bluuebunny/crossref_metadata_2025 huggingface dataset:
Foxq2 determines blue cone identity in zebrafish
Authors: Ogawa Yohey , Shiraki Tomoya , Fukada Yoshitaka , Kojima Daisuke
Published: March 2021

Most vertebrate lineages retain a tetrachromatic visual system, which is supported by a functional combination of spectrally distinct multiple cone photoreceptors, UV, blue, green, and red cones. The blue cone identity is ensured by selective expression of blue (sws2) opsin, and the mechanism is poorly understood becauseSWS2gene has been lost in mammalian species such as mouse, whose visual system has been extensively studied. Here we pursued loss-of-function studies on transcription factors expressed predominantly in zebrafish cone photoreceptors and identified Foxq2 as a core factor drivingsws2gene expression.foxq2is expressed only in the blue cone, and loss offoxq2selectively abolishessws2expression. Comparative genomic analysis revealed that a wide range of vertebrate species retain bothFOXQ2andSWS2genes. We propose that FOXQ2-dependentSWS2expression is a prevalent regulatory mechanism that was acquired at the early stage of vertebrate evolution
Understanding Convergence Between Non-Hispanic Black and White COVID-19 Mortality: A County-Level Approach
Authors: Lawton Ralph , Zheng Kevin , Zheng Daniel , Huang Erich
Published: March 2021

Background

Non-Hispanic Black populations have suffered greater per capita COVID-19 mortality at more than 1.5 times that of White populations. Previous work has established that, over time, rates of Black and White mortality have converged; however, some studies suggest that regional shifts in COVID-19 prevalence may play a role in the relative change between racial groups. This study’s objective was to investigate changes in Black and White COVID-19 mortality over time and uncover potential mechanisms driving these changes.

Methods and Findings

Using county-level COVID-19 mortality data stratified by race, we investigate the trajectory of non-Hispanic Black mortality, White mortality, and the Black/White per capita mortality ratio from June 2020–January 2021. Over this period, in the counties studied, cumulative mortality rose by 56.7% and 82.8% for Black and White populations respectively, resulting in a decrease in mortality ratio of 0.369 (23.8%). These trends persisted even when a county-level fixed-effects model was used to estimate changes over time within counties (controlling for all time-invariant county level characteristics and removing the effects of changes in regional distribution of COVID-19). Next, we leverage county-level variation over time in COVID-19 prevalence to show that the decline in the Black/White mortality ratio can be explained by changes in COVID-19 prevalence. Finally, we study heterogeneity in the time trend, finding that convergence occurs most significantly in younger populations, areas with less dense populations, and outside of the Northeast. Limitations include suppressed data in counties with fewer than 10 deaths in a racial category, and the use of provisional COVID-19 death data that may be incomplete.

Conclusions

The results of this study suggest that convergence in Black/White mortality is not driven by county-level characteristics or changes in the regional dispersion of COVID-19, but instead by changes within counties. Further, declines in the Black/White mortality ratio appear strongly linked to changes in COVID-19 prevalence, rather than a time-specific effect. Further studies on changes in exposure by race over time, or on the vulnerability of individuals who died at different points in the pandemic, may provide crucial insight on mechanisms and strategies to further reduce COVID-19 mortality disparities.
Evaluation of RNA extraction free method for detection of SARS-COV-2 in salivary samples for mass screening for COVID-19
Authors: Mahmoud Sally A. , Ibrahim Esra , Ganesan Subhashini , Thakre Bhagyashree , Teddy Juliet G , Raheja Preeti , Abbas Walid Z
Published: March 2021

In this current COVID - 19 pandemic, there is a dire need for cost effective and less time-consuming alternatives for SARS-COV-2 testing. The RNA extraction free method for detecting SARS-COV-2 in saliva is a promising option, this study found that it has high sensitivity (85.34%), specificity (95.04%) and was comparable to the gold standard nasopharyngeal swab. The method showed good percentage of agreement (kappa coefficient) 0.797 between salivary and NPS samples. However, there are variations in the sensitivity and specificity based on the RT-PCR kit used. The Thermo Fischer-Applied biosystems showed high sensitivity, PPV and NPV but also showed higher percentage of invalid reports. Whereas the BGI kit showed high specificity, better agreement (kappa coefficient) between the results of saliva and NPS samples and higher correlation between the Ct values of saliva and NPS samples. Thus, the RNA extraction free method for salivary sample serves as an effective alternative for SARS-CoV 2-testing.
U.S. adolescents’ mental health and COVID-19-related changes in technology use, Fall 2020
Authors: Burke Taylor A. , Kutok Emily R. , Dunsiger Shira , Nugent Nicole R. , Patena John V. , Riese Alison , Ranney Megan L.
Published: March 2021

Preliminary reports suggest that during COVID-19, adolescents’ mental health has worsened while technology and social media use has increased. Much data derives from early in the pandemic, when schools were uniformly remote and personal/family stressors related to the pandemic were limited. This cross-sectional study, conducted during Fall 2020, examines the correlation between mental wellbeing and COVID-19-related changes in technology use, along with influence of COVID-19-related stressors, school status (in-person versus remote), and social media use for coping purposes, among 978 U.S. adolescents. Results suggest self-reported daily social media and technology use increased significantly from prior to COVID-19 through Fall 2020. Increased social media use was significantly associated with higher levels of anxiety and depressive symptoms regardless of other theoretical moderators or confounders of mental health (e.g., demographics, school status, importance of technology, COVID-19-related stress). Despite literature suggesting that remote learning may result in adverse mental health outcomes, we did not find local school reopening to be associated with current depressive/anxiety symptoms, nor with COVID-19-related increases in technology use. Self-reported use of social media for coping purposes moderated the association between increased social media use and mental health symptoms; in other words, some social media use may have positive effects. Although much prior research has focused on social media use as a marker of stress, we also found that increased video gaming and TV/movie watching were also associated with internalizing symptoms, in accordance with others' work. Future research should explore in more granular detail what, if any, social media and technology use is protective during a pandemic, and for whom, to help tailor prevention efforts.
Safety of administering biologics to IBD patients at an outpatient infusion center In New York City during the COVID-19 pandemic: Sars-CoV-2 seroprevalence and clinical and social characteristics
Authors: Wong Serre-Yu , Gold Stephanie , Accorsi Emma K. , Cowger Tori L. , Wiseman Dean , Navalurkar Reema , Dixon Rebekah , Helmus Drew S. ,   CiTI Study Group, Firpo-Betancourt Adolfo , Mendu Damodara Rao , Zolla-Pazner Susan , Cadwell Ken , Colombel Jean-Frederic
Published: March 2021

Patients with immune-mediated inflammatory diseases (IMIDs) and acquired and genetic immunodeficiencies receiving therapeutic infusions are considered high risk for SARS-CoV-2 infection. However, the seroprevalance in this group and the safety of routine administrations at outpatient infusion centers are unknown. To determine the infection rate and clinical-social factors related to SARS-CoV-2 in asymptomatic patients with IMIDs and immunodeficiencies receiving routine non-cancer therapeutic infusions, we conducted a seroprevalence study at our outpatient infusion center. We report the first prospective SARS-CoV-2 sero-surveillance of 444 IBD/IMID, immunodeficiency, and immune competent patients at an outpatient infusion center in the U.S. showing lower seroprevalence in patients compared with the general population and provide clinical and social characteristics associated with seroprevalence in this group. These data suggest that patients can safely continue infusions at outpatient centers.
COVID-19 with early neurological and cardiac thromboembolic phenomena—timeline of incidence and clinical features
Authors: Sundar Uma , Merchant Sanah , Shah Meera , Mukhopadhyay Amita , Kolte Shaonak , Darole Pramod , Mahajan Sharvari , Bansal Ashank , Gosavi Satish , Asole Dnaneshwar , Karnik Niteen D , Mahajan Ajay , Joshi Anagha
Published: March 2021

Background

At our tertiary care public hospital, we saw COVID-19 presenting with thromboembolic phenomena, indicating a possible early thrombo-inflammatory pathology.

Objectives

We documented patients with cardiac and neurological thromboembolic phenomena as a primary presentation of COVID-19, and compared a subset of COVID associated strokes against COVID-19 patients without thrombotic manifestations.

Methods

We included all COVID-Stroke and COVID-ACS (COVID-19, with ischemic arterial stroke/Acute Coronary Syndrome presenting prior to/simultaneous with/within 72 hours of systemic/respiratory COVID manifestations) admitted from April to November 2020. In the nested case control analysis, we used unpaired T-test and chi-square test to study differences between COVID-Strokes (case group) and non-thrombotic COVID controls.

Results and Conclusions

We noted 68 strokes and 122 ACS associated with COVID-19. ACS peaked in May-June, while stroke admissions peaked later in September-October, possibly because severe strokes may have expired at home during the lockdown.

In the case-control analysis, cases (n=43; 12F:31M; mean age 51.5 years) had significantly higher D-Dimer values than controls (n=50; 9F:41M; mean age 51.6 years). Mortality was significantly higher in cases (51.2% vs. 26.0%; p = 0.018). We noted 7.5 times higher mortality in cases versus controls even among patients needing minimal oxygen support. Imaging in 37 patients showed both anterior and posterior circulation territories affected in seven, with almost half of Carotid territory strokes being large hemispherical strokes. Additionally, CT/MRI angiography in 28 strokes showed large vessel occlusions in 19 patients. Death in cases thus probably occurred before progression to intense respiratory support, due to severe central nervous system insult.

Binary logistic regression analysis showed respiratory support intensity to be the sole independent predictor of mortality among cases. Respiratory distress could have been due to COVID-19 lung infection or aspiration pneumonia resulting from obtunded sensorium. In controls, mortality was predicted by increasing age, female sex, and respiratory support intensity.
Cognitive impairment and functional change in COVID-19 patients undergoing inpatient rehabilitation
Authors: Patel Ruchi , Savrides Irene , Cahalan Christine , Doulatani Gargi , O’Dell Michael W. , Toglia Joan , Jaywant Abhishek
Published: March 2021

Cognitive impairment is increasingly recognized as a sequela of COVID-19. It is unknown how cognition changes and relates to functional gain during inpatient rehabilitation. We administered the Montreal Cognitive Assessment (MoCA) at admission to 77 patients undergoing inpatient rehabilitation for COVID-19 in a large U.S. academic medical center. 45 patients were administered the MoCA at discharge. Functional gain was assessed by change in the Quality Indicator for Self-Care (QI-SC). In the full sample, 80.5% of patients exhibited cognitive impairment on admission, which was associated with prior delirium. Among 45 patients with retest data, there were significant improvements in MoCA and QI-SC. QI-SC score gain was higher in patients who made clinically meaningful changes on the MoCA, an association that persisted after accounting for age and delirium history. Cognitive impairment is frequent among COVID-19 patients, but improves over time and is associated with functional gain during inpatient rehabilitation.
Identifying hidden Zika hotspots in Pernambuco, Brazil: A spatial analysis
Authors: Freitas Laís Picinini , Lowe Rachel , Koepp Andrew E. , Alves Sandra Valongueiro , Dondero Molly , Marteleto Letícia J.
Published: March 2021

Northeast Brazil has the world’s highest rate of Zika-related microcephaly. Yet, in this hard-hit region, traditional case counts of Zika cannot accurately describe Zika risk. Reporting of Zika cases only became mandatory after its association with microcephaly in neonates, when the Zika epidemic was already declining in the region. To advance the study of the Brazilian Zika epidemic and its impacts, we identified hotspots of Zika in Pernambuco state, Northeast Brazil, usingAedes-borne diseases (dengue, chikungunya and Zika) and microcephaly data. We used the Kulldorff’s Poisson purely spatial scan statistic to detect low- and high-risk clusters and combined the results to identify the municipalities most affected by the Zika epidemic. Municipalities were classified as hotspots if they were part of any high-risk cluster, and classified according to a gradient of Zika burden during the epidemic, considering the strength of the evidence. In Pernambuco, officials confirmed 123,934 dengue cases, 167 Zika cases, and 32,983 chikungunya cases between 2014-2017, and 800 microcephaly cases between 2015-2017. We identified 26Aedes-borne diseases clusters (11 high-risk), and 5 microcephaly cases clusters (3 high-risk). Combining the results, sixty-three out of 184 municipalities were identified as hotspots for Zika. The northeast of Pernambuco and the Sertão region were hit hardest by the Zika epidemic. The first is the most populous area, while the second has one of the highest rates of social and economic inequality in Brazil. The identification of Sertão as a Zika hotspot was only possible because the clusters results were combined. The under-reporting of acute infectious diseases is expected to be higher in poor areas. Therefore, using onlyAedes-borne data does not correctly identify the high-risk areas. We successfully identified hidden Zika hotspots using a simple methodology combiningAedes-borne diseases and microcephaly information.
Age specific COVID-19 undercount in Spain from the regional breakdown of 52–week accumulated mortality rates
Authors: Martín-Olalla José María
Published: March 2021

Spanish NUTS3 region records of age specific weekly deaths since the year 2020, records of age specific COVID–19 deaths and age specific population since the year 2020 are used to estimate first age specific all–cause death rates and age specific COVID–19 undercount.

Results shows a statistically significant impact of the pandemic in excess deaths for population aged 40 and elder. Statistically significant COVID–19 undercount is identified only for population aged 80 and elder. Very likely this is the result of the impact of the pandemic in institutionalized population at the early stages of the pandemic.
A Comprehensive Analysis of Allostery in 14-3-3 ζ Docking Proteins using the Spatial Convolution Model (SCM)
Authors: Davis Leroy K.
Published: March 2021

The Spatial Convolution Model (SCM) analyzes allostery based on the spatial evolution of the docking protein elastic media, whereby convolution of the media in response to wave propagation is solved as a function of Z fluctuations and backbone vibration modes. We show that although the elastic media is a complex three-dimensional structure allostery behaves as if it occurs along a stretched oscillating string, where inhomogeneities along the string effect local entropies responsible for ligand binding and transduction of allosteric waves. To identify inhomogeneities along the string, we ignored local density and tension changes during wave propagation and resolved helix wave and physical properties by applying molecular string and beam bending theories. Importantly, we show that allostery occurs at three major scales and that propagation of standing waves create a rolling entropy which drives entropy transfers between fields. Conversion of resonance energy to quantum harmonic oscillators allowed us to consider effects of damping and interactions with the surrounding media as well as to model effects of residue interaction strength on entropy transfer.

Abstract Figure
Cross-species prediction of essential genes in insects through machine learning and sequence-based attributes
Authors: de Castro Giovanni Marques , Hastenreiter Zandora , Monteiro Thiago Augusto Silva , Lobo Francisco Pereira
Published: March 2021

Insects are organisms with a vast phenotypic diversity and key ecological roles. Several insect species also have medical, agricultural and veterinary importance as parasites and vectors of diseases. Therefore, strategies to identify potential essential genes in insects may reduce the resources needed to find molecular players in central processes of insect biology. Furthermore, the detection of essential genes that occur only in certain groups within insects, such as lineages containing insect pests and vectors, may provide a more rational approach to select essential genes for the development of insecticides with fewer off-target effects. However, most predictors of essential genes in multicellular eukaryotes using machine learning rely on expensive and laborious experimental data to be used as gene features, such as gene expression profiles or protein-protein interactions. This information is not available for the vast majority of insect species, which prevents this strategy to be effectively used to survey genomic data from non-model insect species for candidate essential genes. Here we present a general machine learning strategy to predict essential genes in insects using only sequence-based attributes (statistical and physicochemical data). We validate our strategy using genomic data for the two insect species where large-scale gene essentiality data is available: Drosophila melanogaster (fruit fly, Diptera) and Tribolium castaneum (red flour beetle, Coleoptera). We used publicly available databases plus a thorough literature review to obtain databases of essential and non-essential genes for D. melanogaster and T. castaneum, and proceeded by computing sequence-based attributes that were used to train statistical models (Random Forest and Gradient Boosting Trees) to predict essential genes for each species. Both models are capable of distinguishing essential from non-essential genes significantly better than zero-rule classifiers. Furthermore, models trained in one insect species are also capable of predicting essential genes in the other species significantly better than expected by chance. The Random Forest D. melanogaster model can also distinguish between essential and non-essential T. castaneum genes with no known homologs in the fly significantly better than a zero-rule model, demonstrating that it is possible to use our models to predict lineage-specific essential genes in a phylogenetically distant insect order. Here we report, to the best of our knowledge, the development and validation of the first general predictor of essential genes in insects using sequence-based attributes that can, in principle, be computed for any insect species where genomic information is available. The code and data used to predict essential genes in insects are freely available at https://github.com/g1o/GeneEssentiality/.
Bump attractor dynamics underlying stimulus integration in perceptual estimation tasks
Authors: Esnaola-Acebes Jose M. , Roxin Alex , Wimmer Klaus
Published: March 2021

Perceptual decision and continuous stimulus estimation tasks involve making judgments based on accumulated sensory evidence. Network models of evidence integration usually rely on competition between neural populations each encoding a discrete categorical choice and do not maintain information that is necessary for a continuous perceptual judgement. Here, we show that a continuous attractor network can integrate a circular stimulus feature and track the stimulus average in the phase of its activity bump. We show analytically that the network can compute the running average of the stimulus almost optimally, and that the nonlinear internal dynamics affect the temporal weighting of sensory evidence. Whether the network shows early (primacy), uniform or late (recency) weighting depends on the relative strength of the stimuli compared to the bump’s amplitude and initial state. The global excitatory drive, a single model parameter, modulates the specific relation between internal dynamics and sensory inputs. We show that this can account for the heterogeneity of temporal weighting profiles and reaction times observed in humans integrating a stream of oriented stimulus frames. Our findings point to continuous attractor dynamics as a plausible mechanism underlying stimulus integration in perceptual estimation tasks.
dGPredictor: Automated fragmentation method for metabolic reaction free energy prediction andde novopathway design
Authors: Wang Lin , Upadhyay Vikas , Maranas Costas D.
Published: March 2021

Group contribution (GC) methods are conventionally used in thermodynamics analysis of metabolic pathways to estimate the standard Gibbs free energy change (ΔrG′o) of enzymatic reactions from limited experimental measurements. However, these methods are limited by their dependence on manually curated groups and inability to capture stereochemical information, leading to low reaction coverage. Herein, we introduce an automated molecular fingerprint-based thermodynamic analysis tool called dGPredictor that enables the consideration of stereochemistry within metabolite structures and thus increases reaction coverage. dGPredictor has a higher prediction accuracy as compared to existing GC methods and can capture free energy changes for isomerase and transferase reactions, which exhibit no overall group changes. We also demonstrate dGPredictor’s ability to predict the Gibbs free energy change for novel reactions and seamless integration withinde novometabolic pathway design tools such as novoStoic. This enables performing a thermodynamic analysis for synthetic pathways, thus safeguarding against the inclusion of reaction steps with infeasible directionalities. To facilitate easy access to dGPredictor, we developed a graphical user interface to predict the standard Gibbs free energy change for reactions at various pH and ionic strengths. The tool allows customized user input of known metabolites as KEGG IDs and novel metabolites as InChI strings (https://github.com/maranasgroup/dGPredictor).

Author summary

The genome-scale metabolic networks consist of a large number of biochemical reactions interconnected in a complex system. The standard Gibbs free energy change is commonly used to check for the feasibility of enzyme-catalyzed reactions as thermodynamics plays a crucial role in pathway design for biochemical synthesis. The group contribution methods using expert-defined functional groups have been extensively used for estimating standard Gibbs free energy change with limited experimental measurements. However, current methods using functional groups have major issues that limit its ability to cover all the metabolites and reactions as well as the inability to consider stereochemistry leads to erroneous estimation of free energy that undergoes only stereochemical change such as isomerases. Here, we introduce a molecular fingerprint-based thermodynamic tool dGPredictor that enables stereochemistry in metabolites and thus improves the reaction coverage with higher prediction accuracy compared to current GC methods. It also allows the ability to predict free energy change for novel reactions which can aid thede novometabolic pathway design tool to ensure the reaction feasibility. We apply and test our method on reactions in the KEGG database and isobutanol synthesis pathway. In addition, we provide an open-source user-friendly web interface to facilitate easy access for standard Gibbs free energy change of reactions at different physiological states.
Indication-specific tumor evolution and its impact on neoantigen targeting and biomarkers for individualized cancer immunotherapies
Authors: Lo Amy A. , Wallace Andrew , Oreper Daniel , Lounsbury Nicolas , Havnar Charles , Pechuan-Jorge Ximo , Wu Thomas D. , Bourgon Richard , Jones Ryan , Krogh Katrina , Yang Guang-Yu , Zill Oliver A.
Published: March 2021

Individualized neoantigen specific immunotherapy (iNeST) requires robustly expressed clonal neoantigens for efficacy, but tumor mutational heterogeneity, loss of neoantigen expression, and variable tissue sampling present challenges. To characterize these potential obstacles, we combined multi-region sequencing (MR-seq) analysis of five untreated, synchronously sampled metastatic solid tumors with re-analysis of published MR-seq data from 103 patients. Branching evolution in colorectal cancer and renal cell carcinoma led to fewer clonal neoantigens and to clade-specific neoantigens (those shared across a subset of tumor regions but not fully clonal), with the latter not being readily distinguishable in single tumor samples. Prioritizing mutations with higher purity- and ploidy-adjusted variant allele frequency enriched for globally clonal neoantigens (those found in all tumor regions), whereas estimated cancer cell fraction derived from clustering-based tools, surprisingly, did not. Neoantigen quality was associated with loss of neoantigen expression in the bladder cancer case, and HLA-allele loss was observed in the renal and non-small cell lung cancer cases. Our results show that indication type, multi-lesion sampling, neoantigen expression, and HLA allele retention are important factors for iNeST targeting and patient selection.
Leakiness at the human-animal interface in Southeast Asia and implications for the spread of antibiotic resistance
Authors: Nadimpalli Maya L. , Stegger Marc , Viau Roberto , Yith Vuthy , de Lauzanne Agathe , Sem Nita , Borand Laurence , Huynh Bich-tram , Brisse Sylvain , Passet Virginie , Overballe-Petersen Søren , Aziz Maliha , Gouali Malika , Jacobs Jan , Phe Thong , Hungate Bruce A. , Leshyk Victor O. , Pickering Amy J. , Gravey François , Liu Cindy M. , Johnson Timothy J. , Hello Simon Le , Price Lance B.
Published: March 2021

International efforts to curb antimicrobial resistance have focused on drug development and limiting unnecessary use. However, in areas where water, sanitation, and hygiene infrastructure is lacking, and where biosecurity in food-animal production is poor, pathogen-flow between humans and animals could exacerbate the emergence and spread of resistant pathogens. Here, we compared mobile resistance elements amongEscherichia colirecovered from humans and meat in Cambodia, a country with substantial connectivity between humans and animals, unregulated antibiotic use, and poor environmental controls. We identified multiple resistance-encoding plasmids and a novel,blaCTX-MandqnrS1-encoding transposon that were widely dispersed in both humans and animals, a phenomenon rarely observed in high-income settings. Our findings indicate that plugging leaks at human-animal interfaces should be a critical part of addressing antimicrobial resistance in low and middle-income countries.
Compulsive drinking is associated with neural activity patterns reflecting diminished behavioral control and enhanced seeking representations in dorsal medial prefrontal cortex
Authors: Timme Nicholas M. , Ma Baofeng , Linsenbardt David , Cornwell Ethan , Galbari Taylor , Lapish Christopher
Published: March 2021

Drinking despite negative consequences (compulsive drinking) is a central contributor to high-risk alcohol intake and is associated with poor treatment outcomes in humans. We used a rodent model of compulsive drinking to examine the role played by dorsal medial prefrontal cortex (dmPFC), a brain region involved in maladaptive decision-making in addiction, in this clinically critical phenomenon. We developed novel advances in principal component and change point analyses to dissect neural population representations of specific decision-making variables. Compulsive subjects showed weakened representations of behavioral control signals that relate to drinking within a trial, but strengthened session-wide seeking state representations that were associated with drinking engagement at the start of each drinking opportunity. Finally, chemogenetic-based excitation of dmPFC prevented escalation of compulsive drinking. Collectively, these data indicate that compulsive drinking is associated with alterations in dmPFC neural activity that underlie diminished behavioral control and enhanced seeking.
The salmon louse genome: copepod features and parasitic adaptations
Authors: Skern-Mauritzen Rasmus , Malde Ketil , Eichner Christiane , Dondrup Michael , Furmanek Tomasz , Besnier Francois , Komisarczuk Anna Zofia , Nuhn Michael , Dalvin Sussie , Edvardsen Rolf B. , Klages Sven , Huettel Bruno , Stueber Kurt , Grotmol Sindre , Karlsbakk Egil , Kersey Paul , Leong Jong S. , Glover Kevin A. , Reinhardt Richard , Lien Sigbjørn , Jonassen Inge , Koop Ben F. , Nilsen Frank
Published: March 2021

Copepods encompass a range of ecological roles from parasites to phytoplankton grazers linking primary producers to higher trophic levels. Despite these important roles, copepod genome assemblies are scarce.Lepeophtheirus salmonisis an economically and ecologically important ectoparasitic copepod. We present the 695.4 MbpL. salmonisgenome assembly containing ≈60% repetitive regions and 13081 annotated protein-coding genes. The genome comprises 14 autosomes and a ZZ-ZW sex chromosome system. Assembly assessment identified 92.4% of the expected arthropod genes. Transcriptomics validated annotation and revealed a marked shift in gene expression after host attachment, including downregulation of genes related to circadian rhythm coinciding with abandoning diurnal migration. The genome shows evolutionary signatures including loss of peroxisomes, numerous FNII domains, and an incomplete heme homeostasis pathway suggesting heme proteins to be obtained from the host. Despite large capacity to develop resistance against chemical treatmentsL. salmonisexhibits low numbers of many genes involved in detoxification.
Responding kinetic of B-cell receptor repertoire to the Toll-like receptor 7/8 stimulation in non-human primates
Authors: Wang Shiyu , Mandl Judith , Feinberg Mark , Citron Michael , Saksena Nitin K. , Luo Lihua , Li Zida , Zhu Yonggang , Li Tao , Nie Chao , Zhang Xiuqing , Liu Ya , Liu Xiao , Wang I-Ming , Zhang Wei
Published: March 2021

TLR7 and 8 regulate B cell immunity, but the precise details of the mechanism are still unclear. Here, we studied the kinetics of both heavy and light chains (IgKL) of B-cell receptor (BCR) repertoire responding to the TLR7/8 stimulation in two geniuses of non-human primates (NHPs), African green monkeys (AGMs) and rhesus macaques (RMs). We evaluated the activation of lymphocytes by flow cytometry, and studied characteristics of BCR repertoire in terms of gene usage, repertoire diversity, and the number of lineages. Although AGMs had a weaker activation than RMs, and a different responding kinetic, both AGMs and RMs presented an increased IgKL repertoire diversity and lineages expansion. It suggested that the responding time rather than initiation of TLR7/8-induced IgKL repertoire response related to B cell activation. Expanded IgKL lineages with frequency from 0.001% to 1% had an elevated mutation rate and expanded IgH lineages used more IgA/G/E, suggesting that the TLR7/8 stimulation expanded low-frequent but high-mutated lineages. Besides, most of expanded IgKL lineages were λ isotype. In conclusion, TLR7/8 selectively expands IgKL lineages with a high mutation rate, low frequency, and λ isotype. The selective effect of TLR7/8 on BCR repertoire allows TLR7/8 agonists to be adjuvant for selectively accelerating antibody maturation.
Personalized sleep-wake patterns aligned with circadian rhythm relieve daytime sleepiness
Authors: Hong Jaehyoung , Choi Su Jung , Park Se Ho , Hong Hyukpyo , Booth Victoria , Joo Eun Yeon , Kim Jae Kyoung
Published: March 2021

Shift workers and many other groups experience irregular sleep-wake patterns. This can induce excessive daytime sleepiness that decreases productivity and elevates the risk of accidents. However, the degree of daytime sleepiness is not correlated with standard sleep parameters like total sleep time, suggesting other factors are involved. Here, we analyze real-world sleep-wake patterns of shift workers measured by wearables with a newly developed user-friendly computational package that simulates homeostatic sleep pressure – the physiological need for sleep – and the circadian rhythm. This reveals that shift workers who align sleep-wake patterns with their circadian rhythm have lower daytime sleepiness, even if they sleep less. The alignment, quantified by a new parameter, circadian sleep sufficiency, can be increased by dynamically adjusting daily sleep durations according to varying bedtimes. Our computational package provides flexible and personalized real-time sleep-wake patterns for individuals to reduce their daytime sleepiness and could be used with wearable devices to develop smart alarms.
Codependency and mutual exclusivity for gene community detection from sparse single-cell transcriptome data
Authors: Nakajima Natsu , Hayashi Tomoatsu , Fujiki Katsunori , Shirahige Katsuhiko , Akiyama Tetsu , Akutsu Tatsuya , Nakato Ryuichiro
Published: March 2021

Single-cell RNA-seq (scRNA-seq) can be used to characterize cellular heterogeneity in thousands of cells. The reconstruction of a gene network based on coexpression patterns is a fundamental task in scRNA-seq analyses, and the mutual exclusivity of gene expression can be critical for understanding such heterogeneity. Here, we propose an approach for detecting communities from a genetic network constructed on the basis of coexpression properties. The community-based comparison of multiple coexpression networks enables the identification of functionally related gene clusters that cannot be fully captured through differential gene expression-based analysis. We also developed a novel metric referred to as the exclusively expressed index (EEI) that identifies mutually exclusive gene pairs from sparse scRNA-seq data. EEI quantifies and ranks the exclusive expression levels of all gene pairs from binary expression patterns while maintaining robustness against a low sequencing depth. We applied our methods to glioblastoma scRNA-seq data and found that gene communities were partially conserved after serum stimulation despite a considerable number of differentially expressed genes. We also demonstrate that the identification of mutually exclusive gene sets with EEI can improve the sensitivity of capturing cellular heterogeneity. Our methods complement existing approaches and provide new biological insights, even for a large, sparse dataset, in the single-cell analysis field.
The formal demography of kinship III: Kinship dynamics with time-varying demographic rates
Authors: Caswell Hal , Song Xi
Published: March 2021

Background

Kinship models generally assume time-invariant demographic rates, and compute the kinship structures implied by those rates. It is important to compute the consequences of time variation in demographic rates for kinship stuctures.

Objectives

Our goal is to develop a matrix model for the dynamics of kinship networks subject to arbitrary temporal variation in survival, fertility, and population structure.

Methods

We develop a system of equations for the dynamics of the age structure of each type of kin of a Focal individual. The matrices describing survival and fertility vary with time. The initial conditions in the time-invariant model are replaced with a set of boundary conditions for initial time and initial age.

Results

The time-varying model maintains the network structure of the time-invariant model. In addition to the results of the time-invariant model, it provides kinship structures by period, cohort, and age. It applies equally to historical sequences of past rates and to projections of future rates. As an illustration, we analyze the kinship structure of Sweden from 1891 to 2120.

Contribution

The time-varying kinship model makes it possible to analyze the consequences of changing demographic rates, in the past or the future. It is easily computable, requires no simulations, and is readily extended to include additional, more distant relatives in the kinship network. The method can also be used to show the growth of families, lineages, and dynasties in populations across time and place and between social groups.
Response inhibition in premotor cortex corresponds to a complex reshuffle of the mesoscopic information network
Authors: Bardella Giampiero , Giuffrida Valentina , Giarrocco Franco , Brunamonti Emiliano , Pani Pierpaolo , Ferraina Stefano
Published: March 2021

Recent studies have explored functional and effective neural networks in animal models; however, the dynamics of information propagation among functional modules under cognitive control remain largely unknown. Here, we addressed the issue using Transfer Entropy and graph theory methods on mesoscopic neural activities recorded in the dorsal premotor cortex of rhesus monkeys. We focused our study on the decision time of a Stop-signal task, looking for patterns in the network configuration that could influence motor plan maturation when the Stop signal is provided. When comparing trials with successful inhibition to those with generated movement, the nodes of the network resulted organized into four clusters, hierarchically arranged, and distinctly involved in information transfer. Interestingly, the hierarchies and the strength of information transmission between clusters varied throughout the task, distinguishing between generated movements and canceled ones and corresponding to measurable levels of network complexity. Our results suggest a putative mechanism for motor inhibition in premotor cortex: a topological reshuffle of the information exchanged among ensembles of neurons.

AUTHOR SUMMARY

In this study, we investigated the dynamics of information transfer among functionally identified neural modules during cognitive motor control. Our focus was on mesoscopic neural activities in the dorsal premotor cortex of rhesus monkeys engaged in a Stop-signal task. Leveraging multivariate Transfer Entropy and graph theory, we uncovered insights on how behavioral control shapes the topology of information transmission in a local brain network. Task phases modulated the strength and hierarchy of information exchange between modules, revealing the nuanced interplay between neural populations during generated and canceled movements. Notably, during successful inhibition, the network displayed a distinctive configuration, unveiling a novel mechanism for motor inhibition in the premotor cortex: a topological reshuffle of information among neuronal ensembles.
Broccoli sprout Sulforaphane affected hemodynamics and aorta myogenic spontaneous rhythmic contraction in sanitized water uptake mice
Authors: Li Linmei , Gao Lingfeng , Wang Ting , He Tong , Li Jiaxing , Suwardi Rifqah Kurnia , Xu Xuan , Wang Yang
Published: March 2021

Drinking seawater erodes water source will lead to hemodynamic changes in cardiovascular system. The erosion affected vascular biomechanics further interrupt the blood supply in arterial network. In this study, we investigated the carotid arterial hemodynamics in salinity water fed mice, and the relative spontaneous contraction of aorta preparation. The biological effect of Broccoli sprout Sulforaphane was assessed in intake hemodynamic changes.Kunmingmice were randomly divided into seawater feeding group, seawater + Sulforaphane group, freshwater feeding group, fresh water + Sulforaphane group. After 4 weeks of feeding, the pressure waveforms of common carotid artery were analyzedin vivo. The enhanced common carotid arterial pressures were calculated according to the breakpoint of systolic pressure rising phase. The ejection time was calculated according to the dicrotic notch.In vitro, the isolated aorta biomechanical features were tested on a micro stepping platform. The passive tension and relative myogenic spontaneous contraction were evaluated. The results indicated that in salinity water fed mice heart rate, ejection period were significantly accelerated. The systolic pressure breakpoint of the ascending phase was significantly increased; however, the central aortic pressure augment index was decreased.In vitrostudy, the isolated aorta preparations indicated remarkable myogenic spontaneous contraction in salinity water fed mice. The spontaneous contraction indicated a significant cycle pattern, the waveform cluster changes regularly in one cycle, maximal amplitude of myogenic autonomic contraction increased significantly. Spontaneous contraction became more active, however cycle duration shortened. In biological effect of Broccoli sprout supplement, Sulforaphane was effective in reducing the heart rate, prolonging ejection period, improving systolic pressure and pulse pressure amplitude in salinity water fed mice. We concluded that long-term salinity water uptake can form a new hypertension model in mice, which can affect the changes of carotid artery hemodynamics and local blood supply. The Broccoli sprout Sulforaphane can improve the high systolic blood pressure and ejection period of artery, and its mechanism needs further study.
Insights into the drivers of radiating diversification in biodiversity hotspots usingSaussurea(Asteraceae) as a case
Authors: Zhang Xu , Landis Jacob B. , Sun Yanxia , Zhang Huajie , Feng Tao , Lin Nan , Tiamiyu Bashir B. , Huang Xianhan , Deng Tao , Wang Hengchang , Sun Hang
Published: March 2021

The Qinghai-Tibet Plateau (QTP) encompasses areas with a remarkably high degree of biodiversity, harboring exceptional species-rich radiations. How these radiations formed by interacting with geology, climate and ecology remains seldom examined.

We investigate the roles of abiotic (environmental) and biotic (species-intrinsic) factors in driving radiating diversification ofSaussurea(Asteraceae) by deploying a number of time-dependent, paleoenvironment-dependent and trait-dependent models, as well as ecological distribution data.

We show that three main clades ofSaussureabegin to diversify in the Miocene almost simultaneously, with increasing diversification rates toward the present and negative dependence to paleotemperature. Acceleration in diversification rates are correlated with adaptive traits, as well climate lability, niche breadth and species range.

We conclude that fluctuation of paleoclimate along with complex QTP environments provided opportunities for increased diversification rates ofSaussureawith diverse adaptive traits, highlighting the importance of combinations of clade-specific traits and ecological niches in driving rapid radiation.
The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice
Authors: Ciaramelli Elisa , De Luca Flavia , Kwan Donna , Mok Jenkin , Bianconi Francesca , Knyagnytska Violetta , Craver Carl , Green Leonard , Myerson Joel , Rosenbaum R. Shayna
Published: March 2021

Intertemporal choices require trade-offs between short-term and long-term outcomes. Ventromedial prefrontal cortex (vmPFC) damage causes steep discounting of future rewards (delay discounting; DD) and impoverished episodic future thinking (EFT). The role of vmPFC in reward valuation, EFT, and their interaction during intertemporal choice is still unclear. Here, twelve patients with lesions to vmPFC and forty-one healthy controls chose between smaller-immediate and larger-delayed hypothetical monetary rewards while we manipulated reward magnitude and the availability of EFT cues. In the EFT condition, participants imagined personal events to occur at the delays associated with the larger-delayed rewards. We found that DD was steeper in vmPFC patients compared to controls, and not modulated by reward magnitude. However, EFT cues downregulated DD in vmPFC patients as well as controls. These findings indicate that vmPFC integrity is critical for the valuation of (future) rewards, but not to instill EFT in intertemporal choice.
Powering electronic implants by high frequency volume conduction: in human validation
Authors: Minguillon Jesus , Tudela-Pi Marc , Becerra-Fajardo Laura , Perera-Bel Enric , del-Ama Antonio J. , Gil-Agudo Ángel , Megía-García Álvaro , García-Moreno Aracelys , Ivorra Antoni
Published: March 2021

Wireless power transfer (WPT) is frequently used as an alternative to batteries to accomplish miniaturization in electronic medical implants (eMIs). However, established WPT methods require bulky parts within the implant or cumbersome external systems, hindering minimally invasive deployments and the development of networks of eMIs. As an alternative, we propose a WPT approach based on volume conduction of high frequency (HF) current bursts. These currents are applied through external textile electrodes and are collected by the eMIs through two electrodes at their opposite ends. This approach avoids bulky components to obtain power, making it possible to develop implants with a flexible threadlike conformation. In here we study in humans if HF (6.78 MHz) current bursts complying with safety standards and applied through two textile electrodes strapped around a limb can provide substantial powers from pairs of implanted electrodes. Time averaged electric powers obtained from needle electrodes (diameter = 0.4 mm, length = 3 mm, separation = 30 mm) inserted into arms and lower legs of five healthy participants were 5.9 ± 0.7 mW and 2.4 ± 0.3 mW respectively. We also report a procedure to characterize the coupling between the external system and the implants using two-port impedance models generated from medical images. The results demonstrate for the first time in humans that innocuous and imperceptible HF current bursts that flow through the tissues by volume conduction can be used to wirelessly power threadlike eMIs, overcoming the limitations of existing WPT methods in terms of minimal invasiveness and usability.