along‐the‐trough variation in a strain accumulation/release pattern and probably controls the spatial patterns of tsunami generation.
Quantifying a Novel Climate Through Changes in PDO‐Climate and PDO‐Salmon Relationships
Authors: Litzow Michael A. , Malick Michael J. , Bond Nicholas A. , Cunningham Curry J. , Gosselin Jennifer L. , Ward Eric J.
Published: July 2020

We used changing relationships between primary climate variables and the Pacific Decadal Oscillation (PDO) index to quantify novel climate conditions during rapid warming of the Gulf of Alaska in 2014–2019. Using Bayesian regression, we show that the PDO had a weaker relationship with North Pacific sea‐level pressure than in previous decades and was associated with warmer regional temperatures, reduced wind mixing, and weaker alongshore transport. Climate conditions mapping onto the PDO during 2014–2019 appear to be unique in the historical record. The potential for surprising ecological responses to novel climates is highlighted by a switch to unique, negative correlations between the PDO and salmon production, contrasting with positive or neutral correlations during previous decades. Novel climates are emerging globally, and tracking changing associations between primary variables and climate indices may be a useful approach for quantifying both the degree of climate novelty and the potential for surprising ecological responses.
Estimation of the Atmospheric Ice Content Mass, Spatial Distribution, and Long‐Term Changes Based on the ERA5 Reanalysis
Authors: Dou T. , Xiao C. , Huang Y. , Yue H. , Han W.
Published: July 2020

The aerial cryosphere refers to all ice bodies in the atmosphere and has important impacts on the development of weather systems, climate change, and aviation safety. The total mass of the aerial cryosphere is evaluated for the first time based on the fifth generation European Centre for Medium‐Range Weather Forecasts \atmospheric reanalysis (ERA5) reanalysis data set, and the spatiotemporal variability and long‐term change of the aerial cryosphere are investigated. The results show that the total mass of atmospheric ice is approximately 33.1 Gt [29.7–37.0 Gt], covering ~74.3% of the Earth's surface area with obvious latitudinal zonality and seasonal variability. The aerial cryosphere mass has been increasing over the past few decades due to the overall increase in the atmospheric water vapor content caused by rising global temperatures. Moreover, the contribution of warming to the ablation of the aerial cryosphere is negligible since there is no significant trend in the height of the atmospheric freezing point layer.
Global Dam‐Driven Changes to Riverine N:P:Si Ratios Delivered to the Coastal Ocean
Authors: Maavara Taylor , Akbarzadeh Zahra , Van Cappellen Philippe
Published: July 2020

River damming alters nutrient fluxes along the land‐ocean aquatic continuum as a result of biogeochemical processes in reservoirs. Both the changes in riverine nutrient fluxes and nutrient ratios impact ecosystem functioning of receiving water bodies. We utilize spatially distributed mechanistic models of nitrogen (N), phosphorus (P), and silicon (Si) cycling in reservoirs to quantify changes in nutrient stoichiometry of river discharge to coastal waters. The results demonstrate that the growing number of dams decouples the riverine fluxes of N, P, and Si. Worldwide, preferential removal of P over N in reservoirs increases N:P ratios delivered to the ocean, raising the potential for P limitation of coastal productivity. By midcentury, more than half of the rivers discharging to the coastal zone will experience a higher removal of reactive Si relative to reactive P and total N, in response to the rapid pace at which new hydroelectric dams are being built.
Bottom Drag Varies Seasonally With Biological Roughness
Authors: Egan Galen , Chang Grace , Revelas Gene , Monismith Stephen , Fringer Oliver
Published: July 2020

Over the course of a year, we conducted three field deployments in South San Francisco Bay to examine seasonal variability in bottom drag. Our data consisted of turbulence measurements both within and outside the bottom boundary layer and benthic characterization surveys adjacent to our study site. Our results suggest that canopies of benthic worm and amphipod feeding tubes, which were denser during summer, can increase the drag coefficient by up to a factor of three relative to the smoother beds found in winter and spring. The extent of the drag increase varied depending on the measurement device, with the greatest increase inferred by measurements taken further from the bed. The small scale and temporally varying population densities of these living roughness elements pose significant challenges for hydrodynamic models, and future work is needed to begin incorporating benthic biology statistics into drag coefficient parameterizations.
Robust Enhancement of Tropical Convective Activity by the 2019 Antarctic Sudden Stratospheric Warming
Authors: Noguchi S. , Kuroda Y. , Kodera K. , Watanabe S.
Published: July 2020

Tropical tropospheric responses to a sudden stratospheric warming (SSW) event that occurred over Antarctica in September 2019 have been investigated by conducting a series of ensemble forecast experiments. Comparative examinations between the normal forecast and the partially nudged forecast, whose stratospheric circulation is constrained to a reanalysis, reveal a significant enhancement/suppression in the convective activity (upwelling/downwelling) over the northern/southern part of the tropics. Such an acceleration of the Hadley circulation is set up by thermal structural changes in the upper troposphere and lower stratosphere. The tropical cooling caused by the enhanced Brewer‐Dobson circulation destabilizes the environment there and stimulates deep cumulus convections. In this case, the southern area of the Asian monsoon region is particularly sensitive. Although details of the triggered response depend on the adopted cumulus parameterization scheme, a boosting tendency of the convective upwelling via the SSW is robust.
Caldera Collapse Geometry Revealed by Near‐Field GPS Displacements at Kīlauea Volcano in 2018
Authors: Segall Paul , Anderson Kyle R. , Pulvirenti Fabio , Wang Taiyi , Johanson Ingrid
Published: July 2020

We employ near‐field GPS data to determine the subsurface geometry of a collapsing caldera during the 2018 Kīlauea eruption. Collapse occurred in 62 discrete events, with “inflationary” deformation external to the collapse, similar to previous basaltic collapses. We take advantage of GPS data from the collapsing block and independent constraints on the magma chamber geometry from inversion of deflation prior to collapse onset. This provides an unparalleled opportunity to constrain the collapse geometry. Employing an axisymmetric finite element model, the co‐collapse displacements are best explained by piston‐like subsidence along a high angle (∼85°) normal ring fault that may steepen to vertical with depth. Reservoir magma has compressibility of 2→15 × 10−10 Pa−1, indicating bubble volume fractions from 1% to 7% (lower if fault steepens with depth). Magma pressure increases during collapses are 1 to 3 MPa, depending on compressibility. Depressurization of a triaxial point source in a homogeneous half‐space fits the data well but provides a biased representation of the source depth and process.
Arctic Sea Ice in Two Configurations of the CESM2 During the 20th and 21st Centuries
Authors: DeRepentigny Patricia , Jahn Alexandra , Holland Marika M. , Smith Abigail
Published: July 2020

We provide an assessment of the current and future states of Arctic sea ice simulated by the Community Earth System Model version 2 (CESM2). The CESM2 is the version of the CESM contributed to the sixth phase of the Coupled Model Intercomparison Project (CMIP6). We analyze changes in Arctic sea ice cover in two CESM2 configurations with differing atmospheric components: the CESM2(CAM6) and the CESM2(WACCM6). Over the historical period, the CESM2(CAM6) winter ice thickness distribution is biased thin, which leads to lower summer ice area compared to CESM2(WACCM6) and observations. In both CESM2 configurations, the timing of first ice‐free conditions is insensitive to the choice of CMIP6 future emissions scenario. In fact, the probability of an ice‐free Arctic summer remains low only if global warming stays below 1.5°C, which none of the CMIP6 scenarios achieve. By the end of the 21st century, the CESM2 simulates less ocean heat loss during the fall months compared to its previous version, delaying sea ice formation and leading to ice‐free conditions for up to 8 months under the high emissions scenario. As a result, both CESM2 configurations exhibit an accelerated decline in winter and spring ice area, a behavior that had not been previously seen in CESM simulations. Differences in climate sensitivity and higher levels of atmospheric CO2 by 2100 in the CMIP6 high emissions scenario compared to its CMIP5 analog could explain why this winter ice loss was not previously simulated by the CESM.
Groundwater Elusimicrobia are metabolically diverse compared to gut microbiome Elusimicrobia and some have a novel nitrogenase paralog
Authors: Méheust Raphaël , Castelle Cindy J , Matheus Carnevali Paula B , Farag Ibrahim F , He Christine , Chen Lin-Xing , Amano Yuki , Hug Laura A , Banfield Jillian F
Published: July 2020

Currently described members of Elusimicrobia, a relatively recently defined phylum, are animal-associated and rely on fermentation. However, free-living Elusimicrobia have been detected in sediments, soils and groundwater, raising questions regarding their metabolic capacities and evolutionary relationship to animal-associated species. Here, we analyzed 94 draft-quality, non-redundant genomes, including 30 newly reconstructed genomes, from diverse animal-associated and natural environments. Genomes group into 12 clades, 10 of which previously lacked reference genomes. Groundwater-associated Elusimicrobia are predicted to be capable of heterotrophic or autotrophic lifestyles, reliant on oxygen or nitrate/nitrite-dependent respiration, or a variety of organic compounds and Rhodobacter nitrogen fixation (Rnf) complex-dependent acetogenesis with hydrogen and carbon dioxide as the substrates. Genomes from two clades of groundwater-associated Elusimicrobia often encode a new group of nitrogenase paralogs that co-occur with an extensive suite of radical S-Adenosylmethionine (SAM) proteins. We identified similar genomic loci in genomes of bacteria from the Gracilibacteria phylum and the Myxococcales order and predict that the gene clusters reduce a tetrapyrrole, possibly to form a novel cofactor. The animal-associated Elusimicrobia clades nest phylogenetically within two free-living-associated clades. Thus, we propose an evolutionary trajectory in which some Elusimicrobia adapted to animal-associated lifestyles from free-living species via genome reduction.
Correction: Melatonin-induced ApoE expression in mouse astrocytes protects endothelial cells from OGD-R induced injuries
Authors: Xiang Jun , Zhu Wen , Yang Feng , Yu Zhong-Hai , Cai Min , Li Xiang-Ting , Zhang Jing-Si , Zhang Wen , Cai Ding-Fang
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1
Authors: Zhang Lei , Dong Xiaoqiao , Yan Bo , Yu Wenhua , Shan Letian
Published: July 2020

Colorectal cancer (CRC) is a common malignancy with high occurrence and mortality worldwide. In recent years, the overall survival rate of CRC patients has been improved because of the advances in early diagnosis and therapy. However, the prognosis of CRC patients at the advanced stage is still poor due to high recurrence rate and metastasis. The function of circular RNA (circRNA) ArfGAP with FG repeats 1 (circAGFG1) has been explored in non-small-cell lung cancer and triple-negative breast cancer. Nevertheless, its role in CRC is not clear. In this study, circAGFG1 was upregulated in CRC cell lines. CircAGFG1 silencing significantly suppressed cell proliferation, migration, invasion, and stemness, while promoted cell apoptosis in CRC. Meanwhile, we found that circAGFG1 also accelerated CRC tumor growth and metastasis in vivo. Importantly, circAGFG1 activated Wnt/β-catenin pathway through regulating CTNNB1. Afterwards, YY1 was found to transcriptionally activate CTNNB1. Furthermore, circAGFG1 directly sponged miR-4262 and miR-185-5p to upregulate YY1 expression. Eventually, rescue assays demonstrated that the effect of circAGFG1 silencing on CRC cell functions was observably reversed by upregulating YY1 or CTNNB1. In brief, our findings uncovered that circAGFG1 modulated YY1/CTNNB1 axis to drive metastasis and stemness in CRC by sponging miR-4262 and miR-185-5p.
Effects of ZnT8 on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis in diabetic kidney disease
Authors: Zhang Xiuli , Guan Tingwen , Yang Boxuan , Gu Harvest F. , Chi Zhihong
Published: July 2020

Zinc transporter 8 (ZnT8) transports zinc ions for crystallization and storage of insulin in pancreatic beta-cells and ZnT8 dysfunction is involved in pathogenesis of diabetes. The current study aimed to investigate whether ZnT8 has effects in pathophysiology of diabetic kidney disease (DKD) by using animal models for diabetes, including STZ-induced diabetic, db/db, ZnT8-KO, ZnT8-KO-STZ and ZnT8-KO-db/db mice. Results demonstrated that urine albumin to creatinine ratio and epithelial-to-mesenchymal transition (EMT) were increased in kidneys of ZnT8-KO-STZ and ZnT8-KO-db/db mice compared with C57BL/6 J and ZnT8-KO mice, while serum TGF-β1, IL-6, and TNF-α levels were elevated in parallel. In kidneys of mice intercrossed between ZnT8-KO and STZ-induced diabetic or db/db mice, these three inflammatory factors, ACR and EMT were also found to be increased compared with C57BL/6J, db/db and ZnT8-KO mice. Furthermore, ZnT8 up-regulation by hZnT8-EGFP reduced the levels of high glucose (HG)-induced EMT and inflammatory factors in normal rat kidney tubular epithelial cell (NRK-52E cells). Expression of phosphorylated Smad2/Smad3 was up-regulated after HG stimulation and further enhanced by ZnT8 siRNA but down-regulated after hZnT8-EGFP gene transfection. The current study thus provides the first evidence that ZnT8 protects against EMT-tubulointerstitial fibrosis though the restrain of TGF-β1/Smads signaling activation in DKD.
Automated extraction of chemical synthesis actions from experimental procedures
Authors: Vaucher Alain C. , Zipoli Federico , Geluykens Joppe , Nair Vishnu H. , Schwaller Philippe , Laino Teodoro
Published: July 2020

Experimental procedures for chemical synthesis are commonly reported in prose in patents or in the scientific literature. The extraction of the details necessary to reproduce and validate a synthesis in a chemical laboratory is often a tedious task requiring extensive human intervention. We present a method to convert unstructured experimental procedures written in English to structured synthetic steps (action sequences) reflecting all the operations needed to successfully conduct the corresponding chemical reactions. To achieve this, we design a set of synthesis actions with predefined properties and a deep-learning sequence to sequence model based on the transformer architecture to convert experimental procedures to action sequences. The model is pretrained on vast amounts of data generated automatically with a custom rule-based natural language processing approach and refined on manually annotated samples. Predictions on our test set result in a perfect (100%) match of the action sequence for 60.8% of sentences, a 90% match for 71.3% of sentences, and a 75% match for 82.4% of sentences.
Pathways for horizontal gene transfer in bacteria revealed by a global map of their plasmids
Authors: Redondo-Salvo Santiago , Fernández-López Raúl , Ruiz Raúl , Vielva Luis , de Toro María , Rocha Eduardo P. C. , Garcillán-Barcia M. Pilar , de la Cruz Fernando
Published: July 2020

Plasmids can mediate horizontal gene transfer of antibiotic resistance, virulence genes, and other adaptive factors across bacterial populations. Here, we analyze genomic composition and pairwise sequence identity for over 10,000 reference plasmids to obtain a global map of the prokaryotic plasmidome. Plasmids in this map organize into discrete clusters, which we call plasmid taxonomic units (PTUs), with high average nucleotide identity between its members. We identify 83 PTUs in the order Enterobacterales, 28 of them corresponding to previously described archetypes. Furthermore, we develop an automated algorithm for PTU identification, and validate its performance using stochastic blockmodeling. The algorithm reveals a total of 276 PTUs in the bacterial domain. Each PTU exhibits a characteristic host distribution, organized into a six-grade scale (I–VI), ranging from plasmids restricted to a single host species (grade I) to plasmids able to colonize species from different phyla (grade VI). More than 60% of the plasmids in the global map are in groups with host ranges beyond the species barrier.
An FGF15/19-TFEB regulatory loop controls hepatic cholesterol and bile acid homeostasis
Authors: Wang Yifeng , Gunewardena Sumedha , Li Feng , Matye David J. , Chen Cheng , Chao Xiaojuan , Jung Taeyoon , Zhang Yuxia , Czerwiński Maciej , Ni Hong-Min , Ding Wen-Xing , Li Tiangang
Published: July 2020

Bile acid synthesis plays a key role in regulating whole body cholesterol homeostasis. Transcriptional factor EB (TFEB) is a nutrient and stress-sensing transcriptional factor that promotes lysosomal biogenesis. Here we report a role of TFEB in regulating hepatic bile acid synthesis. We show that TFEB induces cholesterol 7α-hydroxylase (CYP7A1) in human hepatocytes and mouse livers and prevents hepatic cholesterol accumulation and hypercholesterolemia in Western diet-fed mice. Furthermore, we find that cholesterol-induced lysosomal stress feed-forward activates TFEB via promoting TFEB nuclear translocation, while bile acid-induced fibroblast growth factor 19 (FGF19), acting via mTOR/ERK signaling and TFEB phosphorylation, feedback inhibits TFEB nuclear translocation in hepatocytes. Consistently, blocking intestinal bile acid uptake by an apical sodium-bile acid transporter (ASBT) inhibitor decreases ileal FGF15, enhances hepatic TFEB nuclear localization and improves cholesterol homeostasis in Western diet-fed mice. This study has identified a TFEB-mediated gut-liver signaling axis that regulates hepatic cholesterol and bile acid homeostasis.
Using sigLASSO to optimize cancer mutation signatures jointly with sampling likelihood
Authors: Li Shantao , Crawford Forrest W. , Gerstein Mark B.
Published: July 2020

Multiple mutational processes drive carcinogenesis, leaving characteristic signatures in tumor genomes. Determining the active signatures from a full repertoire of potential ones helps elucidate mechanisms of cancer development. This involves optimally decomposing the counts of cancer mutations, tabulated according to their trinucleotide context, into a linear combination of known signatures. Here, we develop sigLASSO (a software tool at github.com/gersteinlab/siglasso) to carry out this optimization efficiently. sigLASSO has four key aspects: (1) It jointly optimizes the likelihood of sampling and signature fitting, by explicitly factoring multinomial sampling into the objective function. This is particularly important when mutation counts are low and sampling variance is high (e.g., in exome sequencing). (2) sigLASSO uses L1 regularization to parsimoniously assign signatures, leading to sparse and interpretable solutions. (3) It fine-tunes model complexity, informed by data scale and biological priors. (4) Consequently, sigLASSO can assess model uncertainty and abstain from making assignments in low-confidence contexts.
Engineered CRISPR/Cas9 enzymes improve discrimination by slowing DNA cleavage to allow release of off-target DNA
Authors: Liu Mu-Sen , Gong Shanzhong , Yu Helen-Hong , Jung Kyungseok , Johnson Kenneth A. , Taylor David W.
Published: July 2020

CRISPR/Cas9 is a programmable genome editing tool widely used for biological applications and engineered Cas9s have increased discrimination against off-target cleavage compared with wild-type Streptococcus pyogenes (SpCas9) in vivo. To understand the basis for improved discrimination against off-target DNA containing important mismatches at the distal end of the guide RNA, we performed kinetic analyses on the high-fidelity (Cas9-HF1) and hyper-accurate (HypaCas9) engineered Cas9 variants. We show that DNA cleavage is impaired by more than 100- fold for the high-fidelity variants. The high-fidelity variants improve discrimination by slowing the observed rate of cleavage without increasing the rate of DNA rewinding and release. The kinetic partitioning favors release rather than cleavage of a bound off-target substrate only because the cleavage rate is so low. Further improvement in discrimination may require engineering increased rates of dissociation of off-target DNA.
Determination of interatomic coupling between two-dimensional crystals using angle-resolved photoemission spectroscopy
Authors: Thompson J. J. P. , Pei D. , Peng H. , Wang H. , Channa N. , Peng H. L. , Barinov A. , Schröter N. B. M. , Chen Y. , Mucha-Kruczyński M.
Published: July 2020

Lack of directional bonding between two-dimensional crystals like graphene or monolayer transition metal dichalcogenides provides unusual freedom in the selection of components for vertical van der Waals heterostructures. However, even for identical layers, their stacking, in particular the relative angle between their crystallographic directions, modifies properties of the structure. We demonstrate that the interatomic coupling between two two-dimensional crystals can be determined from angle-resolved photoemission spectra of a trilayer structure with one aligned and one twisted interface. Each of the interfaces provides complementary information and together they enable self-consistent determination of the coupling. We parametrise interatomic coupling for carbon atoms by studying twisted trilayer graphene and show that the result can be applied to structures with different twists and number of layers. Our approach demonstrates how to extract fundamental information about interlayer coupling in a stack of two-dimensional crystals and can be applied to many other van der Waals interfaces.
AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network
Authors: Abu-Thuraia Afnan , Goyette Marie-Anne , Boulais Jonathan , Delliaux Carine , Apcher Chloé , Schott Céline , Chidiac Rony , Bagci Halil , Thibault Marie-Pier , Davidson Dominique , Ferron Mathieu , Veillette André , Daly Roger J. , Gingras Anne-Claude , Gratton Jean-Philippe , Côté Jean-François
Published: July 2020

Aberrant expression of receptor tyrosine kinase AXL is linked to metastasis. AXL can be activated by its ligand GAS6 or by other kinases, but the signaling pathways conferring its metastatic activity are unknown. Here, we define the AXL-regulated phosphoproteome in breast cancer cells. We reveal that AXL stimulates the phosphorylation of a network of focal adhesion (FA) proteins, culminating in faster FA disassembly. Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1. We find that PEAK1 is in complex with the tyrosine kinase CSK to mediate the phosphorylation of PAXILLIN. Uncoupling of PEAK1 from AXL signaling decreases metastasis in vivo, but not tumor growth. Our results uncover a contribution of AXL signaling to FA dynamics, reveal a long sought-after mechanism underlying AXL metastatic activity, and identify PEAK1 as a therapeutic target in AXL positive tumors.
The circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders
Authors: Astiz Mariana , Heyde Isabel , Fortmann Mats Ingmar , Bossung Verena , Roll Claudia , Stein Anja , Grüttner Berthold , Göpel Wolfgang , Härtel Christoph , Obleser Jonas , Oster Henrik
Published: July 2020

During pregnancy, maternal endocrine signals drive fetal development and program the offspring’s physiology. A disruption of maternal glucocorticoid (GC) homeostasis increases the child’s risk of developing psychiatric disorders later in life. We here show in mice, that the time of day of antenatal GC exposure predicts the behavioral phenotype of the adult offspring. Offspring of mothers receiving GCs out-of-phase compared to their endogenous circadian GC rhythm show elevated anxiety, impaired stress coping, and dysfunctional stress-axis regulation. The fetal circadian clock determines the vulnerability of the stress axis to GC treatment by controlling GC receptor (GR) availability in the hypothalamus. Similarly, a retrospective observational study indicates poorer stress compensatory capacity in 5-year old preterm infants whose mothers received antenatal GCs towards the evening. Our findings offer insights into the circadian physiology of feto-maternal crosstalk and assign a role to the fetal clock as a temporal gatekeeper of GC sensitivity.
CircGRIA1 shows an age-related increase in male macaque brain and regulates synaptic plasticity and synaptogenesis
Authors: Xu Kaiyu , Zhang Ying , Xiong Wandi , Zhang Zhongyu , Wang Zhengbo , Lv Longbao , Liu Chao , Hu Zhengfei , Zheng Yong-Tang , Lu Lin , Hu Xin-Tian , Li Jiali
Published: July 2020

Circular RNAs (circRNAs) are abundant in mammalian brain and some show age-dependent expression patterns. Here, we report that circGRIA1, a conserved circRNA isoform derived from the genomic loci of α-mino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit Gria1, shows an age-related and male-specific increase in expression in the rhesus macaque prefrontal cortex and hippocampus. We show circGRIA1 is predominantly localized to the nucleus, and find an age-related increase in its association with the promoter region of Gria1 gene, suggesting it has a regulatory role in Gria1 transcription. In vitro and in vivo manipulation of circGRIA1 negatively regulates Gria1 mRNA and protein levels. Knockdown of circGRIA1 results in an age-related improvement of synaptogenesis, and GluR1 activity-dependent synaptic plasticity in the hippocampal neurons in males. Our findings underscore the importance of circRNA regulation and offer an insight into the biology of brain aging.
Real-time 3D single molecule tracking
Authors: Hou Shangguo , Exell Jack , Welsher Kevin
Published: July 2020

To date, single molecule studies have been reliant on tethering or confinement to achieve long duration and high temporal resolution measurements. Here, we present a 3D single-molecule active real-time tracking method (3D-SMART) which is capable of locking on to single fluorophores in solution for minutes at a time with photon limited temporal resolution. As a demonstration, 3D-SMART is applied to actively track single Atto 647 N fluorophores in 90% glycerol solution with an average duration of ~16 s at count rates of ~10 kHz. Active feedback tracking is further applied to single proteins and nucleic acids, directly measuring the diffusion of various lengths (99 to 1385 bp) of single DNA molecules at rates up to 10 µm2/s. In addition, 3D-SMART is able to quantify the occupancy of single Spinach2 RNA aptamers and capture active transcription on single freely diffusing DNA. 3D-SMART represents a critical step towards the untethering of single molecule spectroscopy.
A universal and independent synthetic DNA ladder for the quantitative measurement of genomic features
Authors: Reis Andre L. M. , Deveson Ira W. , Wong Ted , Madala Bindu Swapna , Barker Chris , Blackburn James , Marcellin Esteban , Mercer Tim R.
Published: July 2020

Standard units of measurement are required for the quantitative description of nature; however, few standard units have been established for genomics to date. Here, we have developed a synthetic DNA ladder that defines a quantitative standard unit that can measure DNA sequence abundance within a next-generation sequencing library. The ladder can be spiked into a DNA sample, and act as an internal scale that measures quantitative genetics features. Unlike previous spike-ins, the ladder is encoded within a single molecule, and can be equivalently and independently synthesized by different laboratories. We show how the ladder can measure diverse quantitative features, including human genetic variation and microbial abundance, and also estimate uncertainty due to technical variation and improve normalization between libraries. This ladder provides an independent quantitative unit that can be used with any organism, application or technology, thereby providing a common metric by which genomes can be measured.
Mapping the oxygen structure of γ-Al2O3 by high-field solid-state NMR spectroscopy
Authors: Wang Qiang , Li Wenzheng , Hung Ivan , Mentink-Vigier Frederic , Wang Xiaoling , Qi Guodong , Wang Xiang , Gan Zhehong , Xu Jun , Deng Feng
Published: July 2020

γ-Al2O3 is one of the most widely used catalysts or catalyst supports in numerous industrial catalytic processes. Understanding the structure of γ-Al2O3 is essential to tuning its physicochemical property, which still remains a great challenge. We report a strategy for the observation and determination of oxygen structure of γ-Al2O3 by using two-dimensional (2D) solid-state NMR spectroscopy at high field. 2D 17O double-quantum single-quantum homonuclear correlation NMR experiment is conducted at an ultra-high magnetic field of 35.2 T to reveal the spatial proximities between different oxygen species from the bulk to surface. Furthermore, 2D proton-detected 1H-17O heteronuclear correlation NMR experiments allow for a rapid identification and differentiation of surface hydroxyl groups and (sub-)surface oxygen species. Our experimental results demonstrate a non-random distribution of oxygen species in γ-Al2O3.
An fMRI study of error monitoring in Montessori and traditionally-schooled children
Authors: Denervaud Solange , Fornari Eleonora , Yang Xiao-Fei , Hagmann Patric , Immordino-Yang Mary Helen , Sander David
Published: July 2020

The development of error monitoring is central to learning and academic achievement. However, few studies exist on the neural correlates of children’s error monitoring, and no studies have examined its susceptibility to educational influences. Pedagogical methods differ on how they teach children to learn from errors. Here, 32 students (aged 8–12 years) from high-quality Swiss traditional or Montessori schools performed a math task with feedback during fMRI. Although the groups’ accuracies were similar, Montessori students skipped fewer trials, responded faster and showed more neural activity in right parietal and frontal regions involved in math processing. While traditionally-schooled students showed greater functional connectivity between the ACC, involved in error monitoring, and hippocampus following correct trials, Montessori students showed greater functional connectivity between the ACC and frontal regions following incorrect trials. The findings suggest that pedagogical experience influences the development of error monitoring and its neural correlates, with implications for neurodevelopment and education.
Neurocognitive patterns dissociating semantic processing from executive control are linked to more detailed off-task mental time travel
Authors: Wang Hao-Ting , Ho Nerissa Siu Ping , Bzdok Danilo , Bernhardt Boris C. , Margulies Daniel S. , Jefferies Elizabeth , Smallwood Jonathan
Published: July 2020

Features of ongoing experience are common across individuals and cultures. However, certain people express specific patterns of thought to a greater extent than others. Contemporary psychological theory assumes that individual differences in thought patterns occur because different types of experience depend on the expression of different neurocognitive processes. Consequently, individual variation in the underlying neurocognitive architecture is hypothesised to determine the ease with which certain thought patterns are generated or maintained. Our study (N = 178) tested this hypothesis using multivariate pattern analysis to infer shared variance among measures of cognitive function and neural organisation and examined whether these latent variables explained reports of the patterns of on-going thoughts people experienced in the lab. We found that relatively better performance on tasks relying primarily on semantic knowledge, rather than executive control, was linked to a neural functional organisation associated, via meta-analysis, with task labels related to semantic associations (sentence processing, reading and verbal semantics). Variability of this functional mode predicted significant individual variation in the types of thoughts that individuals experienced in the laboratory: neurocognitive patterns linked to better performance at tasks that required guidance from semantic representation, rather than those dependent on executive control, were associated with patterns of thought characterised by greater subjective detail and a focus on time periods other than the here and now. These relationships were consistent across different days and did not vary with level of task demands, indicating they are relatively stable features of an individual’s cognitive profile. Together these data confirm that individual variation in aspects of ongoing experience can be inferred from hidden neurocognitive architecture and demonstrate that performance trade-offs between executive control and long-term semantic knowledge are linked to a person’s tendency to imagine situations that transcend the here and now.
Sex differences in visuomotor tracking
Authors: Mathew James , Masson Guillaume S. , Danion Frederic R.
Published: July 2020

There is a growing interest in sex differences in human and animal cognition. However, empirical evidences supporting behavioral and neural sex differences in humans remain sparse. Visuomotor behaviors offer a robust and naturalistic empirical framework to seek for the computational mechanisms underlying sex biases in cognition. In a large group of human participants (N = 127), we investigated sex differences in a visuo-oculo-manual motor task that consists of tracking with the hand a target moving unpredictably. We report a clear male advantage in hand tracking accuracy. We tested whether men and women employ different gaze strategy or hand movement kinematics. Results show no key difference in these distinct visuomotor components. However, highly consistent differences in eye-hand coordination were evidenced by a larger temporal lag between hand motion and target motion in women. This observation echoes with other studies showing a male advantage in manual reaction time to visual stimuli. We propose that the male advantage for visuomotor tracking does not reside in a more reliable gaze strategy, or in more sophisticated hand movements, but rather in a faster decisional process linking visual information about target motion with forthcoming hand, but not eye, actions.
Sirtuin-1 expression and activity is diminished in aged liver grafts
Authors: Scheuermann Uwe , Seyferth Elisabeth R. , Abraham Nader , Kesseli Samuel J. , Halpern Samantha E. , Zhu Minghua , Song Mingqing , Hartwig Matthew G. , Parker William , Kwun Jean , Cherry Anne D. , Lee Jaewoo , Barbas Andrew S.
Published: July 2020

The cellular mechanisms underlying impaired function of aged liver grafts have not been fully elucidated, but mitochondrial dysfunction appears to be contributory. Sirtuin1 has been identified as a key mediator of mitochondrial recovery following ischemia–reperfusion injury. The purpose of this study was to determine whether differences exist in sirtuin-1 expression/activity in old vs. young liver grafts and to determine correlations with mitochondrial function, graft metabolic function, and graft injury. Old and young rat liver grafts (N = 7 per group) were exposed to 12 h of static cold storage (SCS), followed by a 2 h period of graft reperfusion ex vivo. Sirtuin1 expression and activity, mitochondrial function, graft metabolic function, and graft injury were compared. Sirtuin1 expression is upregulated in young, but not old, liver grafts in response to cold storage and reperfusion. This is associated with diminished tissue ATP, antioxidant defense, and graft metabolic function in old liver grafts. There was no evidence of increased inflammation or histologic injury in old grafts. Sirtuin1 expression is diminished in old liver grafts and correlates with mitochondrial and metabolic function. The sirtuin pathway may represent a target for intervention to enhance the function of aged liver grafts.