Search Results (9)

The wild yak (Bos mutus) is a flagship species on the Qinghai–Tibet Plateau, possessing significant ecological functions and conservation value. Using single-nucleotide polymorphism markers from whole-genome resequencing, we systematically analyzed golden wild yak (n = 37), common wild yak (n = 106), and domestic yak (Bos grunniens) (n = 20) to characterize the population genetic structure and adaptive selection signals in the golden wild yak. Genetic diversity analyses revealed that the golden wild yak had the lowest nucleotide diversity (π = 0.00148) and the highest inbreeding coefficient (F_Hom = 0.043). Population structure analyses integrating principal component analysis, phylogenetic tree, and ancestral component clustering indicated that the golden wild yak formed a relatively independent evolutionary lineage. However, its genetic differentiation from sympatric common wild yak population was limited (fixation index = 0.031). Selective sweep analysis identified a set of candidate positively selected genes in the golden wild yak genome associated with key traits and physiological functions, including coat color (TYRP1), hypoxia adaptation (MYH11, POLQ), reproductive function (SLC9C1, SPAG16, CFAP97D1), and immune response (CASP8, PGGT1B, BIRC6). Overall, our study reveals a distinct genetic background and selection signatures in the golden wild yak and provides genomic insights to inform the conservation and management of the wild yak. Full article

Understanding the change in the habitat distributions and abundance of wildlife in space and time is critical for the conservation of biodiversity and mitigate human–wildlife conflicts (HWCs). Tibetan antelope or chiru (Pantholops hodgsonii), Tibetan gazelle or goa (Procapra picticaudata), Tibetan wild ass or kiang (Equus kiang), and Wild yak (Bos mutus) have been sympatric on the Qinghai–Tibetan plateau (QTP) for numerous generations. However, reviews on the habitat distributions and abundance of these four wild herbivores (WHs), as well as the methods examining the changes in these aspects, are still lacking. Here, we firstly review the distributions and abundance of four major WHs on the QTP across different periods, examining the underlying causes of changes and HWCs. Furthermore, we critically compare three aspects of methods: transect surveys, machine learning (ML), and deep learning (DL) methods of studying WHs. The results show that since the 1990s, the distributions and abundance of WHs have exhibited a trend of initial decline followed by recovery, largely attributed to global climate warming and a decrease in illegal hunting. However, in recent years, the primary challenge has shifted from wildlife protection to balancing the human and wildlife interests within the constraints of limited resources. In the future, we should focus on enhancing the ecological functions of habitats to achieve harmonious coexistence between humans and nature, as well as establishing a scientific compensation mechanism to mitigate human–wildlife conflicts. In order to accurately calculate the changes, we should select appropriate models to analyze the habitats of wildlife based on their specific characteristics and the environmental conditions. Additionally, with the advancement of large models, AI (artificial intelligence) should be utilized for precise and rapid wildlife conservation. The findings of this study also provide guidance and reference for addressing the issues related to wildlife habitats and abundance in other regions globally. Full article

Ungulates are essential for maintaining the health of grassland ecosystems on the Tibetan plateau. Increased livestock grazing has caused competition for food resources, threatening ungulates’ survival. The survival risk of food resources for ungulates can be quantified by the grazing pressure index, which requires accurate grassland carrying capacity. Previous research on the grazing pressure index has rarely taken into account the influence of wild ungulates, mainly due to the lack of precise spatial data on their quantity. In this study, we conducted field investigations to construct high-resolution spatial distributions for the four endemic ungulates on the Tibetan plateau. By factoring in the grazing consumption of these ungulates, we recalculated the grassland carrying capacity to obtain the grazing pressure index, which allowed us to assess the survival risks for each species. The results show: (1) Quantity estimates for Tibetan antelope (Pantholops hodgsonii), Tibetan wild donkey (Equus kiang), Tibetan gazelle (Procapra picticaudata), and wild yak (Bos mutus) of the Tibetan plateau are 24.57 × 10⁴, 17.93 × 10⁴, 7.16 × 10⁴, and 1.88 × 10⁴, respectively; they mainly distributed in the northern and western regions of the Tibetan plateau. (2) The grassland carrying capacity of the Tibetan plateau is 69.98 million sheep units, with ungulate grazing accounting for 5% of forage utilization. Alpine meadow and alpine steppe exhibit the highest grassland carrying capacity. (3) The grazing pressure index on the Tibetan plateau grasslands is 2.23, indicating a heightened grazing pressure in the southern and eastern regions. (4) The habitat survival risk analysis indicates that the high survival risk (the grazing pressure index exceeds 1.2) areas for the four ungulate species account for the following proportions of their total habitat areas: Tibetan wild donkeys (49.76%), Tibetan gazelles (47.00%), Tibetan antelopes (40.76%), and wild yaks (34.83%). These high-risk areas are primarily located within alpine meadow and temperate desert steppe. This study provides a quantitative assessment of survival risks for these four ungulate species on the Tibetan plateau grasslands and serves as a valuable reference for ungulate conservation and grassland ecosystem management. Full article

Toxoplasma gondii holds significant therapeutic potential; however, its nonspecific invasiveness results in off-target effects. The purpose of this study is to evaluate whether T. gondii specificity can be improved by surface display of scFv directed against dendritic cells’ endocytic receptor, DEC205, and immune checkpoint PD-L1. Anti-DEC205 scFv was anchored to the T. gondii surface either directly via glycosylphosphatidylinositol (GPI) or by fusion with the SAG1 protein. Both constructs were successfully expressed, but the binding results suggested that the anti-DEC-SAG1 scFv had more reliable functionality towards recombinant DEC protein and DEC205-expressing MutuDC cells. Two anti-PD-L1 scFv constructs were developed that differed in the localization of the HA tag. Both constructs were adequately expressed, but the localization of the HA tag determined the functionality by binding to PD-L1 protein. Co-incubation of T. gondii displaying anti-PD-L1 scFv with tumor cells expressing/displaying different levels of PD-L1 showed strong binding depending on the level of available biomarker. Neutralization assays confirmed that binding was due to the specific interaction between anti-PD-L1 scFv and its ligand. A mixed-cell assay showed that T. gondii expressing anti-PD-L1 scFv predominately targets the PD-L1-positive cells, with negligible off-target binding. The recombinant RH-PD-L1-C strain showed increased killing ability on PD-L1+ tumor cell lines compared to the parental strain. Moreover, a co-culture assay of target tumor cells and effector CD8+ T cells showed that our model could inhibit PD1/PD-L1 interaction and potentiate T-cell immune response. These findings highlight surface display of antibody fragments as a promising strategy of targeting replicative T. gondii strains while minimizing nonspecific binding. Full article

Chronic lymphocytic leukaemia (CLL) is a malignancy of the immune B lymphocyte cells and is the most common leukaemia diagnosed in developed countries. In this paper, we report the synthesis and antiproliferative effects of a series of (E)-9-(2-nitrovinyl)anthracenes and related nitrostyrene compounds in CLL cell lines and also in Burkitt’s lymphoma (BL) cell lines, a rare form of non-Hodgkin’s immune B-cell lymphoma. The nitrostyrene scaffold was identified as a lead structure for the development of effective compounds targeting BL and CLL. The series of structurally diverse nitrostyrenes was synthesised via Henry–Knoevenagel condensation reactions. Single-crystal X-ray analysis confirmed the structure of (E)-9-chloro-10-(2-nitrobut-1-en-1-yl)anthracene (19f) and the related 4-(anthracen-9-yl)-1H-1,2,3-triazole (30a). The (E)-9-(2-nitrovinyl)anthracenes 19a, 19g and 19i–19m were found to elicit potent antiproliferative effects in both BL cell lines EBV⁻MUTU-1 (chemosensitive) and EBV⁺ DG-75 (chemoresistant) with >90% inhibition at 10 μM. Selected (E)-9-(2-nitrovinyl)anthracenes demonstrated potent antiproliferative activity in CLL cell lines, with IC₅₀ values of 0.17 μM (HG-3) and 1.3 μM (PGA-1) for compound 19g. The pro-apoptotic effects of the most potent compounds 19a, 19g, 19i, 19l and 19m were demonstrated in both CLL cell lines HG-3 and PGA-1. The (E)-nitrostyrene and (E)-9-(2-nitrovinyl)anthracene series of compounds offer potential for further development as novel chemotherapeutics for CLL. Full article

This study aimed to investigate the spatially and temporally expressed patterns and biological characteristics of TSSK1B in male yaks and explore the potential correlation between TSSK1B and male sterility of the yak hybrid offspring (termed cattle–yak). First, the coding sequence (CDS) of TSSK1B was cloned by RT-PCR, and bioinformatics analysis was conducted with relevant software. Quantitative real-time PCR (RT-qPCR) was employed to detect the expression profile of TSSK1B in various tissues of male adult yaks, the spatiotemporal expression of TSSK1B in different stages of yak testes, and the differential expression of TSSK1B between yak and cattle–yak testes. The cellular localization of TSSK1B was determined by immunohistochemistry (IHC). Furthermore, the methylation status of the TSSK1B promoter region was analyzed by bisulfite-sequencing PCR (BSP). The results showed that TSSK1B was 1235 bp long, including 1104 bp of the CDS region, which encoded 367 amino acids. It was a conserved gene sharing the highest homology with Bos mutus (99.67%). In addition, the bioinformatics analysis revealed that TSSK1B was an unstable hydrophilic protein mainly containing the alpha helix of 34.06% and a random coil of 44.41%, with a transmembrane structure of 29 amino acids long. The RT-qPCR results demonstrated that TSSK1B was specifically expressed in yak testes compared with that in other tissues and especially highly expressed in adult yak testes. On the contrary, TSSK1B was hardly expressed in the testis of adult cattle–yak. IHC confirmed that TSSK1B protein was more strongly expressed in the testes of adult yaks than in their fetal and juvenile counterparts. Interestingly, nearly no expression was observed in the testes of cattle–yak compared with the corresponding testes of yak. Bisulfite-sequencing PCR (BSP) revealed that the methylated CpG sites in the TSSK1B promoter region of cattle–yak was significantly higher than that in the yak. Taken together, this study revealed that TSSK1B was specifically expressed in yak testes and highly expressed upon sexual maturity. Moreover, the rare expression in cattle–yak may be related to the hypermethylation of the promoter region, thereby providing a basis for further studies on the regulatory mechanism of TSSK1B in male cattle–yak sterility. Full article

New developments in sequencing technology and nucleotide analysis have allowed us to make great advances in reconstructing anuran phylogeny. As a clade of representative amphibians that have radiated from aquatic to arboreal habitats, our understanding of the systematic status and molecular biology of rhacophorid tree frogs is still limited. We determined two new mitogenomes for the genus Polypedates (Rhacophoridae): P. impresus and P. mutus. We conducted comparative and phylogenetic analyses using our data and seven other rhacophorid mitogenomes. The mitogenomes of the genera Polypedates, Buergeria, and Zhangixalus were almost identical, except that the ATP8 gene in Polypedates had become a non-coding region; Buergeria maintained the legacy “LTPF” tRNA gene cluster compared to the novel “TLPF” order in the other two genera; and B. buergeri and Z. dennysi had no control region (CR) duplication. The resulting phylogenetic relationship supporting the above gene rearrangement pathway suggested parallel evolution of ATP8 gene loss of function (LoF) in Polypedates and CR duplication with concerted evolution of paralogous CRs in rhacophorids. Finally, conflicting topologies in the phylograms of 185 species reflected the advantages of phylogenetic analyses using multiple loci. Full article

Lymphomas (cancers of the lymphatic system) account for 12% of malignant diseases worldwide. Burkitt’s lymphoma (BL) is a rare form of non-Hodgkin’s lymphoma in which the cancer starts in the immune B-cells. We report the synthesis and preliminary studies on the antiproliferative activity of a library of 9,10-dihydro-9,10-ethanoanthracene based compounds structurally related to the antidepressant drug maprotiline against BL cell lines MUTU-1 and DG-75. Structural modifications were achieved by Diels-Alder reaction of the core 9-(2-nitrovinyl)anthracene with number of dienophiles including maleic anhydride, maleimides, acrylonitrile and benzyne. The antiproliferative activity of these compounds was evaluated in BL cell lines EBV⁻ MUTU-1 and EBV⁺ DG-75 (chemoresistant). The most potent compounds 13j, 15, 16a, 16b, 16c, 16d and 19a displayed IC₅₀ values in the range 0.17–0.38 μM against the BL cell line EBV⁻ MUTU-1 and IC₅₀ values in the range 0.45–0.78 μM against the chemoresistant BL cell line EBV⁺ DG-75. Compounds 15, 16b and 16c demonstrated potent ROS dependent apoptotic effects on the BL cell lines which were superior to the control drug taxol and showed minimal cytotoxicity to peripheral blood mononuclear cells (PBMCs). The results suggest that this class of compounds merits further investigation as antiproliferative agents for BL. Full article

Infection of Epstein–Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing. We found that the biogenesis of exosomes is upregulated in type III latently infected cells compared with EBV-negative and type I latently infected cells. We also observed that viral and several specific host microRNAs were predominantly incorporated in the exosomes released from the cells in type III latency. We confirmed that multiple viral microRNAs were transferred to the epithelial cells cocultured with EBV-infected B cells. Our findings indicate that EBV infection, in particular in type III latency, modulates the biogenesis of exosomes and the profile of exosomal microRNAs, potentially contributing to phenotypic changes in cells receiving these exosomes. Full article