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Beejan Asady Claudia F. Dick Karen Ehrenman Tejram Sahu Julia D. Romano Isabelle Coppens 《PLoS pathogens》2020,16(12)
Inorganic ions such as phosphate, are essential nutrients required for a broad spectrum of cellular functions and regulation. During infection, pathogens must obtain inorganic phosphate (Pi) from the host. Despite the essentiality of phosphate for all forms of life, how the intracellular parasite Toxoplasma gondii acquires Pi from the host cell is still unknown. In this study, we demonstrated that Toxoplasma actively internalizes exogenous Pi by exploiting a gradient of Na+ ions to drive Pi uptake across the plasma membrane. The Na+-dependent phosphate transport mechanism is electrogenic and functionally coupled to a cipargarmin sensitive Na+-H+-ATPase. Toxoplasma expresses one transmembrane Pi transporter harboring PHO4 binding domains that typify the PiT Family. This transporter named TgPiT, localizes to the plasma membrane, the inward buds of the endosomal organelles termed VAC, and many cytoplasmic vesicles. Upon Pi limitation in the medium, TgPiT is more abundant at the plasma membrane. We genetically ablated the PiT gene, and ΔTgPiT parasites are impaired in importing Pi and synthesizing polyphosphates. Interestingly, ΔTgPiT parasites accumulate 4-times more acidocalcisomes, storage organelles for phosphate molecules, as compared to parental parasites. In addition, these mutants have a reduced cell volume, enlarged VAC organelles, defects in calcium storage and a slightly alkaline pH. Overall, these mutants exhibit severe growth defects and have reduced acute virulence in mice. In survival mode, ΔTgPiT parasites upregulate several genes, including those encoding enzymes that cleave or transfer phosphate groups from phosphometabolites, transporters and ions exchangers localized to VAC or acidocalcisomes. Taken together, these findings point to a critical role of TgPiT for Pi supply for Toxoplasma and also for protection against osmotic stresses. 相似文献
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Berti Francesco Romano Maria Rosaria Micoli Francesca Adamo Roberto 《Glycoconjugate journal》2021,38(4):401-409
Glycoconjugate Journal - Neisseria meningitidis is a major cause of bacterial meningitidis worldwide. Children less than five years and adolescents are particularly affected. Nearly all invasive... 相似文献
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We report the identification of four residual stations for Trifolium michelianum Savi (Fabaceae) in Sicily, whereas the species was documented to be extinct at the Gorgo Cerro station (western Sicily), the only locality previously reported in the literature. In addition to an update on the distribution of the species, a survey on the new Sicilian populations led to their biological, ecological and phytosociological characterization, as well as to an assessment of the risk factors. The species, here relegated to the limit of its distribution area, occurs in particularly sensitive and vulnerable environments, such as the “Mediterranean temporary ponds”, considered “priority” by the Council Directive 92/43/EEC. Moreover, a new Sicilian association (Trifolio micheliani–Glycerietumspicatae ass. nova), framed in the alliance Glycerio-Sparganion (class Phragmito-Magnocaricetea), is described. 相似文献
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Yaniv Harari Gal-Hagit Romano Lior Ungar Martin Kupiec 《Cell cycle (Georgetown, Tex.)》2013,12(22):3465-3470
Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic chromosomes, thus protecting their stability and integrity. They play important roles in DNA replication and repair and are central to our understanding of aging and cancer development. In rapidly dividing cells, telomere length is maintained by the activity of telomerase. About 400 TLM (telomere length maintenance) genes have been identified in yeast, as participants of an intricate homeostasis network that keeps telomere length constant. Two papers have recently shown that despite this extremely complex control, telomere length can be manipulated by external stimuli. These results have profound implications for our understanding of cellular homeostatic systems in general and of telomere length maintenance in particular. In addition, they point to the possibility of developing aging and cancer therapies based on telomere length manipulation. 相似文献
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Anita K. Gandhi Tao Shi Mingyu Li Ulf Jungnelius Alfredo Romano Josep Tabernero Salvatore Siena Peter H. Schafer Rajesh Chopra 《PloS one》2013,8(11)
This study assessed the immunomodulatory effects in previously treated KRAS-mutant metastatic colorectal cancer patients participating in a phase II multicenter, open-label clinical trial receiving lenalidomide alone or lenalidomide plus cetuximab. The main findings show the T cell immunostimulatory properties of lenalidomide as the drug induced a decrease in the percentage CD45RA+ naïve T cells 3-fold while increasing the percentage HLA-DR+ activated T helper cells and percentage total CD45RO+ CD8+ memory T cytotoxic cells, 2.6- and 2.1-fold respectively (p<0.0001). In addition, lenalidomide decreased the percentage of circulating CD19+ B cells 2.6-fold (p<0.0001). Lenalidomide increased a modest, yet significant, 1.4-fold change in the percentage of circulating natural killer cells. Our findings indicate that lenalidomide significantly activates T cells, suggestive of an immunotherapeutic role for this drug in settings of maintenance therapy and tumor immunity. Furthermore, reported for the first time is the effect of lenalidomide in combination with cetuximab on T cell function, including increases in circulating naïve and central memory T cells. In summary, lenalidomide and cetuximab have significant effects on circulating immune cells in patients with colorectal carcinoma.
Trial Registration
ClinicalTrials.gov NCT01032291相似文献80.
Kutralanathan Renganathan Jiayin Gu Mary E. Rayborn John S. Crabb Robert G. Salomon Robert J. Collier Michael A. Kapin Carmelo Romano Joe G. Hollyfield John W. Crabb 《PloS one》2013,8(10)