Search Results (39)

Fruit quality is determined by multiple metabolites, which are mainly affected by plant hormones. In this study, two genes, ethylene-related gene SlACO1 and gibberellin-related gene SlGARP, were overexpressed (OE) and knocked down through RNAi in tomato, and the profiles of carotenoids, flavonoids, volatiles, and hormones were detected in the leaves and fruit. The color index significantly increased in SlACO1-OE fruit but significantly decreased in the SlACO1-RNAi line. Similarly, total carotenoids, volatiles, salicylic acid, and ethylene significantly increased in the fruits of SlACO1-OE and SlGARP-OE, whereas ABA decreased significantly. Some compounds, such as lycopene, 3-hexenal, and d-limonene, significantly increased in the fruit of SlACO1-OE but decreased in the SlACO1-RNAi line, indicating that SlACO1 might play an important role in the accumulation of these compounds. The functional characterization of SlACO1 and SlGARP would facilitate the improvement in tomato fruit quality. Full article

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage “vicious cycle” of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of underappreciated cellular players in this metastatic takeover: megakaryocytes, erythroid lineage cells, and perivascular stromal subsets. Far from being passive bystanders, these cells actively shape the metastatic niche. For instance, megakaryocytes and platelets go beyond their role in transport; they orchestrate immune evasion and dormancy through mechanisms such as transforming growth factor-β1 (TGF-β1) signaling and the physical shielding of tumor cells. In parallel, we uncover a distinct “erythroid-immune” axis: here, stress-induced CD71⁺ erythroid progenitors suppress T-cell responses via arginase-mediated nutrient depletion and checkpoint engagement, forming a potent metabolic barrier against immune attack. Furthermore, leptin receptor–positive (LepR⁺) perivascular stromal cells emerge as key structural players. These stromal subsets not only act as anchoring points for DTCs but also maintain them in protective vascular zones via CXCL12 chemokine gradients. Altogether, these findings reveal that the metastatic bone marrow niche is not static; it is a highly dynamic, multi-lineage ecosystem. By mapping these intricate cellular interactions, we argue for a paradigm shift: targeting these early and cooperative crosstalk, whether through glycoprotein-A repetitions predominant (GARP) blockade, metabolic reprogramming, or other niche-disruptive strategies, could unlock new therapeutic avenues and prevent metastatic relapse at its root. Full article

Disorders of vesicular trafficking and genetic defects in autophagy play a critical role in the development of metabolic and neurometabolic diseases. These processes govern intracellular transport and lysosomal degradation, thereby maintaining cellular homeostasis. In this article, we present two siblings with a novel homozygous variant in VPS51 (Vacuolar protein sorting 51) gene (c.1511C>T; p.Thr504Met), exhibiting developmental delay, a thin corpus callosum, severe intellectual disability, epilepsy, microcephaly, hearing loss, and dysphagia. This study aimed to investigate the effects of the novel VPS51 gene variation at the RNA and protein level in fibroblasts derived from patients. A comparative proteomic analysis, which has not been previously elucidated, was performed to identify uncharacterized proteins associated with vesicular trafficking. Furthermore, the impact of disrupted pathways on mitochondria–lysosome contact sites was assessed, offering a thorough pathophysiological evaluation of GARP/EARP (Golgi Associated Retrograde Protein / Endosome Associated Retrograde Protein) complex dysfunction. An analysis of mRNA expression indicated decreased levels of the VPS51 gene, alongside modifications in the expression of autophagy-related genes (LC3B, p62, RAB7A, TBC1D15). Western blotting demonstrated a reduction in VPS51 and autophagy-related protein levels. Proteomic profiling revealed 585 differentially expressed proteins, indicating disruptions in vesicular trafficking, lysosomal function, and mitochondrial metabolism. Proteins involved in mitochondrial β-oxidation and oxidative phosphorylation exhibited downregulation, whereas pathways related to glycolysis and lipid synthesis showed upregulation. Live-cell confocal microscopy revealed a notable increase in mitochondria–lysosome contact sites in patient fibroblasts, suggesting that VPS51 protein dysfunction contributes to impaired organelle communication. The findings indicate that the novel VPS51 gene variation influences intracellular transport, autophagy, and metabolic pathways, offering new insights into its involvement in neurometabolic disorders. Full article

Background/Objectives: The GARP transcription factor superfamily is crucial for plant growth, development, and stress responses. This study systematically identified and analyzed the GARP family genes in Populus deltoides to explore their roles in plant development and abiotic stress responses. Methods: A total of 58 PdGARP genes were identified using bioinformatics tools. Their physicochemical properties, genomic locations, conserved motifs, gene structures, and phylogenetic relationships were analyzed. Expression patterns under phosphorus and nitrogen deficiency, as well as tissue-specific expression, were investigated using RT-qPCR. Transgenic RNAi lines were generated to validate the function of GLK genes in chlorophyll biosynthesis. Results: The 58 PdGARP genes were classified into five subfamilies based on their evolutionary relationships and protein sequence similarity. Segmental duplication was found to be the primary driver of the PdGARP family’s expansion. Cis-regulatory elements (CREs) related to light, hormones, and abiotic stresses were identified in the promoters of PdGARP genes. Differential expression patterns were observed for NIGT1/HRS1/HHO and PHR/PHL subfamily members under phosphorus and nitrogen deficiency, indicating their involvement in stress responses. KAN subfamily members exhibited tissue-specific expression, particularly in leaves. Structural analysis of the GLK subfamily revealed conserved α-helices, extended chains, and irregular coils. Transgenic RNAi lines targeting GLK genes showed significant reductions in chlorophyll and carotenoid content. Conclusions: This study provides a comprehensive analysis of the GARP transcription factor superfamily in P. deltoides, highlighting their potential roles in nutrient signaling and stress response pathways. The findings lay the foundation for further functional studies of PdGARP genes and their application in stress-resistant breeding of poplar. Full article

The watershed of the Yellow River is an important water conservation area in the Yellow River Basin. Its fragile ecological environment, climate change and unreasonable human activities have led to the continuous degradation of plant community structure in the watershed. This study only considers environmental factors, based on MaxEnt, Garp and other niche models and spatial-temporal analysis methods such as Mess and MoD analysis, to explore the suitable areas of Salix oritrepha Schneid. (First published in C.S.Sargent, Pl. Wilson. 3: 113 (1916)) and Picea crassifolia Kom. (First published in Bot. Mater. Gerb. Glavn. Bot. Sada R.S.F.S.R. 4: 177 (1923)) in the watershed of the Yellow River under different emission scenarios in the future. The results show that the MaxEnt model has a good simulation effect. In terms of spatial distribution, the suitable areas of the two species are mainly concentrated in the southeastern part of the Yellow River source area. Compared with the current period (1970–2000), by 2070, the suitable areas of the two species in each scenario showed a distribution of high in the east and low in the west, with an obvious expansion trend in the area and moving to high altitude and high latitude. According to the analysis of Mess and MoD, the annual average temperature (Bio_1) may be the most important variable affecting the future distribution of the two vegetation types. Full article

PM2.5 (fine particulate matter) is an air pollutant widely present in urban and industrial areas, which has emerged as a significant threat to human health. Specifically, long-term exposure to PM2.5 could lead to various lung diseases, including pulmonary fibrosis and Chronic Obstructive Pulmonary Disease (COPD). The Glycoprotein A Repetitions Predominant (GARP) protein, a key receptor and regulator for TGF-β1, has recently emerged as a vital cytokine in PM2.5-induced pulmonary pathological changes. As a membrane glycoprotein, GARP binds to TGF-β, keeping it in an active state. Herein, PM2.5 treatment upregulated GARP and promoted Epithelial–Mesenchymal Transition (EMT) via TGF-β/SMAD signaling pathway activation. Conversely, lentinan (a shiitake mushroom-derived polysaccharide) effectively reversed the PM2.5-induced GARP upregulation, alleviating EMT. This study elucidates the role of GARP in PM2.5-induced EMT through the TGF-β/SMAD pathway in pulmonary epithelial cells and discusses the therapeutic potential of lentinan. Full article

Introduction: Single-port video-assisted techniques, such as one-trocar-assisted pyeloplasty (OTAP) or Round-Traction-Assisted Pyeloplasty (RoTAP), have proven helpful for correcting congenital ureteropelvic junction obstruction (UPJO), especially in infants. Surgical Technique: This manuscript presents a technical variation based on the gloveport system that allows bimanual endocavitary dissection and protects the surgical wound during the procedure without increasing the cost or technical difficulty. Comment: This new technique, called gloveport-assisted retroperitoneal pyeloplasty (GARP), could be a valuable alternative for this pathology. Full article

The Golden2-like (GLK) transcription factors belong to the GARP family of transcription factors and play significant roles in plant growth, development, and responses to both abiotic and biotic stresses. This study employed bioinformatics and expression analyses to investigate the regulatory roles of wheat GLK proteins under various stress conditions, including abscisic acid (ABA) treatment, osmotic stress, and infection by Fusarium graminearum. The study identified 125 TaGLK proteins and revealed that TaGLKs play a significant role in wheat’s development and response to adverse environmental conditions. The results indicate that TaGLKs may serve as potential transcriptional regulators capable of integrating multiple cellular signals to coordinate various developmental and physiological processes. Evolutionary analysis classified the TaGLK proteins into six subgroups, which shared similar conserved domains and motifs. Protein–protein interaction network analysis revealed that TaGLKs are involved in photoreceptor activity, cell cycle progression, and protein regulation. Gene expression analysis of TaGLKs discovered that they play key functions in wheat development, as well as regulation of biotic and abiotic stress conditions. RT-qPCR analysis showed that TaGLKs regulate earlier and late effects of osmotic stress, F. graminearum infections, and ABA treatment in wheat. These findings provide knowledge for future studies of the functions of TaGLK TFs in wheat stress tolerance and development, which could have significant implications for enhancing wheat tolerance to various environmental stressors. Full article

The GARP transcription factor family is integral to the regulation of plant growth, development, hormone signaling pathways, circadian rhythms, and responses to both biotic and abiotic stressors. Despite its recognized importance, a comprehensive characterization of the GARP gene family in Glycine max remains unexplored. In this study, we identified 126 GmGARP genes across the 16 chromosomes of G. max and elucidated their diverse physicochemical properties. Phylogenetic classification grouped the GmGARP genes into eight distinct subfamilies, based on conserved motifs and gene structures, suggesting functional and evolutionary conservation within these clusters. The discovery of 56 segmentally duplicated gene pairs highlights gene duplication as a key driver of family expansion. Promoter analysis revealed various cis-regulatory elements, while expression profiling demonstrated that GmGARP genes possess significant tissue specificity. Furthermore, qRT-PCR analysis indicated that GmGARP genes are highly responsive to exogenous hormones, such as ABA, MeJA, and GA, as well as to abiotic stresses, including cold, salt, and drought conditions. Notably, GmGARP120 and GmGARP98 contain specific cis-elements linked to hormone responses, with their interaction verified through yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Additionally, 11,195 potential target genes were predicted, underscoring the regulatory potential of the GmGARP transcription factors. These findings provide significant insights into the GmGARP gene family, laying a strong foundation for future studies on its role in G. max development and adaptive responses to environmental stressors. Full article

Regulatory T cells (Tregs) are essential to maintain immune homeostasis by promoting self-tolerance. Reduced Treg numbers or functionality can lead to a loss of tolerance, increasing the risk of developing autoimmune diseases. An overwhelming variety of human Tregs has been described, based on either specific phenotype, tissue compartment, or pathological condition, yet the bulk of the literature only addresses CD25-positive and CD127-negative cells, coined by naturally occurring Tregs (nTregs), most of which express the transcription factor Forkhead box protein 3 (FOXP3). While the discovery of FOXP3 was seminal to understanding the origin and biology of nTregs, there is evidence in humans that not all T cells expressing FOXP3 are regulatory, and that not all Tregs express FOXP3. Namely, the activation of human T cells induces the transient expression of FOXP3, irrespective of whether they are regulatory or inflammatory effectors, while some induced T cells that may be broadly defined as Tregs (e.g., Tr1 cells) typically lack demethylation and do not express FOXP3. Furthermore, it is unknown whether and how many nTregs exist without FOXP3 expression. Several other candidate regulatory molecules, such as GITR, Lag-3, GARP, GPA33, Helios, and Neuropilin, have been identified but subsequently discarded as Treg-specific markers. Multiparametric analyses have uncovered a plethora of Treg phenotypes, and neither single markers nor combinations thereof can define all and only Tregs. To date, only the functional capacity to inhibit immune responses defines a Treg and distinguishes Tregs from inflammatory T cells (Teffs) in humans. This review revisits current knowledge of the Treg universe with respect to their heterogeneity in phenotype and function. We propose that it is unavoidable to characterize human Tregs by their phenotype in combination with their function, since phenotype alone does not unambiguously define Tregs. There is an unmet need to align the expression of specific markers or combinations thereof with a particular suppressive function to coin functional Treg entities and categorize Treg diversity. Full article

Coral reef rehabilitation in the Caribbean is of major ecological and economic importance in the West Indies. Local organizations in Grenada constructed a cement pyramid artificial reef structure with rugosity (termed “The Pyramid”) and placed a number of these artificial reefs in a shallow marine area fringing two major natural reefs in the southwest coastal region of Grenada. Benthic data for two nearby natural reefs were compared to the benthic evaluation of the artificial reef pyramids. This comparison demonstrated that the artificial reef pyramids were similar in many respects to the natural reefs but were significantly different in macro- and coralline algae cover, two key indicators of reef health. This report is the first benthic evaluation of an artificial reef through comparison to natural reefs in Grenada. Full article

The Huangshui River, a vital tributary in the upper reaches of the Yellow River within the eastern Qinghai–Tibet Plateau, is home to the endemic black fly species S. qinghaiense. In this study, we conducted a systematic survey of the distribution of the species in the Huangshui River basin, revealing its predominant presence along the river’s main stem. Based on four ecological niche models—MaxEnt with parameter optimization; GARP; BIOCLIM; and DOMAIN—we conduct a comparative analysis; evaluating the accuracy of AUC and Kappa values. Our findings indicate that optimizing parameters significantly improves the MaxEnt model’s predictive accuracy by reducing complexity and overfitting. Furthermore, all four models exhibit higher accuracy compared to a random model, with MaxEnt demonstrating the highest AUC and Kappa values (0.9756 and 0.8118, respectively), showcasing significant superiority over the other models (p < 0.05). Evaluation of predictions from the four models elucidates that potential areas of S. qinghaiense in the Huangshui River basin are primarily concentrated in the central and southern areas, with precipitation exerting a predominant influence. Building upon these results, we utilized the MaxEnt model to forecast changes in suitable areas and distribution centers during the Last Interglacial (LIG), Mid-Holocene (MH), and future periods under three climate scenarios. The results indicate significantly smaller suitable areas during LIG and MH compared to the present, with the center of distribution shifting southeastward from the Qilian Mountains to the central part of the basin. In the future, suitable areas under different climate scenarios are expected to contract, with the center of distribution shifting southeastward. These findings provide important theoretical references for monitoring, early warning, and control measures for S. qinghaiense in the region, contributing to ecological health assessment. Full article

Glioblastoma (GB) is notoriously resistant to therapy. GB genesis and progression are driven by glioblastoma stem-like cells (GSCs). One goal for improving treatment efficacy and patient outcomes is targeting GSCs. Currently, there are no universal markers for GSCs. Glycoprotein A repetitions predominant (GARP), an anti-inflammatory protein expressed by activated regulatory T cells, was identified as a possible marker for GSCs. This study evaluated GARP for the detection of human GSCs utilizing a multidimensional experimental design that replicated several features of GB: (1) intratumoral heterogeneity, (2) cellular hierarchy (GSCs with varied degrees of self-renewal and differentiation), and (3) longitudinal GSC evolution during GB recurrence (GSCs from patient-matched newly diagnosed and recurrent GB). Our results indicate that GARP is expressed by GSCs across various cellular states and disease stages. GSCs with an increased GARP expression had reduced self-renewal but no alterations in proliferative capacity or differentiation commitment. Rather, GARP correlated inversely with the expression of GFAP and PDGFR-α, markers of astrocyte or oligodendrocyte differentiation. GARP had an abnormal nuclear localization (GARP^NU+) in GSCs and was negatively associated with patient survival. The uniformity of GARP/GARP^NU+ expression across different types of GSCs suggests a potential use of GARP as a marker to identify GSCs. Full article

Several types of cancer spread through the lymphatic system via the sentinel lymph nodes (LNs). Such LN-draining primary tumors, modified by tumor factors, lead to the formation of a metastatic niche associated with an increased number of Foxp3+ regulatory T cells (Tregs). These cells are expected to contribute to the elaboration of an immune-suppressive environment. Activated Tregs express glycoprotein A repetitions predominant (GARP), which binds and presents latent transforming growth factor beta 1 (TGF-β1) at their surface. GARP is also expressed by other non-immune cell types poorly described in LNs. Here, we mapped GARP expression in non-immune cells in human and mouse metastatic LNs. The mining of available (human and murine) scRNA-Seq datasets revealed GARP expression by blood (BEC)/lymphatic (LEC) endothelial, fibroblastic, and perivascular cells. Consistently, through immunostaining and in situ RNA hybridization approaches, GARP was detected in and around blood and lymphatic vessels, in (αSMA+) fibroblasts, and in perivascular cells associated with an abundant matrix. Strikingly, GARP was detected in LECs forming the subcapsular sinus and high endothelial venules (HEVs), two vascular structures localized at the interface between LNs and the afferent lymphatic and blood vessels. Altogether, we here provide the first distribution maps for GARP in human and murine LNs. Full article

Magnolia wufengensis is a newly discovered rare and endangered species endemic to China. The primary objective of this study is to find the most suitable species distribution models (SDMs) by comparing the different SDMs to predict their habitat distribution for protection and introduction in China under climate change. SDMs are important tools for studying species distribution patterns under climate change, and different SDMs have different simulation effects. Thus, to identify the potential habitat for M. wufengensis currently and in the 2050s (2041–2060) and 2070s (2061–2080) under different climate change scenarios (representative concentration pathways RCP2.6, RCP4.5, RCP6.0, and RCP8.5) in China, four SDMs, Maxent, GARP, Bioclim, and Domain, were first used to compare the predicted habitat and explore the dominant environmental factors. The four SDMs predicted that the potential habitats were mainly south of 40° N and east of 97° E in China, with a high distribution potential under current climate conditions. The area under the receiver operating characteristic (ROC) curve (AUC) (0.9479 ± 0.0080) was the highest, and the Kappa value (0.8113 ± 0.0228) of the consistency test and its performance in predicting the potential suitable habitat were the best in the Maxent model. The minimum temperature of the coldest month (−13.36–9.84 °C), mean temperature of the coldest quarter (−6.06–12.66 °C), annual mean temperature (≥4.49 °C), and elevation (0–2803.93 m), were the dominant factors. In the current climate scenario, areas of 46.60 × 10⁴ km² (4.85%), 122.82 × 10⁴ km² (12.79%), and 96.36 × 10⁴ km² (10.03%), which were mainly in central and southeastern China, were predicted to be potential suitable habitats of high, moderate, and low suitability, respectively. The predicted suitable habitats will significantly change by the 2050s (2040–2060) and 2070s (2060–2080), suggesting that M. wufengensis will increase in high-elevation areas and shift northeast with future climate change. The comparison of current and future suitable habitats revealed declines of approximately 4.53%–29.98% in highly suitable habitats and increases of approximately 6.45%–27.09% and 0.77%–21.86% in moderately and lowly suitable habitats, respectively. In summary, these results provide a theoretical basis for the response to climate change, protection, precise introduction, cultivation, and rational site selection of M. wufengensis in the future. Full article