Publications by authors named "Mazzolini R"
Article Synopsis
- A non-pathogenic Mycoplasma pneumoniae is being used to create live biotherapeutic products for treating respiratory diseases, but there are concerns about its connection to Guillain-Barré syndrome (GBS) after infection.
- Research identified galactolipids, particularly galactocerebroside (GalCer), as likely triggers for autoimmune responses linked to GBS, leading scientists to engineer strains without genes for galactolipid biosynthesis.
- Some modified strains showed reduced antibody recognition from GBS patients; however, other glycolipids beyond GalCer were also found to influence this recognition, prompting discussions on selecting safe Mycoplasma strains for potential therapeutic use.
Article Synopsis
- ProTInSeq is a technique for identifying open reading frames (ORFs) in proteins by utilizing transposon insertions that signal when they fall within a protein-coding region.
- In Mycoplasma pneumoniae, ProTInSeq successfully identifies 83% of known proteins and discovers 158 previously unannotated proteins, including small ORF-encoded proteins (SEPs).
- This method enhances the understanding of proteomes by offering insights into translational noise and helps to expand the known SEP count from 27 to 329, with a significant portion predicted to have antimicrobial properties.
Article Synopsis
- * Deleting Snail1 in CAFs reduced their ability to polarize bone-marrow-derived macrophages (BMDMΦs) towards an immunosuppressive phenotype, compared to those exposed to active CAFs, which inhibited macrophage cytotoxicity.
- * Active CAFs also promoted gene expressions related to immunosuppression in macrophages and the activation of regulatory T cells (T-regs), suggesting that CAFs in the tumor microenvironment hinder anti-tumor immunity. *
Article Synopsis
- Engineered live bacteria, specifically a modified version of Mycoplasma pneumoniae, show promise in treating lung infections like ventilator-associated pneumonia, which often has high mortality rates.
- The researchers validated the safety of this modified bacterium in mice and enhanced its function by adding genes that target harmful bacteria and biofilms.
- Results indicate that the engineered strain effectively combats acute lung infections and can break down biofilms in medical devices, possibly improving treatment alongside existing antibiotics.
Article Synopsis
- Mycoplasma pneumoniae is a bacteria that causes atypical pneumonia, with its motility and infectivity linked to proteins P1 and P40/P90, which form an adhesion complex.
- The study determined the structures of P1 and P40/P90 using advanced techniques, revealing that the binding site for sialic acid is actually in P40/P90, not P1 as previously thought.
- Antibodies against the conserved portion of P1 showed potential in inhibiting the bacteria's adhesion, and findings suggest opportunities for developing new vaccines against M. pneumoniae infections.
Article Synopsis
- Aggregates of Pseudomonas aeruginosa create biofilms that protect against antibiotics and the immune system, contributing to various infectious diseases.
- Alginate, a polysaccharide made of β-D-mannuronate and α-L-guluronate, is a key component of these biofilms, and alginate lyases have been proposed as treatments to break them down.
- The study identified two specific alginate lyase enzymes from a crude extract that effectively degrade biofilms, highlighting that only those with both polyM and polyG activities can enhance the effectiveness of antibiotics.
Article Synopsis
- Identification of small open reading frames (smORFs) that encode small proteins (≤ 100 amino acids) is challenging but crucial for genome annotation and protein discovery.
- By using a new bioinformatics tool called RanSEPs alongside other "-omics" techniques, researchers analyzed and validated 109 bacterial small ORFomes through various methods like mass spectrometry.
- The findings indicated that up to 16% of proteins in bacteria could be classified as small proteins, with some potential small proteins originating from previously annotated non-coding RNAs; the study also found that many small proteins play roles in essential biological functions.
Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion, the Snail1 transcriptional factor also provides cells with cancer stem cell features. Since telomere maintenance is essential for stemness, we have examined the control of telomere integrity by Snail1. Fluorescence in situ hybridization (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC) have both a dramatic increase of telomere alterations and shorter telomeres.
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- The study investigates the role of EPHB6 in colorectal tumorigenesis, finding that its manipulation does not impact the growth or movement of colon cancer cells in various models.
- Using EphB6 knockout mice, researchers determined that the inactivation of EPHB6 does not efficiently initiate intestinal tumors or affect survival and tumor characteristics.
- However, introducing EPHB6 into colon cancer cells reduced lung metastasis, suggesting that the loss of EPHB6 is linked to increased metastatic spread in colorectal cancer.
Article Synopsis
- The report examines how antisense transcription influences the expression of the LEF1 transcription factor through a natural antisense transcript (NAT) derived from the LEF1 gene's promoter.
- In mesenchymal cells, the NAT is spliced, while in epithelial cells, it remains silent; however, in cells with mixed characteristics, the unspliced NAT is produced and inhibits LEF1 expression.
- The unspliced NAT interacts with the LEF1 promoter and promotes modifications that reduce LEF1 transcription, while the spliced form can counteract this inhibition by competing for the same promoter interaction.
Article Synopsis
- Adipogenesis, the process of fat cell formation, is primarily regulated by transcription factors like PPARγ and C/EBPα, but recent research shows that Snail inhibits this differentiation in certain cell types.
- A detailed analysis identified 574 proteins affected by Snail, including down-regulation of important transcription factors, with Nr2f6 being crucial for adipocyte differentiation.
- Snail's inhibition of Nr2f6 leads to increased expression of IL-17, which hinders adipogenesis; blocking IL-17 can counteract Snail's effects and promote fat cell development, highlighting Snail and Nr2f6's potential role in combating obesity.
Article Synopsis
- Activation of the small GTPase RHOA is linked to cancer, but its role in colorectal cancer is not well understood.
- Inactivation of RHOA promotes cancer progression and metastasis in colorectal cancer by enhancing Wnt/β-catenin signaling, leading to increased cell growth and invasive behavior.
- The research reveals RHOA as a potential tumor suppressor in colorectal cancer, suggesting that it helps inhibit tumor growth and spread, challenging previous beliefs about RHO GTPases.
Article Synopsis
- - Snail1 is a key transcriptional repressor that triggers epithelial-to-mesenchymal transition (EMT) and is crucial for maintaining stem cells, but its expression is low in adult animals.
- - Increased levels of Snail1 in mesenchymal cells enhance their tumorigenic potential, while its removal reduces tumor growth and prevents mesenchymal stem cells (MSCs) from forming sarcomas.
- - High Snail1 expression is found in human sarcomas, especially in undifferentiated tumors, which are linked to poorer patient outcomes, suggesting a significant role for Snail1 in sarcoma development.
Article Synopsis
- Brush border Myosin Ia (MYO1A) is frequently mutated in colorectal tumors with microsatellite instability (MSI), and mutations in the gene were found at a higher rate in gastric tumors compared to endometrial tumors (46.8% vs. 6.2%).
- In gastric cancer, mutant MYO1A(7A) loses its membrane localization and shows reduced protein stability, suggesting a mechanism by which it might promote tumor growth.
- Promoter hypermethylation of MYO1A negatively affects its expression in non-MSI gastric tumors, indicating that both genetic and epigenetic changes in MYO1A could provide growth advantages to gastric cancer cells.
Article Synopsis
- * A significant observation was that the intestinal-specific protein villin is down-regulated or absent in a large proportion of MSI CRC cases, and its loss is linked to poorly differentiated histology and worse outcomes for patients.
- * The regulation of villin expression is influenced by the homeobox transcription factor Cdx-1, which, when either overexpressed or reduced, directly affects villin promoter activity, indicating that Cdx-1 loss contributes to the poor differentiation seen in these cancers.
Brush border myosin Ia has tumor suppressor activity in the intestine.
Proc Natl Acad Sci U S A
January 2012
The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors.
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- Irinotecan is a common treatment for colorectal cancer but only 20-30% of patients respond positively, highlighting the need for biomarkers to predict patient outcomes.
- Researchers conducted a study identifying aprataxin (APTX) as a potential biomarker linked to irinotecan sensitivity by analyzing colorectal cancer cell lines and patient tumor samples.
- High levels of aprataxin in tumors were associated with poorer survival outcomes, indicating that low aprataxin levels could help identify patients who may benefit more from alternative therapies instead of irinotecan.
Article Synopsis
- * Research using animal models highlights that low levels of EphB4 lead to faster tumor growth and greater proliferation in intestinal tumors, resulting in larger tumors and a reduced lifespan for affected mice.
- * The study shows that EphB4 acts as a tumor suppressor by regulating cell proliferation and the invasive potential of cancer cells through changes in gene expression related to the extracellular matrix and cell attachment.
[The Accademia dei Lincei (1603-1630) and the Accademia del Cimento (1657-1667].
Acta Hist Leopoldina
August 2010
The development of scientific academies during the 17th century in the old Italian States is illustrated on the basis of two examples: that of the Accademia dei Lincei with seat in Rome and that of the Accademia del Cimento with seat in the Grand Duchy of Tuscany. After a short survey of their activities follow some reflections on the causes of their ending.
View Article and Find Full Text PDFThe author places Grmek's editorial within the flux of the historiographical debate which, since the middle of the 1970s, has concentrated on two major crises due to the end of social science-oriented 'scientific history' and to the 'linguistic turn'. He also argues that Grmek's historiographical work of the 1980s and 1990s was to some extent an alternative to certain observed changes in historical fashion and has achieved greater intelligibility because of its commitment to a rational vision of science and historiography.
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