bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience with Telemedicine in a Tertiary Academic Otologic Clinic During the COVID-19 Pandemic
Authors: Xie Katherine Z. , Gottlich Harrison C. , Antezana Luis A. , Yeakel Sarah , Nassiri Ashley M. , Moore Eric J. , Carlson Matthew L.
Published: December 2022

Objective

To examine the utility of telemedicine in a tertiary otologic practice.

Study Design

Retrospective case series.

Setting

Tertiary neurotology clinic.

Patients

Consecutive adult patients presenting via video visit between January 2020 and January 2021.

Intervention(s)

Televideo modality to conduct visits with patients seeking evaluation for new concerns, second opinions, or routine follow-up for established conditions.

Main Outcome Measure(s)

Success of the televideo visit defined by the televideo visit being sufficient for determining a definitive plan and not requiring deferment of recommendations for a subsequent in-person visit.

Results

A total of 102 televideo visits were performed among 100 unique patients. Of those, 92 (90.2%) visits were for second opinions or evaluation of new concerns, most commonly for vestibular schwannoma (n = 32, 31.4%), followed by sensorineural hearing loss (n = 20, 19.6%). Other visits were conducted for early postoperative follow-up and established general follow-up. In 91.2% of cases (n = 93), patients were successfully evaluated and provided recommendations from the initial video visit. All visits with patients having a diagnosis of meningioma (n = 7), and nearly all with vestibular Schwannoma (97%, n = 31) and sensorineural hearing loss (95%, n = 19) were successful. Of the 79 patients offered surgery as one potential treatment option, 31 patients underwent surgery at our institution by time of review. Patients with unsuccessful visits (n = 9, 8.8%) were advised to schedule additional in-person diagnostic imaging, vestibular testing, or cochlear implant candidacy evaluation to establish a more definitive care plan.

Conclusion

Virtual televideo visits were successful for a high percentage of selected patients seen at a tertiary neurotology practice, particularly those seeking evaluation of vestibular schwannoma or sensorineural hearing loss.
Myosin Mutations and Sudden Sensorineural Hearing Loss: Results of Whole Exome Sequencing
Authors: Sharma Rahul K. , Drusin Madeleine , Hostyk Joseph , Baugh Evan H. , Aggarwal Vimla S. , Goldstein David , Kim Ana H.
Published: December 2022

Objective

Idiopathic sudden sensorineural hearing loss (ISSNHL) affects 66,000 patients per year in the United States. Genetic mutations have been associated with progressive hearing loss; however, genetic mutations associated with ISSNHL have not been identified.

Methods

A prospective cohort study of adults older than 18 years presenting with ISSNHL at a tertiary academic medical center. Whole exome sequencing (WES) was conducted using Genome Analysis Toolkit best practices. An automated diagnostic screen employing a variety of models for pathogenicity was conducted across all genes with no specific targets. Candidate pathogenic variants were reviewed by a team of geneticists and clinicians. Variants were crossed-referenced with 92 known hearing loss associated genes.

Results

Twenty-nine patients with SSNHL were screened using WES. The average age of patients was 53 ± 17.1 years, and most patients were White (62%) and men (55%). The mean pure tone average was 64.8 ± 31.3 dB for the affected ear. Using a 0.1% allele frequency screen, 12 (41%) cases had a mutation in any of the nine selected myosin genes. When we restrict to singletons (allele frequency = 0%), 21% (n = 6) of cases have qualifying variants, whereas only 3.8% (n = 481) of 12,577 healthy controls carry qualifying variants (p < 0.01). Most mutations (80%) were missense mutations. Of the novel mutations, one was a frameshift mutation, and two were a stop-gained function. Three were missense mutations.

Conclusion

Myosin mutations may be associated with ISSNHL. However, larger population screening is needed to confirm the association of myosin mutation with ISSNHL and steroid responsiveness.
Antimicrobial properties of English churchyard lichens.
Authors: Taylor J A , Fourie T , Powell M , Chianella I
Published: December 2022

The emergence of multidrug resistant bacteria has driven the need for novel antibiotics. Our investigations have focussed on lichens as they naturally produce a wide range of unique and very effective defence chemicals. The aim of this study was to evaluate the antimicrobial properties of  British churchyard lichens. Crude extracts from ten common lichen species were tested against six bacteria and two fungi by disc diffusion susceptibility testing. Extracts showed inhibition of Gram positive bacteria and dermatophytic fungi. Diploica canescence and Pertusaria amara  showed the most potent antimicrobial activity.
Comparative analysis of clinical breakpoints (CB), normalised resistance interpretation (NRI), and epidemiological cut-offs (ECOFFS), in interpreting antimicrobial resistance of E. coli isolates originating from poultry in different farm types in Tanzania.
Authors: Maganga Ruth , Sindiyo Emmanuel , Musyoki Victor Moses , Shirima Gabriel , Mmbaga Blandina T.
Published: December 2022

Existing breakpoint guidelines are not optimal for interpreting antimicrobial resistance data from animal studies and low-income countries, and therefore their utility for analysing such data is limited. There is need to integrate diverse data sets, such as those from low-income populations and animals, to improve data interpretation. There is very limited research on the relative merits of clinical breakpoints, epidemiological cut-offs, and normalised resistance interpretation breakpoints in interpreting microbiological data, particularly in animal studies and studies from low-income countries. The aim of this study was to compare antimicrobial resistance in E. coli isolates using ECOFFS, CLSI, and NRI breakpoints. A total of 69 non-repetitive poultry isolates were selected for investigation based on lactose fermentation on MacConkey agar and subsequent identification and confirmation as E. coli using chromogenic agar and uidA Polymerase Chain Reaction. Kirby Bauer disc diffusion technique was used for susceptibility testing. For each antimicrobial agent, inhibition zone diameters were measured, and ECOFFs, CLSI, and NRI bespoke breakpoints used for resistance interpretation. According to the interpretation of all breakpoints except ECOFFs, tetracycline resistance was significantly higher (TET) (67.8% – 69.5%), than ciprofloxacin (CIPRO) (18.6%– 32.2%), imipenem (IMI) (3.4% – 35%), and ceftazidime (CEF) (1.7% – 45.8%). Prevalence estimates of antimicrobial resistance (AMR) using CLSI and NRI bespoke breakpoints did not differ for CEF (1.7% CB and 1.7% COWT), IMI (3.4% CB and 4.0% COWT) and TET (67.8% CB and 69.5% COWT). However, with ECOFFs, antimicrobial resistance estimates for CEF, IMI, and CIP were significantly higher (45.8%, 35.6%, and 64.4%, respectively; P < 0.01). Across all the three breakpoints, resistance to ciprofloxacin varied significantly (32.2% CB, 64.4% ECOFFs, and 18.6% COWT). Antimicrobial resistance interpretation is influenced by the breakpoint used, necesscitating further standardisation, especially for microbiological breakpoints, in order to harmonise outputs. The AMR ECOFFs estimates in the present study were significantly higher compared to CLSI and NRI.
Erythrobacter aurantius sp. nov., isolated from intertidal seawater in Taizhou
Authors: Zhang Yu , Hua Jia , Ying Jun-Jie , Dong Han , Li Hao , Xamxidin Maripat , Han Bing-Nan , Sun Cong , Xu Lin
Published: December 2022

A Gram-stain-negative, aerobic, chemoheterotrophic and rod-shaped strain, designated as C5T, was isolated from intertidal surface seawater in Taizhou, Zhejiang Province, PR China and characterized using a polyphasic taxonomic approach. Strain C5T could produce carotenoids and bacteriochlorophyll a. Growth was observed at 20–45 °C, at pH 6.0–9.0 and with 0–8.0 % (w/v) NaCl. The 16S rRNA gene sequence identity analysis revealed that strain C5T was the most closely related to

Qipengyuania nanhaisediminis

CGMCC 1.7715T (98.8%) and

Erythrobacter litoralis

DSM 8509T (98.7%). The phylogenetic reconstruction based on core genes demonstrated that strain C5T was clustered into the members of the genus

Erythrobacter

. The average nucleotide identity and digital DNA–DNA hybridization values between strain C5T and

Erythrobacter

type strains were lower than 76 and 25 %, respectively. The predominant and minor respiratory quinones were identified as ubiquinone-10 and ubiquinone-9. The major fatty acids were summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c) and iso-C18 : 0. Polar lipids included phosphatidylethanolamine, phosphatidylglycerol, a glycosphingolipid and an unidentified aminolipid. Based on the genetic, chemotaxonomic and phenotypic data, strain C5T is concluded to represent a novel species in the genus

Erythrobacter

, for which the name Erythrobacter aurantius sp. nov. is proposed. The type strain is C5T (=MCCC 1K05108T=KCTC 92307T).
Machine learning identifies a COVID-19-specific phenotype in university students using a mental health app
Authors: Shvetcov Artur , Whitton Alexis , Kasturi Suranga , Zheng Wu-Yi , Beames Joanne , Ibrahim Omar , Han Jin , Hoon Leonard , Mouzakis Kon , Gupta Sunil , Venkatesh Svetha , Christensen Helen , Newby Jill
Published: December 2022

Advances in smartphone technology have allowed people to access mental healthcare via digital apps from wherever and whenever they choose. University students experience a high burden of mental health concerns. Although these apps improve mental health symptoms, user engagement has remained low. Studies have shown that users can be subgrouped based on unique characteristics that just-in-time adaptive interventions (JITAIs) can use to improve engagement. To date, however, no studies have examined the effect of the COVID-19 pandemic on these subgroups. Here, we use machine learning to examine user subgroup characteristics across three COVID-19-specific timepoints: during lockdown, immediately following lockdown, and three months after lockdown ended. We demonstrate that there are three unique subgroups of university students who access mental health apps. Two of these, with either higher or lower mental well-being, were defined by characteristics that were stable across COVID-19 timepoints. The third, situational well-being, had characteristics that were timepoint-dependent, suggesting that they are highly influenced by traumatic stressors and stressful situations. This subgroup also showed feelings and behaviours consistent with burnout. Overall, our findings clearly suggest that user subgroups are unique: they have different characteristics and therefore likely have different mental healthcare goals. Our findings also highlight the importance of including questions and additional interventions targeting traumatic stress(ors), reason(s) for use, and burnout in JITAI-style mental health apps to improve engagement.
Spatially and temporally varying selection influence species boundaries in two sympatricMimulus
Authors: Tataru Diana , Wheeler Emma C. , Ferris Kathleen G.
Published: December 2022

Spatially and temporally varying selection can maintain genetic variation within and between populations, but it is less known how these forces influence divergence between closely related species. We identify the interaction of temporal and spatial variation in selection and their role in either reinforcing or eroding divergence between two closely relatedMimulusspecies. Using repeated reciprocal transplant experiments with advanced generation hybrids we compare the strength of selection on quantitative traits involved in adaptation and reproductive isolation inMimulus guttatusandMimulus laciniatusbetween two years with dramatically different water availability. We found strong divergent habitat mediated selection on traits in the direction of species differences during a drought in 2013, suggesting that spatially varying selection maintains species divergence. However, a relaxation in divergent selection on most traits in an unusually wet year (2019), including flowering time which is involved in pre-zygotic isolation, suggests that temporal variation in selection may weaken species differences. Therefore, we find evidence that temporally and spatially varying selection may have opposing roles in mediating species boundaries. Given our changing climate, future growing seasons are expected to be more similar to the dry year, suggesting that in this system climate change may actually increase species divergence.
Investigation of Soft Magnetic Material Cores in Transcranial Magnetic Stimulation Coils and the Effect of Changing Core Shapes on the Induced Electric Field in Small Animals
Authors: Tashli Mohannad , Weistroffer George , Mhaskar Aryan , Kumbhare Deepak , Baron Mark S. , Hadimani Ravi L.
Published: December 2022

Transcranial magnetic stimulation (TMS) is a safe, effective and non-invasive treatment for several psychiatric and neurological disorders. Lately, there has been a surge in research utilizing this novel technology in treating other neurological and psychiatric ailments. The application of TMS on several neurological disorders requires the induced electric and magnetic fields to be focused and targeted to a small region in the brain. TMS of a focal cortical territory will ensure modulation of specific brain circuitry without affecting unwanted surrounding regions. This can be achieved by altering the properties of the magnetic core material used for the TMS system. In this study, soft ferromagnetic materials having high permeability, high saturation magnetization and low coercivity have been investigated as TMS coil cores in finite element simulations. Also, magnetic field measurements have been carried out using different cores in the TMS coil.

Finite element analysis of the rat head model is carried out using Sim4life software while investigating variations associated with changing the ferromagnetic core material and shape in the coil. Materials proposed for the analysis in this study include Iron Cobalt Vanadium alloy (Fe-Co-V) also known as Permendur, Carbon Steel (AISI 1010) and Manganese Zinc ferrites (MnZn ferrites). Simulation results indicated significant magnetic field distribution variation when introducing a ferromagnetic core in TMS coil, concentrating the magnetic field to the targeted region in the rat head model without stimulating adjacent regions. It was observed that the v-tip sharpened core attained the highest magnetic field and best focality among other cores in simulations and experimentally.
BioNetGMMFit: Estimating Parameters of a BioNetGen Model from Time-Stamped Snapshots of Single Cells
Authors: Wu John , Stewart William CL , Jayaprakash Ciriyam , Das Jayajit
Published: December 2022

Background

Mechanistic models are commonly employed to describe signaling and gene regulatory kinetics in single cells and cell populations. Recent advances in single-cell technologies have produced multidimensional datasets where snapshots of copy numbers (or abundances) of a large number of proteins and mRNA are measured across time in single cells. The availability of such datasets presents an attractive scenario where mechanistic models are validated against experiments, and estimated model parameters enable quantitative predictions of signaling or gene regulatory kinetics. To empower the systems biology community to easily estimate parameters accurately from multidimensional single-cell data, we have merged a widely used rule-based modeling software package BioNetGen, which provides a user-friendly way to code for mechanistic models describing biochemical reactions, and the recently introduced CyGMM, that uses cell-to-cell differences to improve parameter estimation for such networks, into a single software package: BioNetGMMFit.

Results

BioNetGMMFit provides parameter estimates of the model, supplied by the user in the BioNetGen markup language (BNGL), which yield the best fit for the observed single-cell, timestamped data of cellular components. Furthermore, for more precise estimates, our software generates confidence intervals around each model parameter. BioNetG-MMFit is capable of fitting datasets of increasing cell population sizes for any mechanistic model specified in the BioNetGen markup language.

Conclusion

By streamlining the process of developing mechanistic models for large single-cell datasets, BioNetGMMFit provides an easily-accessible modeling framework designed for scale and the broader biochemical signaling community.
Biodiversity and local interaction complexity promote sustainable fisheries in large food webs
Authors: Werner Alexandra , Albert Georg , Brose Ulrich , Gauzens Benoit
Published: December 2022

On a global scale, fisheries harvest an estimated 96 million tonnes of fish biomass annually, making them one of the most important drivers of marine ecosystem biodiversity. Yet little is known about the interactions between fisheries and the dynamics of complex food webs in which the harvested species are embedded. We have developed a synthetic model that combines resource economics with complex food webs to examine the direct effects of fishing on exploited species and the indirect impact on other species in the same community. Our model analyses show that the sensitivity of the targeted species increases with its trophic level and decreases with its local interaction complexity (i.e. its number of interactions with prey, predators, and competitors). In addition, we also document a strikingly positive effect of community species richness on the resilience of the harvested species to this disturbance. The indirect effects on other species show specific patterns of spreading across trophic modules that differ systematically from how other disturbances spread across ecological networks. While these results call for further research on how human resource exploitation in general and fishery in particular affect ecological dynamics and biodiversity in naturally complex systems, they also allow for some cautious conclusions. Taken together, our results suggest that the sustainability concerning fishery yield and ecosystem integrity can be maximised by focusing the harvest on low trophic level species with a high local interaction complexity in high biodiversity ecosystems. In this sense, our complex network approach offers a promising avenue for integrating the necessities of generating economic revenue with the protection of natural biodiversity.
Evo-Scope: Fully automated assessment of correlated evolution on phylogenetic trees
Authors: Godfroid Maxime , Coluzzi Charles , Lambert Amaury , Glaser Philippe , Rocha Eduardo P. C. , Achaz Guillaume
Published: December 2022

Correlated evolution describes how multiple biological traits evolve together. Recently developed methods provide increasingly detailed results of correlated evolution, sometimes at elevated computational costs.

Here, we presentevo-scope, a fast and fully-automated pipeline with minimal input requirements to compute correlation between discrete traits evolving on a phylogenetic tree. Notably, we improve two of our previously developed tools that efficiently compute statistics of correlated evolution to characterize the nature, such as synergy or antagonism, and the strength of the interdependence between the traits.

Furthermore, we improved the running time and implemented several additional features, such as genetic mapping, Bayesian Markov Chain Monte Carlo estimation, consideration of missing data and phylogenetic uncertainty.

As an application, we scan a published penicillin resistance data set ofStreptococcus pneumoniaeand characterize genetic mutations that correlate with antibiotic resistance. The pipeline is accessible both as a self-contained github repository (https://github.com/Maxime5G/EvoScope) and through a graphical galaxy interface (https://galaxy.pasteur.fr/u/maximeg/w/evoscope).
Taxonomically mixed blue musselMytiluspopulations are spatially heterogeneous and temporally unstable in the subarctic Barents Sea
Authors: Marchenko Julia , Khaitov Vadim , Katolikova Marina , Sabirov Marat , Malavenda Sergey , Gantsevich Michael , Basova Larisa , Genelt-Yanovsky Evgeny , Strelkov Petr
Published: December 2022

Subarctic populations of blue mussels represented by “cryptic” speciesMytilus edulis(ME) andM. trossulus(MT) have been studied less intensively than Arctic and boreal populations. Ecological features ofMEandMTin sympatry are poorly known everywhere. The knowledge about mussels at the northeasternmost boundary of the Atlantic littoral communities on Murman coast of the Barents Sea is based on data obtained 50-100 years ago. Our study provides the first insight into the long-term dynamics of the Barents Sea mussels, the habitat segregation ofMEandMT, and the interannual dynamics of their mixed settlements. The Tyuva Inlet (Kola Bay), which is 3 km long, was used as the study site. Mussels were found everywhere in the littoral and the sublittoral down to a depth of 4 m. Their characteristic habitats were sandbanks, littoral rocks, sublittoral kelp forests and “the habitat of the mussel bed” in the freshened top of the inlet. The main spatial gradients explaining the variability of demographics of the settlements (abundance, age structure, size) were associated with the depth and the distance from the inlet top.MEandMTwere partially segregated by depth:MEdominated in the sublittoral andMT, in the littoral. In addition,MEdominated both in the littoral and in the sublittoral parts of the mussel bed. The ratio of species in the mixed settlements varied over time: between 2004 and 2010 the proportions ofMTdecreased everywhere, by 22 % on average. Historical data indicate that the abundance of the Murman mussels declined sharply between the 1960s and the 1970s, which coincided with the cooling of the Arctic. It seems that the populations have not completely recovered in the abnormally warm recent decades. The habitat distribution of mussels apparently changed with time, too: unlike today, in the 20th century mussels were rarely observed in kelps. We suggest that the spatial and temporal dynamics of subarctic mussels can be partly explained by the competition betweenMEandMTcombined with their differing sensitivity to environmental factors.
Correction of transposase sequence bias in ATAC-seq data with rule ensemble modeling
Authors: Wolpe Jacob B. , Martins André L. , Guertin Michael J.
Published: December 2022

Chromatin accessibility assays have revolutionized the field of transcription regulation by providing single-nucleotide resolution measurements of regulatory features such as promoters and transcription factor binding sites. ATAC-seq directly measures how well the Tn5 transpose accesses chromatinized DNA. Tn5 has a complex sequence bias that is not effectively scaled with traditional bias-correction methods. We model this complex bias using a rule ensemble machine learning approach that integrates information from many input k-mers proximal to the ATAC sequence reads. We effectively characterize and correct single-nucleotide sequence biases and regional sequence biases of the Tn5 enzyme. Correction of enzymatic sequence bias is an important step in interpreting chromatin accessibility assays that aim to infer transcription factor binding and regulatory activity of elements in the genome.
Comparative Analysis of Global Hepatic Gene Expression in Adolescents and Adults with Non-alcoholic Fatty Liver Disease
Authors: Gawrieh Samer , Karns Rebekah , Kleiner David E. , Olivier Michael , Jenkins Todd , Inge Thomas H. , Chalasani Naga P. , Xanthakos Stavra
Published: December 2022

Introduction

To gain insights into the mechanisms underlying distinct nonalcoholic fatty liver disease (NAFLD) histological phenotypes between children and adults, we compared hepatic gene expression profiles associated with NAFLD phenotypes between the two age groups.

Methods

Histological characteristics of intra-operative liver biopsies from adolescents and adults undergoing bariatric surgery were assessed by the same pathologist using the non-alcoholic steatohepatitis (NASH) Clinical Research Network scoring system. Hepatic gene expression was measured by microarray analysis. Transcriptomic signatures of histological phenotypes between the two groups were compared, with significance defined as p-value <0.05 and a fold change >1.5.

Results

In 67 adolescents and 76 adults, distribution of histological phenotypes was: not-NAFLD (controls) 51% vs 39%, NAFL 39% vs 37%, and NASH 10% vs 24%, respectively. There were 279 differentially expressed genes in adolescents and 213 in adults with NAFLD vs controls. In adolescents, transcriptomes for NAFL vs controls, and borderline vs definite NASH were undifferentiable, whereas in adults, NAFL and borderline NASH demonstrated a transcriptomic gradient between controls and definite NASH. When applied to adolescents, significant adult genes discriminated borderline and definite NASH from control and NAFL, but the majority of significant pediatric genes were not portable to adults. Genes associated with NASH in adolescents and adults showed some ontological consistency but notable differences.

Conclusions

There is some similarity but major differences in the transcriptomic profiles associated with NAFLD between adolescents and adults with severe obesity. These data suggest different mechanisms contribute to the pathogenesis of NAFLD severity at different stages in life.

Study Highlights

WHAT IS KNOWN

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adults

NAFLD histological features and severity differ between children and adults but reasons for these differences are not clear.

WHAT IS NEW HERE

Comparison of hepatic gene expression profiles between adolescents and adults with severe obesity and NAFLD showed some similarities but major differences in expressed genes

The findings suggest the mechanisms driving different NAFLD severity and phenotypes are different at different stages in life.
Effect of Zn fertilization on yield, protein content, protein yield and zinc use efficiency in pearl millet
Authors: Yadav Ganesh Narayan , Summaria Rakesh , Yadav Shankar Lal , Sharma Seema , Yadav L. R.
Published: December 2022

Two year field experiment was conducted at Rajasthan Agriculture Research Institute, Durgapura, during rainy seasons of 2019 and 2020 in factorial block design with three replications to study the growth, productivity and economics of pearl millet – chickpea cropping system by using three genotypes (RHB-173, MPMH-17 and RHB-177) and five treatments of zinc [0, 5, 7.5 kg Zn/ha through ZnSO4.7H2O and 5, 7.5 kg Zn/ha through Zn-EDTA) applied to pearl millet and two foliar spray treatments applied in both of crop at booting stage in pearl millet and pre-flowering stage in chickpea. Results revealed that total nitrogen and zinc contents of chickpea were increased significantly and highest with the residual effect of 7.5 kg Zn/ha through Zn-EDTA and 7.5 kg Zn/ha through ZnSO4.7H2O and phosphorus contents of chickpea was recorded depressive effect on residual zinc fertilization, while, potassium contents was not influenced significantly. However, the significant increase in uptake of nutrients nitrogen, phosphorous, potassium and zinc were obtained with 7.5 kg Zn/ha through Zn-EDTA higher per cent over control, during the years 2019-20 and 2020-21. The highest nitrogen, protein content and zinc contents and uptake values were obtained with 5, 7.5 kg Zn/ha through Zn-EDTA. The residual effect of 7.5 kg Zn/ha through Zn-EDTA was at par with 7.5 kg Zn/ha through ZnSO4.7H2O. The increased in total uptake of nitrogen, it could be ultimately increased protein yield were 16.54 and 27.48 per cent, during respective years over control. The highest nutrient use efficiency was obtain with lowest of fertilizer dose of Zn-EDTA as compare to zinc sulphate.
Identification of the riceRcgene as a main regulator of seed survival under dry storage conditions
Authors: Manjunath Prasad C.T. , Kodde Jan , Angenent Gerco C. , Hay Fiona R. , McNally Kenneth L. , Groot Steven P.C.
Published: December 2022

Seed deterioration during storage results in poor germination, reduced seed vigor, and non-uniform seedling emergence. The rate of aging depends on storage conditions (RH, temperature, and oxygen) and genetic factors. This study aims to identify these genetic factors determining the longevity of rice seeds stored under experimental aging conditions mimicking long-term dry storage. Genetic variation for tolerance to aging was studied in 300Indicarice accessions and storing dry seeds under elevated partial pressure of oxygen (EPPO) condition, using a genome-wide association study. The association analysis yielded eleven unique regions across the genome for all measured germination parameters after aging. These genomic regions differed from regions previously identified in rice under humid experimental aging conditions. The significant single nucleotide polymorphism in the most prominent region was located within theRcgene, encoding a bHLH transcription factor. Storage experiments using isogenic rice lines (SD7-1D(Rc) andSD7-1d(rc)) with the same allelic variation confirmed the functional role of theRcgene, conferring a stronger tolerance to dry EPPO aging. A functionalRcgene results in the accumulation of pro-anthocyanidins in the pericarp of rice seeds, an important sub-class of flavonoids having strong antioxidant activity, which may explain why genotypes with an allelic variation for this gene show variation in seed tolerance to dry EPPO aging.
The phase separated CO2-fixing pyrenoid proteome determined by TurboID
Authors: Lau Chun Sing , Dowle Adam , Thomas Gavin H. , Girr Philipp , Mackinder Luke CM
Published: December 2022

Phase separation underpins many biologically important processes such as RNA metabolism, signaling and CO2fixation. However, determining the composition of a phase separated organelle is often challenging due to their sensitivity to environmental conditions which limits the application of traditional proteomics techniques like organellar purification or affinity purification mass spectrometry to understand their composition. InChlamydomonas reinhardtii, Rubisco is condensed into a crucial phase separated organelle called the pyrenoid that improves photosynthetic performance by supplying Rubisco with elevated concentrations of CO2. Here, we developed a TurboID based proximity labeling technique inChlamydomonaschloroplasts, where proximal proteins are labeled by biotin radicals generated from the TurboID-tagged protein. Through the expression of two core pyrenoid components fused with the TurboID tag, we have generated a high confidence pyrenoid proxiome that contains the majority of known pyrenoid proteins plus a number of novel pyrenoid candidates. Fluorescence protein tagging of 8 previously uncharacterized TurboID-identified proteins showed 7 were localized to a range of sub-pyrenoid regions. The resulting proxiome also suggests new secondary functions for the pyrenoid in RNA-associated processes and redox sensitive iron-sulfur cluster metabolism. This developed pipeline opens the possibility of investigating a broad range of biological processes inChlamydomonasespecially at a temporally resolved sub-organellar resolution.
Ruling the unruly: Innovation in ant larval feeding led to increased caste dimorphism and social complexity
Authors: Matte Arthur , LeBoeuf Adria C.
Published: December 2022

Building differences between genetically equivalent units is a fundamental challenge for every (super)organism with reproductive division of labor. In ants, reproductive or worker fate is typically determined during the larval stage. However, the methods by which adults feed their larvae, thus controlling their development, vary widely across ant species. Similarly, the body size gap between queen and worker is highly heterogeneous, ranging from species with similar-sized individuals to species with queens over 300 times larger than their smallest workers. To investigate the role of alloparental feeding control in caste dimorphism and the evolution of social complexity, we assembled data for queen:worker dimorphism, alloparental care, and larval morphology for a phylogenetically comprehensive sample of several hundred species, along with ecological and life-history traits. Using comparative phylogenetic methods, we analyzed the macroevolution of ant larvae and queen:worker dimorphism on a large scale. Our findings indicate that both extended alloparental feeding care and dimorphism are associated with the evolution of passive larval morphologies. Furthermore, greater queen:worker dimorphism co-evolved with several traits indicative of social complexity, including larger colony sizes, distinct worker subcastes, and the loss of full reproductive potential in workers. In sum, change in larval feeding habits were promoted by dietary shifts from prey to foods necessitating individualized distribution. These innovations granted adults greater capacity to manipulate larval nutrition, and consequently, caste size inequality, with significant implications for social complexity.

Significance statement

Ants are among the rare organisms to have extended reproductive division labor beyond the cells of a multicellular organism. However, the degree of specialization between reproductive and worker castes varies considerably between ant lineages. In this study, we demonstrate that strong caste dimorphism in ants co-evolved with complex eusociality traits, and this strong caste dimorphism was achieved by asserting adult control over larvae’ development. We conclude that this enhanced control over larval caste fate was a critical junction in the major evolutionary transition of ants toward caste specialization.

Graphical abstract
Emergence and Spread of SARS-CoV-2 Variants of Concern in Canada: a Retrospective Analysis from Clinical and Wastewater Data
Authors: Champredon David , Becker Devan , Peterson Shelley W. , Mejia Edgard , Hizon Nikho , Schertzer Andrea , Djebli Mohamed , Xie Yuwei , Oloye Femi F. , Asadi Mohsen , Cantin Jenna , Brinkmann Markus , McPhedran Kerry N. , Giesy John P. , Mangat Chand
Published: December 2022

The spread of SARS-CoV-2 has been studied at unprecedented levels worldwide. In jurisdictions where molecular analysis was performed on large scales, the emergence and competition of numerous SARS-CoV-2 lineages has been observed in near real-time. Lineage identification, traditionally performed from clinical samples, can also be determined by sampling wastewater from sewersheds serving populations of interest. Of particular interest are variants of concern (VOCs), SARS-CoV-2 lineages that are associated with increased transmissibility and/or severity. Here, we consider clinical and wastewater data sources to retrospectively assess the emergence and spread of different VOCs in Canada. We show that, overall, wastewater-based VOC identification provides similar in-sights to the surveillance based on clinical samples. Based on clinical data, we observed a synchrony in VOC introduction as well as similar emergence speeds across most Canadian provinces despite the large geographical size of the country and differences in provincial public health measures. In particular, it took approximately four months for VOC Alpha and Delta to contribute to half of the incidence, whereas VOC Omicron achieved the same contribution in less than one month. By quantifying the timing and rapidity of SARS-CoV-2 VOCs invasion in Canada, this study provides important benchmarks to support preparedness for future VOCs, and to some extent, for future pandemics caused by other pathogens.
Identifying key residues in intrinsically disordered regions of proteins using machine learning
Authors: Ho Wen-Lin , Huang Hsuan-Cheng , Huang Jie-rong
Published: December 2022

Conserved residues in protein homolog sequence alignments are structurally or functionally important. For intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs), however, alignment often fails because they lack a steric structure to constrain evolution. Although sequences vary, the physicochemical features of IDRs may be preserved in maintaining function. Therefore, a method to retrieve common IDR features may help identify functionally important residues. We applied un-supervised contrastive learning to train a model with self-attention neuronal networks on human IDR orthologs. During training, parameters were optimized to match sequences in ortholog pairs but not in other IDRs. The trained model successfully identifies previously reported critical residues from experimental studies, especially those with an overall pattern (e.g. multiple aromatic residues or charged blocks) rather than short motifs. This predictive model can therefore be used to identify potentially important residues in other proteins.

Availability and implementation

The training scripts are available on GitHub (https://github.com/allmwh/IFF). The training datasets have been deposited in an Open Science Framework repository (https://osf.io/jk29b). The trained model can be run from the Jupyter Notebook in the GitHub repository using Binder (mybinder.org). The only required input is the primary sequence.
Foldcomp: a library and format for compressing and indexing large protein structure sets
Authors: Kim Hyunbin , Mirdita Milot , Steinegger Martin
Published: December 2022

Highly accurate protein structure predictors have generated hundreds of millions of protein structures; these pose a challenge in terms of storage and processing. Here we present Foldcomp, a novel lossy structure compression algorithm and indexing system to address this challenge. By using a combination of internal and cartesian coordinates and a bi-directional NeRF-based strategy, Foldcomp improves the compression ratio by a factor of 3 compared to the next best method. Its reconstruction error of 0.08Å is comparable to the best lossy compressor. It is 5 times faster than the next fastest compressor and competes with the fastest decompressors. With its multi-threading implementation and a Python interface that allows for easy database downloads and efficient querying of protein structures by accession, Foldcomp is a powerful tool for managing and analyzing large collections of protein structures.

Availability

Foldcomp is a free open-source library and command-line software available for Linux, macOS and Windows athttps://foldcomp.foldseek.com. Foldcomp provides the AlphaFold Swiss-Prot (2.9GB), TrEMBL (1.1TB) and ESMatlas HQ (114GB) database ready-for-download.
Oncolytic adenovirus serotype 35 mediated tumor growth suppressionviaefficient activation and tumor infiltration of natural killer cells
Authors: Ono Ryosuke , Sakurai Fuminori , Ishii Ken J. , Mizuguchi Hiroyuki
Published: December 2022

Background

Oncolytic adenoviruses (OAds) mediate superior antitumor effects both by inducing direct oncolysis and activating antitumor immunity. Previously, we developed a novel OAd fully composed of human adenovirus serotype 35 (OAd35). OAd35 efficiently killed a variety of human tumor cells; however, OAd35-mediated activation of antitumor immunity remains to be evaluated. In this study, we examined whether OAd35-induced activation of immune cells contributes to the antitumor effects of OAd35.

Methods

Tumor infiltration and activation of immune cells following intratumoral administration of OAd35 in tumor-bearing immune-competent and nude mice were analyzed. The involvement of natural killer (NK) cells in the tumor growth-suppression effects of OAd35 was evaluated in NK cell-depleted mice. The key signals for the OAd35-mediated tumor infiltration of NK cells were examined in interferon (IFN) alpha and beta receptor subunit 1 (IFNAR1) knockout and toll-like receptor 9 (TLR9) knockout mice.

Results

OAd35 efficiently induced tumor infiltration of activated NK cells. NK cell depletion apparently hindered the OAd35-mediated tumor growth suppression. In IFNAR1 knockout mice, OAd35-induced tumor infiltration of activated NK cells was significantly attenuated. OAd35 did not induce tumor infiltration of NK cells in TLR9 knockout mice, although OAd35 significantly activated NK cells and showed tumor growth suppression in TLR9 knockout mice.

Conclusions

OAd35 significantly promoted activation and tumor infiltration of NK cells, leading to OAd35-mediated efficient tumor growth suppression. The type-I IFN signal was crucial for the OAd35-mediated tumor infiltration and activation of NK cells. The TLR9 signal was highly related to tumor infiltration of NK cells, but not NK cell activation and antitumor effects of OAd35. These findings suggest that OAd35 becomes a promising cancer immunotherapy agentviaits enhancement of the antitumor activities of NK cells.
Ecological and evolutionary patterns of virus-host interactions throughout a grassland soil depth profile
Authors: Muscatt George , Cook Ryan , Millard Andrew , Bending Gary D. , Jameson Eleanor
Published: December 2022

Background

Soil microbes play pivotal roles in global carbon cycling, however the fundamental interactions between microbes and their infecting viruses remain unclear. This is exacerbated with soil depth, where the patterns of viral dispersal, ecology, and evolution are markedly underexplored. To investigate viral communities across soil depth, we leveraged a publicly available metagenomic data set sampled from grassland soil in northern California.

Results

10,196 non-redundant vOTUs were recovered from soil sampled from 20 cm to 120 cm below the surface. Viral prevalence was high throughout the soil depth profile, with viruses infecting dominant soil phyla, includingActinomycetota. Contrary to leading hypotheses, lysogeny did not dominate in the soil viral communities. Viral diversity was investigated at both the population-level (i.e., macro diversity) and strain-level (i.e., micro diversity) to reveal diverse ecological and evolutionary patterns of virus-host interactions in surface and subsurface soil.

Conclusions

By investigating viral micro diversity in soil for the first time, we have uncovered patterns of antagonistic co-evolution across both surface and subsurface soils. Furthermore, we have provided evidence of soil viruses augmenting the remineralisation of soil carbon. While we continue to yield a more comprehensive understanding of soil viral ecology, our work appeals to future researchers to continue to investigate subsurface viral communities.
Nanobody CDR3 mimetics enhance SOS1-catalyzed nucleotide exchange on RAS
Authors: Van holsbeeck Kevin , Fischer Baptiste , Gonzalez Simon , Gadais Charlène , Versées Wim , Martins José C. , Martin Charlotte , Wohlkönig Alexandre , Steyaert Jan , Ballet Steven
Published: December 2022

RAS proteins control various intracellular signaling networks. Mutations at specific locations were shown to stabilize their active GTP-bound state, which is associated with the development of multiple cancers. An attractive approach to modulate RAS signaling is through its regulatory guanine nucleotide exchange factor (GEF) son of sevenless 1 (SOS1). With the recent discovery of Nanobody14, which potently enhances SOS1-catalyzed nucleotide exchange on RAS, we explored the feasibility of developing peptide mimetics by structurally mimicking the complementarity-determining region 3 (CDR3). Guided by a biochemical GEF assay and X-ray co-crystal structures, successive rounds of optimization and gradual conformational rigidification led to CDR3 mimetics showing half of the maximal activation potential of the native nanobody. Altogether, this study provides the first proof-of-concept that peptides able to functionally modulate a protein-protein interaction can be obtained by structural mimicry of a nanobody paratope.
The discrete update epidemics: demography, vaccination and transmission with a tensorized update approach
Authors: Guo Xiaohao , Zhao Zeyu , Yang Shiting , Guo Yichao , Chen Tianmu
Published: December 2022

An ordinary differential dynamical model is developed to describe the transmission of infectious diseases, considering heterogeneities of region, age, vaccination, and immigration and real-time vaccination simultaneously using a tenderized formulation. Numerical experiments are performed in Xiamen city, China, with the whole population partitioned into 6 regions × 4 age groups × 4 vaccination status groups, showing the numerical stability of the developed model. The heterogeneity consideration makes our model adequate to evaluate specific interventions accurately within specific sub-populations and carry them out.

Author summary

Not applicable.
A compartmental model forXylella fastidiosadiseases with explicit vector seasonal dynamics
Authors: Giménez-Romero Àlex , Moralejo Eduardo , Matías Manuel A.
Published: December 2022

The bacteriumXylella fastidiosa(Xf) is mainly transmitted by the spittlebug,Philaenus spumarius, in Europe, where it has caused significant economic damage to olive and almond trees. Understanding the factors that determine disease dynamics in pathosystems that share similarities can help design control strategies focused on minimizing transmission chains. Here we introduce a compartmental model for Xf-caused diseases in Europe that accounts for the main relevant epidemiological processes, including the seasonal dynamics ofP. spumarius. The model was confronted with epidemiological data from the two major outbreaks of Xf in Europe, the olive quick disease syndrome (OQDS) in Apulia, Italy, caused by the subspeciespauca, and the almond leaf scorch disease (ALSD) in Majorca, Spain, caused by subspeciesmultiplexandfastidiosa. Using a Bayesian inference framework, we show how the model successfully reproduces the general field data in both diseases. In a global sensitivity analysis, the vector-plant and plant-vector transmission rates, together with the vector removal rate, were the most influential parameters in determining the time of the infected host population peak, the incidence peak and the final number of dead hosts. We also used our model to check different vector-based control strategies, showing that a joint strategy focused on increasing the rate of vector removal while lowering the number of annual newborn vectors is optimal for disease control.
Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation
Authors: Guayasamin Mathias , Depaauw-Holt Lewis R. , Adedipe Ifeoluwa I. , Ghenissa Ossama , Vaugeois Juliette , Duquenne Manon , Rogers Benjamin , Latraverse-Arquilla Jade , Peyrard Sarah , Bosson Anthony , Murphy-Royal Ciaran
Published: December 2022

Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits.

Summary Figure