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In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews.

Dengue, a rapidly spreading mosquito-borne human viral disease caused by dengue virus (DENV), is a public health concern in tropical and subtropical areas due to its expanding geographical range. DENV can cause a wide spectrum of illnesses in humans, ranging from asymptomatic infection or mild dengue fever (DF) to life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is caused by four DENV serotypes; however, dengue pathogenesis is complex and poorly understood. Establishing a useful animal model that can exhibit dengue-fever-like signs similar to those in humans is essential to improve our understanding of the host response and pathogenesis of DENV. Although several animal models, including mouse models, non-human primate models, and a recently reported tree shrew model, have been investigated for DENV infection, animal models with clinical signs that are similar to those of DF in humans have not yet been established. Although animal models are essential for understanding the pathogenesis of DENV infection and for drug and vaccine development, each animal model has its own strengths and limitations. Therefore, in this review, we provide a recent overview of animal models for DENV infection and pathogenesis, focusing on studies of the antibody-dependent enhancement (ADE) effect in animal models.

In vivo images of human cone photoreceptors have been shown to vary in their reflectance both spatially and temporally. While it is generally accepted that the unique anatomy and physiology of the photoreceptors themselves drives this behavior, the exact mechanisms have not been fully elucidated as most studies on these phenomena have been limited to the human retina. Unlike humans, animal models offer the ability to experimentally manipulate the retina and perform direct in vivo and ex vivo comparisons. The thirteen-lined ground squirrel and northern tree shrew are two emerging animal models being used in vision research. Both models feature cone-dominant retinas, overcoming a key limitation of traditional rodent models. Additionally, each possesses unique but well-documented anatomical differences in cone structure compared to human cones, which can be leveraged to further constrain theoretical models of light propagation within photoreceptors. Here we sought to characterize the spatial and temporal reflectance behavior of cones in these species. Adaptive optics scanning light ophthalmoscopy (AOSLO) was used to non-invasively image the photoreceptors of both species at 5 to 10 min intervals over the span of 18 to 25 min. The reflectance of individual cone photoreceptors was measured over time, and images at individual time points were used to assess the variability of cone reflectance across the cone mosaic. Variability in spatial and temporal photoreceptor reflectance was observed in both species, with similar behavior to that seen in human AOSLO images. Despite the unique cone structure in these animals, these data suggest a common origin of photoreceptor reflectance behavior across species. Such data may help constrain models of the cellular origins of photoreceptor reflectance signals. These animal models provide an experimental platform to further explore the morphological origins of light capture and propagation.

Preconditioning by repeated cyclic loads is routinely used in ex vivo mechanical testing of soft biological tissues. The goal of preconditioning is to achieve a steady and repeatable mechanical response and to measure material properties that are representative of the in vivo condition. Preconditioning protocols vary across studies, and their effect on the viscoelastic response of tested soft tissue is typically not reported or analyzed. We propose a methodology to systematically analyze the preconditioning process with application to inflation testing. We investigated the effect of preconditioning on the viscoelastic inflation response of tree shrew posterior sclera using two preconditioning protocols: (i) continuous cyclic loading-unloading without rest and (ii) cyclic loading-unloading with 15-min rest between cycles. Posterior scleral surface strain was measured using three-dimensional Digital Image Correlation (3D-DIC). We used five variables of characterizing features of the stress-strain loop curve to compare the two preconditioning protocols. Our results showed protocol-dependent differences in the tissue response during preconditioning and at the preconditioned state. Incorporating a resting time between preconditioning cycles significantly decreased the number of cycles (10.5 ± 2.9 cycles vs. 3.1 ± 0.5 cycles, p Statement of significance Although applying a preconditioning protocol by repeated cyclic loads is common practice in ex vivo mechanical characterization of soft tissues, the tissue response is typically not reported or analyzed, and the protocol’s potential effect on the response remains unclear. This is partially caused by lack of a standardized methodology to precondition soft tissues. We present the first systematic analysis of two representative preconditioning protocols used during inflation testing in ocular biomechanics. Our results show protocol-dependent differences in the viscoelastic response during the preconditioning process and at the preconditioned state. Consequently, the analysis of the preconditioning response represents an essential part of mechanical testing and a prerequisite to properly characterize the tissue viscoelastic response. The effect of preconditioning on the preconditioned state response must be considered when comparing results across studies with different preconditioning protocols.

The putamen (Put) is necessary for habitual actions, while the nucleus caudate (Cd) is critical for goal-directed actions. However, compared with the natural reward (such as sucrose)-seeking habit, how drug-related dysfunction or imbalance between the Put and Cd is involved in cocaine-seeking habit, which is not easy to bias behavior to goal-directed actions, is absent. Therefore, in our present study, in comparison with sucrose-habitual behavior, we evaluated the distinctive changes of the two subtypes of dopamine (DA) receptors (D1R and D2R) in cocaine-seeking habitual behavior animals. Moreover, the adaptive changes of Cav1.2 and Cav1.3, as prime downstream targets of D1R and D2R respectively, were also assessed. Our results showed that a similar percentage of the animals exhibited habitual seeking behavior after cocaine or sucrose variable-interval self-administration (SA) training in tree shrews. In addition, compared with animals with non-habitual behavior, animals with cocaine habitual behavior showed higher D1Rs and Cav1.2 expression in the Put accompanied with lower D2Rs and Cav1.3 expression in the Cd. However, after sucrose SA training, animals with habitual behavior only showed lower membrane expression of D2R in the Put than animals with non-habitual behavior. These results suggested that the upregulation of D1Rs-Cav1.2 signaling may lead to hyper-excitability of the Put, and the inactivation of D2Rs-Cav1.3 signaling may result in depressed activity in the Cd. This imbalance function between the Put and Cd, which causes an inability to shift between habits and goal-directed actions, may underlie the compulsive addiction habit.

Tree shrews (Tupaia spp.) have been used in neuroscience research since the 1960s due to their evolutionary proximity to primates. The use of and interest in this animal model have recently increased, in part due to the adaptation of modern neuroscience tools in this species. These tools include quantitative behavioral assays, calcium imaging, optogenetics and transgenics. To facilitate the exchange and development of these new technologies and associated research findings, we organized the inaugural “Tree Shrew Users Meeting” which was held online due to the COVID-19 pandemic. Here, we review this meeting and discuss the history of tree shrews as an animal model in neuroscience research and summarize the current themes being investigated using this animal, as well as future directions.

The Chinese tree shrew (Tupaia belangeri chinensis) is emerging as an important experimental animal in multiple fields of biomedical research. Comprehensive reference genome annotation for both mRNA and long non-coding RNA (lncRNA) is crucial for developing animal models using this species. In the current study, we collected a total of 234 high-quality RNA sequencing (RNA-seq) datasets and two long-read isoform sequencing (ISO-seq) datasets and improved the annotation of our previously assembled high-quality chromosome-level tree shrew genome. We obtained a total of 3 514 newly annotated coding genes and 50 576 lncRNA genes. We also characterized the tissue-specific expression patterns and alternative splicing patterns of mRNAs and lncRNAs and mapped the orthologous relationships among 11 mammalian species using the current annotated genome. We identified 144 tree shrew-specific gene families, including interleukin 6 (IL6) and STT3 oligosaccharyltransferase complex catalytic subunit B (STT3B), which underwent significant changes in size. Comparison of the overall expression patterns in tissues and pathways across four species (human, rhesus monkey, tree shrew, and mouse) indicated that tree shrews are more similar to primates than to mice at the tissue-transcriptome level. Notably, the newly annotated purine rich element binding protein A (PURA) gene and the STT3B gene family showed dysregulation upon viral infection. The updated version of the tree shrew genome annotation (KIZ version 3: TS_3.0) is available at http://www.treeshrewdb.org and provides an essential reference for basic and biomedical studies using tree shrew animal models.

In post-natal developing eyes a feedback mechanism uses optical cues to regulate axial growth so as to achieve good focus, a process termed emmetropization. However, the optical cues that the feedback mechanism uses have remained unclear. Here we present evidence that a primary visual cue may be the detection of different image statistics by the short-wavelength sensitive (SWS) and long-wavelength sensitive (LWS) cone photoreceptors, caused by longitudinal chromatic aberration (LCA). We use as a model system the northern tree shrew Tupaia belangeri, diurnal cone-dominated dichromatic mammals closely related to primates. We present an optical model in which the SWS and LWS photoreceptors each represent an image at different levels of defocus and different spectral lighting conditions. The model posits that an imbalance between SWS and LWS image statistics directs eye growth towards the point at which these image statistics are in balance. Under spectrally broadband (“white”) lighting, the focus of the eye is driven to a target point approximately in the middle of the visible spectrum, which is emmetropia. Calculations suggest that the SWS cone array, despite the sparse number of SWS cones, can plausibly detect the wavelength-dependent differences in defocus and guide refractive development. The model is consistent with the effects of various narrow-band illuminants on emmetropization in tree shrews. Simulations suggest that common artificial light spectra do not interfere with emmetropization. Simulations also suggest that multi-spectral multi-focal lenses, where the different optical zones of a multifocal lens have different spectral filtering properties, could be an anti-myopia intervention.

The metabolic switch hypothesis refers to an ability to adjust metabolic rate. It plays a key role in animals adapted to periods of food shortage, enabling them to “switch down” their resting metabolic rate and to survive and maintain their weight indefinitely on limited rations. The present study investigates the energy strategies of a small mammal in response to food shortages as a function of food restriction, metabolic rate and ambient temperature. We subjected tree shrews (Tupaia belangeri) to food restriction and measured body mass, survival rate, resting metabolic rate, non-shivering thermogenesis and cytochrome c oxidase activity of brown adipose tissue. Cold-exposed animals restricted to 80% of ad libitum food intake had significantly increased resting metabolic rate and non-shivering thermogenesis and decreased body mass and survival rates compared with those kept as control group on the same ood restriction level. Animals classified as having a high resting metabolic rate consumed 30.69% more food than those classified as having a low resting metabolic rate, but showed no differences in body mass or survival when restricted to 80% of ad libitum food intake. These results indicate that tree shrews, known for their relatively high metabolic rates, are sensitive to periods of food restriction, which supports the metabolic switch hypothesis. Our findings are also consistent with the prediction that small mammals with food hoarding behaviors, like tree shrews, may have a lower tolerance for food shortages than non-hoarding species.

Obesity involves genetic and environmental factors. The co-expression gene network in relevant tissues in different obesity groups provides an entrance for profiling and identifying associated pathways and genes. We aim to identify the meaningful co-expressed gene network in mRNA extracted from adipose tissues representing different obesity phenotypes in a new tree shrew model. Furthermore, to find the potential drug target based on analyzing the possible pathways and hub genes responsible for obesity. Ten tree shrews were selected from F1 populations and divided into three groups based on their Lee’s index for mRNA sequencing. We identified clusters of highly correlated genes (modules) in differently expressed genes by weighted gene co-expression network analysis. Three modules were firmly correlated with not less than one obesity phenotype (associations ranging from −0.94 to 0.85, P Impact statement We constructed the transcriptomic network in adipose tissue in lean, moderate obesity and severe obesity groups of tree shrew for the first time. Compared to other laboratory animal models, the tree shrew is a prospective laboratory animal that has a closer genetic association with primates than with rodents. It is widely used in biomedical researches. Enrichment analyses revealed several molecular biological processes were involved in the ribosome, lysosome, and ubiquitin-mediated proteolysis process. These results provided insights into new targets for the prevention and therapy of obesity and a novel research model for obesity.

Due to its relatively small size, homology to humans, and susceptibility to human viruses, the tree shrew becomes an ideal alternative animal model for the study of human viral infectious diseases. However, there is still no report for the comprehensive glycan profile of the respiratory tract tissues in tree shrews. In this study, we characterized the structural diversity of N-glycans in the respiratory tract of tree shrews using our well-established TiO2-PGC chip-Q-TOF-MS method. As a result, a total of 219 N-glycans were identified. Moreover, each identified N-glycan was quantitated by a high sensitivity and accurate MRM method, in which 13C-labeled internal standards were used to correct the inherent run-to-run variation in MS detection. Our results showed that the N-glycan composition in the turbinate and lung was significantly different from the soft palate, trachea, and bronchus. Meanwhile, 28 high-level N-glycans in turbinate were speculated to be correlated with the infection of H1N1 virus A/California/04/2009. This study is the first to reveal the comprehensive glycomic profile of the respiratory tract of tree shrews. Our results also help to better understand the role of glycan receptors in human influenza infection and pathogenesis.

During evolution, neural progenitor cells in the subventricular zone (SVZ) have fundamental functions, ranging from brain volume expansion to the generation of a six-layered neocortex. In lissencephalic animal models, such as rodents, the majority of neural progenitors in the SVZ are intermediate progenitor cells (IPCs). Most IPCs in rodents undergo neurogenic division, and only a small portion of them divide a very limited number of times to generate a few neurons. Meanwhile, in gyrencephalic animals, such as primates, IPCs are able to self-renew for up to five successive divisions. However, abundant IPCs with successive proliferative capacity have not been directly observed in nonprimate species. In this study, we examined the development of neural progenitors in the Chinese tree shrew (Tupaia belangeri chinensis), a lissencephalic animal with closer affinity than rodents to primates. We identified an expansion of the SVZ and the presence of outer radial glial (oRG) cells in the neocortex. We also found that IPCs have the capacity to self-amplify multiple times and therefore serve as major proliferative progenitors. To our knowledge, our study provides the first direct evidence of abundant IPCs with proliferative potential in a nonprimate species, further supporting the key role of IPCs in brain expansion.

Background: Umbilical cord mesenchymal stem cell transplantation can treat metabolic syndrome, but the tracing of cells in the body after transplantation has always been a problem. Tree shrew umbilical cord mesenchymal stem cells were labeled with the dark red fluorescent dye DIR and a metabolic syndrome model in tree shrew was generated. The migration, distribution, colonization and survival of the cells were observed. Methods: Tree shrew umbilical cord mesenchymal stem cells were labeled with the dark red fluorescent dye DIR. Three days after the tree shrew model was generated, the pancreas, kidney and liver were placed in a small animal live imager to observe the distribution of the labeled cells. Result: The labeled cells showed deep red fluorescence in the live imager. After treatment with the transplanted cells, dark red fluorescent signals were observed in the liver, kidney and pancreas of the tree shrews but not in the untreated group and no dark red fluorescent signal was observed in the cell distribution.

Systematic classification and determination of various cells in normal peripheral blood of artificially feeding Tupaia belangeri chinensis of different ages and genders and evaluation of the effectiveness of an automatic blood cell classification counter for measuring tree shrew blood cells. Child, young and adult tree shrews (forty for each group) were randomly selected, half male and half female. After the animals were stable, the peripheral blood of each group was collected through the femoral vein, and the morphology of various blood cells of the tree shrew was observed and classified by the manual microscopic counting method and by an automatic blood cell classification counter. The Reference intervals of the normal peripheral blood cell absolute count, cell diameter and white blood cell percentage in tree shrews of different ages and genders has been calculated. White blood cell count and neutrophil relative count increased with age, while lymphocyte relative count decreased. The white blood cell count, neutrophil relative count, and lymphocyte relative count in the child group, as well as lymphocyte relative count in the young group, significantly differed according to gender (P

Tree shrews, possessing higher developed motor function than rats, were more suitable to study neurological behavior after spinal cord injury (SCI). Here, we established a feasible behavioral assessment method to detect the degree of ethology recovery in treeshrew subjected to spinal cord transection (SCT). Tree shrews were divided into normal group, sham group, and SCT group. The tree shrew in sham group was subjected to laminectomy without SCI, while the tree shrews in the SCT group were subjected to a complete SCT in thoracic 10 (T10). A novel neurobehavior assessment scale was established, in which, the behavior index including slow advancement, fast advancement, standing, shaking head, voluntary jump, lateral movement, and tail status, was determined, respectively. Meanwhile, magnetic resonance imaging (MRI) was applied to observe the structure of the spinal cord,and diffusion tensor imaging (DTI)-based white matter mapping was used to show the fibers of the spinal cord. As a result, a marked decrease in locomotor function and consciousness was seen in tree shrews with SCT, and the detection of MRI showed the collapsing of nerve fibers after SCTis completely cut and there is corresponding to the behavior change. Together, the present study provided a novel and feasible method that can be used to assess the neurobehavior in SCT model from tree shrews, which may be useful to the SCI translational study in future preclinic trial. Refereed/Peer-reviewed

Lipids secreted from the meibomian glands form the outermost layer of the tear film and reduce its evaporation. Abnormal changes in the quantities or compositions of lipids present in meibomian gland secretions (meibum) are known to lead to dry eye disease, although the underlying mechanism is not yet well understood. The tree shrew is the non-primate mammal most closely related to humans. To assess the utility of the tree shrew as a model for the study of dry eye disease, we analyzed the lipid profile of tree shrew meibum using an untargeted ESI-MS and MS/MSall shotgun approach. The resulting lipidome shared many similarities with human meibum, while displaying some interesting differences. For example, several classes of lipids, including wax esters, cholesteryl esters, diesters, and (O-acyl)-ω-hydroxy fatty acids, had relatively longer chain lengths in tree shrew meibum. These increases in length may promote more effective reduction of tear evaporation in the tree shrew, which likely underlies the much longer blinking interval of this mammal. Our results suggest that the tree shrew could be an effective model for the study of dry eye.

Avian-origin influenza viruses like H5N1 and H7N9 often cause severe symptoms with high mortality in humans. Animal models are useful for clarification of the mechanisms of pathogenicity of these infections. In this study, to expand the potential utility of the Northern tree shrew (Tupaia belangeri) for influenza virus infection, we assessed the pathogenicity of H5N1 and H7N9 avian influenza viruses in tupaia. Infectious virus was detected continuously from nasal, oral, tracheal, and conjunctival swab samples in the animals infected with these viruses. H5N1 influenza virus infection of tupaia caused severe diffuse pneumonia with fever and weight loss. In contrast, H7N9 influenza virus infection caused focal pneumonia. The severity of pneumonia was correlated with proinflammatory cytokine transcript levels. These results indicated that tupaia can be another suitable animal model for avian influenza virus research.

Angiotensin I-converting enzyme 2 (ACE2), type II transmembrane serine protease 2 and 4 (TMPRSS2 and TMPRSS4) are important receptors for SARS-CoV-2 infection. In this study, the full-length tree shrewACE2 gene was cloned and sequenced, and its biological information was analyzed. The expression levels of ACE2, TMPRSS2 and TMPRSS4 in various tissues or organs of the tree shrew were detected. The results showed that the full-length ACE2 gene in tree shrews was 2,786 bp, and its CDS was 2,418 bp, encoding 805 amino acids. Phylogenetic analysis based on the CDS of ACE2 revealed that tree shrews were more similar to rabbits (85.93%) and humans (85.47%) but far from mice (82.81%) and rats (82.58%). In silico analysis according to the binding site of SARS-CoV-2 with the ACE2 receptor of different species predicted that tree shrews had potential SARS-CoV-2 infection possibility, which was similar to that of rabbits, cats and dogs but significantly higher than that of mice and rats. In addition, various tissues or organs of tree shrews expressed ACE2, TMPRSS2 and TMPRSS4. Among them, the kidney most highly expressed ACE2, followed by the lung and liver. The esophagus, lung, liver, intestine and kidney had relatively high expression levels of TMPRSS2 and TMPRSS4. In general, we reported for the first time the expression of ACE2, TMPRSS2 and TMPRSS4 in various tissues or organs in tree shrews. Our results revealed that tree shrews could be used as a potential animal model to study the mechanism underlying SARS-CoV-2 infection., Graphical abstract

Tree shrew (Tupaia belangeri) is a promising experimental animal in biomedical research, but the equivalent doses of drugs between tree shrew and human and other animals has not been explored, which hinders its further application in a wider scope. The main objective of this article is to provide a method of equivalent dose conversion between tree shrews and other species based on body surface area (BSA). BSA of tree shrews were measured by Image J software, and then the average Km value of tree shrews was figured out based on the body weights and BSA, then the conversion coefficients of equivalent dose among tree shrew and other species of experimental animals were calculated based known data. The Km value of tree shrews was 0.105 ± 0.001. Through BSA conversion, the equivalent dose for tree shrews (D-ts) relative to rats was obtained by formula: D-ts = 1.36 × D-a (rats weighing 200 g as example), and the error was less than 10% when the BW of the tree shrew was 0.09 kg–0.15 kg. The coefficients of equivalent dose transferring from tree shrews to human and other species were calculated in article. These parameters could be used to determine a suitable dosing strategy for tree shrew studies.

Maternal infanticide and cannibalism, whereby a mother killing and consumes her own offspring, occurs in various animal taxa. The ability of the tree shrew (Tupaia belangeri) to kill and consume conspecifics is accepted, but the extent of its occurrence is not fully understood due to difficulty in observation and uneven reporting. Here we discover extra interesting phenomenonand that two tree shrew respectively eating the neonate in two different experiments. This was the first recorded of evidence by dynam

Animal disease models are necessary in medical research, and an appropriate animal model is of great importance for studies about the prevention or treatment of cancer. The most important thing in the selection of animal models is to consider the similarity between animals and humans. The tree shrew (Tupaia belangeri) is a squirrel-like mammal which placed in the order Scandentia. Whole-genome sequencing has revealed that tree shrews are extremely similar to primate and humans than to rodents, with many highly conserved genes, which makes the data from studies that use tree shrews as models more convincing and the research outcomes more easily translatable. In tumor research, tree shrews are often used as animal models for hepatic and mammary cancers. As research has progressed, other types of tree shrew tumor models have been developed and exhibit clinical manifestations similar to those of humans. Combining the advantages of both rodents and primates, the tree shrew is expected to be the most powerful animal model for studying tumors.

Human adenovirus (HAdV) species B can cause severe acute respiratory diseases. However, the researches to combat this infection have been hampered by the lack of an animal model permissive to the virus. Here, we report in vitro and in vivo HAdV species B infections of tree shrews, the closest relative of primates. HAdV-3, -7, -14, and -55 efficiently replicated in primary cell cultures. After intranasal inoculation of tree shrews with HAdV-55, the viral replication in the oropharyngeal region remained high until day 5 post-infection and was still detected until day 12. HAdV-55 in the lung or turbinate bone tissues reached the highest levels between days 3 and 5 post-infection, which indicated viral replication in the upper and lower respiratory tracts. HAdV-55 infection caused severe interstitial pneumonia in the animal. IL-8, IL-10, IL-17A, and IFN-γ expression in the peripheral blood mononuclear cells from infected animals was up-regulated. The pre-vaccination with HAdV-55 cleared the virus faster in the respiratory tract, mitigated lung pathological changes. Finally, HAdV-55 infection was propagated among tree shrews. Our study demonstrated that the tree shrew is a permissive animal model for HAdV species B infection and may serve as a valuable platform for testing multiple anti-viral treatments.

Pathological neovascularization in choroid, a leading cause of blindness, is a characteristic of many fundus diseases, such as diabetic retinopathy and age-related macular degeneration. The present study aimed to elucidate the key signaling pathways in choroidal neovascularization (CNV) by analyzing the mRNA profiles of choroid and retina in tree shrews with CNV. We induced choroidal angiogenesis by laser photocoagulation in 15 tree shrews and obtained mRNA profiles of their choroids and retinas by high-throughput transcriptome sequencing. Hierarchical cluster analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, hematoxylin and eosin (HE) staining, CD31 immunohistochemistry (IHC), and reverse transcription quantitative PCR (RT-qPCR) were performed. After laser photocoagulation, we obtained a total of 350 differentially expressed genes (DEGs) in the choroid, including 59 genes in Module-FASN (“ME-FASN”) module and 28 genes in Module-RPL (“ME-RPL”) module. A total of 69 DEGs in retina, including 20 genes in Module-SLC (“ME-SLC”) module. Bioinformatics analysis demonstrated that DEGs in choroid were mainly involved in membrane transport; DEGs in “ME-RPL” were prominent in pathways associated with IgA production, antigen presentation, and cell adhesion molecules (CAMs) signaling. DEGs in “ME-FASN” were involved in fatty acid metabolism and PPAR signaling pathway, while DEGs in “ME-SLC” were involved in GABAergic synapse, neuroactive life receptor interaction, cholinergic synapse, and retrograde endocannabinoid signaling pathway. PPI network analysis demonstrated that the ribosomal protein family genes (RPL31, RPL7, RPL26L1, and RPL19) are key factors of “ME-RPL,” acyl-CoA superfamily genes (ACACA, ACAT1, ACAA2, and ACACB) and FASN are key factors of “ME-FASN” and superfamily of solid carrier genes (SLC17A6, SLC32A1, SLC12A5, and SLC6A1) and complement genes (C4A, C3, and C2) are key factors of “ME-SLC.” In conclusion, the present study discovered the important signal transductions (fatty acid metabolic pathway and CAMs signaling) and genes (ribosomal protein family and the complement system) in tree shrew CNV. We consider that our findings hold implications in unraveling molecular mechanisms that underlie occurrence and development of CNV.

Understanding human sleep requires appropriate animal models. Sleep has been extensively studied in rodents, although rodent sleep differs substantially from human sleep. Here we investigate sleep in tree shrews, small diurnal mammals phylogenetically close to primates, and compare it to sleep in rats and humans using electrophysiological recordings from frontal cortex of each species. Tree shrews exhibited consolidated sleep, with a sleep bout duration parameter, τ, uncharacteristically high for a small mammal, and differing substantially from the sleep of rodents that is often punctuated by wakefulness. Two NREM sleep stages were observed in tree shrews: NREM, characterized by high delta waves and spindles, and an intermediate stage (IS-NREM) occurring on NREM to REM transitions and consisting of intermediate delta waves with concomitant theta-alpha activity. While IS-NREM activity was reliable in tree shrews, we could also detect it in human EEG data, on a subset of transitions. Finally, coupling events between sleep spindles and slow waves clustered near the beginning of the sleep period in tree shrews, paralleling humans, whereas they were more evenly distributed in rats. Our results suggest considerable homology of sleep structure between humans and tree shrews despite the large difference in body mass between these species., Dimanico et al investigated sleep in tree shrews using electrophysiological recordings and compared it to equivalent read-outs in rats and humans. They reported that there was considerable homology of sleep structure between humans and tree shrews despite the difference in body mass between these species.

Background The domestication of tree shrews represents an important advance in the development of standardized laboratory animals. Little is known regarding the miRNA changes that accompany the transformation of wild tree shrews into domestic tree shrews. Results By performing miRNA-seq analysis on wild and domestic tree shrews, we identified 2410 miRNAs and 30 differentially expressed miRNAs in the hippocampus during tree shrew domestication. A KEGG analysis of the differentially expressed genes showed that the differentially expressed miRNAs were associated with ECM-receptor interaction, the phosphatidylinositol signaling system, protein digestion and absorption, inositol phosphate metabolism, lysine degradation, fatty acid degradation and focal adhesion. Most of these pathways could be classified under environmental information processing, organismal systems and metabolism. The miRNAs exclusively expressed in wild and tame tree shrews GO enriched in terms of divergent functions. The miRNA-mRNA networks suggested that novel-m1388-5p and novel-m0746-5p might play regulatory roles in domestication of tree shrews. Real–time RT-PCR analysis was employed to verify the presence of these miRNAs. Conclusion We identified a number of candidate miRNA-regulated domestication genes that may represent targets for selection during the domestication of tree shrews.

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and Coronavirus disease (COVID-19) were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature particularly in female animals. Low levels of virus shedding and replication in tissues occurred in all three age groups. Notably, young tree shrews (6 months to 12 months) showed virus shedding at the earlier stage of infection than adult (2 years to 4 years) and old (5 years to 7 years) animals that had longer duration of virus shedding comparatively. Histopathological examine revealed that pulmonary abnormalities were the main changes but mild although slight lesions were also observed in other tissues. In summary, tree shrew is less susceptible to SARS-CoV-2 infection compared with the reported animal models and may not be a suitable animal for COVID-19 related researches. However, tree shrew may be a potential intermediate host of SARS-CoV-2 as an asymptomatic carrier.

The recent emerged SARS-CoV-2 may first transmit to intermediate animal host from bats before the spread to humans. The receptor recognition of ACE2 protein by SARS-CoVs or bat-originated coronaviruses is one of the most important determinant factors for the cross-species transmission and human-to-human transmission. To explore the hypothesis of possible intermediate animal host, we employed molecular dynamics simulation and free energy calculation to examine the binding of bat coronavirus with ACE2 proteins of 47 representing animal species collected from public databases. Our results suggest that intermediate animal host may exist for the zoonotic transmission of SARS-CoV-2. Furthermore, we found that tree shrew and ferret may be two putative intermediate hosts for the zoonotic spread of SARS-CoV-2. Collectively, the continuous surveillance of pneumonia in human and suspicious animal hosts are crucial to control the zoonotic transmission events caused by SARS-CoV-2.

Adult male tree shrews vigorously defend against intruding male conspecifics. However, the characteristics of social behavior have not been entirely explored in these males. In this study, male wild-type tree shrews (Tupaia belangeri chinensis) and C57BL/6J mice were first allowed to familiarize themselves with an open-field apparatus. The tree shrews exhibited a short duration of movement (moving) in the novel environment, whereas the mice exhibited a long duration of movement. In the 30 min social preference-avoidance test, target animals significantly decreased the time spent by the experimental tree shrews in the social interaction (SI) zone, whereas experimental male mice exhibited the opposite. In addition, experimental tree shrews displayed a significantly longer latency to enter the SI zone in the second 15 min session (target-present) than in the first 15 min session (target-absent), which was different from that found in mice. Distinct behavioral patterns in response to a conspecific male were also observed in male tree shrews and mice in the first, second, and third 5 min periods. Thus, social behaviors in tree shrews and mice appeared to be time dependent. In summary, our study provides results of a modified social preference-avoidance test designed for the assessment of social behavior in tree shrews. Our findings demonstrate the existence of social avoidance behavior in male tree shrews and prosocial behavior in male mice toward unfamiliar conspecifics. The tree shrew may be a new animal model, which differs from mice, for the study of social avoidance and prosocial behaviors.

Backgroud Current understanding of injury and regeneration of islet β‐cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of primates, and has been widely used in animal experimentation. However, there are few reports on islet cell composition and regeneration of β‐cells in tree shrews. Methods In this study, we examined the changes in islet cell composition and regeneration of β‐cells after streptozotocin (STZ) treatment in tree shrews compared with Sprague‐Dawley rats. Injury and regeneration of islet β‐cells were observed using hematoxylin and eosin (HE) staining and immunohistochemical staining for insulin, glucagon, somatostatin and PDX‐1. Results Our data showed that in rats islet injury was most obvious on day 3 after injection, and islet morphologies were significantly restored by day 21. Regeneration of islet β‐cells was very pronounced in rats, and mainly involved regeneration of centro‐acinar cells and transformation of extra‐islet ductal cells. In tree shrews, the regeneration of islet β‐cells was not as significant. On days 3 and 7, only scattered regenerated cells were observed in the remaining islets. Further, no regeneration of centro‐acinar cells was observed. Conclusion The results suggest that the repair mechanism of islet β‐cells in tree shrews is similar to that of humans.

Purpose Rodent and primate models are commonly used in glaucoma research; however, both have their limitations. The tree shrew (Tupaia belangeri) is an emerging animal model for glaucoma research owing in part to having a human-like optic nerve head anatomy, specifically a collagenous load-bearing lamina. However, the anterior segment anatomy and function have not been extensively studied in the tree shrew. Thus, the purpose of this study was to provide the first detailed examination of the anterior segment anatomy and aqueous outflow facility in the tree shrew. Methods Aqueous outflow dynamics were measured in five ostensibly normal eyes from three tree shrews using the iPerfusion system over a range of pressures. Gross histological assessment and immunohistochemistry were performed to characterize anterior segment anatomy and to localize several key molecules related to aqueous outflow. Results Anterior segment anatomy in tree shrews is similar to humans, demonstrating a scleral spur, a multilayered trabecular meshwork and a circular Schlemm's canal with a single lumen. Average outflow facility was 0.193 µL/min/mm Hg (95% confidence interval, 0.153–0.244), and was stable over time. Outflow facility was more similar between contralateral eyes (approximately 5% average difference) than between eyes of different animals. No significant dependence of outflow facility on time or pressure was detected (pressure–flow nonlinearity parameter of 0.01 (95% % confidence interval, −0.29 to 0.31 CI µL/min/mm Hg). Conclusions These studies lend support to the usefulness of the tree shrew as a novel animal model in anterior segment glaucoma and pharmacology research. The tree shrew's cost, load-bearing collagenous lamina cribrosa, and lack of washout or anterior chamber deepening provides a distinct experimental and anatomic advantage over the current rodent and nonhuman primate models used for translational research.

Background Tree shrews are proposed as an alternative animal model to nonhuman primates due to their close affinity to primates. Neuroimaging techniques are widely used to study brain functions and structures of humans and animals. However, tree shrews are rarely applied in neuroimaging field partly due to the lack of available species specific analysis methods. New method In this study, 10 PET/CT and 10 MRI images of tree shrew brain were used to construct PET and MRI templates; based on histological atlas we reconstructed a three-dimensional digital atlas with 628 structures delineated; then the digital atlas and templates were aligned into a stereotaxic space. Finally, we integrated the digital atlas and templates into a toolbox for tree shrew brain spatial normalization, statistical analysis and results localization. Results We validated the feasibility of the toolbox by simulated data with lesions in laterodorsal thalamic nucleus (LD). The lesion volumes of simulated PET and MRI images were ( 12.97 ± 3.91 ) mm3 and ( 7.04 ± 0.84 ) mm3. Statistical results at p Comparison with existing method(s) To our knowledge, we report the first PET template and digital atlas of tree shrew brain. Compared to the existing MRI templates, our MRI template was aligned into stereotaxic space. And the toolbox is the first software dedicated for tree shrew brain analysis. Conclusions The templates and digital atlas of tree shrew brain, as well as the toolbox, facilitate the use of tree shrews in neuroimaging field.

// Yaohui Tong 1, 2, * , Junjun Hao 3, * , Qiu Tu 2, 4, * , Hualin Yu 5 , Lanzhen Yan 2, 6 , Yuan Li 2, 4, 7 , Longbao Lv 6 , Fei Wang 5 , Antonio Iavarone 8 , Xudong Zhao 2, 6 1 School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China 2 Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China 3 State Key Lab of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 4 Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China 5 Department of Neurological Surgery, The First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, 650032, China 6 Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, Yunnan 650223, China 7 Kunming University of Science and Technology, Kunming, Yunnan, 650500, China 8 Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA * These authors contributed equally to this work Correspondence to: Xudong Zhao, email: zhaoxudong@mail.kiz.ac.cn Keywords: glioblastoma, animal model, tree shrew, P53 Received: June 03, 2016 Accepted: January 16, 2017 Published: February 09, 2017 ABSTRACT Tupaia belangeri (tree shrew), an animal species whose genome has significantly higher similarity to primates than rodents, has been used in biomedical research. To generate animal models that reproduce the human tumors more faithfully than rodents, we present the first report of a cancer model mimicking human tumor genetics in tree shrew. By engineering a lentiviral system for the transduction of mutant H-Ras and a shRNA against tree shrew p53, we successfully generated malignant glioma in tree shrew. The tree shrew glioma exhibited aggressive behavior and a relatively short latency, and markedly reduced animal survival. Remarkably, the biological features of human high-grade glioma (necrosis, microvascular proliferation, pseudopalisading) were all present in tree shrew glioma. Furthermore, genetic analysis of tree shrew glioma revealed that the tumors were clustered within the mesenchymal subgroup of human glioblastoma multiforme. Compared with the corresponding mouse glioma, tree shrew gliomas were markedly more similar to human glioblastoma at gene expression profile. The tree shrew glioma model provides colleagues working in the field of gliomas and cancer in general with a more accurate animal model.

Background Tree shrew is a novel laboratory animal with specific characters for human disease researches in recent years. However, little is known about its characteristics of gut microbial community and intestinal commensal bacteria. In this study, 16S rRNA sequencing method was used to illustrate the gut microbiota structure and commensal Enterobacteriaceae bacteria were isolated to demonstrate their features. Results The results showed Epsilonbacteraeota (30%), Proteobacteria (25%), Firmicutes (19%), Fusobacteria (13%), and Bacteroidetes (8%) were the most abundant phyla in the gut of tree shrew. Campylobacteria, Campylobacterales, Helicobacteraceae and Helicobacter were the predominant abundance for class, order, family and genus levels respectively. The alpha diversity analysis showed statistical significance (P

Tree shrews are most closely related to the primates and so possess a number of advantages in experimental studies; they have been used as an animal model in bacterial and virus infection, cancer, endocrine system disease, and certain nervous system diseases. Their olfactory ensheathing cells (OECs) are able to release several cytokines to promote neuronal survival, regeneration and remyelination. The present study used western blot analysis to identify antibody specificity in protein extracts from whole tree shrew brains to identify the specificity of p75 nerve growth factor receptor (NGFR) derived from rabbits (75 kDa). OECs were cultured and isolated, then stained and identified using the antibodies for p75NGFR. To investigate the capacity of OECs to express cytokines and growth factors, microarray technology was used, and the analysis revealed that OECs were able to express 9,821 genes. Of these genes, 44 genes were from the neurotrophic factor family, which may indicate their potential in transplantation in vivo. The present study considered the function of OECs as revealed by other studies, and may contribute to future research.

Spontaneous retinal venous pulsations (SRVPs), pulsations of branches of the central retinal vein, are affected by intraocular pressure (IOP) and intracranial pressure (ICP) and thus convey potentially-useful information about ICP. However, the exact relationship between SRVPs, IOP, and ICP is unknown. It is not easily feasible to study this relationship in humans, necessitating the use of an animal model. We here propose tree shrews as a suitable animal model to study the complex relationship between SRVPs, IOP, and ICP. Tree shrew SRVP incidence was determined in a population of animals. Following validation of a modified IOP control system to accurately and quickly control IOP, IOP and/or ICP were manipulated in two tree shrews with SRVPs and the effects on SRVP properties were quantified. SRVPs were present in 75% of tree shrews at physiologic IOP and ICP. Altering IOP or ICP produced changes in tree shrew SRVP properties; specifically, increasing IOP caused SRVP amplitude to increase, while increasing ICP caused SRVP amplitude to decrease. In addition, a higher IOP was necessary to generate SRVPs at a higher ICP than at a lower ICP. SRVPs occur with a similar incidence in tree shrews as in humans, and tree shrew SRVPs are affected by changes in IOP and ICP in a manner qualitatively similar to that reported in humans. In view of anatomic similarities, tree shrews are a promising animal model system to further study the complex relationship between SRVPs, IOP, and ICP.

Background Papillomaviruses (PVs) and polyomaviruses (PyVs) infect diverse vertebrates including human and cause a broad spectrum of outcomes from asymptomatic infection to severe disease. There has been no PV and only one PyV detected in tree shrews, though the genomic properties of tree shrews are highly similar to those of the primates. Methods Swab and organ samples of tree shrews collected in the Yunnan Province of China, were tested by viral metagenomic analysis and random PCR to detect the presence of PVs and PyVs. By PCR amplification using specific primers, cloning, sequencing and assembling, genomes of two PVs and one PyV were identified in the samples. Results Two novel PVs and a novel PyV, named tree shrew papillomavirus 1 and 2 (TbelPV1 and TbelPV2) and polyomavirus 1 (TbelPyV1) were characterized in the Chinese tree shrew (Tupaia belangeri chinensis). The genomes of TbelPV1, TbelPV2, and TbelPyV1 are 7410 bp, 7526 bp, and 4982 bp in size, respectively. The TbelPV1 genome contains 7 putative open-reading frames (ORFs) coding for viral proteins E1, E2, E4, E6, E7, L1, and L2; the TbelPV2 genome contains 6 ORFs coding for viral proteins E1, E2, E6, E7, L1, and L2; and the TbelPyV1 genome codes for the typical small and large T antigens of PyV, as well as the VP1, VP2, and VP3 capsid proteins. Genomic comparison and phylogenetic analysis indicated that TbelPV1 and TbelPV2 represented 2 novel PV genera of Papillomaviridae, and TbelPyV1 represented a new species of genus Alphapolyomavirus. Our epidemiologic study indicated that TbelPV1 and TbelPV2 were both detected in oral swabs, while TbelPyV1 was detected in oral swabs and spleens. Conclusion Two novel PVs (TbelPV1 and TbelPV2) and a novel PyV (TbelPyV) were discovered in tree shrews and their genomes were characterized. TbelPV1, TbelPV2, and TbelPyV1 have the highest similarity to Human papillomavirus type 63, Ursus maritimus papillomavirus 1, and Human polyomavirus 9, respectively. TbelPV1 and TbelPV2 only showed oral tropism, while TbelPyV1 showed oral and spleen tropism. Electronic supplementary material The online version of this article (10.1186/s12985-019-1141-9) contains supplementary material, which is available to authorized users.

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused the public health emergency. Recently, we have proved a novel small animal tree shrew was susceptive to ZIKV infection and presented the most common rash symptoms as ZIKV patients. Here we further cultured the primary cells from different tissues of this animal to determine the tissue tropism of ZIKV infection in vitro. The results showed that the primary cells from tree shrew kidney, lung, liver, skin and aorta were permissive to ZIKV infection and could support viral replication by the detection of viral specific RNA intra- and extra-cells. In comparing, the skin fibroblast and vascular endothelial cells were highly permissive to ZIKV infection with high releasing of active virus particles in supernatants proved by its infectivity in established neonatal mouse model. The expressions of ZIKV envelop and nonstructural protein-1, and the effects and strong immune response of primary tree shrew cells were also detected followed by ZIKV infection. These findings provide powerful in vitro cell-level evidence to support tree shrew as animal model of ZIKV infection and may help to explain the rash manifestations in vivo.

Osteoporosis (OP) treatment has always been challenging for elderly menopausal females. An animal model with a closer genetic association to human OP is essential for treatment research. Given its close genetic association to primates, the tree shrew is a suitable candidate for meeting the requirements for such an animal model. In the present study, a tree shrew OP model induced by ovariectomy (OVX), was established. Evaluation by multiple analysis methods, including blood biochemical indicators, uterus coefficients, micro-computed tomography analysis, histochemical analysis and scanning electron microscopic observation indicated that OVX was an appropriate method to establish the OP model in tree shrews. In addition, the biomolecular characteristics of OVX-induced osteoporosis were also assessed by transcriptome sequencing and bioinformatics analysis. The present study provides the methods used to confirm the successful establishment of the OP model in tree shrew, and suggests that the OP model is appropriate for human OP research.

Purpose To evaluate the effect of scleral crosslinking (SXL) on slowing experimental progressive myopia in tree shrew eyes using sub-Tenon's injections of genipin (GEN) at different concentrations and number of injections. Methods Three or five sub-Tenon's injections of GEN at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day starting at 18 days of visual experience. Form deprivation (FD) myopia was induced in the injected eye between 24 and 35 days of visual experience; the fellow eye served as control. Tree shrews were randomly assigned to five experimental groups: FD (n = 8); FD + 5 × sham injections (n = 6); FD + 3 × GEN injections at 10 mM (n = 6) and 20 mM (n = 6); and FD + 5 × GEN injections at 20 mM (n = 6). Refractive state and ocular dimensions were measured daily. Results Compared with the FD group, the sham-injected group showed a transient effect on slowing vitreous chamber elongation. With increasing GEN dose, SXL had an increasing treatment effect on slowing vitreous chamber elongation and myopia progression. In addition, SXL led to a dose-dependent shortening of the aqueous chamber depth and corneal thickening. Lens thickening was observed in the group with the highest concentration. Conclusions We have shown that SXL using GEN can slow axial elongation and myopia progression in tree shrews. The extent of this treatment effect was dose dependent. Several unexpected effects were observed (corneal thickening, decrease of the anterior chamber depth, and lens thickening), which require further optimization of the GEN delivery approach before clinical consideration. Translational relevance The results of this preclinical study suggest that scleral crosslinking using genipin can slow myopia progression.

The Chinese tree shrew (Tupaia belangeri chinensis), a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew (Tupaia belangeri) aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database (www.treeshrewdb.org) has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV) infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.

The tree shrew (Tupaia belangeri) is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.

The sclera uses unknown mechanisms to match the eye’s axial length to its optics during development, producing eyes with good focus (emmetropia). A myopic eye is too long for its own optics. We propose a multi-scale computational model to simulate eye development based on the assumption that scleral growth is controlled by genetic factors while scleral remodeling is driven by genetic factors and the eye’s refractive error. We define growth as a mechanism that changes the tissue volume and mass while remodeling involves internal micro-deformations that are volume-preserving at the macro-scale. The model was fitted against longitudinal refractive measurements in tree shrews of different ages and exposed to three different visual conditions: (i) normal development; (ii) negative lens wear to induce myopia; and (iii) recovery from myopia by removing the negative lens. The model was able to replicate the age- and vision-dependent response of the tree shrew experiments. Scleral growth ceased at younger age than scleral remodeling. The remodeling rate decreased as the eye emmetropized but increased at any age when a negative lens was put on. The predictive power of the model was investigated by calculating the susceptibility to scleral remodeling and the response to form deprivation myopia in tree shrews. Both predictions were in good agreement with experimental data that were not used to fit the model. We propose the first model that distinguishes scleral growth from remodeling. The good agreement of our results with experimental data supports the notion that scleral growth and scleral remodeling are two independently controlled mechanisms during eye development.

Tree shrews are small mammals now commonly classified in the order of Scandentia, but have relatively closer affinity to primates than rodents. The species has a high brain-to-body mass ratio and relatively well-differentiated neocortex, and thus has been frequently used in neuroscience research, especially for studies on vision and neurological/psychiatric diseases. The available atlases on tree shrew brain provided only limited information on white matter (WM) anatomy. In this study, diffusion tensor imaging (DTI) was used to study the WM anatomy of tree shrew, with the goal to establish an image-based WM atlas. DTI and T2-weighted anatomical images were acquired in vivo and from fixed brain samples. Deterministic tractography was used for three-dimensional reconstruction and rendering of major WM tracts. Myelin and neurofilaments staining were used to study the microstructural properties of certain WM tracts. Taking into account prior knowledge on tree shrew neuroanatomy, tractography results, and comparisons to the homologous structures in rodents and primates, an image-based WM atlas of tree shrew brain was constructed, which is available to research community upon request.

Circuits in the visual cortex integrate the information derived from separate ON (light-responsive) and OFF (dark-responsive) pathways to construct orderly columnar representations of stimulus orientation and visual space. How this transformation is achieved to meet the specific topographic constraints of each representation remains unclear. Here we report several novel features of ON-OFF convergence visualized by mapping the receptive fields of layer 2/3 neurons in the tree shrew (Tupaia belangeri) visual cortex using two-photon imaging of GCaMP6 calcium signals. We show that the spatially separate ON and OFF subfields of simple cells in layer 2/3 exhibit topologically distinct relationships with the maps of visual space and orientation preference. The centres of OFF subfields for neurons in a given region of cortex are confined to a compact region of visual space and display a smooth visuotopic progression. By contrast, the centres of the ON subfields are distributed over a wider region of visual space, display substantial visuotopic scatter, and have an orientation-specific displacement consistent with orientation preference map structure. As a result, cortical columns exhibit an invariant aggregate receptive field structure: an OFF-dominated central region flanked by ON-dominated subfields. This distinct arrangement of ON and OFF inputs enables continuity in the mapping of both orientation and visual space and the generation of a columnar map of absolute spatial phase.

We comprehensively characterize spiking and visual evoked potential (VEP) activity in tree shrew V1 and V2 using Cartesian, hyperbolic, and polar gratings. Neural selectivity to structure of Cartesian gratings was higher than other grating classes in both visual areas. From V1 to V2, structure selectivity of spiking activity increased, whereas corresponding VEP values tended to decrease, suggesting that single-neuron coding of Cartesian grating attributes improved while the cortical columnar organization of these neurons became less precise from V1 to V2. We observed that neurons in V2 generally exhibited similar selectivity for polar and Cartesian gratings, suggesting that structure of polar-like stimuli might be encoded as early as in V2. This hypothesis is supported by the preference shift from V1 to V2 toward polar gratings of higher spatial frequency, consistent with the notion that V2 neurons encode visual scene borders and contours. Neural sensitivity to modulations of polarity of hyperbolic gratings was highest among all grating classes and closely related to the visual receptive field (RF) organization of ON- and OFF-dominated subregions. We show that spatial RF reconstructions depend strongly on grating class, suggesting that intracortical contributions to RF structure are strongest for Cartesian and polar gratings. Hyperbolic gratings tend to recruit least cortical elaboration such that the RF maps are similar to those generated by sparse noise, which most closely approximate feedforward inputs. Our findings complement previous literature in primates, rodents, and carnivores and highlight novel aspects of shape representation and coding occurring in mammalian early visual cortex.

Automatic identification of organism evolution still remains a challenging task, which is especially exiting, when the evolution of human is considered. The main aim of this work is to present a new idea to allow organism evolution analysis using neural networks. Here we show that it is possible to identify evolution of any organisms in a fully automatic way using the designed EvolutionXXI program, which contains implemented neural network. The neural network has been taught using cytochrome b sequences of selected organisms. Then, analyses have been carried out for the various exemplary organisms in order to demonstrate capabilities of the EvolutionXXI program. It is shown that the presented idea allows supporting existing hypotheses, concerning evolutionary relationships between selected organisms, among others, Sirenia and elephants, hippopotami and whales, scorpions and spiders, dolphins and whales. Moreover, primate (including human), tree shrew and yeast evolution has been reconstructed.