Cross-species Studies Research Articles

Representation of Anticipated Rewards and Punishments in the Human Brain.

Subjective value is a core concept in neuroeconomics, serving as the basis for decision making. Despite the extensive literature on the neural encoding of subjective reward value in humans, the neural representation of punishment value remains relatively understudied. This review synthesizes current knowledge on the neural representation of reward value, including methodologies, involved brain regions, and the concept of common currency representation of diverse reward types in decision-making and learning processes. We then critically examine existing research on the neural representation of punishment value, highlighting conceptual and methodological challenges in human studies and insights gained from animal research. Finally, we explore how individual differences in reward and punishment processing may be linked to various mental illnesses, with a focus on stress-related psychopathologies. This review advocates for the integration of both rewards and punishments within value-based decision-making and learning frameworks, leveraging insights from cross-species studies and utilizing ecological gamified paradigms to reflect real-life scenarios.

AMIR: a multi-omics data platform for Asteraceae plants genetics and breeding research.

As the largest family of dicotyledon, the Asteraceae family comprises a variety of economically important crops, ornamental plants and numerous medicinal herbs. Advancements in genomics and transcriptomic have revolutionized research in Asteraceae species, generating extensive omics data that necessitate an efficient platform for data integration and analysis. However, existing databases face challenges in mining genes with specific functions and supporting cross-species studies. To address these gaps, we introduce the Asteraceae Multi-omics Information Resource (AMIR; https://yanglab.hzau.edu.cn/AMIR/), a multi-omics hub for the Asteraceae plant community. AMIR integrates diverse omics data from 74 species, encompassing 132 genomes, 4 408 432 genes annotated across seven different perspectives, 3897 transcriptome sequencing samples spanning 131 organs, tissues and stimuli, 42 765 290 unique variants and 15 662 metabolites genes. Leveraging these data, AMIR establishes the first pan-genome, comparative genomics and transcriptome system for the Asteraceae family. Furthermore, AMIR offers user-friendly tools designed to facilitate extensive customized bioinformatics analyses. Two case studies demonstrate AMIR's capability to provide rapid, reproducible and reliable analysis results. In summary, by integrating multi-omics data of Asteraceae species and developing powerful analytical tools, AMIR significantly advances functional genomics research and contributes to breeding practices of Asteraceae.

Cross-Species Studies Reveal That Dysregulated Mitochondrial Gene Expression and Electron Transport Complex I Activity Are Crucial for Sarcopenia

The significance of complex I of the electron transport chain (ETC) in the aging process is widely acknowledged; however, its specific impact on the development of sarcopenia in muscle remains poorly understood. This study elucidated the correlation between complex I inhibition and sarcopenia by conducting a comparative analysis of skeletal muscle gene expression in sarcopenia phenotypes from rats, mice, and humans. Our findings reveal a common mechanistic link across species, particularly highlighting the correlation between the suppression of complex I of ETC activity and dysregulated mitochondrial transcription and translation in sarcopenia phenotypes. Additionally, we observed macrophage dysfunction alongside abnormal metabolic processes within skeletal muscle tissues across all species, implicating their pathogenic role in the onset of sarcopenia. These discoveries underscore the importance of understanding the shared mechanisms associated with complex I of ETC in sarcopenia development. The identified correlations provide valuable insights into potential targets for therapeutic interventions aimed at mitigating the impact of sarcopenia, a condition with substantial implications for aging populations.

Modular, inducible, and titratable expression systems for Escherichia coli and Acinetobacter baumannii.

Gene expression systems that transcend species barriers are needed for cross-species analysis of gene function. In particular, expression systems that can be utilized in both model and pathogenic bacteria underpin comparative functional approaches that inform conserved and variable features of bacterial physiology. In this study, we develop replicative and integrative vectors alongside a novel, IPTG-inducible promoter that can be used in the model bacterium Escherichia coli K-12 as well as strains of the antibiotic-resistant pathogen, Acinetobacter baumannii. We generate modular vectors that transfer by conjugation at high efficiency and either replicate or integrate into the genome, depending on design. Embedded in these vectors, we also developed a synthetic, IPTG-inducible promoter, PabstBR, that induces to a high level but is less leaky than the commonly used trc promoter. We show that PabstBR is titratable at both the population and single-cell levels, regardless of species, highlighting the utility of our expression systems for cross-species functional studies. Finally, as a proof of principle, we use our integrating vector to develop a reporter for the E. coli envelope stress σ factor, RpoE, and deploy the reporter in E. coli and A. baumannii, finding that A. baumannii does not recognize RpoE-dependent promoters unless RpoE is heterologously expressed. We envision that these vector and promoter tools will be valuable for the community of researchers who study the fundamental biology of E. coli and A. baumannii.IMPORTANCEAcinetobacter baumannii is a multidrug-resistant, hospital-acquired pathogen with the ability to cause severe infections. Understanding the unique biology of this non-model bacterium may lead to the discovery of new weaknesses that can be targeted to treat antibiotic-resistant infections. In this study, we provide expression tools that can be used to study the gene function in A. baumannii, including in drug-resistant clinical isolates. These tools are also compatible with the model bacterium, Escherichia coli, enabling cross-species comparisons of gene function. We anticipate that the use of these tools by the scientific community will accelerate our understanding of Acinetobacter biology.

Prediction of the fluoride contents of different crop species via the random forest algorithm.

Fluoride (F) is a trace element that is essential to the human body and occurs naturally in the environment. However, a deficiency or excess of F in the environment can potentially lead to human health issues. The pseudototal amount of F in soil often does not correlate directly with the F content in plants. Instead, the F content within plants tends to have a greater correlation with the bioavailable F in soils. In large-scale soil surveys, only the pseudototal elemental content of soils is typically measured, which may not be highly reliable for developing agricultural zoning plans. There are significant variations in the ability of different plants to accumulate F from soil. Additionally, due to variations in soil elemental absorption mechanisms among different plant species, when multiple crops are grown in an area, it is typically necessary to study the elemental absorption mechanisms of each crop. To address these issues, in this study, we examined the factors influencing F bioaccumulation coefficients in different crops based on 1:50,000 soil geochemical survey data. Using the random forest algorithm, four indicators-bioavailable P, bioavailable Zn, leachable Pb, and Sr-were selected from among 29 parameters to predict the F content within crops to replace bioavailable F in the soil. Compared with the multivariate linear regression (MLR) model, the random forest (RF) model provided more accurate and reliable predictions of the fluoride content in crops, with the RF model's prediction accuracy improving by approximately 95.23%. Additionally, while the partial least squares regression (PLSR) model also offered improved accuracy over MLR, the RF model still outperformed PLSR in terms of prediction accuracy and robustness. Additionally, it maximized the utilization of existing geochemical survey data, enabling cross-species studies for the first time and avoiding redundant evaluations of different types of agricultural products in the same region. In this investigation, we selected the Xining-Ledu region of Qinghai Province, China, as the study area and employed a random forest model to predict the crop F content in soils, providing a new methodological framework for crop production that effectively enhances agricultural quality and efficiency.

Modular, inducible, and titratable expression systems for Escherichia coli and Acinetobacter baumannii.

Gene expression systems that transcend species barriers are needed for cross-species analysis of gene function. In particular, expression systems that can be utilized in both model and pathogenic bacteria underpin comparative functional approaches that inform conserved and variable features of bacterial physiology. Here, we develop replicative and integrative vectors alongside a novel, IPTG-inducible promoter that can be used in the model bacterium Escherichia coli K-12 as well as strains of the antibiotic-resistant pathogen, Acinetobacter baumannii. We generate modular vectors that transfer by conjugation at high efficiency and either replicate or integrate into the genome, depending on design. Embedded in these vectors, we also developed a synthetic, IPTG-inducible promoter, P abstBR , that induces to a high level, but is less leaky than the commonly used trc promoter. We show that P abstBR is titratable at both the population and single cell level, regardless of species, highlighting the utility of our expression systems for cross-species functional studies. Finally, as a proof of principle, we use our integrating vector to develop a reporter for the E. coli envelope stress σ factor, RpoE, and deploy the reporter in E. coli and A. baumannii, finding that A. baumannii does not recognize RpoE-dependent promoters unless RpoE is heterologously expressed. We envision that these vector and promoter tools will be valuable for the community of researchers that study fundamental biology of E. coli and A. baumannii.

Cross-species variability in lobular geometry and cytochrome P450 hepatic zonation: insights into CYP1A2, CYP2D6, CYP2E1 and CYP3A4.

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the most preferable to compare four species. CYP1A2 could be considered as an additional CYP for rodent versus human comparisons, and CYP3A4 for mouse/human comparisons. In conclusion, our image analysis pipeline together with suggestions for species and CYP selection can serve to improve future cross-species and translational drug metabolism studies.

Do rats (Rattus norvegicus) perceive octave equivalence, a critical human cross-cultural aspect of pitch perception?

Octave equivalence describes the perception that two notes separated by a doubling in frequency have a similar quality. In humans, octave equivalence is important to both music and language learning and is found cross-culturally. Cross-species studies comparing human and non-human animals can help illuminate the necessary pre-conditions to developing octave equivalence. Here, we tested whether rats (Rattus norvegicus) perceive octave equivalence using a standardized cross-species paradigm. This allowed us to disentangle concurring hypotheses regarding the evolutionary roots of this phenomenon. One hypothesis is that octave equivalence is directly connected to vocal learning, but this hypothesis is only partially supported by data. According to another hypothesis, the harmonic structure of mammalian vocalizations may be more important. If rats perceive octave equivalence, this would support the importance of vocal harmonic structure. If rats do not perceive octave equivalence, this would suggest that octave equivalence evolved independently in several mammalian clades due to a more complex interplay of different factors such as-but not exclusively-the ability to vocally learn. Evidence from our study suggests that rats do perceive octave equivalence, thereby suggesting that the harmonic vocal structure found in mammals may be a key pre-requisite for octave equivalence. Stage 1 approved protocol: the study reported here was originally accepted as a Registered Report and the study design was approved in Stage 1. We hereby confirm that the completed experiment(s) have been executed and analysed in the manner originally approved with any unforeseen changes in those approved methods and analyses clearly noted. The approved Stage 1 protocol can be found at: https://osf.io/gvf7c/?view_only=76dc1840f31c4f9ab59eb93cbadb98b7.

Species -shared and -unique gyral peaks on human and macaque brains

Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.

Species -shared and -unique gyral peaks on human and macaque brains.

Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.

Look4LTRs: a Long terminal repeat retrotransposon detection tool capable of cross species studies and discovering recently nested repeats

Plant genomes include large numbers of transposable elements. One particular type of these elements is flanked by two Long Terminal Repeats (LTRs) and can translocate using RNA. Such elements are known as LTR-retrotransposons; they are the most abundant type of transposons in plant genomes. They have many important functions involving gene regulation and the rise of new genes and pseudo genes in response to severe stress. Additionally, LTR-retrotransposons have several applications in biotechnology. Due to the abundance and the importance of LTR-retrotransposons, multiple computational tools have been developed for their detection. However, none of these tools take advantages of the availability of related genomes; they process one chromosome at a time. Further, recently nested LTR-retrotransposons (multiple elements of the same family are inserted into each other) cannot be annotated accurately — or cannot be annotated at all — by the currently available tools. Motivated to overcome these two limitations, we built Look4LTRs, which can annotate LTR-retrotransposons in multiple related genomes simultaneously and discover recently nested elements. The methodology of Look4LTRs depends on techniques imported from the signal-processing field, graph algorithms, and machine learning with a minimal use of alignment algorithms. Four plant genomes were used in developing Look4LTRs and eight plant genomes for evaluating it in contrast to three related tools. Look4LTRs is the fastest while maintaining better or comparable F1 scores (the harmonic average of recall and precision) to those obtained by the other tools. Our results demonstrate the added benefit of annotating LTR-retrotransposons in multiple related genomes simultaneously and the ability to discover recently nested elements. Expert human manual examination of six elements — not included in the ground truth — revealed that three elements belong to known families and two elements are likely from new families. With respect to examining recently nested LTR-retrotransposons, three out of five were confirmed to be valid elements. Look4LTRs — with its speed, accuracy, and novel features — represents a true advancement in the annotation of LTR-retrotransposons, opening the door to many studies focused on understanding their functions in plants.

Iterative learning experiments can help elucidate music's origins.

Anglada-Tort et al. Current Biology, 33, 1472-1486.e12, (2023) conducted a large-scale iterative learning study with cross-cultural human participants to understand how musical structure emerges. Together with archaeological, developmental, historical cross-cultural music data, and cross-species studies we can begin to elucidate the origins of music.

Linezolid does not improve bactericidal activity of rifampin-containing first-line regimens in animal models of TB meningitis

Tuberculous meningitis (TB meningitis) is the most devastating form of tuberculosis (TB) and there is a critical need to optimize treatment. Linezolid is approved for multidrug resistant TB and has shown encouraging results in retrospective TB meningitis studies, with several clinical trials underway assessing its additive effects on high-dose (35 mg/kg/day) or standard-dose (10 mg/kg/day) rifampin-containing regimens. However, the efficacy of adjunctive linezolid to rifampin-containing first-line TB meningitis regimens and the tissue pharmacokinetics (PK) in the central nervous system (CNS) are not known. We therefore conducted cross-species studies in two mammalian (rabbits and mice) models of TB meningitis to test the efficacy of linezolid when added to the first-line TB regimen and measure detailed tissue PK (multicompartmental positron emission tomography [PET] imaging and mass spectrometry). Addition of linezolid did not improve the bactericidal activity of the high-dose rifampin-containing regimen in either animal model. Moreover, the addition of linezolid to standard-dose rifampin in mice also did not improve its efficacy. Linezolid penetration (tissue/plasma) into the CNS was compartmentalized with lower than previously reported brain and cerebrospinal fluid (CSF) penetration, which decreased further two weeks after initiation of treatment. These results provide important data regarding the addition of linezolid for the treatment of TB meningitis.

CoSIA: an R Bioconductor package for CrOss Species Investigation and Analysis.

High-throughput sequencing technologies have enabled cross-species comparative transcriptomic studies; however, there are numerous challenges for these studies due to biological and technical factors. We developed CoSIA (Cross-Species Investigation and Analysis), a Bioconductor R package and Shiny app that provides an alternative framework for cross-species transcriptomic comparison of non-diseased wild-type RNA sequencing gene expression data from Bgee across tissues and species (human, mouse, rat, zebrafish, fly, and nematode) through visualization of variability, diversity, and specificity metrics. https://github.com/lasseignelab/CoSIA.

Comparative epidemiological study of breast cancer in humans and canine mammary tumors: insights from Portugal

Dogs spontaneously develop mammary gland tumors (MGT) and exhibit striking similarities in clinical and epidemiological characteristics to human breast cancer (HBC). Descriptive and comparative analysis of HBC and canine MGT with a focus on evaluating similarities and geographical distribution were the aims of this study. HBC cases were obtained from North Regional Oncological Registry (RORENO) (2010–2015) and canine MGT cases from Vet-OncoNet (2019–2022). Analyses were performed based on published and well accepted classification systems (ICD-O-3.2 for humans and Vet-ICD-O-canine-1). Age-standardized incidence risks (ASIR) of Porto district municipalities were calculated using 2021 Portuguese census (INE) and data from the Portuguese animal registration system (SIAC). Among 7,674 HBC cases and 1,140 MGT cases, a similar age and sex distribution pattern was observed. Approximately 69.2% of HBC cases were between 40 and 69 years old, while 66.9% of MGT cases were diagnosed between 7 and 12 years old (mean age of 9.6 years, SD = 2.6). In women, Invasive breast carcinoma (8500/3) was the most common histological type (n = 5,679, 74%) while in dogs it was the Complex Carcinoma (8983.1/3) (n = 205, 39%). Cocker and Yorkshire Terriers exhibited the highest relative risks (3.2 and 1.6, p < 0.05, respectively) when compared to cross breed dogs. The municipalities' ASIR of the two species exhibited a high correlation (R = 0.85, p < 0.01) and the spatial cluster analysis revealed similar geographic hotspots. Also, higher ASIR values both in women and dogs were more frequently found in urbanized areas compared to rural areas. This research sheds light on the shared features and geographical correlation between HBC and canine MGT, highlighting the potential of cross-species environmental oncology studies.

In vivo fluorescent labeling and tracking of extracellular matrix.

Connective tissues are essential building blocks for organ development, repair and regeneration. However, we are at the early stages of understanding connective tissue dynamics. Here, we detail a method that enables in vivo fate mapping of organ extracellular matrix (ECM) by taking advantage of a crosslinking chemical reaction between amine groups and N-hydroxysuccinimide esters. This methodology enables robust labeling of ECM proteins, which complement previous affinity-based single-protein methods. This protocol is intended for entry-level scientists and the labeling step takes between 5 and 10 min. ECM 'tagging' with fluorophores using N-hydroxysuccinimide esters enables visualization of ECM spatial modifications and is particularly useful to study connective tissue dynamics in organ fibrosis, tumor stroma formation, wound healing and regeneration. This in vivo chemical fate mapping methodology is highly versatile, regardless of the tissue/organ system, and complements cellular fate-mapping techniques. Furthermore, as the basic chemistry of proteins is highly conserved between species, this method is also suitable for cross-species comparative studies of ECM dynamics.

Network models to enhance the translational impact of cross-species studies.

Neuroscience studies are often carried out in animal models for the purpose of understanding specific aspects of the human condition. However, the translation of findings across species remains a substantial challenge. Network science approaches can enhance the translational impact of cross-species studies by providing a means of mapping small-scale cellular processes identified in animal model studies to larger-scale inter-regional circuits observed in humans. In this Review, we highlight the contributions of network science approaches to the development of cross-species translational research in neuroscience. We lay the foundation for our discussion by exploring the objectives of cross-species translational models. We then discuss how the development of new tools that enable the acquisition of whole-brain data in animal models with cellular resolution provides unprecedented opportunity for cross-species applications of network science approaches for understanding large-scale brain networks. We describe how these tools may support the translation of findings across species and imaging modalities and highlight future opportunities. Our overarching goal is to illustrate how the application of network science tools across human and animal model studies could deepen insight into the neurobiology that underlies phenomena observed with non-invasive neuroimaging methods and could simultaneously further our ability to translate findings across species.

Integrative mapping of the dog epigenome: Reference annotation for comparative intertissue and cross-species studies

Dogs have become a valuable model in exploring multifaceted diseases and biology relevant to human health. Despite large-scale dog genome projects producing high-quality draft references, a comprehensive annotation of functional elements is still lacking. We addressed this through integrative next-generation sequencing of transcriptomes paired with five histone marks and DNA methylome profiling across 11 tissue types, deciphering the dog’s epigenetic code by defining distinct chromatin states, super-enhancer, and methylome landscapes, and thus showed that these regions are associated with a wide range of biological functions and cell/tissue identity. In addition, we confirmed that the phenotype-associated variants are enriched in tissue-specific regulatory regions and, therefore, the tissue of origin of the variants can be traced. Ultimately, we delineated conserved and dynamic epigenomic changes at the tissue- and species-specific resolutions. Our study provides an epigenomic blueprint of the dog that can be used for comparative biology and medical research.

Step-by-step protocol for alternative injury models in newt cardiac regeneration.

Although the heart is one of the most important organs for animal survival, its regenerative capacity varies among animal species. Notably, adult mammals cannot regenerate their hearts after damage such as acute myocardial infarction. In contrast, some vertebrate animals can regenerate the heart throughout their lives. Cross-species comparative studies are important to understand the full picture of cardiac regeneration in vertebrates. Among the animal species able to regenerate the heart, some urodele amphibians, such as newts, possess a remarkable capacity for this process. Standardized methods of inducing cardiac regeneration in the newt are needed as a platform for studies comparing newts and other animal models. The procedures presented here describe amputation and cryo-injury techniques for the induction of cardiac regeneration in Pleurodeles waltl, an emerging model newt species. Both procedures consist of simplified steps that require no special equipment. We additionally show some examples of the regenerative process obtained using these procedures. This protocol has been developed for P. waltl. However, these methods are also expected to be applicable to other newt and salamander species, facilitating comparative research with other model animals.

Exploring the neurobiology of Merge at a basic level: insights from a novel artificial grammar paradigm.

Human language allows us to generate an infinite number of linguistic expressions. It's proposed that this competence is based on a binary syntactic operation, Merge, combining two elements to form a new constituent. An increasing number of recent studies have shifted from complex syntactic structures to two-word constructions to investigate the neural representation of this operation at the most basic level. This fMRI study aimed to develop a highly flexible artificial grammar paradigm for testing the neurobiology of human syntax at a basic level. During scanning, participants had to apply abstract syntactic rules to assess whether a given two-word artificial phrase could be further merged with a third word. To control for lower-level template-matching and working memory strategies, an additional non-mergeable word-list task was set up. Behavioral data indicated that participants complied with the experiment. Whole brain and region of interest (ROI) analyses were performed under the contrast of "structure > word-list." Whole brain analysis confirmed significant involvement of the posterior inferior frontal gyrus [pIFG, corresponding to Brodmann area (BA) 44]. Furthermore, both the signal intensity in Broca's area and the behavioral performance showed significant correlations with natural language performance in the same participants. ROI analysis within the language atlas and anatomically defined Broca's area revealed that only the pIFG was reliably activated. Taken together, these results support the notion that Broca's area, particularly BA 44, works as a combinatorial engine where words are merged together according to syntactic information. Furthermore, this study suggests that the present artificial grammar may serve as promising material for investigating the neurobiological basis of syntax, fostering future cross-species studies.