bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain network dynamics during working memory are modulated by dopamine and diminished in schizophrenia
Authors: Braun Urs , Harneit Anais , Pergola Giulio , Menara Tommaso , Schäfer Axel , Betzel Richard F. , Zang Zhenxiang , Schweiger Janina I. , Zhang Xiaolong , Schwarz Kristina , Chen Junfang , Blasi Giuseppe , Bertolino Alessandro , Durstewitz Daniel , Pasqualetti Fabio , Schwarz Emanuel , Meyer-Lindenberg Andreas , Bassett Danielle S. , Tost Heike 
Published: June 2021

AbstractDynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory performance entails brain-wide switching between activity states using a combination of functional magnetic resonance imaging in healthy controls and individuals with schizophrenia, pharmacological fMRI, genetic analyses and network control theory. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Individuals with schizophrenia show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations. Our results demonstrate the relevance of dopamine signaling for the steering of whole-brain network dynamics during working memory and link these processes to schizophrenia pathophysiology.
Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue
Authors: Ribas-Latre Aleix , Santos Rafael Bravo , Fekry Baharan , Tamim Yomna M. , Shivshankar Samay , Mohamed Alaa M. T. , Baumgartner Corrine , Kwok Christopher , Gebhardt Claudia , Rivera Angielyn , Gao Zhanguo , Sun Kai , Heiker John T. , Snyder Brad E. , Kolonin Mikhail G. , Eckel-Mahan Kristin L. 
Published: June 2021

AbstractHyperplastic expansion of white adipose tissue (WAT) relies in part on the proliferation of adipocyte precursor cells residing in the stromal vascular cell fraction (SVF) of WAT. This study reveals a circadian clock- and feeding-induced diurnal pattern of cell proliferation in the SVF of visceral and subcutaneous WAT in vivo, with higher proliferation of visceral adipocyte progenitor cells subsequent to feeding in lean mice. Fasting or loss of rhythmic feeding eliminates this diurnal proliferation, while high fat feeding or genetic disruption of the molecular circadian clock modifies the temporal expression of proliferation genes and impinges on diurnal SVF proliferation in eWAT. Surprisingly, high fat diet reversal, sufficient to reverse elevated SVF proliferation in eWAT, was insufficient in restoring diurnal patterns of SVF proliferation, suggesting that high fat diet induces a sustained disruption of the adipose circadian clock. In conclusion, the circadian clock and feeding simultaneously impart dynamic, regulatory control of adipocyte progenitor proliferation, which may be a critical determinant of adipose tissue expansion and health over time.
Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine
Authors: Prattes Michael , Grishkovskaya Irina , Hodirnau Victor-Valentin , Rössler Ingrid , Klein Isabella , Hetzmannseder Christina , Zisser Gertrude , Gruber Christian C. , Gruber Karl , Haselbach David , Bergler Helmut 
Published: June 2021

AbstractThe hexameric AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis and initiates cytoplasmic maturation of the large ribosomal subunit by releasing the shuttling maturation factor Rlp24. Drg1 monomers contain two AAA-domains (D1 and D2) that act in a concerted manner. Rlp24 release is inhibited by the drug diazaborine which blocks ATP hydrolysis in D2. The mode of inhibition was unknown. Here we show the first cryo-EM structure of Drg1 revealing the inhibitory mechanism. Diazaborine forms a covalent bond to the 2′-OH of the nucleotide in D2, explaining its specificity for this site. As a consequence, the D2 domain is locked in a rigid, inactive state, stalling the whole Drg1 hexamer. Resistance mechanisms identified include abolished drug binding and altered positioning of the nucleotide. Our results suggest nucleotide-modifying compounds as potential novel inhibitors for AAA-ATPases.
Mechanistic insights into the R-loop formation and cleavage in CRISPR-Cas12i1
Authors: Zhang Bo , Luo Diyin , Li Yu , Perčulija Vanja , Chen Jing , Lin Jinying , Ye Yangmiao , Ouyang Songying 
Published: June 2021

AbstractCas12i is a newly identified member of the functionally diverse type V CRISPR-Cas effectors. Although Cas12i has the potential to serve as genome-editing tool, its structural and functional characteristics need to be investigated in more detail before effective application. Here we report the crystal structures of the Cas12i1 R-loop complexes before and after target DNA cleavage to elucidate the mechanisms underlying target DNA duplex unwinding, R-loop formation and cis cleavage. The structure of the R-loop complex after target DNA cleavage also provides information regarding trans cleavage. Besides, we report a crystal structure of the Cas12i1 binary complex interacting with a pseudo target oligonucleotide, which mimics target interrogation. Upon target DNA duplex binding, the Cas12i1 PAM-interacting cleft undergoes a remarkable open-to-closed adjustment. Notably, a zipper motif in the Helical-I domain facilitates unzipping of the target DNA duplex. Formation of the 19-bp crRNA-target DNA strand heteroduplex in the R-loop complexes triggers a conformational rearrangement and unleashes the DNase activity. This study provides valuable insights for developing Cas12i1 into a reliable genome-editing tool.
Altered heparan sulfate metabolism during development triggers dopamine-dependent autistic-behaviours in models of lysosomal storage disorders
Authors: De Risi Maria , Tufano Michele , Alvino Filomena Grazia , Ferraro Maria Grazia , Torromino Giulia , Gigante Ylenia , Monfregola Jlenia , Marrocco Elena , Pulcrano Salvatore , Tunisi Lea , Lubrano Claudia , Papy-Garcia Dulce , Tuchman Yaakov , Salleo Alberto , Santoro Francesca , Bellenchi Gian Carlo , Cristino Luigia , Ballabio Andrea , Fraldi Alessandro , De Leonibus Elvira 
Published: June 2021

AbstractLysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism.
Dynamics based on analysis of public data for spreading of disease
Authors: Lima Leonardo S. 
Published: June 2021

AbstractThe stochastic model for epidemic spreading of the novel coronavirus disease based on the data set supply by the public health agencies in countries as Brazil, United States and India is investigated. We perform a numerical analysis using the stochastic differential equation in Itô’s calculus for the estimating of novel cases daily, as well as analytical calculations solving the correspondent Fokker–Planck equation for the probability density distribution of novel cases, P(N(t), t). Our results display that the model based in the Itô’s diffusion fits well to the results due to uncertainty in the official data and to the number of tests realized in populations of each country.
A critical look at the prediction of the temperature field around a laser-induced melt pool on metallic substrates
Authors: Shu Yi , Galles Daniel , Tertuliano Ottman A. , McWilliams Brandon A. , Yang Nancy , Cai Wei , Lew Adrian J. 
Published: June 2021

AbstractThe study of microstructure evolution in additive manufacturing of metals would be aided by knowing the thermal history. Since temperature measurements beneath the surface are difficult, estimates are obtained from computational thermo-mechanical models calibrated against traces left in the sample revealed after etching, such as the trace of the melt pool boundary. Here we examine the question of how reliable thermal histories computed from a model that reproduces the melt pool trace are. To this end, we perform experiments in which one of two different laser beams moves with constant velocity and power over a substrate of 17-4PH SS or Ti-6Al-4V, with low enough power to avoid generating a keyhole. We find that thermal histories appear to be reliably computed provided that (a) the power density distribution of the laser beam over the substrate is well characterized, and (b) convective heat transport effects are accounted for. Poor control of the laser beam leads to potentially multiple three-dimensional melt pool shapes compatible with the melt pool trace, and therefore to multiple potential thermal histories. Ignoring convective effects leads to results that are inconsistent with experiments, even for the mild melt pools here.
Clinical predictors of cybersickness in virtual reality (VR) among highly stressed people
Authors: Kim Hyewon , Kim Dong Jun , Chung Won Ho , Park Kyung-Ah , Kim James D. K. , Kim Dowan , Kim Kiwon , Jeon Hong Jin 
Published: June 2021

AbstractThe use of virtual reality (VR) in the treatment of psychiatric disorders is increasing, and cybersickness has emerged as an important obstacle to overcome. However, the clinical factors affecting cybersickness are still not well understood. In this study, we investigated clinical predictors and adaptation effect of cybersickness during VR application in highly stressed people. Eighty-three healthy adult participants with high stress level were recruited. At baseline, we conducted psychiatric, ophthalmologic, and otologic evaluations and extracted physiological parameters. We divided the participants into two groups according to the order of exposure to VR videos with different degrees of shaking and repetitively administered the Simulator Sickness Questionnaire (SSQ) and the Fast Motion sickness Scale (FMS). There was no significant difference in changes in the SSQ or the FMS between groups. The 40–59 years age group showed a greater increase in FMS compared to the 19–39 years age group. Smoking was negatively associated with cybersickness, and a high Positive Affect and Negative Affect Schedule score was positively associated with cybersickness. In conclusion, changing the intensity of shaking in VR did not affect cybersickness. While smoking was a protective factor, more expression of affect was a risk factor for cybersickness.
Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet
Authors: Yamakage Shu , Oe Yuji , Sato Emiko , Okamoto Koji , Sekimoto Akiyo , Kumakura Satoshi , Sato Hiroshi , Yoshida Mai , Nagasawa Tasuku , Miyazaki Mariko , Ito Sadayoshi , Mackman Nigel , Takahashi Nobuyuki 
Published: June 2021

AbstractPatients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases. However, the role of monocyte myeloid cell TF in CKD progression remains unclear. We aimed to clarify this issue, and the present study found that patients with CKD had elevated levels of D-dimer, a marker of fibrin degradation, which was associated with decreased estimated glomerular filtration rate and increased serum levels of uremic toxins, such as indoxyl sulfate. In vitro studies showed that several uremic toxins increased cellular TF levels in monocytic THP-1 cells. Mice with TF specifically deleted in myeloid cells were fed an adenine diet to cause uremic kidney injury. Myeloid TF deletion reduced tubular injury and pro-inflammatory gene expression in the kidneys of adenine-induced CKD but did not improve renal function as measured by plasma creatinine or blood urea nitrogen. Collectively, our findings suggest a novel concept of pathogenesis of coagulation-mediated kidney injury, in which elevated TF levels in monocytes under uremic conditions is partly involved in the development of CKD.
Novel insights of waterborne human rotavirus A in Riyadh (Saudi Arabia) involving G2 predominance and emergence of a thermotolerant sequence
Authors: Nour Islam , Hanif Atif , Alanazi Ibrahim O. , Al-Ashkar Ibrahim , Alhetheel Abdulkarim , Eifan Saleh 
Published: June 2021

AbstractThe routine evaluation of water environments is necessary to manage enteric virus-mediated fecal contamination and the possible emergence of novel variants. Here, we detected human rotavirus A (HRVA) circulating in two wastewater treatment plants, two lakes, irrigation water and a wastewater landfill located in Riyadh. VP7-derived surface protein sequences were assessed by phylogenetic analyses and inspection of thermotolerance-mediated secondary structure and seasonal variation. HRVA was most prevalent at An-Nazim wastewater landfill (AN-WWLF; 63.89%). Phylogenetic analyzes revealed the predominance of HRVA G2 lineage for the first time in Saudi Arabia. Moreover, a single HRVA sequence (2B64I-ANLF3/2018) was recovered at 45 °C from AN-WWLF; secondary structure prediction indicated that this sequence was thermotolerant with a high hydrophobicity, an absence of Ramachandran outliers, and a higher content of proline patches on the protein surface. Varied relationships were significantly observed between sampling areas influenced by temperature ranges (p < 0.05). HRVA prevalence was influenced by seasonal variations, favoring moderate temperatures in late autumn and early winter in all locations. However, a significant temperature impact was detected in Wadi-Hanifah Lake (p = 0.01). Our study extends the knowledge of currently circulating HRVA genotypes, and indicates the probable emergence of thermotolerant strains and seasonally mediated HRVA prevalence.
Dietary patterns related to zinc and polyunsaturated fatty acids intake are associated with serum linoleic/dihomo-γ-linolenic ratio in NHANES males and females
Authors: Monteiro Jacqueline Pontes , Fuzo Carlos A. , Ued Fábio V. , Kaput Jim 
Published: June 2021

AbstractIdentifying dietary patterns that contribute to zinc (Zn) and fatty acids intake and their biomarkers that may have an impact on health of males and females. The present study was designed to (a) extract dietary patterns with foods that explain the variation of Zn and PUFAs intake in adult men and women; and (b) evaluate the association between the extracted dietary patterns with circulating levels of serum dihomo-γ-linolenic fatty acid (DGLA) or serum linoleic/dihomo-γ-linolenic (LA/DGLA) ratio in males and females. We used reduced rank regression (RRR) to extract the dietary patterns separated by sex in the NHANES 2011–2012 data. A dietary pattern with foods rich in Zn (1st quintile = 8.67 mg/day; 5th quintile = 11.11 mg/day) and poor in PUFAs (5th quintile = 15.28 g/day; 1st quintile = 18.03 g/day) was found in females (S-FDP2) and the same pattern, with foods poor in PUFAs (5th quintile = 17.6 g/day; 1st quintile = 20.7 g/day) and rich in Zn (1st quintile = 10.4 mg/day; 5th quintile = 12.9 mg/day) (S-MDP2), was found in males. The dietary patterns with foods rich in Zn and poor in PUFAs were negatively associated with serum LA/DGLA ratio. This is the first study to associate the LA/DGLA ratio with Zn and PUFAs related dietary patterns in males and females.
Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration
Authors: Guarin Marlly , Faelens Ruben , Giusti Arianna , De Croze Noémie , Léonard Marc , Cabooter Deirdre , Annaert Pieter , de Witte Peter , Ny Annelii 
Published: June 2021

AbstractZebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 µM) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperitoneally (IP) and yolk sac (IY) of 3 dpf zebrafish eleuthero-embryos. By modelling the fluorescence of whole-body contours present in fluorescence images, the main pharmacokinetic (PK) parameter values of the compounds were determined. It was demonstrated that especially in case of short incubations (1–3 h) immersion can result in limited intrabody exposure to compounds. In this case, PC and IP microinjections represent excellent alternatives. Significantly, IY microinjections did not result in a suitable intrabody distribution of the compounds. Performing a QSPkR (quantitative structure-pharmacokinetic relationship) analysis, LogD was identified as the only molecular descriptor that explains the final uptake of the selected compounds. It was also shown that combined administration of compounds (immersion and microinjection) provides a more stable intrabody exposure, at least in case of a prolonged immersion and compounds with LogD value > 1. These results will help reduce the risk of false negative results and can offer an invaluable input for future translational research and safety assessment applications.
Development of a time-series shotgun metagenomics database for monitoring microbial communities at the Pacific coast of Japan
Authors: Yoshitake Kazutoshi , Kimura Gaku , Sakami Tomoko , Watanabe Tsuyoshi , Taniuchi Yukiko , Kakehi Shigeho , Kuwata Akira , Yamaguchi Haruyo , Kataoka Takafumi , Kawachi Masanobu , Ikeo Kazuho , Tan Engkong , Igarashi Yoji , Ohtsubo Masafumi , Watabe Shugo , Suzuki Yutaka , Asakawa Shuichi , Ishino Sonoko , Tashiro Kosuke , Ishino Yoshizumi , Kobayashi Takanori , Mineta Katsuhiko , Gojobori Takashi 
Published: June 2021

AbstractAlthough numerous metagenome, amplicon sequencing-based studies have been conducted to date to characterize marine microbial communities, relatively few have employed full metagenome shotgun sequencing to obtain a broader picture of the functional features of these marine microbial communities. Moreover, most of these studies only performed sporadic sampling, which is insufficient to understand an ecosystem comprehensively. In this study, we regularly conducted seawater sampling along the northeastern Pacific coast of Japan between March 2012 and May 2016. We collected 213 seawater samples and prepared size-based fractions to generate 454 subsets of samples for shotgun metagenome sequencing and analysis. We also determined the sequences of 16S rRNA (n = 111) and 18S rRNA (n = 47) gene amplicons from smaller sample subsets. We thereafter developed the Ocean Monitoring Database for time-series metagenomic data (http://marine-meta.healthscience.sci.waseda.ac.jp/omd/), which provides a three-dimensional bird’s-eye view of the data. This database includes results of digital DNA chip analysis, a novel method for estimating ocean characteristics such as water temperature from metagenomic data. Furthermore, we developed a novel classification method that includes more information about viruses than that acquired using BLAST. We further report the discovery of a large number of previously overlooked (TAG)n repeat sequences in the genomes of marine microbes. We predict that the availability of this time-series database will lead to major discoveries in marine microbiome research.
CubeSats deliver new insights into agricultural water use at daily and 3 m resolutions
Authors: Aragon Bruno , Ziliani Matteo G. , Houborg Rasmus , Franz Trenton E. , McCabe Matthew F. 
Published: June 2021

AbstractEarth observation has traditionally required a compromise in data collection. That is, one could sense the Earth with high spatial resolution occasionally; or with lower spatial fidelity regularly. For many applications, both frequency and detail are required. Precision agriculture is one such example, with sub-10 m spatial, and daily or sub-daily retrieval representing a key goal. Towards this objective, we produced the first cloud-free 3 m daily evaporation product ever retrieved from space, leveraging recently launched nano-satellite constellations to showcase this emerging potential. Focusing on three agricultural fields located in Nebraska, USA, high-resolution crop water use estimates are delivered via CubeSat-based evaporation modeling. Results indicate good model agreement (r2 of 0.86–0.89; mean absolute error between 0.06 and 0.08 mm/h) when evaluated against corrected flux tower data. CubeSat technologies are revolutionizing Earth observation, delivering novel insights and new agricultural informatics that will enhance food and water security efforts, and enable rapid and informed in-field decision making.
Detection of glioma infiltration at the tumor margin using quantitative stimulated Raman scattering histology
Authors: Pekmezci Melike , Morshed Ramin A. , Chunduru Pranathi , Pandian Balaji , Young Jacob , Villanueva-Meyer Javier E. , Tihan Tarik , Sloan Emily A. , Aghi Manish K. , Molinaro Annette M. , Berger Mitchel S. , Hervey-Jumper Shawn L. 
Published: June 2021

AbstractIn the management of diffuse gliomas, the identification and removal of tumor at the infiltrative margin remains a central challenge. Prior work has demonstrated that fluorescence labeling tools and radiographic imaging are useful surgical adjuvants with macroscopic resolution. However, they lose sensitivity at the tumor margin and have limited clinical utility for lower grade histologies. Fiber-laser based stimulated Raman histology (SRH) is an optical imaging technique that provides microscopic tissue characterization of unprocessed tissues. It remains unknown whether SRH of tissues taken from the infiltrative glioma margin will identify microscopic residual disease. Here we acquired glioma margin specimens for SRH, histology, and tumor specific tissue characterization. Generalized linear mixed models were used to evaluate agreement. We find that SRH identified residual tumor in 82 of 167 margin specimens (49%), compared to IHC confirming residual tumor in 72 of 128 samples (56%), and H&E confirming residual tumor in 82 of 169 samples (49%). Intraobserver agreements between all 3 modalities were confirmed. These data demonstrate that SRH detects residual microscopic tumor at the infiltrative glioma margin and may be a promising tool to enhance extent of resection.