bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the First Turtle Organoids: A Model for Investigating Unique Adaptations with Biomedical Potential
Authors: Zdyrski Christopher , Gabriel Vojtech , Gessler Thea B. , Ralston Abigail , Sifuentes-Romero Itzel , Kundu Debosmita , Honold Sydney , Wickham Hannah , Topping Nicholas E. , Sahoo Dipak Kumar , Bista Basanta , Tamplin Jeffrey , Ospina Oscar , Piñeyro Pablo , Meyerholz David K. , Allenspach Karin , Mochel Jonathan P. , Valenzuela Nicole 
Published: February 2023

ABSTRACTPainted turtles are remarkable for their well-developed freeze tolerance and associated resilience to hypoxia/anoxia, oxidative stress, and ability to supercool. They are, therefore, an ideal model for biomedical research on hypoxia-induced injuries (including strokes), tissue cooling during extensive surgeries, and organ cryopreservation. Yet, the seasonal reproduction and slow maturation of turtles hinder basic and applied biomedical research. To overcome these limitations, we developed the first adult stem cell-derived turtle hepatic organoids, which provide 3D self-assembled structures that mimic their original tissue and allow forin vitrotesting and experimentation without constantly harvesting donor tissue and screening offspring. Our pioneering work with turtles represents the first for this vertebrate Order and complements the only other organoid lines from non-avian reptiles, derived from snake venom glands. Here we report the isolation and characterization of hepatic organoids derived from painted, snapping, and spiny softshell turtles spanning ∼175 million years of evolution, with a subset being preserved in a biobank. Morphological and transcriptomics revealed organoid cells resembling cholangiocytes, which was then compared to the tissue of origin. Deriving turtle organoids from multiple species and life stages demonstrates that our techniques are broadly applicable to chelonians, permitting the development of functional genomic tools currently missing in most herpetological research. When combined with genetic editing, this platform will further support studies of genome-to-phenome mapping, gene function, genome architecture, and adaptive responses to climate change, among others. We discuss the unique abilities of turtles, including their overwintering potential, which has implications for ecological, evolutionary, and biomedical research.SIGNIFICANCEHere we developed the first turtle-derived organoid biobank from the liver of multiple chelonians with a subset characterized via histology, RNA sequencing transcriptomics, single-nuclei RNA sequencing, and transmission electron microscopy. Furthermore, we discuss the potential of the 3D organoid model to investigate unique physiological adaptations of turtles which could unravel the molecular mechanisms underlying their overwintering capacity, opening the door forin vitrobiomedical studies relevant to hepatic ischemia-reperfusion injury to organ cryopreservation, beyond fundamental ecology and evolution. This organoid biobank represents a novel resource for the scientific community to support research regarding the unique adaptations of this understudied Order of vertebrates.
Negative affect homogenizes and positive affect diversifies social memory consolidation across people
Authors: Iyer Siddhant , Collier Eleanor , Finn Emily S. , Meyer Meghan L. 
Published: February 2023

AbstractWe are often surprised when an interaction we remember positively is recalled by a peer negatively. What colors social memories with positive versus negative hues? We show that when resting after a social experience, individuals showing similar default network responding subsequently remember more negative information, while individuals showing idiosyncratic default network responding remember more positive information. Results were specific to rest after the social experience (as opposed to before or during the social experience, or rest after a nonsocial experience). The results provide novel neural evidence in support of the “broaden and build” theory of positive emotion, which posits that while negative affect confines, positive affect broadens idiosyncrasy in cognitive processing. For the first time, we identified post-encoding rest as a key moment and the default network as a key brain system in which negative affect homogenizes, whereas positive affect diversifies social memories.
High-throughput screening of functional neo-antigens and their specific TCRs via the Jurkat reporter system combined with droplet microfluidics
Authors: Li Yijian , Qi Jingyu , Liu Yang , Zheng Yuyu , Zhu Haibin , Zang Yupeng , Guan Xiangyu , Xie Sichong , Zhao Hongyan , Fu Yunyun , Xiang Haitao , Zhang Weicong , Chen Huanyi , Liu Huan , Zhao Yuntong , Feng Yu , Bu Fanyu , Liang Yanling , Li Yang , Xu Qumiao , He Ying , Sun Li , Liu Longqi , Gu Ying , Xu Xun , Hou Yong , Dong Xuan , Liu Ya 
Published: February 2023

SummaryT-cell receptor (TCR)-engineered T cells can precisely recognize a broad repertoire of targets derived from both intracellular and surface proteins of tumor cells. TCR-T adoptive cell therapy has shown safety and promising efficacy in solid tumor immunotherapy. However, antigen-specific functional TCR screening is time-consuming and expensive, which limits its application clinically. Here, we developed a novel integrated antigen-TCR screening platform based on droplet microfluidics technology, enabling high-throughput peptide-major histocompatibility complex (pMHC) library-to-TCR library screening with high sensitivity and low background signal. We introduced DNA barcoding technology to label peptide antigen candidate-loaded antigen-presenting cells (APCs) and Jurkat reporter cells to check the specificity of pMHC-TCR candidates. Coupled with the next-generation sequencing pipeline, interpretation of the DNA barcodes and the gene expression level of the Jurkat T-cell activation pathway provided a clear peptide-MHC-TCR recognition relationship. Our proof-of-principle study demonstrates that the platform could achieve unbiased pMHC-TCR library-on-library screening, which is expected to be used in the cross-reactivity and off-target testing of candidate pMHC-TCR libraries in clinical applications.
Microwell-enhanced optical rapid antibiotic susceptibility testing of single bacteria
Authors: Rosłoń Ireneusz , Japaridze Aleksandre , Rodenhuis Stef , Hamoen Lieke , Ghatkesar Murali , Steeneken Peter , Dekker Cees , Alijani Farbod 
Published: February 2023

AbstractBacteria that are resistant to antibiotics present an increasing burden on healthcare. To address this emerging crisis, novel rapid Antibiotic Susceptibility Testing (AST) methods are eagerly needed. Here, we present an optical AST technique that can determine the bacterial viability within one hour down to a resolution of single bacteria. The method is based on measuring intensity fluctuations of a reflected laser focused on a bacterium in reflective microwells. Using numerical simulations, we show that both refraction and absorption of light by the bacterium contribute to the observed signal. By administering antibiotics that kill the bacteria, we show that the variance of the detected fluctuations vanishes within one hour, indicating the potential of this technique for rapid sensing of bacterial antibiotic susceptibility. We envisage the use of this method for massively parallelizable AST tests and fast detection of drug resistant pathogens.
Effects of different tradititonal and commercial aquafeed on proximate composition and growth performance of Grass carp (Ctenopharyngodon idella) reared in the semi-intensive composite culture system
Authors: Zulfiqar Talha , Sarwar Muhammad Sajjad , Ul Hassan Habib , Chaudhry Abdul Shakoor , Hafeez-ur-Rehman Muhammad 
Published: February 2023

AbstractThe objective of the research was to find the effects of numerous traditional and commercial aqua feed on proximate composition and growth performance of Grass carp (Ctenopharyngodon idella) reared in the semi intensive composite culture system. The aqua feeds of various companies (AMG, Supreme, Aqua, Star Floating, Hi-Pro and Punjab feed) used as commercial feed. Farm made feeds were Maize gluten and Rice polish. For confidentiality, these feeds were randomly assign code T1, T2, T3, T4, T5, T6, T7 and T8 which were only known to investigating staffs. There were two replicates for each treatment. In this research, significantly maximum growth was recorded in T3 as compared to other treatments. Lesser weight gain was observed in the T1 (270.30±60.5).The maximum body length (19.25±2.19) was found in T3. Similarly, the minimum body length (5.97±2.94) was seen in T2. FCR ratio (2.36±0.01) was recorded in T3. Simultaneously, FCR (1.86±0.002) was also recorded in T4 that is the perfect ratio for fish farmers. Higher SGR was found in T3 (1.62±0.05). Overall, T4 showed lesser SGR (1.05±0.001). T4 showed the higher Crude protein (28.66±0.24%). T3 showed more fat content level (5.46±0.33%) in the body. These outcomes also supported that enrichment in the dietary amount of protein and lipid level improve lipids content and crude protein in fish body weight. Thus, based on growth performance, survival and proximate composition, it is concluded that T3 & T4 may be recommended for commercial culture ofCtenopharyngodon idella.
A conserved gene regulatory network controls root epidermal cell patterning in superrosid species
Authors: Zhu Yan , Schiefelbein John 
Published: February 2023

SummaryIn superrosid species, root epidermal cells differentiate into root hair cells and non-hair cells. In some superrosids, the root hair cells and non-hair cells are distributed randomly (Type I pattern) and in others, they are arranged in a position-dependent manner (Type III pattern). The model plant Arabidopsis (Arabidopsis thaliana) adopts the Type III pattern, and the gene regulatory network (GRN) that controls this pattern has been defined. However, it is unclear whether the Type III pattern in other species is controlled by a similar GRN as in Arabidopsis, and it is not known how the different patterns evolved.In this study, we analyzed superrosid speciesRhodiola rosea,Boehmeria nivea,andCucumis sativusfor their root epidermal cell patterns. Combining phylogenetics, transcriptomics, and cross-species complementation, we analyzed homologs of the Arabidopsis patterning genes from these species.We identifiedR.roseaandB.niveaas Type III species andC.sativusas Type I species. We discovered substantial similarities in structure, expression, and function of Arabidopsis patterning gene homologs inR.roseaandB.nivea, and major changes inC.sativus.We propose that in superrosids, diverse Type III species inherited the patterning GRN from a common ancestor, whereas Type I species arose by mutations in multiple lineages.
Cardinal v3 - a versatile open source software for mass spectrometry imaging analysis
Authors: Bemis Kylie Ariel , Föll Melanie Christine , Guo Dan , Lakkimsetty Sai Srikanth , Vitek Olga 
Published: February 2023

AbstractCardinal v3 is an open source software for reproducible analysis of mass spectrometry imaging experiments. A major update from its previous versions, Cardinal v3 supports most mass spectrometry imaging workflows. Its analytical capabilities include advanced data processing such as mass re-calibration, advanced statistical analyses such as single-ion segmentation and rough annotation-based classification, and memory-efficient analyses of large-scale multi-tissue experiments.
Proteome allocation is linked to transcriptional regulation through a modularized transcriptome
Authors: Patel Arjun , McGrosso Dominic , Hefner Ying , Campeau Anaamika , Sastry Anand V. , Maurya Svetlana , Rychel Kevin , Gonzalez David J , Palsson Bernhard O. 
Published: February 2023

AbstractIt has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigated whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions could be modularized in the same way to reveal novel relationships between their compositions. We found that; 1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, 2) the modules in the proteome often represent combinations of modules from the transcriptome, 3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and 4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.
Targeting the MR1-MAIT Cell Axis Improves Vaccine Efficacy and Affords Protection against Viral Pathogens
Authors: Rashu Rasheduzzaman , Ninkov Marina , Wardell Christine M. , Benoit Jenna M. , Wang Nicole I. , D’Agostino Michael R. , Zhang Ali , Feng Emily , Saeedian Nasrin , Bell Gillian I. , Vahedi Fatemeh , Hess David A. , Troyer Ryan M. , Kang C. Yong , Ashkar Ali A. , Miller Matthew S. , Haeryfar S.M. Mansour 
Published: February 2023

AbstractMucosa-associated invariant T (MAIT) cells are MR1-restricted, innate-like T lymphocytes with tremendous antibacterial and immunomodulatory functions. MAIT cells also sense and respond to viral infections in an MR1-independent fashion. However, whether they can be directly targeted in immunization strategies against viral pathogens is unknown. We addressed this question in multiple wild-type and genetically altered but clinically relevant mouse strains using several vaccine platforms against influenza viruses, poxviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a riboflavin-based MR1 ligand of bacterial origin, can synergize with viral vaccines to expand MAIT cells in multiple tissues, reprogram them towards a pro-inflammatory MAIT1 phenotype, license them to bolster mainstream virus-specific CD8+T cell responses, and potentiate heterosubtypic antiviral protection. Repeated 5-OP-RU administration did not render MAIT cells anergic, thus allowing for its inclusion in prime-boost immunization protocols. Mechanistically, tissue MAIT cell accumulation was due to their robust proliferation, as opposed to altered migratory behavior, and required viral vaccine replication competency, Toll-like receptor 3 (TLR3) and cell-autonomous type I interferon receptor signaling. Furthermore, the observed phenomenon was manifest in young and old female and male mice, and could also be recapitulated in a human cell culture system in which peripheral blood mononuclear cells were exposed to replicating virions and 5-OP-RU. In conclusion, although viruses and virus-based vaccines are devoid of the riboflavin biosynthesis machinery that supplies MR1 ligands, targeting MR1 enhances the efficacy of vaccine-elicited antiviral immunity. We propose 5-OP-RU as a non-classic but potent and versatile vaccine adjuvant against respiratory viruses.
Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response
Authors: Sarkar Soumyadeep , Elliott Emily C. , Henry Hayden R. , Ludovico Ivo Díaz , Melchior John T. , Frazer-Abel Ashley , Webb-Robertson Bobbie-Jo , Davidson W. Sean , Holers V. Michael , Rewers Marian J. , Metz Thomas O. , Nakayasu Ernesto S. 
Published: February 2023

ABSTRACTAimsType 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development.MethodsThis systematic review was registered with Open Science Framework (DOI 10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria.ResultsA total of 13 studies met our inclusion criteria, resulting in the identification of 251 unique proteins, with 27 (11%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found a subset of 3 proteins (C3, KNG1 & CFAH), 6 proteins (C3, C4A, APOA4, C4B, A2AP & BTD) and 7 proteins (C3, CLUS, APOA4, C6, A2AP, C1R & CFAI) have consistent regulation between multiple studies in samples from individuals at pre-seroconversion, post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development.ConclusionsBiomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.
Metabolic sensor AMPK licenses CD103+dendritic cells to induce Treg responses
Authors: Patente Thiago A , Brombacher Eline C , Heieis Graham A , Pelgrom Leonard R , Zawistowska-Deniziak Anna , Otto Frank , Ozir-Fazalalikhan Arifa , van der Ham Alwin J , Guigas Bruno A , Barbuto José AM , Everts Bart 
Published: February 2023

AbstractDendritic cells (DCs) play a crucial role in promoting tolerance through priming of regulatory T cells (Treg). Several studies indicate DC tolerogenicity is dependent on catabolic metabolism. However, the role of AMP-activated Kinase (AMPK), a key energy and nutrient sensor driving catabolic metabolism, in this process is unclear. We found that human retinoic acid-induced tolerogenic CD103+DCs (RA-DCs) display increased AMPK signaling. Interestingly, RA-DCs, but not vitamin-D3- or dexamethasone-induced tolerogenic DCs, required AMPK for Treg induction. Mechanistically, AMPK underpinned RA-driven tolerogenicity by promoting RALDH activity in a FoxO3-dependent manner. Correspondingly, mice deficient for AMPK in DCs (CD11cΔAMPKα1) harbored reduced frequencies of intestinal CD103+CD11b+DCs with impaired RALDH activity. Importantly, upon infection with parasitic wormSchistosoma mansoni, that elicits strong Th2 and Treg responses, CD11cΔAMPKα1mice showed a defect in Treg accumulation and concomitantly, displayed an impaired ability to control Type 2 immunity-driven granulomatous inflammation against the parasite eggs. Together, our findings identify AMPK as a key regulator of tolerance by CD103+DCs.SummaryDendritic cells (DCs) are critical for inducing tolerance. However, how metabolic cues control their tolerogenicity is still poorly understood. Patente et al demonstrate that AMPK is crucial for Treg induction by retinoic acid-primed tolerogenic CD103+DCs.
Transgenerational exposure to deoxygenation and warming disrupts mate-detection inGammarus locusta
Authors: Pereira Beatriz P. , Neff Simon , Borges Francisco O. , Otjacques Eve , Barreto Guilherme , Ranucci Maddalena , Court Mélanie , Rosa Rui , Repolho Tiago , Paula José Ricardo 
Published: February 2023

AbstractOcean deoxygenation and warming have been shown to pose a growing threat to the health of marine organisms and ecosystems. Yet, the potential for acclimation and adaptation to these threats remains poorly understood. The aim of this study was to evaluate the effects of transgenerational exposure to reduced oxygen availability and elevated seawater temperature on the chemosensory-dependent mating mechanisms of male amphipodsGammarus locusta. After exposure, the number of individuals that reached adulthood (in F0 and F2) was gauged, and adult males from F0 and F1 were subjected to behavioral trials to assess their capacity of long-distance female cue detection through quantification of (i) response time; (ii) first direction of movement; (iii) activity rate and (iv) proportion of time spent in female scent cues. Ocean warming induced mortality (especially in F2), and reduced oxygen availability had adverse effects on each of the investigated behavioral traits, which were amplified when combined with elevated temperature. Still, when compared to F0, the F1 generation demonstrated more adaptability (i.e., higher activity rate and preference for female odors) to the combination of the two stressors, suggesting positive carry-over effects. Nevertheless, full recovery to control levels was not observed. Altogether, this study indicates that future scenarios of ocean deoxygenation and warming have the potential to disrupt chemosensory-dependent mate-detection in amphipods, but also suggests possible behavioral adaptations. We call for greater research efforts on long-term impacts of ocean change on the behavioral and physiological processes of benthic coastal communities.
The evolution of morphological castes under decoupled control
Authors: Flintham Lewis , Field Jeremy 
Published: February 2023

AbstractEusociality, where units that previously reproduced independently function as one entity, is of major interest in evolutionary biology. Obligate eusociality is characterised by morphologically differentiated castes and reduced conflict. We explore conditions under which morphological castes may arise in the Hymenoptera and factors constraining their evolution. Control over offspring morphology and behaviour seem likely to be decoupled. Provisioners (queens and workers) can influence offspring morphology directly through the nutrition they provide, while adult offspring control their own behaviour. Provisioners may, however, influence worker behaviour indirectly if offspring modify their behaviour in response to their morphology. If manipulation underlies helping, we should not see helping evolve before specialised worker morphology, yet empirical observations suggest that behavioural castes precede morphological castes. We use evolutionary invasion analyses to show how the evolution of a morphologically differentiated worker caste depends on the prior presence of a behavioural caste: specialist worker morphology will be mismatched with behaviour unless some offspring already choose to work. A mother’s certainty about her offspring’s behaviour is also critical – less certainty results in greater mismatch. We show how baseline worker productivity can affect the likelihood of a morphological trait being favoured by natural selection. We then show how under a decoupled control scenario, morphologically differentiated castes should be less and less likely to be lost as they become more specialised. We also suggest that for eusociality to be evolutionarily irreversible, workers must be unable to functionally replace reproductives and reproductives must be unable to reproduce without help from workers.