BMC Biology最新文献

Background: Urbanization is rapidly altering our ecosystem. While most wild species refrain from entering urban habitats, some flourish in cities and adapt to the new opportunities these offer. Urban individuals of various species have been shown to differ in physiology, morphology, and behavior compared to their rural counterparts. While several studies have suggested that urban dwelling alters the reproductive cycle in birds, such evidence currently has not been shown for mammals. Egyptian fruit bats are highly flexible mammals that roost and forage in both urban and rural habitats. Urban-dwelling fruit bats encounter higher average temperatures and a richer supply of food (mainly fruit) during winter.

Results: Here, we set out to determine whether urban-dwelling fruit bats take advantage of urbanization and reproduce earlier in the annual cycle than rural fruit bats. We sampled ten fruit bat colonies located in different urbanization levels, over 3 years. We monitored the bats' reproductive state and the size of the pups following parturition. Indeed, we found that urban fruit bats gave birth ~ 2.5 weeks earlier in spring than rural fruit bats. We also found that roosting in urban colonies did not decrease the bats' reproductive success, in contrast to what has been suggested for some urban birds.

Conclusions: Our study provides new insights into the adaptation to urban living and its exploitation by one of the most common mammalian groups found in cities worldwide-bats.

Background: Silver arowana (Osteoglossum bicirrhosum) is a basal fish species with sexual monomorphism, while its sex determination mechanism has been poorly understood, posing a significant challenge to its captive breeding efforts.

Results: We constructed two high-quality chromosome-level genome assemblies for both female and male silver arowana, with scaffold N50 values over 10 Mb. Combining re-sequencing data of 109 individuals, we identified a female-specific region, which was localized in a non-coding region, i.e., around 26-kb upstream of foxl2 gene (encoding forkhead box L2). Its strong interaction with the neighboring foxl2 on the same chromosome suggests foxl2 as a candidate sex-related gene in silver arowana. We subsequently propose a complex gene network in the sex determination process of silver arowana, with foxl2 acting as the central contributor. Transcriptome sequencing of gonads support our hypothesis that the regulation of foxl2 can be influenced by the spatial proximity of the female-specific fragment, thereby promoting ovarian function or inhibiting testicular function to stimulate gonadal differentiation. Furthermore, we found the sex chromosomes to be homomorphic with a potentially recent origin, as a linkage disequilibrium analysis proved minor recombination suppression.

Conclusions: These results taken together serve as a crucial foundation for conducting extensive investigations on the evolution and differentiation of sex-determining mechanisms, as well as the emergence and development of sex chromosomes in various fishes.

Background: The high-frequency induction rate of haploid is crucial for double haploid (DH) breeding. The combination of multiple haploid-induced genes, such as ZmPLA1/MATL/NLD and ZmDMP, can synergistically enhance the haploid induction rate (HIR) in maize. However, the potential synergistic effects between OsMATL and OsDMP genes in rice remain unclear.

Results: Knocking out OsMATL in both HuaHang No.48 (HH48) and Nipponbare (NIP) cultivars resulted in reduced seed setting rate (SSR) and haploid induction (HI). Notably, in this study, the HI capacity of OsMATL knockout mutants in indica rice surpassed that of japonica rice knockout mutants, with the proton active site in the third exon exhibiting a higher HIR compared to the first and fourth exons. Furthermore, when OsDMP1 or OsDMP3 was combined with OsMATL, they increased HIR, and an antagonistic relationship was observed between HIR and SSR in HH48 ^matl4dmp1 and HH48 ^matl4dmp3.

Conclusions: In rice, the proton active site in the third exon of OsMATL exhibited higher induction efficiency, and OsDMP1 or OsDMP3 exerted a synergistic effect with OsMATL. These findings provide a foundation for further research on DH breeding in rice.

Background: Poliovirus receptor (PVR) and its receptor system, including TIGIT, CD226, and CD96, play a pivotal role in orchestrating tumor immune evasion. Upon engagement with PVR on tumor cells, CD96 exerts inhibitory effects on the function of T cells and NK cells, thereby fostering tumor immune evasion. Therefore, screening of immune checkpoint inhibitors (ICIs) targeting the CD96/PVR pathway will provide promising candidates for tumor immunotherapy.

Results: In this investigation, we employed MOE software to conduct virtual screening of small molecules from the FDA-approved drug library. Our results demonstrated that Epinastine exhibited high affinity for CD96, thereby effectively disrupting the interaction between CD96 and PVR. In vitro co-culture experiments further revealed that Epinastine effectively restored the ability of Jurkat cells to secrete IL-2. In the MC38 tumor-bearing model, Epinastine significantly enhanced the infiltration of T cells and NK cells into the tumor site and augmented their secretion of IFN-γ, leading to effective suppression of tumor growth.

Conclusions: Our results demonstrated that the development of small molecule inhibitor Epinastine targeting CD96/PVR pathway, which proposed a promising strategy and drug candidate for cancer immunotherapy.

Background: Recent advancements in single-cell RNA sequencing have greatly expanded our knowledge of the heterogeneous nature of tissues. However, robust and accurate cell type annotation continues to be a major challenge, hindered by issues such as marker specificity, batch effects, and a lack of comprehensive spatial and interaction data. Traditional annotation methods often fail to adequately address the complexity of cellular interactions and gene regulatory networks.

Results: We proposed scMCGraph, a comprehensive computational framework that integrates gene expression with pathway activity to accurately annotate cell types within diverse scRNA-seq datasets. Initially, our model constructs multiple pathway-specific views using various pathway databases, which reflect both gene expression and pathway activities. These pathway-specific views are then integrated into a consensus graph. The consensus graph is subsequently utilized to reconstruct the multiple pathway views. Our model demonstrated exceptional robustness and accuracy across various analyses, including cross-platform, cross-time, cross-sample, and clinical dataset evaluations.

Conclusions: scMCGraph represents a significant advance in cell type annotation. The experiments have demonstrated that introducing pathway information significantly improves the learning of cell-cell graphs, with their resulting consensus graph enhancing the predictive performance of cell type prediction. Different pathway databases provide complementary data, and an increase in the number of pathways can also boost model performance. Extensive testing shows that in various cross-dataset application scenarios, scMCGraph consistently exhibits both accuracy and robustness.

Background: HuR/ELAV1, a ubiquitous RNA-binding protein, belongs to the RNA-binding protein family and is crucial for stabilizing and regulating the translation of various mRNA targets, influencing gene expression. Elevated HuR levels are associated with multiple disorders, including cancer and neurodegenerative diseases. Despite the identification of small molecule inhibitors targeting HuR, their detailed characterization remains limited. Recently, Eltrombopag, an FDA-approved drug for immune thrombocytopenic purpura and chemotherapy-induced thrombocytopenia, emerged as a potential HuR inhibitor. However, the specific molecular pathways influenced by both HuR and Eltrombopag are not fully understood.

Results: Our study demonstrates that Eltrombopag operates via HuR inhibition, affecting gene expression regulation at the posttranscriptional level. We show that both HuR knockout and Eltrombopag treatment modulate iron metabolism by decreasing ferritin heavy chain (FTH1) and light chain (FTL) synthesis while increasing the expression of iron-regulatory protein 2 (IRP2), a key regulator of ferritin translation. Additionally, HuR inhibition reduces the levels of glycoprotein hormones, alpha polypeptide (CGA), a marker associated with hormone-induced tumors, suggesting a potential use of Eltrombopag in treatment of cancers overexpressing CGA. We observed that the main of control is manifested at the level of translation inhibition, with proteasome-mediated regulation also playing an important role.

Conclusions: These findings uncover novel posttranscriptional mechanisms governed by HuR and its inhibitor, elucidating pathways relevant to HuR-mediated regulation and molecular therapies aimed at targeting this protein.

Background: Grape (Vitis vinifera) crops encounter significant challenges in overcoming bud endodormancy in warm winter areas worldwide. Research on the mechanisms governing bud dormancy release has focused primarily on stress regulation; however, cell wall regulation of bud meristem regrowth mechanism during the dormancy release remains obscure.

Results: In this study, transmission electron microscopy revealed significant changes in the grape bud cell wall following hydrogen cyanamide (HC) treatment, accompanied by an increase in β-1,3-glucanase activity. We then investigated the potential contribution of β-1,3-glucanases (GLUs) to the regulation of cell wall remodeling. Forty-eight VvGLUs distributed in clades α, β, and γ were identified and nominated based on the genome data of V. vinifera. Three γ-clade VvGLUs (VvGLU1, VvGLU16, and VvGLU32) were upregulated by dormancy-releasing stimuli, including HC, sodium azide (AZ), ethylene and hypoxia. Among these, VvGLU1 presented increased gene transcription and protein expression in response to HC and ethylene treatment. The VvGLU1 promoter positively responded to ethylene, and its activity could be activated by VvERF57. Using both immunogold labeling and GFP fusion protein analysis, we observed that VvGLU1 localized in the endoplasmic reticulum, accumulated in the vacuole, and was secreted into the cell wall during HC-triggered dormancy release.

Conclusions: Based on these findings, we propose that ethylene-regulated VvGLU1 plays a pivotal role in cell wall remodeling, thereby facilitating the regrowth of the bud meristem.

Background: Echolocating bats face an intense arms race with insect prey that can detect bat calls and initiate evasive maneuvers. Their high closing speeds and short biosonar ranges leave bats with only a few 100 ms between detection and capture, suggesting a reactive sensory-motor operation that might preclude tracking of escaping prey. Here we test this hypothesis using greater mouse-eared bats (Myotis myotis) as a model species. With high-resolution biologging tags, we recorded bats hunting aerial prey in the wild and we also collected data from trained conspecifics in the laboratory facing simulated prey escapes of various speeds and distances.

Results: We show that wild bats employed flexible buzz durations during hunting. In the laboratory, such dynamic vocal responses were driven by moving targets, where faster and longer movements led to longer buzzes. During these buzzes, the bats engaged in acute vocal-motor tracking via increased call intervals within 240 ms of evasive prey maneuvers.

Conclusions: Echolocating bats can track evasive prey via a fast vocal-motor feedback loop allowing them to expand their acoustic depth of field. This echo-guided sensory adjustment contributes to the hunting superiority of bats as the most formidable insectivorous predator of the night skies.

Background: Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the impact of global deregulation of pre-miR-1307 and its individual mature miRNAs in breast cancer has not been investigated in breast cancer, yet.

Results: Here, we found significant upregulation of three mature miRNA species derived from pre-miR-1307 in human breast cancer tissue. Surprisingly, the overexpression of pre-miR-1307 in breast cancer cell lines resulted in reduced xenograft growth and impaired angiogenesis. Mechanistically, overexpression of miR-1307-5p altered the secretome of breast cancer cells and reduced endothelial cell sprouting. Consistently, expression of miR-1307-5p was inversely correlated with endothelial cell fractions in human breast tumors pointing at an anti-angiogenic role of miR-1307-5p. Importantly, the arm usage of miR-1307 and other miRNAs was highly correlated, which suggests an undefined common regulatory mechanism.

Conclusions: In summary, miR-1307-5p reduces angiogenesis in breast cancer, thereby antagonizing the oncogenic effects of miR-1307-3p. Our results emphasize the importance of future research on the regulation of miRNA arm selection in cancer. The underlying mechanisms might inspire new therapeutic strategies aimed at shifting the balance towards tumor-suppressive miRNA species.

Background: Glioblastoma multiforme (GBM) is characterized by its cellular complexity, with a microenvironment consisting of diverse cell types, including oligodendrocyte precursor cells (OPCs) and neoplastic CD133 + radial glia-like cells. This study focuses on exploring the distinct cellular transitions in GBM, emphasizing the role of alternative polyadenylation (APA) in modulating microRNA-binding and post-transcriptional regulation.

Results: Our research identified unique APA profiles that signify the transitional phases between neoplastic cells and OPCs, underscoring the importance of APA in cellular identity and transformation in GBM. A significant finding was the disconnection between differential APA events and gene expression alterations, indicating that APA operates as an independent regulatory mechanism. We also highlighted the specific genes in neoplastic cells and OPCs that lose microRNA-binding sites due to APA, which are crucial for maintaining stem cell characteristics and DNA repair, respectively. The constructed networks of microRNA-transcription factor-target genes provide insights into the cellular mechanisms influencing cancer cell survival and therapeutic resistance.

Conclusions: This study elucidates the APA-driven regulatory framework within GBM, spotlighting its influence on cell state transitions and microRNA network dynamics. Our comprehensive analysis using single-cell RNA sequencing data to investigate the microRNA-binding sites altered by APA profiles offers a robust foundation for future research, presenting a novel approach to understanding and potentially targeting the complex molecular interplay in GBM.