bluuebunny/crossref_metadata_2025 huggingface dataset:
The In Vivo Source of Type I and Type III IFNs is Pathogen Dependent
Authors: Sandoval Marvin J. , Tseng Hsiang-Chi , Risman Heidi P. , Smirnov Sergey , Li Qing , Lin Jian-Da , Rivera Amariliz , Durbin Russell K. , Kotenko Sergei V. , Durbin Joan E.
Published: October 2021

Type I (-α, β) and type III (-λ) interferons (IFNs) are produced in response to virus infection and upregulate a largely overlapping set of IFN stimulated genes which mediate the protective effects of these antiviral cytokines. In vitro studies have demonstrated the redundancy of these two cytokine families which activate the same transcription factor, IFN stimulated gene factor 3 (ISGF3), via distinct ligands and receptors. However, in vivo, these IFN types do have distinct functions based on receptor distribution, but also ligand availability. Using a newly generated IFN-λ reporter mouse strain we have observed that both type I and type III IFNs are produced in response to respiratory tract infection by Newcastle disease virus (NDV) and influenza A virus (IAV). In the case of NDV these IFNs are synthesized by different cell types. Type I IFNs are produced primarily by alveolar macrophages, type III IFNs are made only by epithelial cells, and production of either is dependent on MAVS. While epithelial cells of the respiratory tract represent the primary target of IAV infection, we found that they did not significantly contribute to IFN-λ production, and IFN-λ protein levels were largely unaffected in the absence of MAVS. Instead we found that pDCs, a cell type known for robust IFN-α production via TLR/MyD88 signaling, were the major producers of IFN-λ during IAV infection, with pDC depletion during influenza infection resulting in significantly reduced levels of both IFN-α and IFN-λ. In addition, we were able to demonstrate that pDCs rely on type I IFN for optimal IFN-λ production. These studies therefore demonstrate that the in vivo producers of Type III IFNs in response to respiratory virus infection are pathogen dependent, a finding which may explain the varying levels of cytokine production induced by different viral pathogens.
Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis
Authors: Pillet Benjamin , Méndez-Godoy Alfonso , Murat Guillaume , Favre Sébastien , Stumpe Michael , Falquet Laurent , Kressler Dieter
Published: October 2021

The biogenesis of eukaryotic ribosomes involves the ordered assembly of around 80 ribosomal proteins. Supplying equimolar amounts of assembly-competent ribosomal proteins is complicated by their aggregation propensity and the spatial separation of their location of synthesis and pre-ribosome incorporation. Recent evidence has highlighted that dedicated chaperones protect individual, unassembled ribosomal proteins on their path to the pre-ribosomal assembly site. Here, we show that the co-translational recognition of Rpl3 and Rpl4 by their respective dedicated chaperone, Rrb1 or Acl4, prevents the degradation of the encoding RPL3 and RPL4 mRNAs in the yeast Saccharomyces cerevisiae. In both cases, negative regulation of mRNA levels occurs when the availability of the dedicated chaperone is limited and the nascent ribosomal protein is instead accessible to a regulatory machinery consisting of the nascent-polypeptide associated complex and the Caf130-associated Ccr4-Not complex. Notably, deregulated expression of Rpl3 and Rpl4 leads to their massive aggregation and a perturbation of overall proteostasis in cells lacking the E3 ubiquitin ligase Tom1. Taken together, we have uncovered an unprecedented regulatory mechanism that adjusts the de novo synthesis of Rpl3 and Rpl4 to their actual consumption during ribosome assembly and, thereby, protects cells from the potentially detrimental effects of their surplus production.
A Hierarchical Reinforcement Learning Model Explains Individual Differences in Attentional Set Shifting
Authors: Talwar Anahita , Huys Quentin , Cormack Francesca , Roiser Jonathan P
Published: October 2021

Attentional set shifting refers to the ease with which the focus of attention is directed and switched. Cognitive tasks such as CANTAB IED reveal great variation in set shifting ability in the general population, with notable impairments in those with psychiatric diagnoses. The attentional and learning processes underlying this cognitive ability, and how they lead to the observed variation remain unknown. To directly test this, we used a modelling approach on two independent large-scale online general-population samples performing CANTAB IED and psychiatric symptom assessment. We found a hierarchical model that learnt both feature values and dimension attention best explained the data, and that compulsive symptoms were associated with slower learning and higher attentional bias to the first relevant stimulus dimension. This data showcase a new methodology to analyse data from the CANTAB IED task, and suggest a possible mechanistic explanation for the variation in set shifting performance, and its relationship to compulsive symptoms.
Chromatin binding of survivin regulates glucose metabolism in the IFN-γ producing CD4+T cells
Authors: Erlandsson Malin C. , Andersson Karin M.E. , Oparina Nina Y. , Chandrasekaran Venkataragavan , Damdimopoulos Anastasios , Garcia-Bonete Maria-Jose , Einbeigi Zakaria , Silfverswärd Sofia T. , Pekna Marcela , Katona Gergely , Bokarewa Maria I.
Published: October 2021

Interferon-gamma (IFNγ) producing T cells develop metabolic adaptation required for their effector functions in tumour biology, autoimmunity and antiviral defence.

Using sorted CD4+cells we demonstrated that glycolytic switch and high glucose uptake in IFNγ-producing cells was associated with survivin expression. Inhibition of survivin restored glycolysis by upregulating the transcription of phosphofructokinase PFKFB3 and reducing glucose uptake. Integration of the whole-genome sequencing of the chromatin immunoprecipitated with survivin with transcription changes in CD4+cells after survivin inhibition revealed co-localization of survivin, IRF1 and SMAD3 in the regulatory elements paired to the differentially expressed genes. Western blot demonstrated direct binding of survivin to IRF1 and SMAD3. Functionally, inhibition of survivin repressed IFNγ signalling and activated SMAD3-dependent protein remodelling, which resulted in the effector-to-memory transition of CD4+cells. These findings demonstrate the key role of survivin in IFNγ-dependent metabolic adaptation and identify survivin inhibition as an attractive strategy to counteract these effects.
The structure and robustness of tripartite ecological networks
Authors: Domínguez-García Virginia , Kéfi Sonia
Published: October 2021

Until recently, most ecological network analyses have focused on a single interaction type. In nature, however, diverse interactions co-occur, each of them forming a layer of a ‘multilayer’ network. Data including information on multiple interactions has recently started to emerge, giving us the opportunity to have a first glance at possible commonalities in the structure of these networks. We studied the structural features of 44 tripartite ecological networks from the literature, each composed of two layers of interactions (e.g. herbivory, parasitism, pollination), and investigated their fragility to species losses. We found that the way in which the different layers of interactions are connected to each other affect how perturbations spread in ecological communities. Our results highlight the importance of considering multiple interactions simultaneously to better gauge the robustness of ecological communities to species loss and to more reliably identify the species that are important for robustness.
DetecDiv, a generalist deep-learning platform for automated cell division tracking and survival analysis
Authors: Aspert Théo , Hentsch Didier , Charvin Gilles
Published: October 2021

Automating the extraction of meaningful temporal information from sequences of microscopy images represents a major challenge to characterize dynamical biological processes. So far, strong limitations in the ability to quantitatively analyze single-cell trajectories have prevented large-scale investigations to assess the dynamics of entry into replicative senescence in yeast. Here, we have developed DetecDiv, a microfluidic-based image acquisition platform combined with deep learning-based software for high-throughput single-cell division tracking. We show that DetecDiv can automatically reconstruct cellular replicative lifespans with high accuracy and performs similarly with various imaging platforms and geometries of microfluidic traps. In addition, this methodology provides comprehensive temporal cellular metrics using time-series classification and image semantic segmentation. Last, we show that this method can be further applied to automatically quantify the dynamics of cellular adaptation and the real-time cell survival upon exposure to environmental stress. Hence, this methodology provides an all-in-one toolbox for high-throughput phenotyping for cell cycle, stress response, and replicative lifespan assays.
Engineered natural killer cells impede the immunometabolic CD73-adenosine axis in solid tumors
Authors: Chambers Andrea M. , Lupo Kyle B. , Wang Jiao , Cao Jingming , Toregrosa-Allen Sandra , Elzey Bennett D. , Pine Sharon R. , Jalal Shadia , Utturkar Sagar , Lanman Nadia A. , Bernal-Crespo Victor , Matosevic Sandro
Published: October 2021

Immunometabolic reprogramming due to CD73-produced adenosine is a recognized immunosuppressive mechanism contributing to immune evasion in solid tumors. Adenosine is not only known to contribute to tumor progression, but it has specific roles in driving dysfunction of immune cells, including natural killer (NK) cells. Here, we engineered NK cells to directly target the CD73-adenosine axis by blocking the enzymatic activity of CD73. In doing so, the engineered NK cells not only impaired adenosinergic metabolism driven by the hypoxic uptake of ATP by cancer cells, but also mediated killing of tumor cells due to the specific recognition of overexpressed CD73. This results in a “single agent” immunotherapy that combines antibody specificity, blockade of purinergic signaling, and killing of targets mediated by NK cells. We also showed that CD73-targeted NK cells are potent in vivo and result in tumor arrest, while promoting NK cell infiltration into CD73+ tumors and enhanced intratumoral activation.
The Epigenetic Pacemaker is a more sensitive tool than penalized regression for identifying moderators of epigenetic aging
Authors: Farrell Colin , Lapborisuth Kalsuda , Hu Chanyue , Pu Kyle , Snir Sagi , Pellegrini Matteo
Published: October 2021

Epigenetic clocks, DNA methylation based chronological age prediction models, are commonly employed to study age related biology. The error between the predicted and observed age is often interpreted as a form of biological age acceleration and many studies have measured the impact of environmental and other factors on epigenetic age. Epigenetic clocks are fit using approaches that minimize the error between the predicted and observed chronological age and as a result they reduce the impact of factors that may moderate the relationship between actual and epigenetic age. Here we compare the standard methods used to construct epigenetic clocks to an evolutionary framework of epigenetic aging, the epigenetic pacemaker (EPM) that directly models DNA methylation as a function of a time dependent epigenetic state. We show that the EPM is more sensitive than epigenetic clocks for the detection of factors that moderate the relationship between actual age and epigenetic state (ie epigenetic age). Specifically, we show that the EPM is more sensitive at detecting sex and cell type effects in a large aggregate data set and in an example case study is more sensitive sensitive at detecting age related methylation changes associated with polybrominated biphenyl exposure. Thus we find that the pacemaker provides a more robust framework for the study of factors that impact epigenetic age acceleration than traditional clocks based on linear regression models.
Riboswitch Folds to Holo-Form Like Structure Even in the Absence of Cognate Ligand at High Mg2+ Concentration
Authors: Kumar Sunil , Reddy Govardhan
Published: October 2021

Riboswitches are non-coding RNA that regulate gene expression by folding into specific three-dimensional structures (holo-form) upon binding by their cognate ligand in the presence of Mg2+. Riboswitch functioning is also hypothesized to be under kinetic control requiring large cognate ligand concentrations. We ask the question under thermodynamic conditions, can the riboswitches populate holo-form like structures in the absence of their cognate ligands only in the presence of Mg2+. We addressed this question using thiamine pyrophosphate (TPP) riboswitch as a model system and computer simulations using a coarse-grained model for RNA. The folding free energy surface (FES) shows that with the initial increase in Mg2+ concentration ([Mg2+]), TPP AD undergoes a barrierless collapse in its dimensions. On further increase in [Mg2+], intermediates separated by barriers appear on the FES, and one of the intermediates has a TPP ligand-binding competent structure. We show that site-specific binding of the Mg2+ aids in the formation of tertiary contacts. For [Mg2+] greater than physiological concentration, AD folds into its holo-form like structure even in the absence of the TPP ligand. The folding kinetics shows that it populates an intermediate due to the misalignment of the two arms in the TPP AD, which acts as a kinetic trap leading to larger folding timescales. The predictions of the intermediate structures from the simulations are amenable for experimental verification.
Sequencing of Argonaute-bound miRNA/mRNA hybrids reveals regulation of the unfolded protein response by microRNA-320a
Authors: Fields Christopher J. , Li Lu , Hiers Nicholas M. , Li Tianqi , Sheng Peike , Huda Taha , Shan Jixiu , Gay Lauren , Gu Tongjun , Bian Jiang , Kilberg Michael S. , Renne Rolf , Xie Mingyi
Published: October 2021

MicroRNAs (miRNA) are short non-coding RNAs widely implicated in gene regulation. Most metazoan miRNAs utilize the RNase III enzymes Drosha and Dicer for biogenesis. One notable exception is the RNA polymerase II transcription start sites (TSS) miRNAs whose biogenesis does not require Drosha. The functional importance of the TSS-miRNA biogenesis is uncertain. To better understand the function of TSS-miRNAs, we applied a modifiedCrosslinking,Ligation, andSequencing ofHybrids on Argonaute (AGO-qCLASH) to identify the targets for TSS-miRNAs in HCT116 colorectal cancer cells with or withoutDROSHAknockout. We observed that miR-320a hybrids dominate in TSS-miRNA hybrids identified by AGO-qCLASH. Targets for miR-320a are enriched in the eIF2 signaling pathway, a downstream component of the unfolded protein response. Consistently, in miR-320a mimic- and antagomir- transfected cells, differentially expressed genes are enriched in eIF2 signaling. Within the AGO-qCLASH data, we identified the endoplasmic reticulum (ER) chaperone Calnexin as a direct miR-320a target, thus connecting miR-320a to the unfolded protein response. During ER stress, but not amino acid deprivation, miR-320a up-regulates ATF4, a critical transcription factor for resolving ER stress. Our study investigates the targetome of the TSS-miRNAs in colorectal cancer cells and establishes miR-320a as a regulator of unfolded protein response.
Peripherally targeted analgesia via AAV-mediated sensory neuron-specific inhibition of multiple pronociceptive sodium channels in rat
Authors: Shin Seung Min , Itson-Zoske Brandon , Qiu Chensheng , Rahman Mahmudur , Gani Uarda , Fan Fan , Cummins Theodore R. , Hogan Quinn H. , Yu Hongwei
Published: October 2021

This study reports that targeting intrinsically disordered regions (IDRs) of NaV1.7 protein facilitated discovery of sodium channel inhibitory peptide aptamers (NaviPA) for adeno-associated virus (AAV)-mediated, sensory neuron-specific analgesia. A multipronged inhibition of INa1.7, INa1.6, and INa1.3, but not INa1.5and INa1.8was found for a prototype, named NaviPA1, which was derived from the NaV1.7 intracellular loop 1 and is conserved among the TTXs NaVsubtypes. NaviPA1 expression in primary sensory neurons (PSNs) of dorsal root ganglia (DRG) produced significant inhibition of TTXs INabut not TTXr INa. DRG injection of AAV6-encoded NaviPA1 significantly attenuated evoked and spontaneous pain behaviors in both male and female rats with neuropathic pain induced by tibial nerve injury (TNI). Whole-cell current-clamp of the PSNs showed that NaviPA1 expression normalized PSN excitability in TNI rats, suggesting that NaviPA1 attenuated pain by reversal of injury-induced neuronal hypersensitivity. Immunohistochemistry revealed efficient NaviPA1 expression restricted in PSNs and their central and peripheral terminals, indicating PSN-restricted AAV biodistribution. Inhibition of sodium channels by NaviPA1 was replicated in the human iPSC-derived sensory neurons. These results summate that NaviPA1 is a promising analgesic lead that, combined with AAV-mediated PSN-specific block of multiple TTXs NaVs has potential as peripheral nerve-restricted analgesic therapeutics.
Quantitative modeling of fine-scale variations in theArabidopsis thalianacrossover landscape
Authors: Hsu Yu-Ming , Falque Matthieu , Martin Olivier C.
Published: October 2021

In essentially all species where meiotic crossovers have been studied, they occur preferentially in open chromatin, typically near gene promoters and to a lesser extent at the end of genes. Here, in the case ofArabidopsis thaliana, we unveil further trends arising when one considers contextual information, namely summarized epigenetic status, size of underlying genomic regions and degree of divergence between homologs. For instance we find that intergenic recombination rate is reduced if those regions are less than 1.5 kb in size. Furthermore, we propose that the presence of single nucleotide polymorphisms is a factor driving enhanced crossover rate compared to when homologous sequences are identical, in agreement with previous works comparing rates in homozygous and heterozygous blocks. Lastly, by integrating these different factors, we produce a quantitative and predictive model of the recombination landscape that reproduces much of the experimental variation.
Machine Learning Speeding Up the Development of Portfolio of New Crop Varieties to Adapt to and Mitigate Climate Change
Authors: Bari A. , Ouabbou H. , Jilal A. , Khazaei H. , Stoddard F.L. , Sillanpää M.J.
Published: October 2021

Climate change poses serious challenges to achieving food security in a time of a need to produce more food to keep up with the world’s increasing demand for food. There is an urgent need to speed up the development of new high yielding varieties with traits of adaptation and mitigation to climate change. Mathematical approaches, including ML approaches, have been used to search for such traits, leading to unprecedented results as some of the traits, including heat traits that have been long sought-for, have been found within a short period of time.
Model to measure the effect of the integration of information in business processes. Example: bidding process for an industry
Authors: Rodríguez-Rios Claudia Yadira , Roa-Sánchez Jorge Enrique
Published: October 2021

Purpose

The main contribution of the research is to propose a quantitative model based on indicators designed by the authors, to measure the effect on the performance of the process caused by an improvement in the integration of information.

Design/methodology/approach

It is a descriptive and exploratory investigation, immersed in a case study; the bidding process was selected by senior management due to the high complexity and impact of this process on the organization. The protocol for carrying out the study involved interviews with the owner of the process and all the officials involved, as sources of information, inputs to model in BPMN2.0 at the activity level and a statistical validation of the model was carried out, to sustain an acceptable confidence of the same.

Findings

Among the most outstanding results of the research are that the effects of the improvements or changes in the activities were reflected or evidenced in subsequent activities, not in the immediate ones or in which the improvement is applied. This confirms the theorization of the systemic approach to processes since the effects of the improvements are not close to their application.

Research limitations/implications

For the proposed model, it was evident that the measurement of the efficiency and quality dimensions of the process activities required verification in transactional databases where nonconformities and nonquality costs related to orders are recorded.

Originality/value

In the reviewed literature, there are no models or reference frameworks that quantitatively measure the effects of the integration of information on the performance of processes.
Experimental studies on the development of a self-healing cementitious matrix for repair and retrofitting of concrete structures
Authors: Adak Dibyendu , Marbaniang Donkupar Francis , Dutta Subhrajit
Published: October 2021

Purpose

Self-healing concrete is a revolutionary building material that will generally reduce the maintenance cost of concrete constructions. Self-healing of cracks in concrete structure would contribute to a longer service life of the concrete and would make the material more durable and more sustainable. The cementitious mortar with/without incorporating encapsulates at different percentages of slag replacement with the cement mix improves autogenous healing at different ages. Therefore, this study’s aim is to develop a self-healing cementitious matrix for repair and retrofitting of concrete structures.

Design/methodology/approach

In the present work, waste straw pipes are used as a capsule, filled with the solution of sodium hydroxide (NaOH), sodium silicate (Na2SiO3) and colloidal nano-silica as self-healing activators. An artificial micro-crack on the control and blended mortar specimens at different percentages of slag replacement with cement (with/without encapsulation) is developed by applying a compressive load of 50% of its ultimate load-carrying capacity. The mechanical strength and ultrasonic pulse velocity, water absorption and chloride ion penetration test are conducted on the concrete specimen before and after the healing period. Finally, the self-healing activity of mortar mixes with/without encapsulation is analysed at different ages.

Findings

The encapsulated mortar mix with 10% of slag content has better self-healing potential than all other mixes considering mechanical strength and durability. The enhancement of the self-healing potential of such mortar mix is mainly due to hydration of anhydrous slag on the crack surface and transformation of amorphous slag to the crystalline phase in presence of encapsulated fluid.

Research limitations/implications

The self-healing activities of the slag-based cementitious composite are studied for a healing period of 90 days only. The strength and durability performance of the cracked specimen may be increased after a long healing period.

Practical implications

The outcome of the work will help repair the cracks in the concrete structure and enhances the service life.

Originality/value

This study identifies the addition encapsulates with a self-healing activator fluid that can recover its strength after minor damage.
The effect of knowledge management on intellectual capital, social capital, and firm innovation
Authors: Salehi Mahdi , Fahimi Mohammad Ali , Zimon Grzegorz , Homayoun Saeid
Published: October 2021

Purpose

This study aims to analyze the literature on knowledge management on intellectual capital, social capital and its contribution to Iranian companies’ innovation.

Design/methodology/approach

To investigate knowledge management’s relationship on intellectual capital, social capital and innovation, using structural equation modeling based on data collected from 205 chief executive officers, production managers and marketing managers of Iranian companies. The research instrument is a standard questionnaire consisting of 109 questions in which 5 of them are demographic questions, 26 questions were asked to reveal the knowledge management process, 40 questions for intellectual capital, 21 for social capital and 17 for innovation.

Findings

The results show that knowledge management has a positive and significant relationship between intellectual capital and social capital. Knowledge management did not have a significant effect on innovation. However, intellectual capital and social capital have a significant effect on innovation. On the other hand, knowledge management mediated by intellectual capital and social capital has a positive and significant indirect effect on innovation.

Originality/value

The paper includes the implications for developing knowledge management and intellectual, social capital leading to innovation in manufacturing companies. Knowledge management can improve the innovation performance of a company if it is shared and applied effectively. This study addresses an important subject and the findings may be used by professionals and managers or another person interested in advancing knowledge management that leads to innovation.
The Gendered Harassment of Parliamentary Candidates in the UK
Authors: Collignon Sofía , Campbell Rosie , Rüdig Wolfgang
Published: October 2021

This article explores the role gender plays in the harassment, abuse and intimidation (HAI) of parliamentary candidates in the UK at election time. Using data from the Representative Audit of Britain surveys (2015–2019) this article takes an intersectional approach to investigate whether trends identified in 2017 suggesting that women candidates reported more incidences of HAI and were more likely to be concerned for their personal safety as a result than men, remain apparent in the subsequent election. Results suggest that HAI is getting worse for candidates in general, and the gender gap is widening. About three in every four women experienced some levels of fear while campaigning.
Service trade network structure and its determinants in the Belt and Road based on the temporal exponential random graph model
Authors: Feng Lianyue , Xu Helian , Wu Gang , Zhang Wenting
Published: October 2021

Service trade has become an important engine of world economic growth. Using complex network method and temporal exponential random graph models, we constructed the Belt and Road service trade networks (BR‐STNs) and global service trade networks (G‐STNs) in 2010–2017, systematically analysed the features of BR‐STNs compared with G‐STNs, and tested the factors affecting their evolution. We find that (a) the scale of BR‐STNs is small, but potential is huge. The BR‐STNs present the features of small‐world, larger degree disassortativity, lower reciprocity, and smaller heterogeneity than G‐STNs. (b) The BR‐STNs are divided into three communities and their pattern is more stable than G‐STNs. (c) Luxembourg, Italy and Singapore are the core in BR‐STNs, but there is a gap compared with the USA, the UK and Germany. (d) Reciprocity, structural embeddedness, the clustering effect and stability play important roles in the evolution of BR‐STNs and these effects increased after the proposal of the BRI. Economy‐pairs with similar trade openness, urbanization rates and quality of institution, and with different GDP and per capita GDP are more likely to trade. Countries with higher GDP, trade openness or quality of institution are active. Sharing a language, religion, colonial relationship or border, signing regional trade agreements and using a common currency facilitate service trade between countries in BR.
Artificial intelligence for microbial biotechnology: beyond the hype
Authors: Robinson Serina L.
Published: October 2021

It has been a landmark year for artificial intelligence (AI) and biotechnology. Perhaps the most noteworthy of these advances was Google DeepMind’s AlphaFold2 algorithm which smashed records in protein structure prediction (Jumper et al., 2021, Nature, 596, 583) complemented by progress made by other research groups around the globe (Baek et al., 2021, Science, 373, 871; Zheng et al., 2021, Proteins). For the first time in history, AI achieved protein structure models rivalling the accuracy of experimentally determined structures. The power of accurate protein structure prediction at our fingertips has countless implications for drug discovery, de novo protein design and fundamental research in chemical biology. While acknowledging the significance of these breakthroughs, this perspective aims to cut through the hype and examine some key limitations using AlphaFold2 as a lens to consider the broader implications of AI for microbial biotechnology for the next 15 years and beyond.
Taxon‐specific or universal? Using target capture to study the evolutionary history of rapid radiations
Authors: Yardeni Gil , Viruel Juan , Paris Margot , Hess Jaqueline , Groot Crego Clara , de La Harpe Marylaure , Rivera Norma , Barfuss Michael H. J. , Till Walter , Guzmán‐Jacob Valeria , Krömer Thorsten , Lexer Christian , Paun Ovidiu , Leroy Thibault
Published: October 2021

Target capture has emerged as an important tool for phylogenetics and population genetics in nonmodel taxa. Whereas developing taxon‐specific capture probes requires sustained efforts, available universal kits may have a lower power to reconstruct relationships at shallow phylogenetic scales and within rapidly radiating clades. We present here a newly developed target capture set for Bromeliaceae, a large and ecologically diverse plant family with highly variable diversification rates. The set targets 1776 coding regions, including genes putatively involved in key innovations, with the aim to empower testing of a wide range of evolutionary hypotheses. We compare the relative power of this taxon‐specific set, Bromeliad1776, to the universal Angiosperms353 kit. The taxon‐specific set results in higher enrichment success across the entire family; however, the overall performance of both kits to reconstruct phylogenetic trees is relatively comparable, highlighting the vast potential of universal kits for resolving evolutionary relationships. For more detailed phylogenetic or population genetic analyses, for example the exploration of gene tree concordance, nucleotide diversity or population structure, the taxon‐specific capture set presents clear benefits. We discuss the potential lessons that this comparative study provides for future phylogenetic and population genetic investigations, in particular for the study of evolutionary radiations.
Large‐scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma
Authors: Smith Alisha M. , Ramirez Robert M. , Harper Nathan , Jimenez Fabio , Branum Anne P. , Meunier Justin A. , Pandranki Lavanya , Carrillo Andrew , Winter Caitlyn , Winter Lauryn , Rather Cynthia G. , Ramirez Daniel A. , Andrews Charles P. , Restrepo Marcos I. , Maselli Diego J. , Pugh Jacqueline A. , Clark Robert A. , Lee Grace C. , Moreira Alvaro G. , Manoharan Muthu Saravanan , Okulicz Jason F. , Jacobs Robert L. , Ahuja Sunil K.
Published: October 2021

Background

Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens.

Methods

We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC).

Results

Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non‐endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T‐cells, eosinophils, and T‐cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T‐cells than eosinophils, neutrophils, or HDM‐specific IgE.

Conclusions

Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T‐cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.
Distribution and association of visual impairment with myopic maculopathy across age groups among highly myopic eyes – based on the new classification system (ATN)
Authors: Ye Luyao , Chen Qiuying , Hu Guangyi , Xie Jiamin , Lv Hanyi , Shi Ya , Yin Yao , Zhu Jianfeng , Fan Ying , He Jiangnan , Xu Xun
Published: October 2021

Purpose

To investigate the percentages and risk factors for visual impairment (VI) across age groups in a highly myopic cohort with a wide range of age (18–93 years).

Methods

A total of 2099 eyes (1220 participants) were enrolled. All participants underwent detailed ocular examinations. Myopic maculopathy (MM) was assessed as myopic atrophy maculopathy (MAM), myopic traction maculopathy (MTM) or myopic neovascular maculopathy (MNM) based on the ATN system.

Results

Most participants younger than 50 years had normal vision, while the cumulative risk of VI and blindness gradually increased after 50–59 years. The percentage of each type of MM increased nonlinearly with ageing (all p < 0.001), with an accelerated period of increase after 45 years for MAM, and after 50 years for MTM and MNM. Axial length (AL) ≥30 mm was the only associated factor for mild VI or worse in participants aged 18–39 years (p < 0.001). Older age, AL ≥30 mm and the presence of MAM were predictors for mild VI or worse in the group aged 40–49 years (all p < 0.05). In participants aged ≥50 years, older age, female sex, longer AL and increased severity of MM were risk factors for VI and blindness (all p < 0.05).

Conclusion

The percentages of MM and related VI increased nonlinearly with older age, with a turning point at 45 years for MAM, preceding that of MTM, MNM and VI by 5 years, warranting future longitudinal studies to confirm. Different age groups presented different risk factors for VI. Timely screening should be in place for middle‐aged high myopes.
Effects of the supplementation of a calcium soap containing medium‐chain fatty acids on the fecal microbiota of pigs, lactating cows, and calves
Authors: Matsui Hiroki , Imai Taichi , Kondo Makoto , Ban‐Tokuda Tomomi , Yamada Yutaka
Published: October 2021

Medium‐chain fatty acids (MCFAs) have antialgal, antibacterial, antifungal, antiprotozoan, and antiviral activities. However, antibacterial activities of MCFAs in the hindgut of pigs and cattle are still unknown. We report the effects of the supplementation of MCFAs on fecal bacteria of pigs, lactating cows, and Japanese Black calves. Lactobacillus spp., Bifidobacterium spp., eaeA(+) Escherichia coli, Salmonella spp., Campylobacter jejuni, and Clostridium perfringens in the feces of animals were quantified by real‐time PCR assay. There was no significant increase or decrease in Lactobacillus spp. and Bifidobacterium spp. in the three animals. In the pig feces, eaeA(+) E. coli was reduced to less than a third in the treatment group (P < 0.01). C. jejuni in the pig feces was also significantly less in the treatment group compared with the control (P < 0.01). In the lactating cow, eaeA(+) E. coli was reduced to one fifth of that in the control (P < 0.01). Salmonella spp. was halved in calf feces (P < 0.01). Thus, a reduction in Gram‐negative pathogenic bacteria was observed. In conclusion, supplementation of a MCFA calcium soap in the diet would be beneficial to growing pigs, lactating cow, and calves by reducing pathogenic bacteria.
Impaired robust interhemispheric function integration of depressive brain from REST‐meta‐MDD database in China
Authors: Deng Ke , Yue Ji‐Hui , Xu Jian , Ma Ping‐Ping , Chen Xiao , Li Le , Bai Tong‐Jian , Bo Qi‐Jing , Cao Jun , Chen Guan‐Mao , Chen Ning‐Xuan , Chen Wei , Cheng Chang , Cui Xi‐Long , Duan Jia , Fang Yi‐Ru , Gong Qi‐Yong , Guo Wen‐Bin , Hou Zheng‐Hua , Hu Lan , Kuang Li , Li Feng , Li Tao , Liu Yan‐Song , Liu Zhe‐Ning , Long Yi‐Cheng , Luo Qing‐Hua , Meng Hua‐Qing , Peng Dai‐Hui , Qiu Hai‐Tang , Qiu Jiang , Shi Yu‐Shu , Si Tian‐Mei , Tang Yan‐Qin , Wang Fei , Wang Kai , Wang Li , Wang Xiang , Wang Ying , Wu Xiao‐Ping , Wu Xin‐Ran , Xie Chun‐Ming , Xie Guang‐Rong , Xie Hai‐Yan , Xie Peng , Yang Hong , Yang Jian , Yao Jia‐Shu , Yao Shu‐Qiao , Yin Ying‐Ying , Yuan Yong‐Gui , Zhang Ai‐Xia , Zhang Hong , Zhang Ke‐Rang , Zhang Lei , Zhang Zhi‐Jun , Zhou Ru‐Bai , Zhou Yi‐Ting , Zhu Jun‐Juan , Zou Chao‐Jie , Zhou Cong , Zuo Xi‐Nian , Yan Chao‐Gan , Xu Xiu‐Feng , Cheng Yu‐Qi
Published: October 2021

Background

Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations.

Methods

In this study, we obtained resting‐state functional magnetic resonance imaging (R‐fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18–60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel‐mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns.

Results

As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = −7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age‐related change in males instead of females. Besides, the reduction in MTG was found to be a male‐special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First‐episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs.

Conclusions

We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.
Patient's perception of recovery after sinus membrane elevation and blood coagulum compared with 1:1 mixture of autogenous bone graft and deproteinized porcine bone mineral. Secondary outcomes from a single‐blinded randomized controlled trial
Authors: Starch‐Jensen Thomas , Bruun Niels Henrik
Published: October 2021

Objective

The objective was to assess patient's perception of recovery after maxillary sinus membrane elevation (MSME) and blood coagulum (test) compared with maxillary sinus floor augmentation (MSFA) and 1:1 mixture of autogenous bone graft from the buccal antrostomy and deproteinized porcine bone mineral (DPBM) (control).

Materials and methods

Forty healthy patients were randomly allocated to test or control. Oral health‐related quality of life (OHRQoL) was evaluated by Oral Health Impact Profile‐14 (OHIP‐14) at enrollment and 1 week postsurgical. Recovery was estimated by questionnaires and visual analog scale assessing pain, social and working isolation, physical appearance, eating and speaking ability, diet variations, sleep impairment, and discomfort after 1 week and 1 month. Mean differences were expressed with 95% confidence interval (CI). Association between OHRQoL and recovery was estimated. p‐value below .05 was considered statistically significant.

Results

Maxillary sinus membrane elevation revealed 2.1 less days of pain (p = .03, 95% CI: 0.2–4.1) and 1.2 days of sick leave (p = .01, 95% CI: 0.3–2.1) compared with MSFA. No significant difference was observed in eating and speaking ability, physical appearance, work performance, and sleep impairment. No significant association between impaired OHRQoL and recovery was observed. Females reported 4.77 higher OHIP‐14 score compared with males (p = .01, 95% CI: 1.60–7.94), while association between age and OHIP‐14 was −0.10 (p = .28, 95% CI: −0.28 to 0.08).

Conclusion

Maxillary sinus membrane elevation revealed significantly less days of pain and sick leave compared with MSFA. Harvesting of autogenous bone graft seems, therefore, to have a significant impact on perception of recovery.
Acute paediatric mastoiditis in the UK before and during the COVID‐19 pandemic: A national observational study
Authors: Smith Matthew E. , Jones G. Huw , Hardman John C. , Nichani Jaya , Khwaja Sadie ,   The INTEGRATE (The UK ENT Trainee Research Network) UK Acute Paediatric Mastoiditis Audit Collaborators, Bruce Iain A. , Rea Peter
Published: October 2021

Objectives

To explore the impact of COVID‐19 on the management and outcomes of acute paediatric mastoiditis across the UK.

Design

National retrospective and prospective audit.

Setting

48 UK secondary care ENT departments.

Participants

Consecutive children aged 18 years or under, referred to ENT with a clinical diagnosis of mastoiditis.

Main outcome measures

Cases were divided into Period 1 (01/11/19‐15/03/20), before the UK population were instructed to reduce social contact, and Period 2 (16/03/20‐30/04/21), following this. Periods 1 and 2 were compared for population variables, management and outcomes. Secondary analyses compared outcomes by primary treatment (medical/needle aspiration/surgical).

Results

286 cases met criteria (median 4 per site, range 0–24). 9.4 cases were recorded per week in period 1 versus 2.0 in period 2, with no winter increase in cases in December 2020‐Febraury 2021. Patient age differed between periods 1 and 2 (3.2 vs 4.7 years respectively, p < 0.001). 85% of children in period 2 were tested for COVID‐19 with a single positive test. In period, 2 cases associated with P. aeruginosa significantly increased. 48.6% of children were scanned in period 1 vs 41.1% in period 2. Surgical management was used more frequently in period 1 (43.0% vs 24.3%, p = 0.001). Treatment success was high, with failure of initial management in 6.3%, and 30‐day re‐admission for recurrence in 2.1%. The adverse event rate (15.7% overall) did not vary by treatment modality or between periods 1& 2.

Conclusion

The COVID‐19 pandemic led to a significant change in the presentation and case mix of acute paediatric mastoiditis in the UK.
Pitches that Wire Together Fire Together: Scale Degree Associations Across Time Predict Melodic Expectations
Authors: Verosky Niels J. , Morgan Emily
Published: October 2021

The ongoing generation of expectations is fundamental to listeners’ experience of music, but research into types of statistical information that listeners extract from musical melodies has tended to emphasize transition probabilities and n‐grams, with limited consideration given to other types of statistical learning that may be relevant. Temporal associations between scale degrees represent a different type of information present in musical melodies that can be learned from musical corpora using expectation networks, a computationally simple method based on activation and decay. Expectation networks infer the expectation of encountering one scale degree followed in the near (but not necessarily immediate) future by another given scale degree, with previous work suggesting that scale degree associations learned by expectation networks better predict listener ratings of pitch similarity than transition probabilities. The current work outlines how these learned scale degree associations can be combined to predict melodic continuations and tests the resulting predictions on a dataset of listener responses to a musical cloze task previously used to compare two other models of melodic expectation, a variable‐order Markov model (IDyOM) and Temperley's music‐theoretically motivated model. Under multinomial logistic regression, all three models explain significant unique variance in human melodic expectations, with coefficient estimates highest for expectation networks. These results suggest that generalized scale degree associations informed by both adjacent and nonadjacent relationships between melodic notes influence listeners’ melodic predictions above and beyond n‐gram context, highlighting the need to consider a broader range of statistical learning processes that may underlie listeners’ expectations for upcoming musical events.
The Formal Structure of Kind Representations
Authors: Haward Paul , Carey Susan , Prasada Sandeep
Published: October 2021

Kind representations, concepts liketable, triangle, dog, and planet, underlie generic language. Here, we investigate theformal structureof kind representations—the structure that distinguishes kind representations from other types of representations. The present studies confirm that participants distinguish generic‐supporting properties of individuals (e.g., this watch is made of steel) and accidental properties (e.g., this watch is on the nightstand). Furthermore, work dating back to Aristotle establishes thatonly somegeneric‐supporting properties bear aprincipled connectionto the kind, that is, are true of an individual by virtue of its being a member of a specific kind (e.g., telling time for a watch). The present studies tested the hypothesis that principled connections are part of the formal structure of kind representations. Specifically, they tested whether they structure a newly learned kind representation. Experiment 1 found that introducing a property of a newly encountered novel kind in any one of four linguistic frames that provide evidence that a property has a principled connection to a kind (e.g., “It has fur because it is a blick”) led participants to infer adifferentconceptual consequence of principled connections (i.e., “There is something wrong with this blick, which does not have fur”) for which they had no direct evidence. Two introduction frames that provided no evidence for principled connections (e.g., “Almost all blicks have fur”) did not generate the same consequence. Experiment 2 found that all of the targeted properties were generic licensing, irrespective of the introduction frame. That the distinction between properties that bear principled connections to their kinds, and merely generic‐supporting properties structuresnovelkind representations, provides strong evidence that this distinction is part of the formal structure of kind representations.