Project description:Transmembrane sodium-ion gradients provide energy that can be harnessed by 'secondary transporters' to drive the translocation of solute molecules into a cell. Decades of study have shown that such sodium-coupled transporters are involved in many physiological processes, making them targets for the treatment of numerous diseases. Within the past year, crystal structures of several sodium-coupled transporters from different families have been reported, showing a remarkable structural conservation between functionally unrelated transporters. These atomic-resolution structures are revealing the mechanism of the sodium-coupled transport of solutes across cellular membranes.
Project description:Ovarian cancer (OC) is a common gynecological cancer worldwide. Unfortunately, the lack of early detection methods translates into a substantial cohort of women grappling with the pressing health crisis. The discovery of extracellular vesicles (EVs) (their major subpopulation exosomes, microvesicles, and apoptotic bodies) has provided new insights into the understanding of cancer. Exosomes, a subpopulation of EVs, play a crucial role in cellular communication and reflect the cellular status under both healthy and pathological conditions. Tumor-derived exosomes (TEXs) dynamically influence ovarian cancer progression by regulating uncontrolled cell growth, immune suppression, angiogenesis, metastasis, and the development of drug and therapeutic resistance. In the field of OC diagnostics, TEXs offer potential biomarkers in various body fluids. On the other hand, exosomes have also shown promising abilities to cure ovarian cancer. In this review, we address the interlink between exosomes and ovarian cancer and explore their theragnostic signature. Finally, we highlight future directions of exosome-based ovarian cancer research.
Project description:Dorper sheep is popular among farming enterprises with strong adaptability, disease resistance, and roughage tolerance, and an unique characteristic of natural shedding of wool. In a large number of observations on experimental sheep farms, it was found that the wool of some sheep still had not shed after May, thus manual shearing was required. Therefore, understanding the molecular mechanisms of normal hair follicles (HFs) development is crucial to revealing the improvement of sheep wool-related traits and mammalian skin-related traits. In this study, transcriptome analysis was performed on skin tissues of adult Dorper ewes in the shedding (S) and non-shedding (N) groups in September 2019, January 2020, and March 2020, respectively. The results identified 3,278 differentially expressed transcripts (DETs) in the three comparison groups within the S group, 720 DETs in the three comparison groups within the N group, and 1,342 DETs in the three comparison groups between the S-vs-N groups. Time-series expression analysis revealed 2 unique expression patterns in HF development, namely, elevated expression in the anagen phase (A pattern) and the telogen phase (T pattern). DETs with stage-specific expression had a significant presence in processes related to the hair cycle and skin development, and several classic signaling pathways involved in sheep HF development, such as Rap1, estrogen, PI3K-Akt, and MAPK, were detected. Combined analysis of DETs, time-series expression data, and weighted gene co-expression network analysis identified core genes and their transcripts influencing HF development, such as DBI, FZD3, KRT17, ZDHHC21, TMEM79, and HOXC13. Additionally, alternative splicing analysis predicted that the isoforms XM_004004383.4 and XM_012125926.3 of ZDHHC21 might play a crucial role in sheep HF development. This study is a valuable resource for explaining the morphology of normal growth and development of sheep HFs and the genetic foundation of mammalian skin-related traits. It also offers potential insights into factors influencing human hair advancement.
Project description:BackgroundThis study employed RNA-seq technology and meta-analysis to unveil the molecular mechanisms of neuropsychiatric systemic lupus erythematosus (NPSLE) within the central nervous system.MethodsDownloaded transcriptomic data on systemic lupus erythematosus (SLE) from the Gene Expression Omnibus (GEO) and analyzed differential genes in peripheral blood samples of NPSLE patients and healthy individuals. Employed WGCNA to identify key genes related to cognitive impairment and validated findings via RNA-seq. Conducted GO, KEGG, and GSEA analyses, and integrated PPI networks to explore gene regulatory mechanisms. Assessed gene impacts on dendritic cells and blood-brain barrier using RT-qPCR, ELISA, and in vitro models.ResultsPublic databases and RNA-seq data have revealed a significant upregulation of CCL2 (C-C motif chemokine ligand 2) in the peripheral blood of both SLE and NPSLE patients, primarily secreted by mature dendritic cells. Furthermore, the secretion of CCL2 by mature dendritic cells may act through the RSAD2-ISG15 axis and is associated with the activation of the NLRs (Nod Like Receptor Signaling Pathway) signaling pathway in vascular endothelial cells. Subsequent in vitro cell experiments confirmed the high expression of CCL2 in peripheral blood dendritic cells of NPSLE patients, with its secretion being regulated by the RSAD2-ISG15 axis and inducing vascular endothelial cell pyroptosis through the activation of the NLRs signaling pathway. Clinical trial results ultimately confirmed that NPSLE patients exhibiting elevated CCL2 expression also experienced cognitive decline.ConclusionsThe secretion of CCL2 by dendritic cells induces pyroptosis in vascular endothelial cells, thereby promoting blood-brain barrier damage and triggering cognitive impairment in patients with systemic lupus erythematosus.
Project description:ImportanceLimited nitrogen supply can prevent the completion of alcoholic fermentation. Supplementation through peptides as an alternative, natural source of nitrogen for yeast offers an interesting solution for this issue. In this work, the S. cerevisiae peptide transporters of the Opt and Fot families were studied. We demonstrated that Fot and Opt2 have a broader peptide length preference than previously reported, enabling yeasts to acquire sufficient nitrogen from peptides without requiring additional ammonia or amino acids to complete fermentation. On the contrary, Opt1 was unable to consume any peptide in the given conditions, whereas it has been described elsewhere as the main peptide transporter for peptides longer than three amino acid residues in experiments in laboratory conditions. This controversy signifies the need in applied sciences for approaching experimental conditions to those prevalent in the industry for its more accurate characterization. Altogether, this work provides further evidence of the importance of peptides as a nitrogen source for yeast and their consequent positive impact on fermentation kinetics.
Project description:Involving 1 million people a year, suicide represents one of the major topics of psychiatric research. Despite the focus in recent years on neurobiological underpinnings, understanding and predicting suicide remains a challenge. Many sociodemographical risk factors and prognostic markers have been proposed but they have poor predictive accuracy. Biomarkers can provide essential information acting as predictive indicators, providing proof of treatment response and proposing potential targets while offering more assurance than psychological measures. In this framework, the aim of this study is to open the way in this field and evaluate the correlation between blood levels of serotonin, brain derived neurotrophic factor, tryptophan and its metabolites, IL-6 and homocysteine levels and suicidality. Blood samples were taken from 24 adults with autism, their first-degree relatives, and 24 controls. Biochemical parameters were measured with enzyme-linked immunosorbent assays. Suicidality was measured through selected items of the MOODS-SR. Here we confirm the link between suicidality and autism and provide more evidence regarding the association of suicidality with increased homocysteine (0.278) and IL-6 (0.487) levels and decreased tryptophan (-0.132) and kynurenic acid (-0.253) ones. Our results suggest a possible transnosographic association between these biochemical parameters and increased suicide risk.
Project description:Drug resistance continues to be a significant problem in cancer therapy, leading to relapse and associated mortality. Although substantial progress has been made in understanding drug resistance, significant knowledge gaps remain concerning the molecular underpinnings that drive drug resistance and which processes are unique to certain drug classes. The NCI-60 cell line panel program has evaluated the activity of numerous anticancer agents against many common cancer cell line models and represents a highly valuable resource to study intrinsic drug resistance. Furthermore, great efforts have been undertaken to collect high-quality omics datasets to characterize these cell lines. The current study takes these two sources of data-drug response and omics profiles-and uses a multi-omics investigation to uncover molecular networks that differentiate cancer cells that are sensitive or resistant to antifolates, which is a commonly used class of anticancer drugs. Results from a combination of univariate and multivariate analyses showed numerous metabolic processes that differentiate sensitive and resistant cells, including differences in glycolysis and gluconeogenesis, arginine and proline metabolism, beta-alanine metabolism, purine metabolism, and pyrimidine metabolism. Further analysis using multivariate and integrated pathway analysis indicated purine metabolism as the major metabolic process separating cancer cells sensitive or resistant to antifolates. Additional pathways differentiating sensitive and resistant cells included autophagy-related processes (e.g., phagosome, lysosome, autophagy, mitophagy) and adhesion/cytoskeleton-related pathways (e.g., focal adhesion, regulation of actin cytoskeleton, tight junction). Volcano plot analysis and the receiver operating characteristic (ROC) curves of top selected variables differentiating Q1 and Q4 revealed the importance of genes involved in the regulation of the cytoskeleton and extracellular matrix (ECM). These results provide novel insights toward mechanisms of intrinsic antifolate resistance as it relates to interactions between nucleotide metabolism, autophagy, and the cytoskeleton. These processes should be evaluated in future studies to potentially derive novel therapeutic strategies and personalized treatment approaches to improve antifolate response.
Project description:Apple production holds a prominent position in Morocco's Rosaceae family. However, annual production can fluctuate due to substantial losses caused by fungal diseases affecting stored apples. Our findings emphasize that the pre-storage treatment of apples, disinfection of storage facilities, box type, and fruit sorting are pivotal factors affecting apple losses during storage. Additionally, the adopted preservation technique was significantly correlated with the percentage of damage caused by fungal infections. Blue mold accounts for nearly three-quarters of the diseases detected, followed by gray rot with a relatively significant incidence. This study has revealed several fungal diseases affecting stored apples caused by pathogens such as Penicillium expansum, Botrytis cinerea, Alternaria alternata, Trichothecium roseum, Fusarium avenaceum, Cadophora malorum, and Neofabraea vagabunda. Notably, these last two fungal species have been reported for the first time in Morocco as pathogens of stored apples. These data affirm that the high losses of apples in Morocco, attributed primarily to P. expansum and B. cinerea, pose a significant threat in terms of reduced production and diminished fruit quality. Hence, adopting controlled atmosphere storage chambers and implementing good practices before apple storage is crucial.