bluuebunny/crossref_metadata_2025_split huggingface dataset:
The hepatocyte insulin receptor is required to program rhythmic gene expression and the liver clock
Authors: Fougeray Tiffany , Polizzi Arnaud , Régnier Marion , Fougerat Anne , Ellero-Simatos Sandrine , Lippi Yannick , Smati Sarra , Lasserre Frédéric , Tramunt Blandine , Huillet Marine , Dopavogui Léonie , Smith Lorraine , Naylies Claire , Sommer Caroline , Benani Alexandre , Haas Joel T. , Wahli Walter , Duez Hélène , Gourdy Pierre , Gamet-Payrastre Laurence , Burnol Anne-Françoise , Loiseau Nicolas , Postic Catherine , Montagner Alexandra , Guillou Hervé 
Published: February 2021

SUMMARYIn mammalian cells, gene expression is rhythmic and sensitive to various environmental and physiological stimuli. A circadian clock system helps to anticipate and synchronize gene expression with daily stimuli including cyclic light and food intake, which control the central and peripheral clock programs, respectively. Food intake also regulates insulin secretion. How much insulin contributes to the effect of feeding on the entrainment of the clock and rhythmic gene expression remains to be investigated.An important component of insulin action is mediated by changes in insulin receptor (IR)-dependent gene expression. In the liver, insulin at high levels controls the transcription of hundreds of genes involved in glucose homeostasis to promote energy storage while repressing the expression of gluconeogenic genes. In type 2 diabetes mellitus (T2DM), selective hepatic insulin resistance impairs the inhibition of hepatic glucose production while promoting lipid synthesis. This pathogenic process promoting hyperlipidemia as well as non-alcoholic fatty liver diseases.While several lines of evidence link such metabolic diseases to defective control of circadian homeostasis, the hypothesis that IR directly synchronizes the clock has not been studiedin vivo. Here, we used conditional hepatocyte-restricted gene deletion to evaluate the role of IR in the regulation and oscillation of gene expression as well as in the programming of the circadian clock in adult mouse liver.
Correction of measurement error in a commercial multiple-breath washout device
Authors: Wyler Florian , Oestreich Marc-Alexander , Frauchiger Bettina S. , Ramsey Kathryn , Latzin Philipp 
Published: February 2021

AbstractRationaleNitrogen multiple-breath washout (N2MBW) is an established technique to assess functional residual capacity (FRC) and ventilation inhomogeneity in the lung. Accurate measurement of gas concentrations is essential for the appropriate calculation of clinical outcomes.ObjectivesWe investigated the accuracy of oxygen and carbon dioxide measurements used for the indirect calculation of nitrogen concentration in a commercial MBW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and its impact on FRC and lung clearance index (LCI).MethodsHigh precision calibration gas mixtures and mass spectrometry were used to evaluate sensor output. We assessed the impact of corrected signal processing on FRC and LCI in a dataset of healthy children and children with cystic fibrosis using custom analysis software.ResultsWe found inadequate correction for the cross sensitivity of the oxygen and carbon dioxide sensors in the Exhalyzer D device. This results in an overestimation of expired nitrogen concentration, and consequently FRC and LCI outcomes. Breath-by-breath correction of this error reduced mean (SD) FRC by 8.9 (2.2)% and LCI by 11.9 (4.0)%. It also resulted in almost complete disappearance of the tissue nitrogen signal at the end of measurements.ConclusionsInadequate correction for cross sensitivity between the oxygen and carbon dioxide gas sensors of the Exhalyzer D device leads to an overestimation of FRC and LCI. Correction of this error is possible and could be applied by re-analysing the measurements breath-by-breath in an updated software version.Grants, Gifts, Equipment, DrugsEco Medics AG (Duernten, Switzerland) provided a research version of their commercial software Spiroware 3.2.1 including insight on signal processing algorithms and helped with the acquisition of mass spectrometry measurements. This project was funded by the Swiss National Science Foundation, Grant Nr. 182719 (P. Latzin) and 168173 (K. Ramsey)
Chronic Obstructive Pulmonary Disease Does Not Impair Responses to Resistance Training
Authors: Mølmen Knut S. , Hammarström Daniel , Falch Gunnar S. , Grundtvig Morten , Koll Lise , Hanestadhaugen Marita , Khan Yusuf , Ahmad Rafi , Malerbakken Bente , Rødølen Tore J. , Lien Roger , Rønnestad Bent R. , Raastad Truls , Ellefsen Stian 
Published: February 2021

AbstractRationaleSubjects with chronic obstructive pulmonary disease (COPD) are prone to accelerated decay of muscle strength and mass with advancing age. This is mediated by systemic pathophysiologies, which are also believed to impair responses to exercise training, a notion that remains largely unstudied.ObjectivesTo investigate the presence of impaired training responsiveness in COPD, measured as responses to resistance training compared to healthy participants.MethodsCOPD (GOLD grade II-III, n=20, age 69±5) and Healthy (n=58, age 67±4) conducted identical whole-body resistance training interventions, consisting of two weekly, supervised training sessions for 13 weeks. Leg exercises were performed unilaterally, with one leg conducting high-load training (10 repetitions maximum; RM) and the contralateral leg conducting low-load training (30RM).Measurements and Main ResultsMeasurements included muscle strength (n=7), endurance performance (n=6), muscle mass (n=2), muscle quality, muscle biology (vastus lateralis; muscle fiber characteristics, RNA content including transcriptome) and health-related variables (body composition, blood). For core outcome domains, weighted combined factors were calculated from the range of singular assessments.COPD showed marked improvements in lower-limb muscle strength/mass/quality and lower-limb/whole-body endurance performance, resembling or exceeding those of Healthy, measured as both relative and absolute change terms. This was accompanied by similar changes in muscle biological hallmarks (total RNA/rRNA content↑, muscle fiber cross-sectional area↑, type IIX proportions↓, changes in the mRNA transcriptome). Neither of the core outcome domains were differentially affected by resistance training load.ConclusionsCOPD showed marked, unimpaired and hitherto unrecognized responsiveness to resistance training, rejecting the notion of disease-related impairments in training responsiveness.
Assessment & mitigation of O2 therapy driven spread of COVID-19
Authors: Kudrolli Arshad , Chang Brian , Consalvi Jade , Deti Anton , Frechette Christopher , Scoville Helen , Sheinfeld Geoffrey R. , McGee William T. 
Published: February 2021

AbstractBACKGROUNDExhalation exposure from patients to healthcare workers (HCWs), while using a nasal cannula or simple O2 mask used in treating COVID-19 and other respiratory diseases, is a present and future risk. Little is known on exhalation dispersal through these devices, and on mitigating the viral exposure to those in the vicinity.METHODSRespiration through O2 therapy devices was studied with a supine manikin equipped with a controllable mechanical lung by measuring aerosol density and flow with direct imaging. Dispersal direction and distances were quantified while placing a surgical mask loosely over the devices and contrasted with unmitigated oxygenation device use. Exhalation jets were examined over the entire range of oxygenation rates used in treatment.RESULTSExhalation jets travel 0.35 ± 0.02 m upward while wearing a nasal cannula, and 0.29 ± 0.02 m laterally while wearing a simple O2 mask posing significant inhalation risk. Placing a surgical facemask loosely over the oxygenation device is demonstrated to alleviate exposure by reducing and deflecting the exhalation jets from being launched forward, and by reducing exhalations from being launched directly higher over a supine patient. Less than 12% of the exhaled breath is observed to reach above a masked face where HCWs would be present, independent of oxygen flow rates.CONCLUSIONSExhalation jets from both the nasal cannula or simple O2 mask were found to concentrate aerosol-laden exhalations directly in front of a patient’s face. Exposure is effectively mitigated with a surgical mask which reduces and redirects the exhalation downward away from HCWs.
Neuronal activity promotes nuclear proteasome-mediated degradation of PDCD4 to regulate activity-dependent transcription
Authors: Herbst Wendy A. , Deng Weixian , Wohlschlegel James A. , Achiro Jennifer M. , Martin Kelsey C. 
Published: February 2021

AbstractActivity-dependent gene expression is critical for synapse development and plasticity. To elucidate novel mechanisms linking neuronal activity to changes in transcription, we compared the nuclear proteomes of tetrodotoxin-silenced and bicuculline-stimulated cultured rodent neurons using nuclear-localized APEX2 proximity biotinylation and mass spectrometry. The tumor suppressor protein PDCD4 was enriched in the silenced nuclear proteome, and PDCD4 levels rapidly decreased in the nucleus and cytoplasm of stimulated neurons. The activity-dependent decrease of PDCD4 was prevented by inhibitors of both PKC and proteasome activity and by a phospho-incompetent mutation of Ser71 in the βTRCP ubiquitin ligase-binding motif of PDCD4. We compared the activity-dependent transcriptomes of neurons expressing wildtype or degradation-resistant (S71A) PDCD4. We identified 91 genes as PDCD4 targets at the transcriptional level, including genes encoding proteins critical for synapse formation, remodeling, and transmission. Our findings indicate that regulated degradation of nuclear PDCD4 facilitates activity-dependent transcription in neurons.
Emergence of Probabilistic Representation in the Neural Network of Primary Visual Cortex
Authors: Li Ang A. , Wang Fengchao , Zhang Xiaohui , Wu Si 
Published: February 2021

AbstractDuring the early development of mammalian visual system, the distribution of neuronal preferred orientations in the primary visual cortex (V1) gradually shifts to match the major orientation features of an environment, achieving optimal representation of the environment. By combining the computational modeling and experimental electrophysiological recording, we provide a circuitry plasticity mechanism that underlies the developmental emergence of such matched representation in the visual cortical network. Specifically, in a canonical circuit of densely interconnected pyramidal cells and inhibitory parvalbumin-expressing (PV+) fast-spiking interneurons in the V1 layer 2/3, our model successfully simulates the experimental observations and further reveals that the non-uniform inhibition, mediated by local interneurons, exerts a key role in shaping the network representation through spike timing-dependent synaptic modifications. The experimental results confirm that PV+ interneurons in the V1 are capable of providing such non-uniform inhibition during a short period after the vision onset. Thus, our study elucidates a circuitry mechanism for acquisition of the prior knowledge of environment for optimal inference in sensory neural system.
A water-reward task assay for evaluating mouse mutualistic cooperative behavior
Authors: Feng Weixi , Zhang Yanli , Wang Ze , Wang Tianqi , Pang Yingting , Zou Ying , Huang Huang , Sheng Chengyu , Xiao Ming 
Published: February 2021

AbstractSocial cooperation is fundamentally important for group animals but rarely studied with mice because of their natural aggressiveness. In the present work, we induced pairs of mice to develop a mutualistic cooperative behavior in a non-divided chamber. Each mouse was first trained to learn to use a water dispenser by occupying a particular zone served as a switch to the dispenser. Two trained mice were then put into a chamber containing two separate zones jointly controlling two dispensers. We recorded the latency before each co-drinking, the number and cumulated time of co-drinking each day during the test. These parameters served as quantitative measurements of cooperative behavior in mice. The whole procedure includes preparation, training and testing phases, which take 15 days in total. This assay provides detailed procedures and analytical methods for investigators to characterize and quantify the mutualistic cooperative behavior. The use of mice as subjects allows convenient coupling to other behavior assays and is amiable to genetic manipulations for mechanistic study.
The ribose methylation enzyme FTSJ1 has a conserved role in neuron morphology and learning performance
Authors: Brazane Mira , Dimitrova Dilyana G , Pigeon Julien , Paolantoni Chiara , Ye Tao , Marchand Virginie , Da Silva Bruno , Schaefer Elise , Angelova Margarita T , Stark Zornitza , Delatycki Martin , Dudding-Byth Tracy , Gecz Jozef , Placais Pierre-Yves , Teysset Laure , Preat Thomas , Piton Amélie , Hassan Bassem A. , Roignant Jean-Yves , Motorin Yuri , Carré Clément 
Published: February 2021

ABSTRACTFTSJ1 is a conserved human 2’-O-methyltransferase (Nm-MTase) that modifies several transfer RNAs (tRNAs) at position 32 and the wobble position 34 in the AntiCodon Loop (ACL). Its loss of function has been linked to Non-Syndromic X-Linked Intellectual Disability (NSXLID), and more recently to cancers. However, the molecular mechanisms underlying these pathologies are currently unclear. Here we report a novelFTSJ1pathogenic variant from a NSXLID patient. Using blood cells derived from this patient and other affected individuals carryingFTSJ1mutations, we performed an unbiased and comprehensive RiboMethSeq analysis to map the ribose methylation (Nm) on all human tRNAs and identify novel targets. In addition, we performed a transcriptome analysis in these cells and found that several genes previously associated with intellectual disability and cancers were deregulated. We also found changes in the miRNA population that suggest potential cross-regulation of some miRNAs with these key mRNA targets. Finally, we show that differentiation of FTSJ1-depleted human neuronal progenitor cells (NPC) into neurons displays long and thin spine neurites compared to control cells. These defects are also observed inDrosophilaand are associated with long term memory deficit in this organism. Altogether, our study adds insight into FTSJ1 pathologies in human and flies by the identification of novel FTSJ1 targets and the defect in neuron morphology.
Precise, Fast and Comprehensive Analysis of Intact Glycopeptides and Modified Saccharide Units with pGlyco3
Authors: Zeng Wen-Feng , Cao Wei-Qian , Liu Ming-Qi , He Si-Min , Yang Peng-Yuan 
Published: February 2021

AbstractWe present a glycan-first glycopeptide search engine, pGlyco3, to comprehensively analyze intact N- and O-glycopeptides, including glycopeptides with modified saccharide units. A novel glycan ion-indexing algorithm developed in this work for glycan-first search makes pGlyco3 5-40 times faster than other glycoproteomic search engines without decreasing the accuracies and sensitivities. By combining electron-based dissociation spectra, pGlyco3 integrates a fast, dynamic programming-based algorithm termed pGlycoSite for site-specific glycan localization (SSGL). Our evaluation based on synthetic and natural glycopeptides showed that the SSGL probabilities estimated by pGlycoSite were proved to be appropriate to localize site-specific glycans. With pGlyco3, we found that N-glycopeptides and O-mannose glycopeptides in yeast samples were extensively modified by ammonia adducts on Hex (aH) and verified the aH-glycopeptide identifications based on released N-glycans and15N/13C-labeled data. Thus pGlyco3, which is freely available onhttps://github.com/pFindStudio/pGlyco3/releases, is an accurate and flexible tool to identify glycopeptides and modified saccharide units.
Comparison analysis on transcriptomic of different human trophoblast development model
Authors: Liu Yajun , Guo Yilin , Gao Ya , Hu Guiming , Ren Jingli , Ma Jun , Cui Jinquan 
Published: February 2021

AbstractAimsMultiple models of trophoblastic cell development were developed. However, systematic comparisons of these cell models are lacking.Methods and ResultsIn this study, first-trimester chorionic villus and decidua tissues were collected. Transcriptome data was acquired by RNA-seq and the expression levels of trophoblast specific transcription factors were identified by immunofluorescence and RNA-seq data analysis.Differentially expressed genes between chorionic villus and decidua tissues and its related biological functions were identified. We identified genes that were relatively highly expressed and enriched transcription factors in trophoblast cells of different trophoblast cell models.ConclusionsThis analysis is of certain significance for further exploration of the development of placenta and the occurrence of pregnancy-related diseases in the future. The datasets and analysis provide a useful source for the researchers in the field of the maternal-fetal interface and the establishment of pregnancy.
Prevention of Diabetic Foot Ulcer in High Risk Patient: The Role of Internist in Providing Adequate Foot Care
Authors: Kshanti Ida Ayu , Soebijanto Nanang , Magfira Nadya , Epriliawati Marina , Nasarudin Jerry , Mokoagow Md Ikhsan 
Published: February 2021

ABSTRACTBackground and aimThe awareness and practice of diabetes foot prevention by internist through routine examination and patient education remains less than optimal. This study aimed to evaluate the quality of care of internist in performing foot care in high-risk patients.MethodsA cross sectional study was conducted in a tertiary care hospital in Jakarta, Indonesia. Type 2 diabetes mellitus subjects with high-risk foot complication were included in this study. Each subject filled-in a questionnaire investigating whether they had received information about proper foot care practice and whether they have ever had their feet examined by an internist at their present consultation. Multivariate logistic regression were performed.Results368 patients were recruited, 130 of them (35.3%) treated by endocrinologists. 71.20% patients did not received any information on foot care and 54.08% patients did not received any foot examination. Foot care information was 1.6 times more frequently provided to patient with longer diabetes duration and 2 times more frequently provided to those who had history of diabetic foot ulcer. Meanwhile, foot examination was 1.5 times more frequently provided to those with longer diabetes duration and had a history of Lower Extremity Amputation. Compare to non-endocrinologist internist, endocrinologists tend to provide foot education and perform foot examination 2.2 to 2.5 times more frequently than non-endocrinologists.ConclusionMost of patients with high risk foot problems were not offered adequate foot care. It is necessary to develop strategies to improve the care and awareness among health professionals treating patients with diabetes especially internist.
Discovery of cardiac imaging biomarkers by training neural network models across diagnostic modalities
Authors: Goto Shinichi , Werdich Andreas A. , Homilius Max , John Jenine E. , Gan Li-Ming , MacRae Calum A. , DiCarli Marcelo F. , Deo Rahul C. 
Published: February 2021

AbstractMachines can be readily trained to automate medical image interpretation, with the primary goal of replicating human capabilities. Here, we propose an alternative role: using machine learning to discover pragmatic imaging-based biomarkers by interpreting one complex imaging modality via a second, more ubiquitous, lower-cost modality. We applied this strategy to train convolutional neural network models to estimate positron emission tomography (PET)-derived myocardial blood flow (MBF) at rest and with hyperemic stress, and their ratio, coronary flow reserve (CFR), using contemporaneous two-dimensional echocardiography videos as inputs. The resulting parameters, echoAI-restMBF, echoAI-stressMBF, and echoAI-CFR modestly approximated the original values. However, using echocardiograms of 5,393 (derivation) and 5,289 (external validation) patients, we show they sharply stratify individuals according to disease comorbidities and combined with baseline demographics, are strong predictors for heart failure hospitalization (C-statistic derivation: 0.79, 95% confidence interval 0.77-0.81; validation: 0.81, 0.79-0.82) and acute coronary syndrome (C-statistic derivation: 0.77, 0.73-0.80; validation: 0.75, 0.73-0.78). Using echocardiograms of 3,926 genotyped individuals, we estimate narrow-sense heritability of 9.2%, 20.4% and 6.5%, respectively for echoAI-restMBF, echoAI-stressMBF, and echoAI-CFR. MBF indices show inverse genetic correlation with impedance-derived body mass indices, such as fat-free body mass (e.g., ρ=−0.43, q=0.05 for echoAI-restMBF) and resolve conflicting historical data regarding body mass index and CFR. In terms of diseases, genetic association with ischemic heart disease is seen most prominently for echoAI-stressMBF (ρ=−0.37, q=2.4×10−03). We hypothesize that interpreting one imaging modality through another represents a type of “information bottleneck”, capturing latent features of the original physiologic measurements that have relevance across tissues. Thus, we propose a broader potential role for machine learning algorithms in developing scalable biomarkers that are anchored in known physiology, representative of latent biological factors, and are readily deployable in population health applications.
Performance of three SARS-CoV-2 immunoassays, three rapid lateral flow tests and a novel bead-based affinity surrogate test for the detection of SARS-CoV-2 antibodies in human serum
Authors: Krone Manuel , Gütling Julia , Wagener Johannes , Lâm Thiên-Trí , Schoen Christoph , Vogel Ulrich , Stich August , Wedekink Florian , Wischhusen Jörg , Kerkau Thomas , Beyersdorf Niklas , Klingler Silvana , Backes Simone , Dölken Lars , Gasteiger Georg , Kurzai Oliver , Schubert-Unkmeir Alexandra 
Published: February 2021

AbstractFor the control of immunity in COVID-19 survivors and vaccinated subjects there is an urgent need for reliable and rapid serological assays.Based on samples from 63 COVID-19 survivors up to seven months after symptom onset, and on 50 serum samples taken before the beginning of the pandemic, we compared the performance of three commercial immunoassays for the detection of SARS-CoV-2 IgA and IgG antibodies (Euroimmun SARS-COV-2 IgA/IgG, Mikrogen recomWell SARS-CoV-2 IgA/IgG, and SERION ELISA agile SARS-CoV-2 IgA/IgG) and three rapid lateral flow (immunochromatographic) tests (Abbott Panbio COVID-19 IgG/IgM, NADAL COVID-19 IgG/IgM, and Cleartest Corona 2019-nCOV IgG/IgM) with a plaque-reduction neutralization test (PRNT50) representing the gold standard. In addition, we report and validate a novel, non-commercial flow cytometry bead-based surrogate test.57 out of 63 PCR-confirmed COVID-19 patients (90 %) showed neutralizing antibodies. The sensitivity of the seven assays ranged from 7.0 % to 98.3 %, the specificity from 86.0 % to 100.00 %. Only one commercial immunoassay showed a sensitivity and specificity of greater than 98 %. These data indicate abundant interassay variability.