bluuebunny/crossref_metadata_2025 huggingface dataset:
Independent associations of sleep timing, duration and quality with adiposity and weight status in a national sample of adolescents: the UK Millennium Cohort Study
Authors: Collings Paul J
Published: February 2021

Background

There is evidence that short sleep elevates obesity risk in youth, but sleep is a multidimensional construct and few studies have investigated parameters beyond duration.

Objectives

To investigate if sleep onset time, duration, latency, and night waking frequency are independently associated with adiposity and weight status in adolescents.

Methods

This was a cross-sectional observational study of 10,619 13-15y olds who provided self-reported sleep characteristics and underwent an anthropometric assessment to determine adiposity (body mass index (BMI) z-score and percent body fat (%BF)) and weight status. Adjusted linear and logistic regressions were used to investigate associations.

Results

Compared to a sleep onset time before 10pm, later sleep was associated with higher adiposity and higher likelihood of overweight and obesity in boys (after midnight, odds ratio (95% CI): 1.76 (1.19 to 2.60), p=0.004) and girls (between 11-11:59pm: 1.36 (1.17 to 1.65), p=0.002). Compared to sleeping for >9-10 hours, sleeping for ≤8 hours was associated with higher likelihood of overweight and obesity (boys: 1.80 (1.38 to 2.35), p<0.001); girls: 1.38 (1.06 to 1.79), p=0.016); there was evidence of a U-shaped association in girls for whom >10 hours of sleep was also associated with higher likelihood of overweight and obesity (1.31 (1.06 to 1.62); p=0.014). In girls, relative to a sleep latency of 16-30 minutes, sleep latencies ≥46 minutes were associated with higher adiposity (46-60 minutes, %BF: 1.47 (0.57 to 2.36), p=0.001) and higher likelihood of overweight and obesity (46-60 minutes: 1.39 (1.05 to 1.83); p=0.020). Often as opposed to never waking in the night was also associated with higher adiposity in girls (BMI z-score: 0.24 (0.08 to 0.41), p=0.004; %BF: 1.44 (0.44 to 2.44), p=0.005).

Conclusions

Sleep duration and timing, and sleep quality in girls, are independently associated with adiposity and weight status in adolescence and may be important targets for obesity prevention.
Is the quality of hospital EHR data sufficient to evidence its ICHOM outcomes performance in heart failure? A pilot evaluation
Authors: Aerts Hannelore , Kalra Dipak , Saez Carlos , Ramírez-Anguita Juan Manuel , Mayer Miguel-Angel , Garcia-Gomez Juan M. , Durá Hernández Marta , Thienpont Geert , Coorevits Pascal
Published: February 2021

There is increasing recognition that healthcare providers need to focus attention, and be judged against, the impact they have on the health outcomes experienced by patients. The measurement of health outcomes as a routine part of clinical documentation is probably the only scalable way of collecting outcomes evidence, since secondary data collection is expensive and error prone. However, there is uncertainty about whether routinely collected clinical data within EHR systems includes the data most relevant to measuring and comparing outcomes, and if those items are collected to a good enough data quality to be relied upon for outcomes assessment, since several studies have pointed out significant issues regarding EHR data availability and quality.

In this paper, we first describe a practical approach to data quality assessment of health outcomes, based on a literature review of existing frameworks for quality assessment of health data and multi-stakeholder consultation. Adopting this approach, we perform a pilot study on a subset of 21 International Consortium for Health Outcomes Measurement (ICHOM) outcomes data items from patients with congestive heart failure. To this end, all available registries compatible with the diagnosis of heart failure within the IMASIS-2 data repository connected to the Hospital del Mar network (142,345 visits of 12,503 patients) were extracted and mapped to the ICHOM format. We focus our pilot assessment on five commonly used data quality dimensions: completeness, correctness, consistency, uniqueness and temporal stability.

Overall, this pilot study reveals high scores on the consistency, completeness and uniqueness dimensions. Temporal stability analyses show some changes over time in the reported use of medication to treat heart failure, as well as in the recording of past medical conditions. Finally, investigation of data correctness suggests several issues concerning the proper characterization of missing data values. Many of these issues appear to be introduced while mapping the IMASIS-2 relational database contents to the ICHOM format, as the latter requires a level of detail which is not explicitly available in the coded data of an EHR.

To truly examine to what extent hospitals today are able to routinely collect the evidence of their success in achieving good health outcomes, future research would benefit from performing more extensive data quality assessments, including all data items from the ICHOM heart failure standard set, across multiple hospitals.
Prioritizing allocation of COVID-19 vaccines based on social contacts increases vaccination effectiveness
Authors: Chen Jiangzhuo , Hoops Stefan , Marathe Achla , Mortveit Henning , Lewis Bryan , Venkatramanan Srinivasan , Haddadan Arash , Bhattacharya Parantapa , Adiga Abhijin , Vullikanti Anil , Srinivasan Aravind , Wilson Mandy L , Ehrlich Gal , Fenster Maier , Eubank Stephen , Barrett Christopher , Marathe Madhav
Published: February 2021

We study allocation of COVID-19 vaccines to individuals based on the structural properties of their underlying social contact network. Even optimistic estimates suggest that most countries will likely take 6 to 24 months to vaccinate their citizens. These time estimates and the emergence of new viral strains urge us to find quick and effective ways to allocate the vaccines and contain the pandemic. While current approaches use combinations of age-based and occupation-based prioritizations, our strategy marks a departure from such largely aggregate vaccine allocation strategies. We propose a novel agent-based modeling approach motivated by recent advances in (i) science of real-world networks that point to efficacy of certain vaccination strategies and (ii) digital technologies that improve our ability to estimate some of these structural properties. Using a realistic representation of a social contact network for the Commonwealth of Virginia, combined with accurate surveillance data on spatio-temporal cases and currently accepted models of within- and between-host disease dynamics, we study how a limited number of vaccine doses can be strategically distributed to individuals to reduce the overall burden of the pandemic. We show that allocation of vaccines based on individuals’ degree (number of social contacts) and total social proximity time issignificantly more effectivethan the currently used age-based allocation strategy in terms of number of infections, hospitalizations and deaths. Our results suggest that in just two months, by March 31, 2021, compared to age-based allocation, the proposed degree-based strategy can result inreducing an additional 56–110k infections, 3.2–5.4k hospitalizations, and 700–900 deaths just in the Commonwealth of Virginia. Extrapolating these results for the entire US, this strategy can lead to 3–6 million fewer infections, 181–306k fewer hospitalizations, and 51–62k fewer deaths compared to age-based allocation.The overall strategy is robust even: (i) if the social contacts are not estimated correctly; (ii) if the vaccine efficacy is lower than expected or only a single dose is given; (iii) if there is a delay in vaccine production and deployment; and (iv) whether or not non-pharmaceutical interventions continue as vaccines are deployed. For reasons of implementability, we have used degree, which is a simple structural measure and can be easily estimated using several methods, including the digital technology available today. These results are significant, especially for resource-poor countries, where vaccines are less available, have lower efficacy, and are more slowly distributed.
Outdoor air pollution and the risk of asthma exacerbations in single lag0 and lag1 exposure patterns: A systematic review and meta-analysis
Authors: Huang Junjun , Yang Xiaoyu , Fan Fangfang , Hu Yan , Wang Xi , Zhu Sainan , Ren Guanhua , Wang Guangfa
Published: February 2021

Background

Asthma exacerbations accelerate the disease progression, as well as increases the incidence of hospitalizations and deaths. There have been studies on the effects of outdoor air pollution and asthma exacerbations; however, evidence regarding single lag0 and lag1 exposure patterns is inconclusive.

Objective

To synthesize evidence regarding the relationship between outdoor air pollution and the asthma exacerbation risk in single lag0 and lag1 exposure patterns.

Methods

We performed a systematic literature search using PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials, China National Knowledge Internet, Chinese BioMedical, and Wanfang databases until August 1st, 2020. Additionally, we reviewed the reference lists of the relevant articles. Two authors independently evaluated the eligible articles and performed structured extraction of relevant information. Pooled relative risks (RRs) and 95% confidence intervals (CIs) of lag0 and lag1 exposure patterns were estimated using the random-effect models.

Results

Eighty-four studies met the eligibility criteria and provided sufficient information for meta-analysis. Outdoor air pollutants were associated with significantly increased risks of asthma exacerbations in both single lag0 and lag1 exposure patterns [lag0: RR (95%CI) (pollutants), 1.057(1.011, 1.103) (air quality index; AQI), 1.007(1.005, 1.010) (PM2.5), 1.009(1.005, 1.012) (PM10), 1.010(1.006, 1.014) (NO2), 1.030(1.011, 1.048) (CO), 1.005(1.002, 1.009) (O3); lag1: RR (95%CI) (pollutants), 1.064(1.022, 1.106) (AQI), 1.005(1.002, 1.008) (PM2.5), 1.007(1.004, 1.011) (PM10), 1.008(1.004, 1.012) (NO2), 1.025(1.007, 1.042) (CO), 1.010(1.006, 1.013) (O3)], except SO2 [lag0: RR (95%CI), 1.004(1.000, 1.007); lag1: RR (95%CI), 1.003(0.999, 1.006)]. Subgroup analyses revealed stronger effects in children and asthma exacerbations associated with other events (including symptoms, lung function changes, and medication use as required).

Conclusion

These findings demonstrate that outdoor air pollution significantly increases the asthma exacerbation risk in single lag0 and lag1 exposure patterns.

PROSPERO registration number

CRD42020204097 (https://www.crd.york.ac.uk/PROSPERO).

Strengths and limitations of this study

We performed a systematic literature search of six databases (with no specified start date or language limitation).

Secondary references were included.

Publication bias was assessed by applying Begg’s and Egger’s tests.

This study focused on the association between outdoor air pollution and the asthma exacerbation risk in single lag0 and lag1 exposure patterns.

There were few available studies regarding the AQI, other events, and death analyses.
Demographic and clinical characteristics of patients with functional motor disorders: the prospective Salpêtrière cohort
Authors: Garcin Béatrice , Villain Nicolas , Mesrati Francine , Naccache Lionel , Roze Emmanuel , Degos Bertrand
Published: February 2021

Functional motor disorders (FMD) are common and disabling. They are known to affect predominantly women and to start at young or middle age but to date, large case series are lacking, and demographic and clinical characteristics of patients with FMD rely on data from small cohorts. The current study aimed at describing the demographic and clinical characteristics of a large cohort of FMD patients.

Methods

We prospectively collected data from FMD patients who were referred to the Neurophysiology Department of the Pitié-Salpêtrière University Hospital between 2008 and 2016 for treatment with repeated transcranial magnetic stimulation.

Results

482 patients were included. There was a majority of women (73.7%) with a median age of 40 years old at TMS treatment. Median age at symptoms onset was 35.5 years old and symptoms were mostly characterized by an acute (47.3%) or subacute (46%) onset. Only 23% of patients were active workers while 58.3% were unemployed for medical reasons. Half of the patients suffered from functional motor weakness (n= 241) and the other half suffered from movement disorders (n=241), mainly represented by tremor (21.15%) and dystonia (20.5%). 33.6% had no psychiatric comorbidity and 17.4% reported no history of trauma. No significant differences were found in age or gender according to clinical phenotypes.

Conclusion

We present the largest cohort of patients with FMD to date. This cohort will contribute to a better understanding of FMDs and their risk factors.
Vaccine Efficacy at a Point in Time
Authors: Follmann Dean , Fay Michael
Published: February 2021

Vaccine trials are generally designed to assess efficacy on clinical disease. The vaccine effect on infection, while important both as a proxy for transmission and to describe a vaccine’s total effects, requires frequent longitudinal sampling to capture all infections. Such sampling may not always be feasible. A logistically easy approach is to collect a sample to test for infection at a regularly scheduled visit. Such point or cross-sectional sampling does not permit estimation of classic vaccine effiacy on infection, as long duration infections are sampled with higher probability. Building on work by Rinta-Kokko and others (2009) we evaluate proxies of the vaccine effect on transmission at a point in time; the vaccine efficacy on prevalent infection and on prevalent viral load, VEPI and VEPV L, respectively. Longer infections with higher viral loads should have more transmission potential and prevalent vaccine efficacy naturally captures this aspect. We apply a proportional hazards model for infection risk and show how these metrics can be estimated using longitudinal or cross-sectional sampling. We also introduce regression models for designs with multiple cross-sectional sampling. The methods are evaluated by simulation and a phase III vaccine trial with PCR cross-sectional sampling for subclinical infection is analyzed.
Symptom Prediction and Mortality Risk Calculation for COVID-19 Using Machine Learning
Authors: Jamshidi Elham , Asgary Amirhossein , Tavakoli Nader , Zali Alireza , Dastan Farzaneh , Daaee Amir , Badakhshan Mohammadtaghi , Esmaily Hadi , Jamaldini Seyed Hamid , Safari Saeid , Bastanhagh Ehsan , Maher Ali , Babajani Amirhesam , Mehrazi Maryam , Kashi Mohammad Ali Sendani , Jamshidi Masoud , Sendani Mohammad Hassan , Rahi Sahand Jamal , Mansouri Nahal
Published: February 2021

Background

Early prediction of symptoms and mortality risks for COVID-19 patients would improve healthcare outcomes, allow for the appropriate distribution of healthcare resources, reduce healthcare costs, aid in vaccine prioritization and self-isolation strategies, and thus reduce the prevalence of the disease. Such publicly accessible prediction models are lacking, however.

Methods

Based on a comprehensive evaluation of existing machine learning (ML) methods, we created two models based solely on the age, gender, and medical histories of 23,749 hospital-confirmed COVID-19 patients from February to September 2020: a symptom prediction model (SPM) and a mortality prediction model (MPM). The SPM predicts 12 symptom groups for each patient: respiratory distress, consciousness disorders, chest pain, paresis or paralysis, cough, fever or chill, gastrointestinal symptoms, sore throat, headache, vertigo, loss of smell or taste, and muscular pain or fatigue. The MPM predicts the death of COVID-19-positive individuals.

Results

The SPM yielded ROC-AUCs of 0.53-0.78 for symptoms. The most accurate prediction was for consciousness disorders at a sensitivity of 74% and a specificity of 70%. 2440 deaths were observed in the study population. MPM had a ROC-AUC of 0.79 and could predict mortality with a sensitivity of 75% and a specificity of 70%. About 90% of deaths occurred in the top 21 percentile of risk groups. To allow patients and clinicians to use these models easily, we created a freely accessible online interface at www.aicovid.org.

Conclusions

The ML models predict COVID-19-related symptoms and mortality using information that is readily available to patients as well as clinicians. Thus, both can rapidly estimate the severity of the disease, allowing shared and better healthcare decisions with regard to hospitalization, self-isolation strategy, and COVID-19 vaccine prioritization in the coming months.

Abstract Figure
Five hours total sleep deprivation does not affect CA1 dendritic length or spine density
Authors: Brodin Alvin T.S. , Gabulya Sarolta , Wellfelt Katrin , Karlsson Tobias E.
Published: February 2021

Sleep is essential for long term memory function. However the neuroanatomical consequences of sleep loss are disputed. Sleep deprivation has been reported to cause both decreases and increases of dendritic spine density. Here we use Thy1-GFP expressing transgenic mice to investigate the effects of acute sleep deprivation on the dendritic architecture of hippocampal CA1 pyramidal neurons. We found that five hours of sleep deprivation had no effect on either dendritic length or dendritic spine density. Our work suggests that no major neuroanatomical changes result from one episode of sleep deprivation.
ASigNTF: Agnostic Signature using NTF – a universal agnostic strategy to estimate cell-types abundance from transcriptomic datasets
Authors: Fogel Paul , Boldina Galina , Rocher Corinne , Bettembourg Charles , Luta George , Augé Franck
Published: February 2021

Abstract

Background

Molecular signatures for deconvolution of immune cell types have been proposed, based on a methodology that relies on the biological classification of the cell types being studied. When working with less known biological material, a data-driven approach is needed to uncover the underlying classes and construct ad hoc signatures.

Results

We introduce a new approach, ASigNTF: Agnostic Signature using Non-negative Tensor Factorization, to perform the deconvolution of cell types from transcriptomics data (RNAseq and microarray). ASigNTF, which is based on two complementary statistical/mathematical tools: non-negative tensor factorization (for dimensionality reduction) and the Herfindahl-Hirschman index (for signature selection), can be applied to any type of tissue as long as transcriptomic data on isolated cells is available. As a direct result of the new method, we propose two new signatures for the deconvolution of immune cell types, one consisting of a relatively small set of 415 genes, which is more compatible with microarray platforms, and a larger set of 915 genes. Using external datasets, our two signatures outperform the CIBERSORT LM22 signature in deconvolution of RNA-seq data. Our signature with 415 genes allows to recognize a larger number of cell types compared to the ABIS microarray signature.

Conclusions

The paper proposes a new method, ASigNTF; applies the method, and also provides a software implementation that allows to identify molecular signatures for deconvolution of complex tissues and specifically up to 16 immune cell types from micro-array or RNA-seq data.

Highlights

Several signatures of immune cell types have been proposed, which follow a methodology deeply rooted in the known biological classification of the investigated cell types.

When working with less known biological material, a more agnostic, data-driven approach is required to uncover the underlying classes and construct ad hoc signatures.

We present ASigNTF, a new agnostic approach to cell type classification and signature selection supported by an application software.

We discuss the results of benchmarking our proposed signatures, ABIS-seq and CIBERSORT on external datasets.
The epoxyeicosatrienoic pathway is intact in endothelial and smooth muscle cells exposed to aldosterone excess
Authors: Brunnenkant Laura , Meng Yao , Sun Jing , Marques Jair Gonzalez , Koletzko Berthold , Schnitzler Michael Mederos Y , Gudermann Thomas , Williams Tracy Ann , Beuschlein Felix , Heinrich Daniel A , Adolf Christian , Reincke Martin , Schneider Holger
Published: February 2021

Objectives

Endothelial dysfunction (ED) is considered to be a major driver of the increased incidence of cardiovascular disease in primary aldosteronism (PA). Whether the epoxyeicosatrienoic acid (EET) pathway, involving the release of beneficial endothelium-derived lipid mediators, contributes to ED in PA is unknown. Preclinical evidence suggests this pathway to be relevant in the pathogenesis in various models of experimental hypertension. In addition, an orally available soluble epoxide hydrolase inhibitor, which halts the breakdown of EETs, has already passed a phase 1 clinical trial.

We, therefore, exposed primary human coronary artery endothelial cells to 1 nM aldosterone.

Methods

We used qPCR to investigate changes in the expression levels of essential genes for the synthesis and degradation of EETs as well as mass spectrometry to determine endothelial synthetic capacity to release EETs upon stimulation. We also assessed primary human coronary artery smooth muscle cells for expression of putative EET receptor ion channels or downstream mediators as well as for the calcium response to EETs using calcium imaging.

Results

No major aldosterone-related expression changes were detected on the endothelial as well as the smooth muscle side. Stimulated release of endothelial EETs was unaffected. Likewise, the smooth muscle calcium response was unchanged after aldosterone excess.

Conclusions

The EET pathway is not negatively affected by increased aldosterone concentrations as seen in PA. Modulating the EET pathway with therapeutic intent in patients with PA might therefore be assessed in future preclinical and clinical trials to address ED.
Pharmacokinetics of Orally Administered GS-441524 in Dogs
Authors: Yan Victoria C. , Pham Cong-Dat , Yan Matthew J. , Yan Alexander J. , Khadka Sunada , Arthur Kenisha , Ackroyd Jeffrey J. , Georgiou Dimitra K. , Roon Laura E. , Bushman Lane R. , Anderson Peter L. , Li Chun , Muller Florian L.
Published: February 2021

Despite being FDA-approved for COVID-19, the clinical efficacy of remdesivir (Veklury®) remains contentious. We previously pointed out pharmacokinetic, pharmacodynamic and toxicology reasons for why its parent nucleoside GS-441524, is better suited for COVID-19 treatment. Here, we assess the oral bioavailability of GS-441524 in beagle dogs and show that plasma concentrations ∼24-fold higher than the EC50against SARS-CoV-2 are easily and safely sustained. These data support translation of GS-441524 as an oral agent for COVID-19.
Ovine CD14- an immune response gene has a role against gastrointesinal nematodeHaemonchus contortus-a novel report
Authors: Rawat Kavita , Pal Aruna , Banerjee Samiddha , Pal Abantika , Mandal Subhas Chandra , Batabyal Subhashis
Published: February 2021

CD14 (also known as monocyte differentiation antigen) is an important immune response gene known to be primarily responsible for innate immunity against bacterial pathogen and as pattern recognition receptor (PRR) binds with LPS (endotoxin), lipoproteins, lipotechoic acid of bacteria.So far very limited work has been conducted in parasitic immunology. In the current study, we reported the role of CD14 in parasitic immunology in livestock species (sheep) for the first time. Ovine CD14 is characterized as a horse-shoe shaped as a bent solenoid with a hydrophobic amino-terminal pocket for CD14 along with domains. High mutation frequency was observed, out of total 41 mutations identified, 23 mutations were observed to be thermodynamically unstable and 11 mutations were deleterious in nature, causing major functional alteration of important domains of CD14, an indicative for variations in individual susceptibility for sheeps againstHaemonchus contortusinfestations.In silicostudies with molecular docking reveals a role of immune response againstHaemonchus contortusin sheep, which is later confirmed with experimental evidence through differential mRNA expression analysis for sheep, which revealed better expression of CD14 inHaemonchus contortusinfected sheep compared to that of healthy sheep. We confirmed the above findings with supportive evidences with haematological and biochemical analyses. Phylogenetic analysis was conducted to assess the evolutionary relationship with respect to human and observed that sheep may well be used as model organism due better genetic closeness compared to that of mouse.
Prevalence, complete genome and metabolic potentials of a phylogenetically novel cyanobacterial symbiont in the coral-killing sponge,Terpios hoshinota
Authors: Chen Yu-Hsiang , Chen Hsing-Ju , Yang Cheng-Yu , Shiu Jia-Ho , Hoh Daphne Z. , Chiang Pei-Wen , Chow Wenhua Savanna , Chen Chaolun Allen , Shih Tin-Han , Lin Szu-Hsien , Yang Chi-Ming , Reimer James Davis , Hirose Euichi , Iskandar Budhi Hascaryo , Huang Hui , Schupp Peter J. , Tan Chun Hong James , Yamashiro Hideyuki , Liao Ming-Hui , Tang Sen-Lin
Published: February 2021

Terpios hoshinotais a ferocious, space-competing sponge that kills a variety of stony corals by overgrowth. Outbreaks of this species have led to intense coral reef damage and declines in living corals on the square kilometer scale in many geographical locations. Our large-scale 16S rRNA gene survey across three oceans revealed that the core microbiome ofT.hoshinotaincluded operational taxonomic units (OTUs) related toProchloron,Endozoicomonas,Pseudospirillum, SAR116,Magnetospira, andRuegeria. AProchloron- related OTU was the most dominant cyanobacterium inT.hoshinotain the western Pacific Ocean, South China Sea, and Indian Ocean. The complete metagenome-assembled genome of theProchloron-related cyanobacterium and our pigment analysis revealed that this bacterium had phycobiliproteins and phycobilins and lacked chlorophyllb, inconsistent with the iconic definition ofProchloron. Furthermore, the phylogenetic analyses based on 16S rRNA genes and 120 single-copy genes demonstrated that the bacterium was phylogenetically distinct toProchloron, strongly suggesting that it should be a sister taxon toProchloron; we therefore proposed this symbiotic cyanobacterium as a novel species under a new genus:CandidatusParaprochloron terpiosii. With the recovery of the complete genome, we characterized the metabolic potentials of the novel cyanobacterium in carbon and nitrogen cycling and proposed a model for the interaction betweenCa.Pp. terpiosi LD05 andT. hoshinota.In addition, comparative genomics analysis revealed thatCa.Paraprochloron andProchloronshowed distinct features in transporter systems and DNA replication.

Importance

The finding that one species predominates cyanobacteria inT.hoshinotafrom different geographic locations indicates that this sponge andCa. Pp. terpiosi LD05 share a tight relationship. This study builds the foundation forT.hoshinota’s microbiome and paves a way for understanding the ecosystem, invasion mechanism, and causes of outbreak of this coral-killing sponge. Also, the firstProchloron-related complete genome enables us to study this bacterium with molecular approaches in the future and broadens our knowledge of the evolution of symbiotic cyanobacteria.
Functional traits of carabid beetles reveal seasonal variation in community assembly in annual crops
Authors: Marrec Ronan , Gross Nicolas , Badenhausser Isabelle , Dupeyron Aurélie , Caro Gaël , Bretagnolle Vincent , Roncoroni Marilyn , Gauffre Bertrand
Published: February 2021

Trait-based community assembly studies have mostly been addressed along spatial gradients, and do not consider explicitly a fundamental dimension governing community assembly, the time. Nevertheless, such consideration seems particularly necessary in systems in which organisms have to face regular disturbances and rapid changes in vegetation phenology, such as in intensively managed farmlands.

In this study, we aimed at understanding how the functional diversity of carabid beetle communities varied across the growing season in response to crop type. We tested three alternative hypotheses on mechanisms underlying the community assembly.

We used data from a long-term monitoring conducted over nine years in an intensively-managed farmland in central western France, in a total of 625 fields. First, we measured morphological traits related to body size, dispersal mode, and resource acquisition on the 13 dominant carabid species (> 85 % of all trapped individuals) and identified three independent dimensions of functional specialization within our species pool along axes of a PCA and highlighted key traits for community assembly. Second, we evaluated the community assembly temporal dynamics and the impact of habitat filtering and niche differentiation in the different crop types with time, using linear mixed-effects models.

We showed that functional species assembly of carabid beetle communities occurring in crop fields varies importantly intra-annually, with strong variations in these dynamics depending on crop type and crop phenology. Each crop acted as a filter on carabid communities for body size and resource-acquisition traits, and functional differentiation between crops increased with time. We did not find any evidence of habitat filtering on traits related to dispersal mode.

Our results emphasize the major role of crop phenology but also disturbances involved by agricultural practices such as crop harvesting on changes in community assembly, likely due to seasonal and inter-annual redistributions of species in agricultural landscapes in response to such changes. The temporal dimension cannot be ignored to understand the assembly of local carabid communities in farmlands.
A dynamically-structured matrix population model based on renewal processes for accumulative development under variable environmental conditions
Authors: Erguler Kamil , Mendel Jacob
Published: February 2021

Arthropod vectors are responsible for the transmission of pathogens in humans and other species. The transmission rate depends on the size and activity of the vector population, factors which are in turn strongly affected by environmental conditions. Therefore, in order to develop realistic representations of vector population dynamics, it is necessary to properly account for the impact of a changing environment on the duration of life processes. Here, we use a pseudo-stage-structured population to model the accumulative process of development as a renewal process with a variable rate that depends on the environment. We incorporate this into sPop, formerly an age-structured population dynamics model. This framework allows the modeller to represent realistic life stage durations by choosing from three alternative probability schemes: an Erlang distribution, a Pascal distribution, or a fixed duration, while enabling the model to respond appropriately to variations in stage duration characteristics. Using this approach, we demonstrate that introducing random variation into the environmental conditions, which results in fluctuating development rates, on average decreases the time required for stage completion. An exception to this is an already optimum development rate being perturbed by noise towards a less efficient course. The proposed framework is suitable for performing inverse modelling with data collected from highly variable environmental conditions, the results of which can be used to develop realistic climate-driven population dynamics models.
Differences in interactions between transmembrane domains tune the activation of metabotropic glutamate receptors
Authors: Thibado Jordana K. , Tano Jean-Yves , Lee Joon , Salas-Estrada Leslie , Provasi Davide , Strauss Alexa , Lamim Ribeiro Joao Marcelo , Xiang Guoqing , Broichhagen Johannes , Filizola Marta , Lohse Martin , Levitz Joshua
Published: February 2021

The metabotropic glutamate receptors (mGluRs) form a family of neuromodulatory G protein-coupled receptors that contain both a seven-helix transmembrane domain (TMD) and a large extracellular ligand-binding domain (LBD) which enables stable dimerization. While numerous studies have revealed variability across subtypes in the initial activation steps at the level of LBD dimers, an understanding of inter-TMD interaction and rearrangement remains limited. Here we use a combination of single molecule fluorescence, molecular dynamics, functional assays, and conformational sensors to reveal that distinct TMD assembly properties drive differences between mGluR subtypes. We uncover a variable region within transmembrane helix 4 (TM4) that contributes to homo- and heterodimerization in a subtype-specific manner and tunes orthosteric, allosteric and basal activation. We also confirm a critical role for a conserved inter-TM6 interface in stabilizing the active state during orthosteric or allosteric activation. Together this study informs a working model of inter-TMD rearrangement that drives mGluR function.
New lessons on TDP-43 from the killifishN. furzeri
Authors: Louka Alexandra , Bagnoli Sara , Rupert Jakob , Esapa Benjamin , Tartaglia Gian Gaetano , Cellerino Alessandro , Pastore Annalisa , Tozzini Eva Terzibasi
Published: February 2021

Frontotemporal dementia and amyotrophic lateral sclerosis are fatal and incurable neurodegenerative diseases linked to the pathological aggregation of the TDP-43 protein. This is an essential DNA/RNA binding protein involved in transcription regulation, pre-RNA processing and RNA transport. Having suitable animal models to study the mechanisms of TDP-43 aggregation is crucial to develop treatments against disease. We have previously demonstrated that the killifishNothobranchius furzerioffers the unique advantage as a model system that it is an organism with compressed lifespan and a conserved ageing phenotype that develops within months, making this organism the available shortest-lived vertebrate with a clear ageing phenotype. Here, we show that the two paralogs of TDP-43 from the killifishN. furzerishare high sequence homology with the human protein and recapitulate its cellular and biophysical behaviour. We prove that, during ageing,N. furzeriTDP-43 spontaneously forms insoluble intracellular TDP-43 aggregates that have amyloid characteristics and colocalize with the stress granule core protein G3BP. Our results propose this organism as a valuable model of TDP-43-related pathologies and show that even minute differences between the human andN. furzeriproteins may help to shed new light onto the role of TDP-43 in RNA recognition and granule formation.
Quantifying full-length circular RNAs in cancer
Authors: Yu Ken Hung-On , Shi Christina Huan , Wang Bo , Chow Savio Ho-Chit , Chung Grace Tin-Yun , Tan Ke-En , Lim Yat-Yuen , Tsang Anna Chi-Man , Lo Kwok-Wai , Yip Kevin Y.
Published: February 2021

Circular RNAs (circRNAs) are abundantly expressed in cancer. Their resistance to exonucleases enables them to have potentially stable interactions with different types of biomolecules. Alternative splicing can create different circRNA isoforms that have different sequences and unequal interaction potentials. The study of circRNA function thus requires knowledge of complete circRNA sequences. Here we describe psirc, a method that can identify full-length circRNA isoforms and quantify their expression levels from RNA sequencing data. We confirm the effectiveness and computational efficiency of psirc using both simulated and actual experimental data. Applying psirc on transcriptome profiles from nasopharyngeal carcinoma and normal nasopharynx samples, we discover and validate circRNA isoforms differentially expressed between the two groups. Compared to the assumed circular isoforms derived from linear transcript annotations, some of the alternatively spliced circular isoforms have 100 times higher expression and contain substantially fewer microRNA response elements, demonstrating the importance of quantifying full-length circRNA isoforms.
Footprints to Singularity: A global population model explains late 20th century slow-down and predicts peak within ten years
Authors: Bystroff Christopher
Published: February 2021

Projections of future global human population are traditionally made using birth/death trend extrapolations, but these methods ignore limits. Expressing humanity as a K-selected species whose numbers are limited by the global carrying capacity produces a different outlook. Population data for the second millennium up to the year 1970 was fit to a hyper-exponential growth equation, where the rate constant for growth itself grows exponentially due to growth of life-saving technology. The discrepancies between the projected growth and the actual population data since 1970 are accounted for by a decrease in the global carrying capacity due to ecosystem degradation. A system dynamics model that best fits recent population numbers suggests that the global biocapacity may already have been reduced to one-half of its historical value and global carrying capacity may be at its 1965 level and falling. Simulations suggest that population may soon peak or may have already peaked. Population projections depend strongly on the unknown fragility or robustness of the Earth’s essential ecosystem services that affect agricultural production. Numbers for the 2020 global census were not available for this study.
JNK activation in TA and EDL muscle is load-dependent in rats receiving identical excitation patterns
Authors: Eftestøl Einar , Franchi Martino V. , Kasper Stephanie , Flück Martin
Published: February 2021

ABSTACT

Aim

As the excitation-contraction coupling is inseparable during voluntary exercise, the relative contribution of the mechanical and neural input is poorly understood. Herein, we use a rat in-vivo strength training setup with an electrically induced standardized excitation pattern previously shown to lead to a load-dependent increase in myonuclear number and hypertrophy, to study acute effects of load per se on molecular signalling.

Methods

Anaesthetized rats were subjected to unliteral identical electrically-paced contractions of the TA and EDL muscles under a high or low load for a duration of 2, 10 or 28-minutes. Muscle soluble proteins were extracted, and abundance and specific phosphorylations of FAK, mTOR, p70S6K and JNK were measured. Effects of exercise, load, muscle and exercise duration were assessed.

Results

Specific phosphorylation of S2448-mTOR, T421/S424-p70S6K and T183/Y185-JNK was increased after 28-minutes of exercise under the high- and low-load protocol. Elevated phosphorylation of mTOR and JNK was detectable already after 2 and 10 minutes of exercise, respectively, but greatest after 28-minutes of exercise. T183/Y185-JNK and S2448-mTOR demonstrated a load-dependent increase in phosphorylation in the exercised muscles that for mTOR depended on muscle type. The abundance of all four kinases was higher in TA compared to EDL muscle. FAK and JNK abundance was reduced after 28 minutes of exercise in both the exercised and control muscle.

Conclusion

The current study shows that JNK and mTOR activation is load-driven, and together with muscle-type specific mTOR and p70S6K effects it may drive muscle-type specific exercise and load-responses.
Nutritional redundancy in the human diet and its application in phenotype association studies
Authors: Wang Xu-Wen , Hu Yang , Menichetti Giulia , Grodstein Francine , Bhupathiraju Shilpa N. , Sun Qi , Zhang Xuehong , Hu Frank B. , Weiss Scott T. , Liu Yang-Yu
Published: February 2021

Studying human dietary intake may help us identify effective measures to treat or prevent many chronic diseases whose natural histories are influenced by nutritional factors. Here, by examining five cohorts with dietary intake data collected on different time scales, we show that the food intake profile varies substantially across individuals and over time, while the nutritional intake profile appears fairly stable. We refer to this phenomenon as ‘nutritional redundancy’ and attribute it to the nested structure of the food-nutrient network. This network enables us to quantify the level of nutritional redundancy for each diet assessment of any individual. Interestingly, this nutritional redundancy measure does not strongly correlate with any classical healthy diet scores, but its performance in predicting healthy aging shows comparable strength. Moreover, after adjusting for age, we find that a high nutritional redundancy is associated with lower risks of cardiovascular disease and type 2 diabetes.
13C tracer analysis identifies extensive recycling of endogenous CO2in vivo
Authors: Duan Likun , Cooper Daniel E. , Scheidemantle Grace , Locasale Jason W. , Kirsch David G. , Liu Xiaojing
Published: February 2021

13C tracing analysis is increasingly used to monitor cellular metabolism in vivo and in intact cells, but data interpretation is still the key element to unveil the complexity of metabolic activities. We have performed [U-13C]-glucose and [U-13C]-glutamine tracing in sarcoma-bearing mice (in vivo) and in cancer cell lines (in vitro).13C enrichment of metabolites in cultured cells and tissues was determined by liquid chromatography coupled with high-resolution mass spectrometer (LC-HRMS). As expected, citrate M+2 or M+4 is the dominant mass isotopologue in vitro. However, citrate M+1 was unexpectedly the dominant isotopologue in mice receiving [U-13C]-glucose or [U-13C]-glutamine infusion. One plausible explanation is that13CO2produced from the oxidation of13C tracers in vitro is negligible due to the dilution of HCO3-supplemented to cell culture when sodium bicarbonante is used and diffusible volume of CO2in the culture incubator, while endogenous13CO2in vivo is substantial and is fixed into the TCA cycle, purine, and serine, resulting in M+1 isotopologues. A time course study shows the generation of high abundance citrate M+1 early in plasma, which may serve as a potent non-invasive biomarker of tissue pyruvate carboxylase activity. Altogether, our results show that recycling of endogenous CO2is substantial in vivo and provides important insights into the experimental design and data interpretation of13C tracing assays.
Standing Variations Modeling Captures Inter-Individual Heterogeneity in a Deterministic Model of Prostate Cancer Response to Combination Therapy
Authors: Jain Harsh Vardhan , Sorribes Inmaculada C , Handelman Samuel K , Barnaby Johnna , Jackson Trachette L
Published: February 2021

Sipuleucel-T (Provenge) is the first live cell vaccine approved for advanced, hormonally refractive prostate cancer. However, survival benefit is modest and the optimal combination or schedule of sipuleucel-T with androgen depletion remains unknown. We employ a nonlinear dynamical systems approach to modeling the response of hormonally refractive prostate cancer to sipuleucel-T. Our mechanistic model incorporates the immune response to the cancer elicited by vaccination, and the effect of androgen depletion therapy. Because only a fraction of patients benefit from sipuleucel-T treatment, inter-individual heterogeneity is clearly crucial. Therefore, we introduce our novel approach, Standing Variations Modeling, which exploits inestimability of model parameters to capture heterogeneity in a deterministic model. We use data from mouse xenograft experiments to infer distributions on parameters critical to tumor growth and to the resultant immune response. Sampling model parameters from these distributions allows us to represent heterogeneity, both at the level of the tumor cells and the individual (mouse) being treated. Our model simulations explain the limited success of sipuleucel-T observed in practice, and predict an optimal combination regime that maximizes predicted efficacy. This approach will generalize to a range of emerging cancer immunotherapies.
Rampant tooth loss across 200 million years of frog evolution
Authors: Paluh Daniel J. , Riddell Karina , Early Catherine M. , Hantak Maggie M. , Jongsma Gregory F.M. , Keeffe Rachel M. , Magalhães Silva Fernanda , Nielsen Stuart V. , Vallejo-Pareja María Camila , Stanley Edward L. , Blackburn David C.
Published: February 2021

Teeth have been broadly maintained across most clades of vertebrates but have been lost completely at least once in actinopterygian fishes and several times in amniotes. Using phenotypic data collected from over 500 genera via micro-computed tomography, we provide the first rigorous assessment of the evolutionary history of dentition across all major lineages of amphibians. We demonstrate that dentition is invariably present in caecilians and salamanders, but teeth have been lost completely more than 20 times in frogs, a much higher occurrence of edentulism than in any other vertebrate group. The repeated loss of teeth in anurans is associated with a specialized diet of small invertebrate prey as well as shortening of the lower jaw, but it is not correlated with a reduction in body size. Frogs provide an unparalleled opportunity for investigating the molecular and developmental mechanisms of convergent tooth loss on a large phylogenetic scale.
Drosophila STING protein has a role in lipid metabolism
Authors: Akhmetova Katarina , Balasov Maxim , Chesnokov Igor
Published: February 2021

Stimulator of interferon genes (STING) plays an important role in innate immunity by controlling type I interferon response against invaded pathogens. In this work we describe a direct but previously unknown role of STING in lipid metabolism inDrosophila. Flies withSTINGdeletion are sensitive to starvation and oxidative stress, have reduced lipid storage and downregulated expression of lipid metabolism genes. We found thatDrosophilaSTING interacts with lipid synthesizing enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). ACC and FAS also interact with each other, indicating that all three proteins may be components of a large multi-enzyme complex. The deletion ofDrosophila STINGleads to disturbed ACC localization and decreased FAS enzyme activity. Together, our results demonstrate a direct role of STING in lipid metabolism inDrosophila.