bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic diversity of wild and cultured Yesso scallopMizuhopecten yessoensisfrom Japan and Canada
Authors: Sutherland Ben J. G. , Itoh Naoki , Gilchrist Korrina , Boyle Brian , Roth Myron , Green Timothy J. 
Published: June 2023

AbstractThe Yesso scallopMizuhopecten yessoensisis an important aquaculture species that was introduced to Western Canada from Japan to establish an economically viable scallop farming industry. This highly fecund species has been propagated in Canadian aquaculture hatcheries for the past 40 years, raising questions about genetic diversity and genetic differences among hatchery stocks. In this study, we compare cultured Canadian and wild Japanese populations of Yesso scallop using double-digest restriction site-associated DNA (ddRAD)-sequencing to genotype 21,048 variants in 71 wild-caught scallops from Japan, 65 scallops from the Vancouver Island University breeding population, and 37 scallops obtained from a commercial farm off Vancouver Island, British Columbia. The wild scallops are largely comprised of equally unrelated individuals, whereas cultured scallops are comprised of multiple families of related individuals. The polymorphism rate estimated in wild scallops was 1.7%, whereas in the cultured strains it ranged between 1.35% and 1.07%. Interestingly, heterozygosity rates were highest in the cultured populations, which is likely due to shellfish hatchery practices of crossing divergent strains to gain benefits of heterosis and to avoid inbreeding. Evidence of founder effects and drift were observed in the cultured strains, including high genetic differentiation between cultured populations and between cultured populations and the wild population. Cultured populations had effective population sizes ranging from 9-26 individuals whereas the wild population was estimated at 25-50K individuals. Further, a depletion of low frequency variants was observed in the cultured populations. These results indicate significant genetic diversity losses in cultured scallops in Canadian breeding programs.Article SummaryYesso scallop was introduced to breeding programs in Canada around 40 years ago and has become a valuable aquaculture species in the country with little information regarding its genetic diversity. This work genotypes over 20K genetic variants in wild Yesso scallops from Japan and compares to a major broodstock collection in British Columbia, Canada, as well as a commercial farm in the same region. Reduced polymorphism but elevated heterozygosity indicates value of using genetic information to guide breeding programs.
Detection and characterization of novel luchacoviruses, genusAlphacoronavirus, shed in saliva and feces of meso-carnivores in the northeastern United States
Authors: Olarte-Castillo Ximena A. , Plimpton Laura , McQueary Holly , Sun Yining , Yu Y. Tina , Cover Sarah , Richardson Amy N. , Jin Yuhan , Grenier Jennifer K. , Cummings Kevin J. , Bunting Elizabeth , Diuk-Wasser Maria , Needle David , Schuler Krysten , Stanhope Michael J. , Whittaker Gary , Goodman Laura B. 
Published: June 2023

AbstractSmall to mid-sized carnivores, or meso-carnivores, comprise a group of diverse mammals, many of which can adapt to anthropogenically disturbed environments. Wild meso-carnivores living in urban areas may get exposed to or spread pathogens to other species, including stray/feral domestic animals. Several coronaviruses (CoVs) have been detected in domesticated and farmed meso-carnivores, but knowledge of CoVs circulating in free-ranging wild meso-carnivores remains limited. In this study, we analyzed 321 samples collected between 2016 and 2022 from 9 species of free-ranging wild meso-carnivores and stray/feral domestic cats in the northeastern United States. Using a pan-CoV PCR, we screened tissues, feces, and saliva, nasal, and rectal swabs. We detected CoV RNA in fecal and saliva samples of animals in four species: fisher (Pekania pennanti), bobcat (Lynx rufus), red fox (Vulpes vulpes), and domestic cat(Felis catus). Next-generation sequencing revealed that all these viruses belonged to theLuchacovirussubgenus (Alphacoronavirusgenus), previously reported only in rodents and lagomorphs (i.e., rabbits). Genetic comparison of the 3’-end of the genome (∼12,000bp) revealed that although the viruses detected group with, and have a genetic organization similar to other luchacoviruses, they are genetically distinct from those from rodents and lagomorphs. Genetic characterization of the spike protein revealed that the meso-carnivore luchacoviruses do not have an S1/S2 cleavage motif but do have highly variable structural loops containing cleavage motifs similar to those identified in certain pathogenic CoVs. This study highlights the importance of characterizing the spike protein of CoVs in wild species for further targeted epidemiologic monitoring.ImportanceSeveral coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases, and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast USA as a potential “hotspot” area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene that are relevant for virus-host interactions.
Contributions of early and mid-level visual cortex to high-level object categorization
Authors: Kramer Lily E. , Chen Yi-Chia , Long Bria , Konkle Talia , Cohen Marlene R. 
Published: June 2023

AbstractThe complexity of visual features for which neurons are tuned increases from early to late stages of the ventral visual stream. Thus, the standard hypothesis is that high-level functions like object categorization are primarily mediated by higher visual areas because they require more complex image formats that are not evident in early visual processing stages. However, human observers can categorize images as objects or animals or as big or small even when the images preserve only some low- and mid-level features but are rendered unidentifiable (‘texforms’, Long et al., 2018). This observation suggests that even the early visual cortex, in which neurons respond to simple stimulus features, may already encode signals about these more abstract high-level categorical distinctions. We tested this hypothesis by recording from populations of neurons in early and mid-level visual cortical areas while rhesus monkeys viewed texforms and their unaltered source stimuli (simultaneous recordings from areas V1 and V4 in one animal and separate recordings from V1 and V4 in two others). Using recordings from a few dozen neurons, we could decode the real-world size and animacy of both unaltered images and texforms. Furthermore, this neural decoding accuracy across stimuli was related to the ability of human observers to categorize texforms by real-world size and animacy. Our results demonstrate that neuronal populations early in the visual hierarchy contain signals useful for higher-level object perception and suggest that the responses of early visual areas to simple stimulus features display preliminary untangling of higher-level distinctions.
genomicBERT and data-free deep-learning model evaluation
Authors: Chen Tyrone , Tyagi Navya , Chauhan Sarthak , Peleg Anton Y. , Tyagi Sonika 
Published: June 2023

AbstractThe emerging field of Genome-NLP (Natural Language Processing) aims to analyse biological sequence data using machine learning (ML), offering significant advancements in data-driven diagnostics. Three key challenges exist in Genome-NLP. First, long biomolecular sequences require “tokenisation” into smaller subunits, which is non-trivial since many biological “words” remain unknown. Second, ML methods are highly nuanced, reducing interoperability and usability. Third, comparing models and reproducing results are difficult due to the large volume and poor quality of biological data.To tackle these challenges, we developed the first automated Genome-NLP workflow that integrates feature engineering and ML techniques. The workflow is designed to be species and sequence agnostic. In this workflow: a) We introduce a new transformer-based model for genomes calledgenomicBERT, which empirically tokenises sequences while retaining biological context. This approach minimises manual preprocessing, reduces vocabulary sizes, and effectively handles out-of-vocabulary “words”. (b) We enable the comparison of ML model performance even in the absence of raw data.To facilitate widespread adoption and collaboration, we have madegenomicBERTavailable as part of the publicly accessible conda package calledgenomeNLP. We have successfully demonstrated the application ofgenomeNLPon multiple case studies, showcasing its effectiveness in the field of Genome-NLP.HighlightsWe provide a comprehensive classification of genomic data tokenisation and representation approaches for ML applications along with their pros and cons.We infer k-mers directly from the data and handle out-of-vocabulary words. At the same time, we achieve a significantly reduced vocabulary size compared to the conventional k-mer approach reducing the computational complexity drastically.Our method is agnostic to species or biomolecule type as it is data-driven.We enable comparison of trained model performance without requiring original input data, metadata or hyperparameter settings.We present the first publicly available, high-level toolkit that infers the grammar of genomic data directly through artificial neural networks.Preprocessing, hyperparameter sweeps, cross validations, metrics and interactive visualisations are automated but can be adjusted by the user as needed.
BrainAGE as a measure of maturation during early adolescence
Authors: Whitmore Lucy B. , Weston Sara J. , Mills Kathryn L. 
Published: June 2023

AbstractThe Brain-Age Gap Estimation (BrainAGE) is an important new tool that purports to evaluate brain maturity when used in adolescent populations. However, it is unclear whether BrainAGE tracks with other maturational metrics in adolescence. In the current study, we related BrainAGE to metrics of pubertal and cognitive development using both a previously validated model and a novel model trained specifically on an early adolescent population. The previously validated model was used to predict BrainAGE in two age bands, 9-11 and 10-13 years old, while the novel model was used with 9-11 year olds only. Across both models and age bands, an older BrainAGE was related to more advanced pubertal development. The relationship between BrainAGE and cognition was less clear, with conflicting relationships across the two models. Additionally, longitudinal analysis revealed moderate to high stability in BrainAGE across early adolescence. The results of the current study provide initial evidence that BrainAGE tracks with some metrics of maturation, including pubertal development. However, the conflicting results between BrainAGE and cognition lead us to question the utility of these models for non-biological processes.
Wolbachia-induced inhibition of O’nyong nyong virus inAnophelesmosquitoes is mediated by Toll signaling and modulated by cholesterol
Authors: Pujhari Sujit , Hughes Grant L , Pakpour Nazzy , Suzuki Yasutsugu , Rasgon Jason L 
Published: June 2023

ABSTRACTEnhanced host immunity and competition for metabolic resources are two main competing hypotheses for the mechanism ofWolbachia-mediated pathogen inhibition in arthropods. Using anAnophelesmosquito – somaticWolbachiainfection – O’nyong nyong virus (ONNV) model, we demonstrate that the mechanism underpinningWolbachia-mediated virus inhibition is up-regulation of the Toll innate immune pathway. However, the viral inhibitory properties ofWolbachiawere abolished by cholesterol supplementation. This result was due toWolbachia-dependent cholesterol-mediated suppression of Toll signaling rather than competition for cholesterol betweenWolbachiaand virus. The inhibitory effect of cholesterol was specific toWolbachia-infectedAnophelesmosquitoes and cells. These data indicate that bothWolbachiaand cholesterol influence Toll immune signaling inAnophelesmosquitoes in a complex manner and provide a functional link between the host immunity and metabolic competition hypotheses for explainingWolbachia-mediated pathogen interference in mosquitoes. In addition, these results provide a mechanistic understanding of the mode of action ofWolbachia-induced pathogen blocking in Anophelines, which is critical to evaluate the long-term efficacy of control strategies for malaria andAnopheles-transmitted arboviruses.HIGHLIGHTSWolbachiainhibits O’nyong nyong virus (ONNV) inAnophelesmosquitoes.Enhanced Toll signaling is responsible forWolbachia-induced interference of ONNV.Cholesterol suppresses Toll signaling to modulateWolbachia-induced ONNV interference.
Functional Genomics of GastrointestinalEscherichia coliIsolated from Patients with Cancer and Diarrhea
Authors: Carter Hannah , Clark Justin , Carlin Lily G. , Vaughan Ellen , Rajan Anubama , Olvera Adilene , Yu Xiaomin , Zeng Xi-Lei , Kambal Amal , Holder Michael , Qin Xiang , Gibbs Richard A. , Petrosino Joseph F. , Muzny Donna M. , Doddapaneni Harsha , Menon Vipin K. , Hoffman Kristi L. , Meng Qingchang , Ross Matthew C. , Javornik Cregeen Sara J. , Metcalf Ginger , Jenq Robert , Blutt Sarah , Estes Mary K. ,   TMC-GCID team, Maresso Anthony , Okhuysen Pablo C. 
Published: June 2023

AbstractWe describe the epidemiology and clinical characteristics of 29 patients with cancer and diarrhea in whom EnteroaggregativeEscherichia coli(EAEC) was initially identified by GI BioFire panel multiplex.E. colistrains were successfully isolated from fecal cultures in 14 of 29 patients. Six of the 14 strains were identified as EAEC and 8 belonged to other diverseE. coligroups of unknown pathogenesis. We investigated these strains by their adherence to human intestinal organoids, cytotoxic responses, antibiotic resistance profile, full sequencing of their genomes, and annotation of their functional virulome. Interestingly, we discovered novel and enhanced adherence and aggregative patterns for several diarrheagenic pathotypes that were not previously seen when co-cultured with immortalized cell lines. EAEC isolates displayed exceptional adherence and aggregation to human colonoids compared not only to diverse GIE. coli, but also compared to prototype strains of other diarrheagenicE. coli. Some of the diverseE. colistrains that could not be classified as a conventional pathotype also showed an enhanced aggregative and cytotoxic response. Notably, we found a high carriage rate of antibiotic resistance genes in both EAEC strains and diverse GIE. coliisolates and observed a positive correlation between adherence to colonoids and the number of metal acquisition genes carried in both EAEC and the diverseE. colistrains. This work indicates thatE. colifrom cancer patients constitute strains of remarkable pathotypic and genomic divergence, including strains of unknown disease etiology with unique virulomes. Future studies will allow for the opportunity to re-defineE. colipathotypes with greater diagnostic accuracy and into more clinically relevant groupings.
Ribosomal protein control of hematopoietic stem cell transformation through direct, non-canonical regulation of metabolism
Authors: Harris Bryan , Singh Dinesh K. , Verma Monika , Fahl Shawn P. , Rhodes Michele , Sprinkle Shanna R. , Wang Minshi , Zhang Yong , Perrigoue Jaqueline , Kessel Rachel , Peri Suraj , West Joshua , Giricz Orsi , Boultwood Jacqueline , Pellagatti Andrea , Ramesh KH , Montagna Cristina , Pradhan Kith , Tyner Jeffrey W. , Kennedy Brian K. , Holinstat Michael , Steidl Ulrich , Sykes Stephen , Verma Amit , Wiest David L. 
Published: June 2023

SummaryWe report here that expression of the ribosomal protein, RPL22, is frequently reduced in human myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML); reduced RPL22 expression is associated with worse outcomes. Mice null for Rpl22 display characteristics of an MDS-like syndrome and develop leukemia at an accelerated rate. Rpl22-deficient mice also display enhanced hematopoietic stem cell (HSC) self-renewal and obstructed differentiation potential, which arises not from reduced protein synthesis but from increased expression of the Rpl22 target, ALOX12, an upstream regulator of fatty acid oxidation (FAO). The increased FAO mediated by Rpl22-deficiency also persists in leukemia cells and promotes their survival. Altogether, these findings reveal that Rpl22 insufficiency enhances the leukemia potential of HSC via non-canonical de-repression of its target, ALOX12, which enhances FAO, a process that may serve as a therapeutic vulnerability of Rpl22 low MDS and AML leukemia cells.HighlightsRPL22 insufficiency is observed in MDS/AML and is associated with reduced survivalRpl22-deficiency produces an MDS-like syndrome and facilitates leukemogenesisRpl22-deficiency does not impair global protein synthesis by HSCRpl22 controls leukemia cell survival by non-canonical regulation of lipid oxidationeTOC:Rpl22 controls the function and transformation potential of hematopoietic stem cells through effects on ALOX12 expression, a regulator of fatty acid oxidation.
Progress toward the development of an effective vaccine for Extraintestinal pathogenicE. coli(ExPEC): The application of the multiple-protein subunits vaccine in different murine models
Authors: Xing Yikun , Clark Justin R. , Chang James D. , Zulk Jacob J. , Chirman Dylan M. , Piedra Felipe-Andres , Patras Kathryn A. , Maresso Anthony W. 
Published: June 2023

AbstractExtraintestinal pathogenicE. coli(ExPEC) is the primary Gram-negative bacterial pathogen, and the leading cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The emergence and increasing prevalence of multidrug-resistance (MDR) ExPEC strains have led to considerable treatment failures, increased hospitalization rates, morbidity, and mortality. A prophylactic vaccine against ExPEC has the potential to reduce severe infection-related morbidity and mortality, helping to address the escalating antimicrobial resistance (AMR) crisis worldwide. The α-hemolysin (HlyA) is a critical, frequently detected secreted cytotoxic virulence factor in ExPEC, with HlyA-expressing ExPEC strains correlating with increased severity and infection dissemination in clinical levels. In this study, we assessed the protective efficacy of pro-HlyA (the inactive and immature precursor of HlyA) and Dual-Hit (a combination of pro-HlyA and SinH-3, the previously reported immunoglobulin-like domain-3 of the invasin-like autotransporter protein SinH), as ExPEC vaccine candidates. We demonstrated that immunizing mice with pro-HlyA or Dual-Hit significantly reduced bacterial burden and increased survival rates against pandemic ExPEC sequence type strains, ST73 (CFT073) and ST95 (UTI89), in the model of bacteremia and mortality. Both pro-HlyA or Dual-Hit immunizations also provided significant protection against UTI89 colonization in the bladder in the murine UTI model. Furthermore, vaccination with Dual-Hit provided enduring and robust protection against a mixture of ten typical high-virulent sequence types of ExPEC strains, resulting in a promising broad-spectrum vaccine candidate. These findings suggest that pro-HlyA and Dual-Hit might serve as highly effective vaccine targets and highlight the potential of these vaccine candidates for further development and evaluation.
TheToxoplasma gondiieffector GRA83 modulates the host’s innate immune response to regulate parasite infection
Authors: Thind Amara C. , Mota Caroline M. , Gonçalves Ana Paula N. , Sha Jihui , Wohlschlegel James A. , Mineo Tiago W.P. , Bradley Peter J. 
Published: June 2023

AbstractToxoplasma gondii’s propensity to infect its host and cause disease is highly dependent on its ability to modulate host cell functions. One of the strategies the parasite uses to accomplish this is via the export of effector proteins from the secretory dense granules. Dense granule (GRA) proteins are known to play roles in nutrient acquisition, host cell cycle manipulation, and immune regulation. Here, we characterize a novel dense granule protein named GRA83, which localizes to the parasitophorous vacuole in tachyzoites and bradyzoites. Disruption ofGRA83results in increased virulence, weight loss, and parasitemia during the acute infection, as well as a marked increase in the cyst burden during the chronic infection. This increased parasitemia was associated with an accumulation of inflammatory infiltrates in tissues in both the acute and chronic infection. Murine macrophages infected with Δgra83tachyzoites produced less interleukin-12 (IL-12)in vitro, which was confirmed with reduced IL-12 and interferon gamma (IFN-γ)in vivo. This dysregulation of cytokines correlates with reduced nuclear translocation of the p65 subunit of the NF-κB complex. While GRA15 similarly regulates NF-κB, infection with Δgra83/Δgra15parasites did not further reduce p65 translocation to the host cell nucleus, suggesting these GRAs function in converging pathways. We also used proximity labelling experiments to reveal candidate GRA83 interactingT. gondiiderived partners. Taken together, this work reveals a novel effector that stimulates the innate immune response, enabling the host to limit parasite burden.ImportanceToxoplasma gondiiposes a significant public health concern as it is recognized as one of the leading foodborne pathogens in the United States. Infection with the parasite can cause congenital defects in neonates, life-threatening complications in immunosuppressed patients, and ocular disease. Specialized secretory organelles, including the dense granules, play an important role in the parasite’s ability to efficiently invade and regulate components of the host’s infection response machinery to limit parasite clearance and establish an acute infection.Toxoplasma’s ability to avoid early clearance, while also successfully infecting the host long enough to establish a persistent chronic infection, is crucial in allowing for its transmission to a new host. While multiple GRAs directly modulate host signaling pathways, they do so in various ways highlighting the parasite’s diverse arsenal of effectors that govern infection. Understanding how parasite-derived effectors harness host functions to evade defenses yet ensure a robust infection are important for understanding the complexity of the pathogen’s tightly regulated infection. In this study, we characterize a novel secreted protein named GRA83 that stimulates the host cell’s response to limit infection.