bluuebunny/crossref_metadata_2025 huggingface dataset:
Community density patterns estimated by species distribution modeling: the case study of an insect virus interaction
Authors: Dupas Stéphane , Zeddam Jean-Louis , Orbe Katherine , Gloria Patricia Barrera Cubillos , Villamizar Laura Fernanda , Mora Patricia , Suquillo Jovanni , Dangles Olivier , Lopez-Avilla Aristóbulo , Cotes-Prado Alba-Marina , Silvain Jean-Francois
Published: February 2024

Time delays complicates the analysis of trophic dependence, which requires large time series data to study local associations.

Here we propose using species distribution modeling. This approach removes confounding time lag effects and allows using data obtained separately in the different species.

Since the approach is correlative, it cannot be interpreted in terms of causality.

We apply the method to the interaction between the invasive potato moth Tecia solanivora and its granulovirus PhoGV in the Northern Andes. Host density was analyzed based on 1206 pheromone trap data from 106 sampled sites in Ecuador, Colombia and Venezuela. Virus prevalence was evaluated in 15 localities from 3 regions in Ecuador and Colombia. glm models were optimized for both variables on bioclimatic variables. Predicted virus prevalence was not significantly correlated to host density in the sampled virus sites. Across the climatic range covered by the study, correlation was R=−0.053. Of the total population of insect in this range, 26% were expected to be infected.

Infection status was also analyzed for spatial structure at different scales: storage bag, storage room, field, locality, country. Locality and storage bag explained respectively 8% and 26% of the total deviance in infection status in glm analysis. Field and storage structure differed within locality but not always in the same direction.

This basic method may help studying statistical relationships between species density across a number of trophic models making use of existing non sympatric data, with none or limited additional sampling effort.
PLA-complexity ofk-mer multisets
Authors: Abrar Md. Hasin , Medvedev Paul
Published: February 2024

Motivation

Understanding structural properties ofk-mer multisets is crucial to designing space-efficient indices to query them. A potentially novel source of structure can be found in the rank function of ak-mer multiset. In particular, the rank function of ak-mer multiset can be approximated by a piece-wise linear function with very few segments. Such an approximation was shown to speed up suffix array queries and sequence alignment. However, a more comprehensive study of the structure of rank functions ofk-mer multisets and their potential applications is lacking.

Results

We study a measure of ak-mer multiset complexity, which we call the PLA-complexity. The PLA-complexity is the number of segments necessary to approximate the rank function of ak-mer multiset with a piece-wise linear function so that the maximum error is bounded by a predefined threshold. We describe, implement, and evaluate the PLA-index, which is able to construct, compact, and query a piece-wise linear approximation of thek-mer rank function. We examine the PLA-complexity of more than 500 genome spectra and several other genomic multisets. Finally, we show how the PLA-index can be applied to several downstream applications to improve on existing methods: speeding up suffix array queries, decreasing the index memory of a short-read aligner, and decreasing the space of a direct access table ofk-mer ranks.

Availability

The software and reproducibility information is freely available athttps://github.com/medvedevgroup/pla-index
Related PP2C phosphatases Pic3 and Pic12 negatively regulate immunity in tomato toPseudomonas syringae
Authors: Xia Fan , Zhang Ning , Smith Renee E. , Chakraborty Joydeep , Sobol Guy , Tang Xuemei , Fei Zhangjun , Sessa Guido , Martin Gregory B.
Published: February 2024

Type 2C protein phosphatases (PP2Cs) constitute a large family in most plant species but relatively few of them have been implicated in immunity. To identify and characterize PP2C phosphatases that affect tomato immunity, we used CRISPR/Cas9 to generate loss-of-function mutations in 11 PP2C-encoding genes whose expression is altered in response to immune elicitors or pathogens. We report that two closely related PP2C phosphatases, Pic3 and Pic12, are involved in regulating resistance to the bacterial pathogenPseudomonas syringaepv.tomato(Pst). Loss-of-function mutations inPic3lead to enhanced resistance toPstin older but not younger leaves, whereas such mutations inPic12resulted in enhanced resistance in both older and younger leaves. Overexpression of Pic3 and Pic12 proteins in leaves ofNicotiana benthamianainhibited resistance toPstand this effect was dependent on Pic3/12 phosphatase activity and an N-terminal palmitoylation motif associated with localization to the cell periphery. Pic3 but not Pic12 had a slight negative effect on flagellin-associated reactive oxygen species generation, although their involvement in the response toPstappeared independent of flagellin. RNA-sequencing analysis of Rio Grande (RG)-PtoR wild-type plants and two independent RG-pic3 mutants revealed that the enhanced disease resistance in RG-pic3 older leaves is associated with increased transcript abundance of multiple defense related genes. RG-pic3/RG-pic12 double mutant plants exhibited stronger disease resistance than RG-pic3 or RG-pic12 single mutants. Together, our results reveal that Pic3 and Pic12 negatively regulate tomato immunity in an additive manner through flagellin-independent pathways.
Microsporidian coinfection reduces fitness of a fungal pathogen due to rapid host mortality
Authors: Dziuba Marcin K. , McIntire Kristina M. , Davenport Elizabeth S. , Baird Emma , Huerta Cristian , Jaye Riley , Corcoran Fiona , McCreadie Paige , Nelson Taleah , Duffy Meghan A.
Published: February 2024

Infection outcomes can be strongly context-dependent, shifting a host-symbiont relationship along a parasitism-mutualism continuum. Numerous studies show that under stressful conditions, symbionts that are typically mutualistic can become parasitic. The reverse possibility – a parasite becoming mutualistic – has received much less study. We investigated whether the parasitic microsporidiumOrdospora pajuniican become beneficial for its hostDaphnia dentiferain the presence of the more virulent fungal pathogenMetschnikowia bicuspidata. We found that, even though infection withO. pajuniireduces the frequency of penetration ofM. bicuspidataspores into the host body cavity, it does not improve the survival or reproduction of the host; conversely, coinfection increased the mortality ofDaphnia. However, the shorter lifespan of coinfected hosts disrupted the life cycle ofM. bicuspidata, greatly reducing its fitness. Thus, coinfection with both pathogens was detrimental to the host at the individual level, but might be beneficial for the host population as a result of greatly reduced production ofM. bicuspidataspores. If so, this would mean thatO. pajuniioutbreaks should delay or preventM. bicuspidataoutbreaks. In support of this, in an analysis of dynamics of naturally occurring outbreaks in two lakes where these pathogens co-occur, we found a time lag in occurrence betweenO. pajuniiandM. bicuspidata, withM. bicuspidataepidemics only occurring after the collapse ofO. pajuniiepidemics. Thus, these results suggest that the interaction between co-occurring symbionts – and the net impact of a symbiont on a host – might be qualitatively different at different scales.

Importance

Understanding the factors that modify infection probability and virulence is crucial for identifying the drivers of infection outbreaks and modeling disease epidemic progression, and increases our ability to control diseases and reduce the harm they cause. One factor that can strongly influence infection probability and virulence is the presence of other pathogens. However, while coexposures and coinfections are incredibly common, we still have only a limited understanding of how pathogen interactions alter infection outcomes, or whether their impacts are scale-dependent. We used a system of one host and two pathogens to show that sequential coinfection can have a tremendous impact on the host and on the infecting pathogens, and that the outcome of (co-)infection can be negative or positive depending on the focal organization level.
Spatial Multi-Omics Connect SHROOM3 and COL18A1 in Chronic Kidney Disease
Authors: Gaheer Pukhraj S. , Uppal Nikhil , Paul Amy , Mohammadi-Shemirani Pedrum , Perrot Nicolas , Paré Guillaume , Bridgewater Darren , Lanktree Matthew B.
Published: February 2024

Shroom Family Member 3 (SHROOM3)encodes an actin-binding protein that impacts kidney development. Genome-wide association studies (GWAS) identified CKD-associated common variants aroundSHROOM3andShroom3knock-out mice develop glomerular abnormalities. We sought to evaluate the impact of genetically predictedSHROOM3expression on kidney traits and the circulating proteome, and validate findings in a mouse model. Genetic instruments forSHROOM3expression in distinct kidney compartments (glomerular n=240, tubulointerstitial n=311) were constructed using single cell sequencing data from NephQTL2. Using two-sample Mendelian randomization, we evaluated the effects of glomerular and tubulointerstitialSHROOM3expression on kidney traits and the concentration of 1,463 plasma proteins in the UK Biobank and CKDGen Consortium. Genetically predicted tubulointerstitialSHROOM3expression colocalized with the genetic signals for eGFR and albuminuria. A 34% reduction in genetically predicted tubulointerstitialSHROOM3expression was associated with a 0.3% increase in cross-sectional eGFR (P= 6.8×10-4), a 1.5% increase in albuminuria (P= 0.01), and a 2.2% reduction in plasma COL18A1 concentration (P= 1.2×10-5). In contrast, genetically predicted glomerularSHROOM3expression showed neither colocalization nor significant Mendelian randomization results. Using immunofluorescence, heterozygousShroom3knockout mice had a concordant reduction of Col18a1 in their kidneys, primarily around the tubules. Thus, reduced tubulointerstitialSHROOM3expression, but not glomerular, is associated with increased cross-sectional eGFR, increased uACR, and reduced plasma COL18A1 andShroom3knockout leads to reduced kidney Col18a1, agnostically linkingSHROOM3andCOL18A1in CKD pathogenesis.

Lay Summary

TheSHROOM3gene is consistently linked to kidney disease, but we have yet to fully understand why. We looked at how genetic changes affectingSHROOM3impact different regions of the kidney. We found that lessSHROOM3in kidney tubules led to increased kidney filtration, but also increased leakage of protein into the urine. After looking at over 1000 proteins, we identified a new link betweenSHROOM3and a collagen protein called COL18A1. We then confirmed the link between SHROOM3 and COL18A1 by imaging the kidneys of mice designed to have less SHROOM3. Our results suggest an interaction of SHROOM3 and COL18A1 leads to increased pressure on the kidney filtration system.
A platform for brain network sensing and stimulation with quantitative behavioral tracking: Application to limbic circuit epilepsy
Authors: Kremen Vaclav , Sladky Vladimir , Mivalt Filip , Gregg Nicholas M. , Balzekas Irena , Marks Victoria , Brinkmann Benjamin H. , Lundstrom Brian Nils , Cui Jie , St Louis Erik K. , Croarkin Paul , Alden Eva C , Fields Julie , Crockett Karla , Adolf Jindrich , Bilderbeek Jordan , Hermes Dora , Messina Steven , Miller Kai J. , Van Gompel Jamie , Denison Timothy , Worrell Gregory A.
Published: February 2024

Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures. These seizures often originate from limbic networks and people also experience chronic comorbidities related to memory, mood, and sleep (MMS). Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is a proven therapy, but the optimal stimulation parameters remain unclear. We developed a neurotechnology platform for tracking seizures and MMS to enable data streaming between an investigational brain sensing-stimulation implant, mobile devices, and a cloud environment. Artificial Intelligence algorithms provided accurate catalogs of seizures, interictal epileptiform spikes, and wake-sleep brain states. Remotely administered memory and mood assessments were used to densely sample cognitive and behavioral response during ANT-DBS. We evaluated the efficacy of low-frequency versus high-frequency ANT-DBS. They both reduced seizures, but low-frequency ANT-DBS showed greater reductions and better sleep and memory. These results highlight the potential of synchronized brain sensing and behavioral tracking for optimizing neuromodulation therapy.
Infection-on-Chip: anin vitrohuman vessel model to studyNeisseria meningitidiscolonization and vascular damages
Authors: Pinon Léa , Chabaud Mélanie , Nivoit Pierre , Wong-Ng Jérôme , Nguyen Tri Tho , Paul Vanessa , Bouquerel Charlotte , Goussard Sylvie , Frachon Emmanuel , Obino Dorian , Gobaa Samy , Duménil Guillaume
Published: February 2024

Systemic infections leading to sepsis are life-threatening conditions that remain difficult to treat, and the development of innovative therapies is hampered by the limitations of current experimental models. Animal models are constrained by species-specific differences, while 2D cell culture systems fail to capture the complex pathophysiology of infection. To overcome these limitations, we developed a laser photoablation-based, three-dimensional microfluidic model of meningococcal vascular colonization, a human-specific bacterium that causes sepsis and meningitis. We coined our model “Infection-on-Chip”. Laser photoablation-based hydrogel engineering allows the reproduction of vascular networks that are major infection target sites, and this model provides the relevant microenvironment reproducing the physiological endothelial integrity and permeabilityin vitro. By comparing with human-skin xenograft mouse model, we show that the Infection-on-Chip system not only replicatesin vivokey features of the infection, but also enables quantitative assessment with a higher spatio-temporal resolution of bacterial microcolony growth, endothelial cy-toskeleton rearrangement, vascular E-selectin expression, and neutrophil response upon infection. Our device thus provides a robust solution bridging the gap between animal and 2D cellular models, and paving the way for a better understanding of disease progression and the development of innovative therapeutics.
Selective enrichment of high-affinity clade II N2O-reducers in a mixed culture
Authors: Laureni Michele , Rubio Francesc Corbera , Kim DaeHyun Daniel , Browne Savanna , Roothans Nina , Weissbrodt David G. , Olavaria Karel , de Jonge Nadieh , Yoon Sukhwan , Pabst Martin , van Loosdrecht Mark C.M.
Published: February 2024

Microorganisms encoding for the N2O reductase (NosZ) are the only known biological sink of the potent greenhouse gas N2O, and are central to global N2O mitigation efforts. Yet, the ecological constraints selecting for different N2O-reducers strains and controlling the assembly of N2O-respiring communities remain largely unknown. Of particular biotechnological interest are clade II NosZ populations, which usually feature high N2O affinities and often lack other denitrification genes. Two planktonic N2O-respiring mixed cultures were enriched under limiting and excess dissolved N2O availability to assess the impact of substrate affinity and N2O cytotoxicity, respectively. Genome-resolved metaproteomics was used to infer the metabolism of the enriched populations. We show that clade II N2O-reducers outcompete clade I affiliates for N2O at sufficiently low sludge dilution rates (0.006 h-1), a scenario previously only theorized based on pure-cultures. Under N2O limitation, all enriched N2O-reducers encoded and expressed only clade II NosZ, while also possessing other denitrification genes. TwoAzonexusandThaueragenera affiliates dominated the culture. We explain their coexistence with the genome-inferred metabolic exchange of cobalamin intermediates. Conversely, under excess N2O, clade I and II populations coexisted. Notably, the single dominant N2O-reducer (genusAzonexus) expressed most cobalamin biosynthesis marker genes, likely to contrast the continuous cobalamin inactivation by dissolved cytotoxic N2O concentrations (400 µM). Ultimately, we demonstrate that the solids dilution rate controls the selection among NosZ clades, albeit the conditions selecting for genomes possessing the solenosZremain elusive. Additionally, we suggest the significance of N2O-cobalamin interactions in shaping the composition of N2O-respiring microbiomes.
Trehalose mediates salinity-stress tolerance in a crustacean
Authors: Santos Joana L. , Nick Fabienne , Adhitama Nikko , Fields Peter D. , Stillman Jonathon H. , Kato Yasuhiko , Watanabe Hajime , Ebert Dieter
Published: February 2024

Salinization poses an increasing problem worldwide, threatening freshwater organisms and raising questions about ability to adapt. We explore the mechanisms enabling a planktonic crustacean to tolerate elevated salinity. By gradually raising water salinity in clonal cultures from 185Daphnia magnapopulations, we showed that salt tolerance strongly correlates with native habitat salinity, indicating local adaptation. A GWAS revealed a major effect of theAlpha,alpha-trehalose-phosphate synthase(TPS) gene, suggesting that trehalose production facilitates salinity tolerance. We found a positive correlation between water salinity and trehalose concentrations in tolerant animals, while intolerant animals failed to produce trehalose. Using CRISPR/Cas9, a silencedTPSgene supported the role of trehalose under salt stress. Our study highlights how a keystone freshwater animal adapts to salinity stress using an evolutionarily conserved mechanism known in plants and bacteria, but not in metabolic-active animals.

Highlights

Salinity tolerance is a locally adapted trait inDaphnia magna

The trehaloseTPSgene shows a strong association with salinity tolerance

Trehalose content increases with water salinity allowing survival of tolerant genotypes

Non-functionalTPSgenes reduce salinity tolerance by preventing trehalose production
The highly repetitive genome of Myxobolus sp., a myxozoan parasite of fathead minnows
Authors: Muthye Viraj R. , Leon Coria Aralia , Liu Hongrui , Finney Constance A. M. , Goater Cameron P. , Wasmuth James D.
Published: February 2024

Background: The Myxozoa is a group of at least 2,400 endoparasites within the phylum Cnidaria. All myxozoans have greatly reduced in size and morphology compared to free-living members of the phylum. They are best known for causing disease in economically important fish across the world; for example, Myxobolus cerebralis causes Whirling Disease, which can kill 90% of infected juvenile salmonid fish. In 2017, a potentially new myxozoan species was identified in Alberta. Myxobolus sp. causes distinct lesions in fathead minnows, which are ultimately fatal. Here, we sequenced, assembled and analyzed the genome of Myxobolus sp. to understand how the parasite interacts with its fish host and identify potential strategies to counter this emerging threat. Results: At 185 Mb, the Myxobolus sp. genome is the largest myxozoan genome sequenced so far. This large genome size is, in part, due to the high repetitive content; 68% of the genome was interspersed repeats, with the MULE-MuDR transposon covering 18% of the Myxobolus sp. genome. Similar to myxozoan genomes, the Myxobolus sp. genome has lost many genes well conserved in other eukaryotes. However, we also identified multiple expansions in gene families (serine proteases, hexokinases, and FLYWCH-domain containing proteins) which suggests their functional importance in the parasite. The mitochondrial genome of Myxobolus sp. encodes only five of the thirteen protein-coding genes typically found in animals. We found that the mitochondrial gene atp6 was transferred to the nucleus and acquired a mitochondria-targeting signal in Myxobolus sp. Conclusions: Our study provides valuable insights into myxozoan biology and identify promising avenues for future research. We also propose that M. rasmusseni is promising myxozoan model to explore host-parasite interactions in these parasites.
Liquid footprinting: A novel approach for DNA footprinting using short double-stranded cell-free DNA from plasma
Authors: Müller Jan , Hartwig Christina , Sonntag Mirko , Bitzer Lisa , Adelmann Christopher , Vainshtein Yevhen , Glanz Karolina , Decker Sebastian O. , Brenner Thorsten , Weber Georg F. , Haeseler Arndt von , Sohn Kai
Published: February 2024

The diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not been recognized, yet. Here, we present a method for enrichment of double-stranded cfDNA with an average length of about 40 base pairs from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we found significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA-methylation, positively with H3K4me3 histone modifications and gene transcription. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic with post-operative controls, we identified 731 and 1,107 differentially enriched loci, respectively. Using these differentially enriched loci, the disease types can be clearly distinguished by principal component analysis demonstrating the diagnostic potential of short double-stranded cfDNA signals as a new class of biomarkers for liquid biopsies.
Phylogenetic analysis ofMycobacterium bovisReveals Evidence Of Animal And Zoonotic Tuberculosis Transmission Between Morocco And European Countries
Authors: Yahyaoui Azami Hind , Perea Claudia , Stuber Tod , Bouslikhane Mohammed , Berrada Jaouad , Aboukhassib Hamid , Allepuz Palau Alberto Oscar , Reis Ana C. , Cunha Mónica V. , Thacker Tyler C , Robbe-Austerman Suelee , Salvador Liliana C. M. , Quinn Frederick
Published: February 2024

Livestock production is a fundamental pillar of the Moroccan economy. Infectious diseases of cattle and other species represent a significant threat to the livestock industry, animal health, and food safety and security. Bovine tuberculosis (bTB), mainly caused byMycobacterium bovis(M. bovis), generates considerable direct and indirect economic losses, in addition to the unknown human health burden caused by zoonotic transmission. Previous studies have suggested likelyM. bovistransmission links between Morocco and Southern Europe, however, limitations inherent with the methods used prevented more definitive conclusions from being drawn. In this study, we employed whole genome sequencing analysis of a large set ofM. bovisisolates to better define the phylogenetic links between strains from Morocco and neighboring countries. A total of 780M. bovissequences representing 36 countries were included in the study. The results of SNP analysis showed a close genetic relationship betweenM. bovisfrom Morocco and each of Spain, France, Portugal and Germany, this is supported by animal trade between Morocco and these countries, in addition to the important human migration from Morocco to Europe and North America.

Regarding zoonotic tuberculosis (TB) transmission, we were able to find genetic links betweenM. bovisisolates from cattle in Morocco and humans in Italy, Germany, and the UK. These results support our hypothesis of significant transmission ofM. bovisfrom cattle to humans, which calls for further investigations of zoonotic TB transmission in Morocco and in other countries.

The fact that noM. bovissequences from North Africa in the present database were classified as AF1 or AF2 clonal complexes suggests that the Sahara might play a role in preventingM. bovistransmission between North Africa and Sub-Saharan Africa. Our study benefits from a large sample size and a rich dataset that includes sequences from cattle, wildlife, and humans from Morocco and neighboring countries, enabling the delineation ofM. bovistransmission routes within the animal-human interface.
Host-specific effects of a generalist parasite of mosquitoes
Authors: Zeferino Tiago G. , Koella Jacob C.
Published: February 2024

Microsporidians are obligate parasites of many animals, including mosquitoes. Some microsporidians have been proposed as potential agents for the biological control of mosquitoes and the diseases they transmit due to their detrimental impact on larval survival and adult lifespan. To get a more complete picture of their potential use as agents of biological control, we measured the impact ofVavraia culicison several life-history traits ofAedes aegyptiandAnopheles gambiae. We measured the infection dynamics and clearance rate for the two species, and we assessed sexual dimorphism in infection dynamics within each species. Our results show differences in infection dynamics, withAe. aegyptilife-history traits being more affected during its aquatic stage and exhibiting higher clearance of the infection as adults. In contrast,An. gambiaewas unable to clear the infection. Additionally, we found evidence of sexual dimorphism in parasite infection inAn. gambiae, with males having a higher average parasite load. These findings shed light and improve our knowledge of the infection dynamics ofV. culicis, a microsporidian parasite previously recognized as a potential control agent of malaria.
What “unexplored” means: Mapping undersampled regions in natural history collections
Authors: Ball Laymon , Bedoya Ana M. , Machado Sheila Rodriguez , Paredes-Burneo Diego , Rutledge Samantha , Boyd David , Vander Pluym David , Babb-Biernacki Spenser , Chipps Austin S. , Ozturk Rafet C. , Terzi Yahya , Chakrabarty Prosanta
Published: February 2024

We examined global records of accessible natural history voucher collections (with publicly available data) for terrestrial and freshwater vascular plants, fungi, freshwater fishes, birds, mammals, and herpetofauna (amphibians and reptiles) and highlight areas of the world that would be considered undersampled and sometimes called “unexplored” (i.e., have relatively low, or no evidence of, past sampling efforts) under typical Western-scientific descriptions. We also question what “unexplored” may actually mean in these contexts and explain how retiring the term in favor of more nuanced phrasing can mitigate future misunderstandings of natural history science.
Human coronavirus 229E infection inactivates pyroptosis executioner gasdermin D but ultimately leads to lytic cell death partly mediated by gasdermin E
Authors: Martiáñez-Vendrell Xavier , Bloeme Jonna , Hutchinson Roy , Guy Coralie , Bowie Andrew , Kikkert Marjolein
Published: February 2024

Human coronavirus 229E (HCoV-229E) is associated with upper respiratory tract infections and causes local respiratory symptoms. It has been reported that HCoV-229E can cause cell death in a variety of cellsin vitro. However, the molecular pathways that lead to virus-induced cell death remain poorly characterized. Here, we show that the main protease (Mpro) of HCoV-229E can cleave the pyroptosis executioner gasdermin D (GSDMD) within its active N-terminal domain at two different sites (Q29 and Q193) to generate fragments unable to cause pyroptosis. Despite GSDMD cleavage by HCoV-229E Mpro, we show that HCoV-229E infection leads to lytic cell death. We further demonstrate that virus-induced lytic cell death is partially dependent on the activation of caspases-3 and -8. Interestingly, inhibition of caspases does not only reduce lytic cell death upon infection, but also sustains the release of virus particles over time, which suggests that caspase-mediated cell death is a mechanism to limit virus replication and spread. Finally, we show that pyroptosis is partially dependent on another gasdermin family member, gasdermin E (GSDME). During HCoV-229E infection, GSDME is cleaved to yield its N-terminal pore-forming domain (p30). Accordingly, GSDME knockout cells show a significant decrease in lytic cell death upon virus, whereas this is not the case for GSDMD knockout cells, which aligns with the observation that GSDMD is also inactivated by caspase-3 during infection. These results suggest that GSDMD is inactivated during HCoV-229E infection, and point to GSDME as an important player in the execution of virus-induced cell death.

Importance

Recently, it has been shown that the Mpros of coronaviruses possess accessory functions other than their main role in the proteolytic processing of the viral polyproteins. Although the SARS-CoV-2 outbreak has fuelled the discovery of host cellular substrates of SARS-CoV-2 Mpro, less is known about the interplay of less pathogenic human coronavirus Mpros with host proteins. We demonstrate that HCoV-229E Mpro cleaves GSDMD at two sites within its pore-forming domain, which disrupts GSDMD-mediated pyroptosis. These results point to a new strategy for HCoV-229E to escape the host antiviral response. Additionally, we show that GSDME contributes to virus-induced lytic cell death upon activation by caspase-3, shedding light on a previously undescribed cell death mechanism occurring in HCoV-229E infected cells.
Iguanas from above: Citizen scientists provide reliable counts of endangered Galápagos marine iguanas from drone imagery
Authors: Varela-Jaramillo Andrea , Winkelmann Christian , Rivas-Torres Gonzalo , Guayasamin Juan M. , Steinfartz Sebastian , MacLeod Amy
Published: February 2024

Population surveys are vital for wildlife management, yet traditional methods often demand excessive time and resources, leading to data gaps for many species. Modern technologies such as drones can facilitate field surveys but may also increase data analysis challenges. Citizen Science (CS) can address this issue by engaging non-specialists for data collection and analysis. We evaluated CS for population monitoring using the endangered Galápagos marine iguana as a case study, assessing online volunteers’ ability to detect and count animals in aerial images. Comparing against a Gold Standard dataset of expert counts in 4345 images, we explored optimal aggregation methods from CS inputs, considering image quality and filtering data from infrequent and anonymous participants. During three phases of our project — hosted on the Zooniverse platform — over 13,000 volunteers made 1,375,201 classifications from 57,838 aerial images; each being independently classified 20 (phases 1 & 2) or 30 (phase 3) times. Volunteers achieved 68% to 94% accuracy in detecting iguanas, with more false negatives than false positives. Image quality strongly influenced accuracy; by excluding data from suboptimal pilot-phase images, volunteers counted with 90% to 92% of accuracy. For detecting presence or absence of iguanas, the commonly used ‘majority vote’ aggregation approach (where the answer selected is that given by the majority of individual inputs) produced less accurate results than when a minimum threshold of five (from the 20/30 independent classifications) was used. For counting iguanas, HDBSCAN clustering yielded the best results. Excluding inputs from anonymous and inexperienced volunteers decreased accuracy. We conclude that online volunteers can accurately identify and count marine iguanas from drone images, though a tendency to underestimate warrants further consideration. CS-based data analysis is faster than manual counting but still resource-intensive, underscoring the need to develop a Machine Learning approach.
Polygenic basis of Bt Cry resistance evolution in wildHelicoverpa zea
Authors: Taylor Katherine L , Quackenbush Jane , Lamberty Cara , Hamby Kelly A , Fritz Megan L
Published: February 2024

Strong and shifting selective pressures of the anthropocene are rapidly shaping phenomes and genomes of organisms worldwide. One major selective force on insect genomes is crops expressing pesticidal proteins fromBacillus thuringiensis(Bt). Here we characterize a rapid response to selection by Bt crops in a major crop pest,Helicoverpa zea. We reveal the polygenic architecture of Bt resistance evolution inH. zeaand identify multiple genomic regions underlying this trait. In the genomic region of largest effect, we identified a gene cluster amplification, where resistant individuals showed variation in copy number for multiple genes. Signals of this amplification increased over time, consistent with the history of field-evolved Bt resistance evolution. Modern wild populations from disparate geographical regions are positive for this variant at high, but not fixed, allele frequencies. We also detected selection against single copy variants at this locus in wildH. zeacollected from Bt expressing plants, further supporting its role in resistance. Seven trypsin genes were present in this genomic region and all appeared to be significantly upregulated in Bt resistantH. zea. Biochemically inhibiting trypsin activity decreasedH. zea’s tolerance to Bt. These findings characterize rapid genome evolution in a major crop pest following anthropogenic selection and highlight the role that gene copy number variants can have in rapid evolutionary responses.
Brain activation during the N-back working memory task in individuals with spinal cord injury: a functional near-infrared spectroscopy study
Authors: Chen Donna Y. , Di Xin , Amaya Nayyar , Sun Hai , Pal Saikat , Biswal Bharat B.
Published: February 2024

Cognitive impairments have frequently been reported in individuals with spinal cord injury (SCI) across different domains such as working memory, attention, and executive function. The mechanism of cognitive impairment after SCI is not well understood due to the heterogeneity of SCI sample populations, and may possibly be due to factors such as cardiovascular dysfunction, concomitant traumatic brain injury (TBI), hypoxia, sleep disorders, and body temperature dysregulation. In this study, we implement the Neuropsychiatric Unit Cognitive Assessment Tool (NUCOG) to assess cognitive differences between individuals with SCI and age-matched able-bodied (AB) controls. We then use an N-back working memory task and functional near-infrared spectroscopy (fNIRS) to elucidate the neurovascular correlates of cognitive function in individuals with SCI. We observed significant differences between the SCI and AB groups on measures of executive function on the NUCOG test. On the N-back task, across the three levels of difficulty: 0-back, 2-back, and 3-back, no significant differences were observed between the SCI and AB group; however, both groups performed worse as the level of difficulty increased. Although there were no significant differences in N-back performance scores between the two groups, functional brain hemodynamic activity differences were observed between the SCI and AB groups, with the SCI group exhibiting higher maximum oxygenated hemoglobin concentration in the right inferior parietal lobe. These findings support the use of fNIRS to study cognitive function in individuals with SCI and may provide a useful tool during rehabilitation to obtain quantitative functional brain activity metrics.
The Mouse Inferior Colliculus Responds Preferentially to Non-Ultrasonic Vocalizations
Authors: Tehrani Mahtab , Shanbhag Sharad , Huyck Julia J. , Patel Rahi , Kazimiersky Diana , Wenstrup Jeffrey J.
Published: February 2024

The inferior colliculus (IC), the midbrain auditory integration center, analyzes information about social vocalizations and provides substrates for higher level processing of vocal signals. We used multi-channel recordings to characterize and localize responses to social vocalizations and synthetic stimuli within the IC of female and male mice, both urethane-anesthetized and unanesthetized. We compared responses to ultrasonic vocalizations (USVs) with other vocalizations in the mouse repertoire and related vocal responses to frequency tuning, IC subdivisions, and sex. Responses to lower frequency, broadband social vocalizations were widespread in IC, well represented throughout the tonotopic axis, across subdivisions, and in both sexes. Responses to USVs were much more limited. Although we observed some differences in tonal and vocal responses by sex and subdivision, representations of vocal responses by sex and subdivision were largely the same. For most units, responses to vocal signals occurred only when frequency response areas overlapped with spectra of the vocal signals. Since tuning to frequencies contained within the highest frequency USVs is limited (< 15% of IC units), responses to these vocalizations are correspondingly limited (< 5% of sound-responsive units). These results highlight a paradox of USV processing in some rodents: although USVs are the most abundant social vocalization, their representation and the representation of corresponding frequencies is less than lower frequency social vocalizations. We interpret this paradox in light of observations suggesting that USVs with lower frequency elements (<50 kHz) are associated with increased emotional intensity and engage a larger population of neurons in the mouse auditory system.

SIGNIFICANCE STATEMENT

The inferior colliculus (IC) integrates multiple inputs to analyze information about social vocalizations. In mice, we show that the most common type of social vocalization, the ultrasonic vocalization or USV, was poorly represented in IC compared to lower frequency vocalizations. For most neurons, responses to vocal signals occurred only when frequency response areas overlapped with vocalization spectra. These results highlight a paradox of USV processing in some rodent auditory systems: although USVs are the most abundant social vocalization, their representation and representation of corresponding frequencies is less than lower frequency social vocalizations. These results suggest that USVs with lower frequency elements (<50 kHz)—associated with increased emotional intensity—will engage a larger population of neurons in the mouse auditory system.
A Composite Biomarker Signature of Type 1 Diabetes Risk Identified via Augmentation of Parallel Multi-Omics Data from a Small Cohort
Authors: Alcazar Oscar , Chuang Sung-Ting , Ren Gang , Ogihara Mitsunori , Webb-Robertson Bobbie-Jo M. , Nakayasu Ernesto S. , Buchwald Peter , Abdulreda Midhat H.
Published: February 2024

Background

Biomarkers of early pathogenesis of type 1 diabetes (T1D) are crucial to enable effective prevention measures in at-risk populations before significant damage occurs to their insulin producing beta-cell mass. We recently introduced the concept of integrated parallel multi-omics and employed a novel data augmentation approach which identified promising candidate biomarkers from a small cohort of high-risk T1D subjects. We now validate selected biomarkers to generate a potential composite signature of T1D risk

Methods

Twelve candidate biomarkers, which were identified in the augmented data and selected based on their fold-change relative to healthy controls and cross-reference to proteomics data previously obtained in the expansive TEDDY and DAISY cohorts, were measured in the original samples by ELISA

Results

All 12 biomarkers had established connections with lipid/lipoprotein metabolism, immune function, inflammation, and diabetes, but only 7 were found to be markedly changed in the high-risk subjects compared to the healthy controls: ApoC1 and PON1 were reduced while CETP, CD36, FGFR1, IGHM, PCSK9, SOD1, and VCAM1 were elevated

Conclusions

Results further highlight the promise of our data augmentation approach in unmasking important patterns and pathologically significant features in parallel multi-omics datasets obtained from small sample cohorts to facilitate the identification of promising candidate T1D biomarkers for downstream validation. They also support the potential utility of a composite biomarker signature of T1D risk characterized by the changes in the above markers.
Coordinated Immune Cell Networks in the Bone Marrow Microenvironment Define the Graft versus Leukemia Response with Adoptive Cellular Therapy
Authors: Maurer Katie , Park Cameron Y. , Mani Shouvik , Borji Mehdi , Penter Livius , Jin Yinuo , Zhang Jia Yi , Shin Crystal , Brenner James R. , Southard Jackson , Krishna Sachi , Lu Wesley , Lyu Haoxiang , Abbondanza Domenic , Mangum Chanell , Olsen Lars Rønn , Neuberg Donna S. , Bachireddy Pavan , Farhi Samouil L. , Li Shuqiang , Livak Kenneth J. , Ritz Jerome , Soiffer Robert J. , Wu Catherine J. , Azizi Elham
Published: February 2024

Understanding how intra-tumoral immune populations coordinate to generate anti-tumor responses following therapy can guide precise treatment prioritization. We performed systematic dissection of an established adoptive cellular therapy, donor lymphocyte infusion (DLI), by analyzing 348,905 single-cell transcriptomes from 74 longitudinal bone-marrow samples of 25 patients with relapsed myeloid leukemia; a subset was evaluated by protein-based spatial analysis. In acute myelogenous leukemia (AML) responders, diverse immune cell types within the bone-marrow microenvironment (BME) were predicted to interact with a clonally expanded population ofZNF683+GZMB+CD8+ cytotoxic T lymphocytes (CTLs) which demonstratedin vitrospecificity for autologous leukemia. This population, originating predominantly from the DLI product, expanded concurrently with NK and B cells. AML nonresponder BME revealed a paucity of crosstalk and elevatedTIGITexpression in CD8+ CTLs. Our study highlights recipient BME differences as a key determinant of effective anti-leukemia response and opens new opportunities to modulate cell-based leukemia-directed therapy.
Structural characterization of the ACDC domain from ApiAP2 proteins of the malaria parasite
Authors: Le Berre Marine , Tubiana Thibault , Reuterswärd Waldner Philippa , Lazar Noureddine , Li de la Sierra Ines , Santos Joana Mendonca , Llinás Manuel , Nessler Sylvie
Published: February 2024

The Apicomplexan AP2 (ApiAP2) proteins are the best characterized family of DNA-binding proteins in the malaria parasite. Apart from the AP2 DNA-binding domain, there is little sequence similarity between ApiAP2 proteins and no other functional domains have been extensively characterized. One protein domain, which is present in a subset of the ApiAP2 proteins, is the conserved AP2-coincident domain mostly at the C-terminus (ACDC domain). Here we solved for the first time the crystal structure of the ACDC domain from two distinctPlasmodium falciparumApiAP2 proteins and one orthologue fromP. vivax, revealing a non-canonical four-helix bundle. Despite little sequence conservation between the ACDC domains from the two proteins, the structures are remarkably similar and do not resemble that of any other known protein domains. Due to their unique protein architecture and lack of homologues in the human genome, we performedin silicodocking calculations against a library of known antimalarial compounds and we identified a small molecule that can potentially bind to any Apicomplexan ACDC domain within a pocket highly conserved amongst ApiAP2 proteins. Inhibitors based on this compound would disrupt the function of the ACDC domain and thus of the ApiAP2 proteins containing it, providing a new therapeutic window for targeting the malaria parasite and other Apicomplexans.
Differential Conservation and Loss of CR1 Retrotransposons in Squamates Reveals Lineage-Specific Genome Dynamics across Reptiles
Authors: Gable Simone M. , Bushroe Nicholas , Mendez Jasmine , Wilson Adam , Pinto Brendan , Gamble Tony , Tollis Marc
Published: February 2024

Transposable elements (TEs) are repetitive DNA sequences which create mutations and generate genetic diversity across the tree of life. In amniotic vertebrates, TEs have been mainly studied in mammals and birds, whose genomes generally display low TE diversity. Squamates (Order Squamata; ∼11,000 extant species of lizards and snakes) show as much variation in TE abundance and activity as they do in species and phenotypes. Despite this high TE activity, squamate genomes are remarkably uniform in size. We hypothesize that novel, lineage-specific dynamics have evolved over the course of squamate evolution to constrain genome size across the order. Thus, squamates may represent a prime model for investigations into TE diversity and evolution. To understand the interplay between TEs and host genomes, we analyzed the evolutionary history of the CR1 retrotransposon, a TE family found in most tetrapod genomes. We compared 113 squamate genomes to the genomes of turtles, crocodilians, and birds, and used ancestral state reconstruction to identify shifts in the rate of CR1 copy number evolution across reptiles. We analyzed the repeat landscapes of CR1 in squamate genomes and determined that shifts in the rate of CR1 copy number evolution are associated with lineage-specific variation in CR1 activity. We then used phylogenetic reconstruction of CR1 subfamilies across amniotes to reveal both recent and ancient CR1 subclades across the squamate tree of life. The patterns of CR1 evolution in squamates contrast other amniotes, suggesting key differences in how TEs interact with different host genomes and at different points across evolutionary history.
The contribution of movement to social network structure and spreading dynamics under simple and complex transmission
Authors: Chimento Michael , Farine Damien R.
Published: February 2024

The structure of social networks fundamentally influences spreading dynamics. In general, the more contact between individuals, the more opportunity there is for the transmission of information or disease to take place. Yet, contact between individuals, and any resulting transmission events, are determined by a combination of spatial (where individuals choose to move) and social rules (who they choose to interact with or learn from). Here we examine the effect of the social-spatial interface on spreading dynamics using a simulation model. We quantify the relative effects of different movement rules (localized, semi-localized, nomadic, and resource-based movement) and social transmission rules (simple transmission, anti-conformity, proportional, conformity, and threshold rules) to both the structure of social networks and spread of a novel behaviour. Localized movement created weakly connected sparse networks, nomadic movement created weakly connected dense networks, and resource-based movement generated strongly connected modular networks. The resulting rate of spreading varied with different combinations of movement and transmission rules, but— importantly—the relative rankings of transmission rules changed when running simulations on static versus dynamic representations of networks. Our results emphasize that individual-level social and spatial behaviours influence emergent network structure, and are of particular consequence for the spread of information under complex transmission rules.
SomaScan Bioinformatics: Normalization, Quality Control, and Assessment of Pre-Analytical Variation
Authors: Candia Julián
Published: February 2024

SomaScan is an aptamer-based proteomics assay designed for the simultaneous measurement of thousands of human proteins with a broad range of endogenous concentrations. In its most current version released on November 1, 2023, the 11K SomaScan assay v5.0 is capable of measuring 10,776 human proteins covering major biological processes and disease areas, including cardiology, inflammation, neurology, and oncology. Here, I review bioinformatic approaches to perform normalization, quality control, and variability assessments.