-
Brazilian Journal of Microbiology :... Jul 2024Fusarium oxysporum is a cross-kingdom pathogen that infects humans, animals, and plants. The primary concern regarding this genus revolves around its resistance profile...
Fusarium oxysporum is a cross-kingdom pathogen that infects humans, animals, and plants. The primary concern regarding this genus revolves around its resistance profile to multiple classes of antifungals, particularly azoles. However, the resistance mechanism employed by Fusarium spp. is not fully understood, thus necessitating further studies to enhance our understanding and to guide future research towards identifying new drug targets. Here, we employed an untargeted proteomic approach to assess the differentially expressed proteins in a soil isolate of Fusarium oxysporum URM7401 cultivated in the presence of amphotericin B and fluconazole. In response to antifungals, URM7401 activated diverse interconnected pathways, such as proteins involved in oxidative stress response, proteolysis, and lipid metabolism. Efflux proteins, antioxidative enzymes and M35 metallopeptidase were highly expressed under amphotericin B exposure. Antioxidant proteins acting on toxic lipids, along with proteins involved in lipid metabolism, were expressed during fluconazole exposure. In summary, this work describes the protein profile of a resistant Fusarium oxysporum soil isolate exposed to medical antifungals, paving the way for further targeted research and discovering new drug targets.
PubMed: 38954219
DOI: 10.1007/s42770-024-01417-8 -
Journal of Agricultural and Food... Jul 2024Pea-protein-based ingredients are gaining attention in the food industry due to their nutritional benefits and versatility, but their bitter, astringent, green, and...
Pea-protein-based ingredients are gaining attention in the food industry due to their nutritional benefits and versatility, but their bitter, astringent, green, and beany off-flavors pose challenges. This study applied fermentation using microbial cultures to enhance the sensory qualities of pea-protein-based beverages. Using UHPLC-TOF-MS analyses along with sensory profile comparisons, microbial species such as , , , , and were preselected from an entire culture collection and found to be effective in improving the overall flavor impression by reducing bitter off-notes and enhancing aroma profiles. Notably, NCC533 and NCC660 exhibited controlled proteolytic activities after 48 h of fermentation, enriching the matrix with taste-active amino acids, nucleotides, and peptides and improving umami and salty flavors while mitigating bitterness. This study has extended traditional volatile analyses, including nonvolatile metabolomic, proteomic, and sensory analyses and offering a detailed view of fermentation-induced biotransformations in pea-protein-based food. The results highlight the importance of combining comprehensive screening approaches and sensoproteomic techniques in developing tastier and more palatable plant-based protein products.
PubMed: 38953212
DOI: 10.1021/acs.jafc.4c02316 -
Nucleic Acids Research Jul 2024Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments...
Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments derive from just one source, 5' untranslated regions. Across the human genome we find evidence for 192 translated upstream regions, most of which would produce protein isoforms with extended N-terminal ends. Almost all of these N-terminal extensions are from highly abundant genes, which suggests that the novel regions we detect are just the tip of the iceberg. These upstream regions have characteristics that are not typical of coding exons. Their GC-content is remarkably high, even higher than 5' regions in other genes, and a large majority have non-canonical start codons. Although some novel upstream regions have cross-species conservation - five have orthologues in invertebrates for example - the reading frames of two thirds are not conserved beyond simians. These non-conserved regions also have no evidence of purifying selection, which suggests that much of this translation is not functional. In addition, non-conserved upstream regions have significantly more peptides in cancer cell lines than would be expected, a strong indication that an aberrant or noisy translation initiation process may play an important role in translation from upstream regions.
PubMed: 38953162
DOI: 10.1093/nar/gkae571 -
PeerJ 2024Cervical cancer remains a prevalent cancer among women, and reliance on surgical and radio-chemical therapies can irreversibly affect patients' life span and quality of...
BACKGROUND
Cervical cancer remains a prevalent cancer among women, and reliance on surgical and radio-chemical therapies can irreversibly affect patients' life span and quality of life. Thus, early diagnosis and further exploration into the pathogenesis of cervical cancer are crucial. Mass spectrometry technology is widely applied in clinical practice and can be used to further investigate the protein alterations during the onset of cervical cancer.
METHODS
Employing labeled-free quantitative proteomics technology and bioinformatics tools, we analyzed and compared the differential protein expression profiles between normal cervical squamous cell tissues and cervical squamous cell cancer tissues. GEPIA is an online website for analyzing the RNA sequencing expression data of tumor and normal tissue data from the TCGA and the GTEx databases. This approach aided in identifying qualitative and quantitative changes in key proteins related to the progression of cervical cancer.
RESULTS
Compared to normal samples, a total of 562 differentially expressed proteins were identified in cervical cancer samples, including 340 up-regulated and 222 down-regulated proteins. Gene ontology functional annotation, and KEGG pathway, and enrichment analysis revealed that the differentially expressed proteins mainly participated in metabolic pathways, spliceosomes, regulation of the actin cytoskeleton, and focal adhesion signaling pathways. Specifically, desmoplakin (DSP), protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L) and ANXA8 may be involved in cervical tumorigenesis by inhibiting apoptotic signal transmission. Moreover, we used GEPIA database to validate the expression of DSP, PPP1R13L and ANXA8 in human cancers and normal cervix.
CONCLUSION
In this study, we identified 562 differentially expressed proteins, and there were three proteins expressed higher in the cervical cancer tissues. The functions and signaling pathways of these differentially expressed proteins lay a theoretical foundation for elucidating the molecular mechanisms of cervical cancer.
Topics: Humans; Female; Uterine Cervical Neoplasms; Proteomics; Carcinoma, Squamous Cell; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Computational Biology
PubMed: 38952985
DOI: 10.7717/peerj.17444 -
Vavilovskii Zhurnal Genetiki I Selektsii Jun 2024We report the results of taxonomic studies on members of the family Micrococcaceae that, according to the 16S rRNA, internal transcribed spacer 1 (ITS1), average...
Phylogenetic and pangenomic analyses of members of the family Micrococcaceae related to a plant-growth-promoting rhizobacterium isolated from the rhizosphere of potato (Solanum tuberosum L.).
We report the results of taxonomic studies on members of the family Micrococcaceae that, according to the 16S rRNA, internal transcribed spacer 1 (ITS1), average nucleotide identity (ANI), and average amino acid identity (AAI) tests, are related to Kocuria rosea strain RCAM04488, a plant-growth-promoting rhizobacterium (PGPR) isolated from the rhizosphere of potato (Solanum tuberosum L.). In these studies, we used whole-genome phylogenetic tests and pangenomic analysis. According to the ANI > 95 % criterion, several known members of K. salina, K. polaris, and K. rosea (including K. rosea type strain ATCC 186T) that are related most closely to isolate RCAM04488 in the ITS1 test should be assigned to the same species with appropriate strain verification. However, these strains were isolated from strongly contrasting ecological and geographical habitats, which could not but affect their genotypes and phenotypes and which should be taken into account in evaluation of their systematic position. This contradiction was resolved by a pangenomic analysis, which showed that the strains differed strongly in the number of accessory and strain-specific genes determining their individuality and possibly their potential for adaptation to different ecological niches. Similar results were obtained in a full-scale AAI test against the UniProt database (about 250 million records), by using the AAI-profiler program and the proteome of K. rosea strain ATCC 186T as a query. According to the AAI > 65 % criterion, members of the genus Arthrobacter and several other genera belonging to the class Actinomycetes, with a very wide geographical and ecological range of sources of isolation, should be placed into the same genus as Kocuria. Within the paradigm with vertically inherited phylogenetic markers, this could be regarded as a signal for their following taxonomic reclassification. An important factor in this case may be the detailing of the gene composition of the strains and the taxonomic ratios resulting from analysis of the pangenomes of the corresponding clades.
PubMed: 38952705
DOI: 10.18699/vjgb-24-35 -
Aging Cell Jul 2024Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration...
Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aβ accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.
PubMed: 38952076
DOI: 10.1111/acel.14231 -
BMC Veterinary Research Jun 2024Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant...
BACKGROUND
Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant metastasis, thereby improving overall survival rates. While acquiring molecular data before surgery offers significant potential benefits, the current protein biomarkers for monitoring disease progression in non-metastatic FMC (NmFMC) and metastatic FMC (mFMC) are limited. The objective of this study was to investigate the serum peptidome profiles of NmFMC and mFMC using liquid chromatography-tandem mass spectrometry. A cross-sectional study was conducted to compare serum peptidome profiles in 13 NmFMC, 23 mFMC and 18 healthy cats. The liquid chromatography-tandem mass spectrometry analysis was performed on non-trypsinized samples.
RESULTS
Out of a total of 8284 expressed proteins observed, several proteins were found to be associated with human breast cancer. In NmFMC, distinctive protein expressions encompassed double-stranded RNA-binding protein Staufen homolog 2 (STAU2), associated with cell proliferation, along with bromodomain adjacent to zinc finger domain 2A (BAZ2A) and gamma-aminobutyric acid type A receptor subunit epsilon (GABRE), identified as potential treatment targets. Paradoxically, positive prognostic markers emerged, such as complement C1q like 3 (C1QL3) and erythrocyte membrane protein band 4.1 (EPB41 or 4.1R). Within the mFMC group, overexpressed proteins associated with poor prognosis were exhibited, including B-cell lymphoma 6 transcription repressor (BCL6), thioredoxin reductase 3 (TXNRD3) and ceruloplasmin (CP). Meanwhile, the presence of POU class 5 homeobox (POU5F1 or OCT4) and laminin subunit alpha 1 (LAMA1), reported as metastatic biomarkers, was noted.
CONCLUSION
The presence of both pro- and anti-proliferative proteins was observed, potentially indicating a distinctive characteristic of NmFMC. Conversely, proteins associated with poor prognosis and metastasis were noted in the mFMC group.
Topics: Animals; Female; Cat Diseases; Cats; Tandem Mass Spectrometry; Mammary Neoplasms, Animal; Biomarkers, Tumor; Chromatography, Liquid; Cross-Sectional Studies; Neoplasm Metastasis; Proteomics
PubMed: 38951817
DOI: 10.1186/s12917-024-04148-y -
Chemosphere Jun 2024Marine ecosystems are under escalating threats from myriad environmental stressors, necessitating a deeper understanding of their impact on biodiversity and the health...
Marine ecosystems are under escalating threats from myriad environmental stressors, necessitating a deeper understanding of their impact on biodiversity and the health of sentinel organisms. In this study, we carried out a spatiotemporal multi-omic analysis of liquid biopsies collected from mussels (Mytilus spp.) in marine ecosystems of a national park. We delved into the epigenomic, transcriptomic, glycomic, proteomic, and microbiomic profiles to unravel the intricate interplay between ecosystem biodiversity and mussels' biological response to their environments. Our analysis revealed temporal fluctuations in the alpha diversity of the circulating microbiome associated with human activities. Analysis of the hemolymphatic circulating cell-free DNA (ccfDNA) provided information on the biodiversity and the presence of potential pathogens. Epigenomic analysis revealed widespread hypomethylation sites within the mitochondrial (mtDNA). Comparative transcriptomic and glycomic analyses highlighted differences in metabolic pathways and genes associated with immune and wound healing functions. This study demonstrates the potential of multi-omic analysis of liquid biopsy in sentinel to provide a holistic view of human activities' environmental impacts on marine coastal ecosystems. Overall, this approach has the potential to enhance the effectiveness and efficiency of various conservation efforts, leading to more informed decision-making and better outcomes for biodiversity and ecosystem conservation.
PubMed: 38950751
DOI: 10.1016/j.chemosphere.2024.142714 -
Proceedings of the National Academy of... Jul 2024-methyladenosine (mA) is a fundamentally important RNA modification for gene regulation, whose function is achieved through mA readers. However, whether and how mA...
-methyladenosine (mA) is a fundamentally important RNA modification for gene regulation, whose function is achieved through mA readers. However, whether and how mA readers play regulatory roles during fruit ripening and quality formation remains unclear. Here, we characterized SlYTH2 as a tomato mA reader protein and profiled the binding sites of SlYTH2 at the transcriptome-wide level. SlYTH2 undergoes liquid-liquid phase separation and promotes RNA-protein condensate formation. The target mRNAs of SlYTH2, namely mA-modified and associated with volatile synthesis, are enriched in SlYTH2-induced condensates. Through polysome profiling assays and proteomic analysis, we demonstrate that knockout of expedites the translation process of and , resulting in augmented production of aroma-associated volatiles. This aroma enrichment significantly increased consumer preferences for CRISPR-edited fruit over wild type. These findings shed light on the underlying mechanisms of mA in plant RNA metabolism and provided a promising strategy to generate fruits that are more attractive to consumers.
Topics: Solanum lycopersicum; Fruit; Adenosine; Gene Expression Regulation, Plant; Plant Proteins; Protein Biosynthesis; Odorants
PubMed: 38950372
DOI: 10.1073/pnas.2405100121 -
ACS Nano Jul 2024Raman spectroscopy has made significant progress in biosensing and clinical research. Here, we describe how surface-enhanced Raman spectroscopy (SERS) assisted with... (Review)
Review
Raman spectroscopy has made significant progress in biosensing and clinical research. Here, we describe how surface-enhanced Raman spectroscopy (SERS) assisted with machine learning (ML) can expand its capabilities to enable interpretable insights into the transcriptome, proteome, and metabolome at the single-cell level. We first review how advances in nanophotonics-including plasmonics, metamaterials, and metasurfaces-enhance Raman scattering for rapid, strong label-free spectroscopy. We then discuss ML approaches for precise and interpretable spectral analysis, including neural networks, perturbation and gradient algorithms, and transfer learning. We provide illustrative examples of single-cell Raman phenotyping using nanophotonics and ML, including bacterial antibiotic susceptibility predictions, stem cell expression profiles, cancer diagnostics, and immunotherapy efficacy and toxicity predictions. Lastly, we discuss exciting prospects for the future of single-cell Raman spectroscopy, including Raman instrumentation, self-driving laboratories, Raman data banks, and machine learning for uncovering biological insights.
PubMed: 38950145
DOI: 10.1021/acsnano.4c04282