bluuebunny/crossref_metadata_2025 huggingface dataset:
A recurrent cortical model can parsimoniously explain the effect of expectations on sensory processes
Authors: Urgen Buse M. , Boyaci Huseyin
Published: February 2021

The effect of prior knowledge and expectations on perceptual and decision-making processes have been extensively studied. Yet, the computational mechanisms underlying those effects have been a controversial issue. Recently, using a recursive Bayesian updating scheme, unmet expectations have been shown to entail further computations, and consequently delay perceptual processes. Here we take a step further and model these empirical findings with a recurrent cortical model, which was previously suggested to approximate Bayesian inference (Heeger, 2017). Our model fitting results show that the cortical model can successfully predict the behavioral effects of expectation. That is, when the actual sensory input does not match with the expectations, the sensory process needs to be completed with additional, and consequently longer, computations. We suggest that this process underlies the delay in perceptual thresholds in unmet expectations. Overall our findings demonstrate that a parsimonious recurrent cortical model can explain the effects of expectation on sensory processes.
Large-scale tandem mass spectrum clustering using fast nearest neighbor searching
Authors: Bittremieux Wout , Laukens Kris , Noble William Stafford , Dorrestein Pieter C.
Published: February 2021

Rationale

Advanced algorithmic solutions are necessary to process the ever increasing amounts of mass spectrometry data that is being generated. Here we describe thefalconspectrum clustering tool for efficient clustering of millions of MS/MS spectra.

Methods

falconsucceeds in efficiently clustering large amounts of mass spectral data using advanced techniques for fast spectrum similarity searching. First, high-resolution spectra are binned and converted to low-dimensional vectors using feature hashing. Next, the spectrum vectors are used to construct nearest neighbor indexes for fast similarity searching. The nearest neighbor indexes are used to efficiently compute a sparse pairwise distance matrix without having to exhaustively perform all pairwise spectrum comparisons within the relevant precursor mass tolerance. Finally, density-based clustering is performed to group similar spectra into clusters.

Results

Several state-of-the-art spectrum clustering tools were evaluated using a large draft human proteome dataset consisting of 25 million spectra, indicating that alternative tools produce clustering results with different characteristics. Notably,falcongenerates larger highly pure clusters than alternative tools, leading to a larger reduction in data volume without the loss of relevant information for more efficient downstream processing.

Conclusions

falconis a highly efficient spectrum clustering tool. It is publicly available as open source under the permissive BSD license athttps://github.com/bittremieux/falcon.
Somatostatin-positive Interneurons Contribute to Seizures inSCN8AEpileptic Encephalopathy
Authors: Wengert Eric R. , Wedgwood Kyle C.A. , Wagley Pravin K. , Strohm Samantha M. , Panchal Payal S. , Majidi Abrar Idrissi , Wenker Ian C. , Gaykema Ronald P. , Patel Manoj K.
Published: February 2021

SCN8Aepileptic encephalopathy is a devastating epilepsy syndrome caused by mutantSCN8Awhich encodes the voltage-gated sodium channel NaV1.6. To date, it is unclear if and how inhibitory interneurons, which express NaV1.6, influence disease pathology. We found that selective expression of the R1872W mutation in somatostatin (SST) interneurons was sufficient to convey susceptibility to audiogenic seizures. SST interneurons from mutant mice were hyperexcitable but hypersensitive to action potential failure via depolarization block under normal and seizure-like conditions. Remarkably, GqDREADD-mediated activation of wild-type SST interneurons resulted in prolonged electrographic seizures and was accompanied by SST hyperexcitability and depolarization block. Aberrantly large persistent sodium currents, a hallmark ofSCN8Amutations, were observed and were found to contribute directly to aberrant SST physiology in computational and pharmacological experiments. These novel findings demonstrate a critical and previously unidentified contribution of SST interneurons to seizure generation not only inSCN8Aencephalopathy, but epilepsy in general.
Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors
Authors: Friedman Ryan Z. , Granas David M. , Myers Connie A. , Corbo Joseph C. , Cohen Barak A. , White Michael A.
Published: February 2021

Enhancers and silencers often depend on the same transcription factors (TFs) and are conflated in genomic assays of TF binding or chromatin state. To identify sequence features that distinguish enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX in mouse retinas. Both enhancers and silencers contain more TF motifs than inactive sequences, but relative to silencers, enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. The ability of information content to distinguish enhancers and silencers targeted by the same TF illustrates how motif context determines the activity ofcis-regulatory sequences.
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

In 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

Rationale

Nitrogen 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.

Objectives

We 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).

Methods

High 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.

Results

We 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.

Conclusions

Inadequate 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, Drugs

Eco 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

Rationale

Subjects 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.

Objectives

To investigate the presence of impaired training responsiveness in COPD, measured as responses to resistance training compared to healthy participants.

Methods

COPD (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 Results

Measurements 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.

Conclusions

COPD 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

BACKGROUND

Exhalation 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.

METHODS

Respiration 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.

RESULTS

Exhalation 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.

CONCLUSIONS

Exhalation 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

Activity-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

During 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

Social 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

FTSJ1 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

We 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

Aims

Multiple models of trophoblastic cell development were developed. However, systematic comparisons of these cell models are lacking.

Methods and Results

In 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.

Conclusions

This 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

Background and aim

The 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.

Methods

A 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.

Results

368 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.

Conclusion

Most 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

Machines 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

For 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.
Explaining ethnic disparities in COVID-19 mortality: population-based, prospective cohort study
Authors: Batty G. David , Gaye Bamba , Gale Catharine R , Hamer Mark , Lassale Camille
Published: February 2021

Ethnic disparities in COVID-19 hospitalizations and mortality have been reported but there is scant understanding of how these inequalities are embodied. The UK Biobank prospective cohort study comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on ethnic background and potential explanatory factors was captured. Study members were linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 354 deaths were ascribed to COVID-19 between 5th March and the end of follow-up on 17th September 2020. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced around seven times the risk of COVID-19 mortality (odds ratio; 95% confidence interval: 7.25; 4.65, 11.33), while there was a doubling in the Asian group (1.98; 1.02, 3.84). Controlling for baseline comorbidities, socioeconomic circumstances, and lifestyle factors explained 53% of the differential in risk for Asian people (1.37; 0.68, 2.77) and 27% in Black study members (4.28; 2.67, 6.86). The residual risk in ethnic minority groups for COVID-19 deaths may be ascribed to unknown genetic factors or unmeasured phenotypes, most obviously racial discrimination.
Effects of Resistant Starch on Symptoms, Fecal Markers and Gut Microbiota in Parkinson’s Disease – The RESISTA-PD Trial
Authors: Becker Anouck , Schmartz Georges Pierre , Gröger Laura , Grammes Nadja , Galata Valentina , Philippeit Hannah , Weiland Jacqueline , Ludwig Nicole , Meese Eckart , Tierling Sascha , Walter Jörn , Schwiertz Andreas , Spiegel Jörg , Wagenpfeil Gudrun , Faßbender Klaus , Keller Andreas , Unger Marcus M.
Published: February 2021

The composition of the gut microbiome is linked to multiple diseases, including Parkinson’s disease (PD). Bacteria producing short-chain fatty acids (SCFAs) and fecal SCFA concentrations are reduced in PD. SCFAs exert various beneficial functions in humans. In the interventional, monocentric, open-label clinical trial RESISTA-PD (NCT02784145) we aimed at altering fecal SCFAs by an 8-week prebiotic intervention with resistant starch (RS). We enrolled 87 subjects in three study-arms: 32 PD patients receiving RS (PD + RS), 30 control subjects receiving RS, and 25 PD patients receiving solely dietary instructions. We performed paired-end 100 base pair length metagenomic sequencing of fecal samples using the BGISEQ platform at an average of 9.9 GB. RS was well-tolerated. In PD + RS, fecal butyrate concentrations increased significantly and fecal calprotectin concentrations dropped significantly after 8 weeks of RS. Clinically, we observed a reduction in non-motor symptoms load in PD + RS. The reference-based analysis of metagenomes highlighted stable alpha-diversity and beta-diversity across the three groups, including bacteria producing SCFAs. Reference-free analysis suggested punctual, yet pronounced differences in the metagenomic signature in PD + RS. RESISTA-PD highlights that a prebiotic treatment with RS is safe and well-tolerated in PD. The stable alpha-diversity and beta-diversity alongside altered fecal butyrate and calprotectin concentrations calls for long-term studies, also investigating whether RS is able to modify the clinical course of PD.
Leaf economics explained by optimality principles
Authors: Wang Han , Prentice I. Colin , Wright Ian J. , Qiao Shengchao , Xu Xiangtao , Kikuzawa Kihachiro , Stenseth Nils Chr.
Published: February 2021

The worldwide leaf economics spectrum relates leaf lifespan (LL) to leaf dry mass per unit area (LMA)1. By combining three well-supported principles2-4, we show that an isometric relationship between these two quantities maximizes the leaf’s net carbon gain. This theory predicts a spectrum of equally competent LMA-LL combinations in any given environment, and how their optimal ratio varies across environments. By analysing two large, independent leaf-trait datasets for woody species1,5, we provide quantitative empirical support for the predicted dependencies of LL on LMA and environment in evergreen plants, and for the distinct predicted dependencies of LMA on light, temperature, growing-season length and aridity in evergreen and deciduous plants. We thereby resolve the long-standing question of why deciduous LMA tends to increase (with increasing LL) towards the equator, while evergreen LMA and LL decrease6. We also show how the statistical distribution of LMA within communities can be modelled as an outcome of environmental selection on the global pool of species with diverse values of LMA and LL.
Transcriptomic and genetic analyses identify the Krüppel-like factor dar1 as a master regulator of tube-shaped long tendon development
Authors: Quentin Laurichesse , Blandine Moucaud , Krzysztof Jagla , Cédric Soler
Published: February 2021

To ensure locomotion and body stability, the active role of muscle contractions relies on a stereotyped muscle pattern set in place during development. This muscle patterning requires a precise assembly of the muscle fibers with the skeleton via a specialized connective tissue, the tendon. Despite evident disparities, little is known about the molecular basis of tendon diversity. Like in vertebrate limbs,Drosophilaleg muscles make connections with specific long tendons that extend through different segments. During leg disc development, cell precursors of long tendons rearrange and collectively migrate to form a tube-shaped structure. A specific developmental program underlies this unique feature of tendon-like cells in theDrosophilamodel. We provide for the first time a transcriptomic profile of leg tendon precursors through fluorescence-based cell sorting. From promising candidates, we identified the Krüppel-like factor dar1 as a critical actor of leg tendon development. Specifically expressed in leg tendon precursors, loss ofdar1disrupts actin-rich filopodia formation and tendon elongation. Our findings show that dar1 acts downstream of stripe as a critical regulator of cytoskeleton remodeling and mediates the recruitment of new stripe-positive tendon progenitors in a cell non-autonomous manner.
A structured reflective process supports student awareness of employability skills development in a science placement module
Authors: Mello Luciane V. , Varga-Atkins Tunde , Edwards Steve W.
Published: February 2021

Placements are often an extra-curricular activity of a science degree. This study reports on the outcomes of a final year credit-bearing 6-week placement module that was specifically designed to develop and enhance students’ employability skills. A key element of this module was that the student placements were not just evaluated from a science perspective, but with an emphasis on meaningful reflection and evaluation of employability skills development. Students recorded their levels of confidence in skills before, during and after the placement via an Online Reflective Log, as part of a module’s summative assessment. First, results showed that taking part in the placement and conducting their own independent research helped students to make connections between their scientific knowledge, otherwise constrained within the walls of the undergraduate science lab, and the wider impact of their research on society. Another theme that emerged concerned career choices and aspirations, and the placement experience either confirmed prior choices or opened new horizons. The Online Reflective Log helped students to feel supported by their university supervisor who were at a distance, while feedback on their tasks challenged them to reflect on the scientific and personal skills as they were engaged in scientific activities during placement. Students agreed that they had further developed their employability skills during the placement. Students acknowledged it was challenging to have to acquire evidence of skills development but appreciated the usefulness of this reflection in relation to their future careers.
Maternal behavioural thermoregulation facilitated evolutionary transitions from egg laying to live birth
Authors: Pettersen Amanda K. , Feiner Nathalie , Noble Daniel W.A. , While Geoffrey M. , Uller Tobias , Cornwallis Charlie K.
Published: February 2021

Live birth is a key innovation that has evolved from egg laying ancestors over 100 times in reptiles. However, egg-laying lizards and snakes often possess preferred body temperatures that are lethal to developing embryos, which should select against egg retention. Here, we demonstrate that thermal mismatches between mothers and offspring are widespread across the squamate phylogeny. This mismatch is resolved by gravid females adjusting their body temperature towards the thermal optimum of embryos. Importantly, phylogenetic reconstructions suggest this thermoregulatory behaviour evolved in egg-laying species prior to the evolution of live birth. Maternal thermoregulatory behaviour therefore bypasses the constraints imposed by a slowly evolving thermal physiology and has likely been a key facilitator in the repeated transitions to live birth.
Loss of PABPC1 is compensated by elevated PABPC4 and correlates with transcriptome changes
Authors: Xie Jingwei , Wei Xiaoyu , Chen Yu
Published: February 2021

Cytoplasmic poly(A) binding protein (PABP) is an essential translation factor that binds to the 3’ tail of mRNAs to promote translation and regulate mRNA stability. PABPC1 is the most abundant of several PABP isoforms that exist in mammals. Here, we used the CRISPR/Cas genome editing system to shift the isoform composition in HEK293 cells. Disruption of PABPC1 elevated PABPC4 levels. Transcriptome analysis revealed that the shift in the dominant PABP isoform was correlated with changes in key transcriptional regulators. This study provides insight into understanding the role of PABP isoforms in development and differentiation.
A model of working memory for latent representations
Authors: Hedayati Shekoofeh , O′Donnell Ryan , Wyble Brad
Published: February 2021

Visual knowledge obtained from our lifelong experience of the world plays a critical role in our ability to build short-term memories. We propose a mechanistic explanation of how working memories are built from the latent representations of visual knowledge and can then be reconstructed. The proposed model, Memory for Latent Representations (MLR), features a variational autoencoder with an architecture that corresponds broadly to the human visual system and an activation-based binding pool of neurons that binds items’ attributes to tokenized representations. The simulation results revealed that the shapes of familiar items can be encoded and retrieved efficiently from latents in higher levels of the visual hierarchy. On the other hand, novel patterns that are completely outside the training set can be stored from a single exposure using only latents from early layers of the visual system. Moreover, a given stimulus in working memory can have multiple codes, representing specific visual features such as shape or color, in addition to categorical information. Finally, we validated our model by testing a series of predictions against behavioral results obtained from WM tasks. The model provides a compelling demonstration of how visual knowledge yields compact visual representation for efficient memory encoding.
Plasmodium falciparumKelch13 and its artemisinin-resistant mutants assemble as hexamers in solution: a SAXS data driven shape restoration study
Authors: Goel Nainy , Dhiman Kanika , Kalidas Nidhi , Mukhopadhyay Anwesha , Ashish  , Bhattacharjee Souvik
Published: February 2021

Artemisinin-resistant mutations in PfKelch13 identified worldwide are mostly confined to its BTB/POZ and KRP domains. To date, only two crystal structures of the BTB/POZ-KRP domains as tight dimers are available, which limits structure-based interpretations of its functionality. Our solution Small-Angle X-ray Scattering (SAXS) data driven shape restoration of larger length of protein brought forth that: i) PfKelch13 forms a stable hexamer in P6 symmetry, ii) interactions of the N-termini drive the hexameric assembly, and iii) the six KRP domains project independently in space, forming a cauldron-like architecture. While artemisinin-sensitive mutant A578S packed like the wild-type, hexameric assemblies of dominant artemisinin-resistant mutant proteins R539T and C580Y displayed detectable differences in spatial positioning of their BTB/POZ-KRP domains. Lastly, mapping of mutations known to enable artemisinin resistance explained that most mutations exist mainly in these domains because they are non-detrimental to assembly of mutant PfKelch13 and yet can alter the flux of downstream events essential for susceptibility to artemisinin.
Beverage made from babassu nut kernels and grape fruit: physicochemical properties and sensory acceptance
Authors: Silva Euzedith Sousa , Mendonça Gislane Romano , Pinto Rodrigo Anacleto , Lemos Tatiana de Oliveira , Abreu Virgínia Kelly Gonçalves , Pereira Ana Lúcia Fernandes
Published: February 2021

Purpose

The purpose of this study was to develop plant-based babassu milk flavored with grape fruit (GF).

Design/methodology/approach

A four mixed beverages formulations containing 15%, 25%, 35% and 45% GF were produced. The pH, titratable acidity (TA), soluble solids (SS), sugar: acid ratio and color analysis were performed. Sensory evaluation was measured by the hedonic scale, just-about-right (JAR) scale and purchase intent. Moreover, a check-all-that-apply (CATA) form was applied to obtain description data on the formulations.

Findings

The pH values of mixed beverages decreased (p < 0.05) when the concentration of GF increased, while the TA and the SS increased (p < 0.05). The GF addition provided the product with greater opaque and redness. Sensory evaluation revealed good consumer acceptance. For the hedonic scale, 35% and 45% GF contributed to the higher acceptance of color, appearance, flavor and overall liking attributes. For JAR data, the flavor grape term was highest in the JAR region (51%) with 45% GF. Based on the frequency of terms cited by consumers in the CATA test, the treatment with 15% GF was described by babassu flavor, strange and low astringency terms. For purchase intent, most consumers would buy the product with 35% and 45% GF.

Originality/value

This study demonstrates that babassu, an almond little used industrially, is an alternate to plant-based milk. The higher sensory acceptance occurs when 45% GF is used for its flavoring. The CATA indicated that ideal sweetness, striking, acid and ideal grape flavor described the better beverage.
Photogrammetry versus 3D scanner: producing 3D models of museums’ artifacts
Authors: Khries Hashem Mohammad
Published: February 2021

Purpose

This paper aims to help archaeologists, museums’ curators and technicians in understanding the principle of using the photogrammetry and 3D scanner for the museum archaeological objects in a practical way by presenting specific examples for both methods. Another purpose is to evaluate the performance offered by the photogrammetry and the three-dimensional (3D) scanner device, with the aim of providing a suitable solution to the different shapes and sizes of the archaeological objects.

Design/methodology/approach

The author used the camera Canon EOS 1300 D for photographing and Einscan Pro 2X Plus as a 3D scanning device for several years on different kinds of objects made of various materials, including ceramic, stone, glass and metal.

Findings

This paper showed that both approaches create 3D models with high resolution in easy and different ways.

Practical implications

Handling objects and preparing them for photographing or scanning has involved a number of caveats and challenges regarding the risk of damage that the author had to bear in mind.

Originality/value

This paper is completely based on the author’s personal experiences of creating 3D image of various objects in the project of Documentation of Objects in the Jordanian Archaeological Museums.
Construction process innovation on Brock Commons Tallwood House
Authors: Staub-French Sheryl , Pilon Angelique , Poirier Erik , Fallahi Azadeh , Kasbar Mohamed , Calderon Francisco , Teshnizi Zahra , Froese Thomas
Published: February 2021

Purpose

The purpose of this paper is to present the construction process innovations that enabled the successful delivery of the hybrid mass timber high-rise building in Canada, the Brock Commons Tallwood House at the University of British Columbia. It is one of a set of papers examining the project, including companion papers that describe innovations in the mass timber design process and the impact of these innovations on construction performance. The focus of this paper is on innovation in the construction phase and its relationship to innovations implemented in previous project phases.

Design/methodology/approach

A mixed-method, longitudinal case study approach was used in this research project to investigate and document the Tallwood House project over a three-year period. Both quantitative and qualitative data collection and analysis techniques were used. Members of the research team observed prefabrication and construction, conducted periodic interviews and reviewed project artefacts.

Findings

The research identified three innovation “clusters,” including the use of innovative tools, techniques and strategies in the design and construction processes and the role they played in delivering the project. The “clusters” were further characterized according to the type of “connectivity” they afforded, either facilitation, operationalization or materialization. These two perspectives support a compounding view on innovation and help to understand how it can flow throughout a project’s life cycle and across its supply chain. Three process-based innovations were initiated during the design phase, integrated design process, building information modeling and virtual design and construction and flowed through to the construction phase. These were seen to enable the creation of connections that were crucial to the overall success of the project. These innovations were operationalized and enacted through the construction phase as design for manufacturing and assembly and prefabrication, staged construction and just-in-time delivery, integration of safety and risk management and a rigorous quality control and quality assurance process. Finally, a full-scale mock-up was produced for practice and constructability assessment, materializing the radical product innovation that was the mass timber structure. These strategies are used together for a synergistic and integrated approach to increase productivity, expedite the construction schedule and develop an innovative building product.

Originality/value

This paper details an in-depth investigation into the diffusion dynamics of multiple systemic innovations for the construction process of a unique building project, the tools and techniques used by the construction manager and team, and the challenges, solutions and lessons learned.