A conserved U-rich RNA region implicated in regulation of translation in Plasmodium female gametocytes.

Translational repression (TR) plays an important role in post-transcriptional regulation of gene expression and embryonic development in metazoans. TR also regulates the expression of a subset of the cytoplasmic mRNA population during development of fertilized female gametes of the unicellular malaria parasite, Plasmodium spp. which results in the formation of a polar and motile form, the ookinete. We report the conserved and sex-specific regulatory role of either the 3’- or 5’-UTR of a subset of translationally repressed mRNA species as shown by almost complete inhibition of expression of a GFP reporter protein in the female gametocyte. A U-rich, TR-associated element, identified previously in the 3’-UTR of TR-associated transcripts, played an essential role in mediating TR and a similar region could be found in the 5’-UTR shown in this study to be active in TR. The silencing effect of this 5’-UTR was shown to be independent of its position relative to its ORF, as transposition to a location 3’ of the ORF did not affect TR. These results demonstrate for the first time in a unicellular organism that the 5’ or the 3’-UTR of TR-associated transcripts play an important and conserved role in mediating TR in female gametocytes

Optical Imaging of Tumor Response to Hyperbaric Oxygen Treatment and Irradiation in an Orthotopic Mouse Model of Head and Neck Squamous Cell Carcinoma

Purpose: Hyperbaric oxygen therapy (HBOT) is used in the treatment of radiation-induced tissue injury but its effect on (residual) tumor tissue is indistinct and therefore investigated in this study. Procedures: Orthotopic FaDu tumors were established in mice, and the response of the (irradiated) tumors to HBOT was monitored by bioluminescence imaging. Near infrared fluorescence imaging using AngioSense750 and Hypoxisense680 was applied to detect tumor vascular permeability and hypoxia. Results: HBOT treatment resulted in accelerated growth of non-irradiated tumors, but mouse survival was improved. Tumor vascular leakiness and hypoxia were enhanced after HBOT, whereas histological characteristics, epithelial-to-mesenchymal transition markers, and metastatic incidence were not influenced. Conclusions: Squamous cell carcinoma responds to HBOT with respect to tumor growth, vascular permeability, and hypoxia, which may have implications for its use in cancer patients. The ability to longitudinally analyze tumor characteristics highlights the versatility and potential of optical imaging methods in oncological research

The role of the neuroendocrine polypeptide 7B2: a molecular chaperone for prohormone convertase PC2 in the secretory pathway

Contains fulltext : mmubn000001_210329475.pdf (publisher's version ) (Open Access)Promotor : G. Martens167 p

The Neuroendocrine Chaperone 7b2 Can Enhance in-Vitro Pomc Cleavage by Prohormone Convertase Pc2

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Dissociation of the complex between the neuroendocrine chaperone 7B2 and prohormone convertase PC2 is not associated with proPC2 maturation

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Structural organization of the gene encoding the neuroendocrine chaperone 7B2

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The function of 7B2 as a molecular chaperone for a prohormone convertase

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Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo

Adherence of parasite-infected red blood cells (irbc) to the vascular endothelium of organs plays a key role in the pathogenesis of Plasmodium falciparum malaria. The prevailing hypothesis of why irbc adhere and sequester in tissues is that this acts as a mechanism of avoiding spleen-mediated clearance. Irbc of the rodent parasite Plasmodium berghei ANKA sequester in a fashion analogous to P. falciparum by adhering to the host receptor CD36. To experimentally determine the significance of sequestration for parasite growth, we generated a mutant P. berghei ANKA parasite with a reduced CD36-mediated adherence. Although the cognate parasite ligand binding to CD36 is unknown, we show that nonsequestering parasites have reduced growth and we provide evidence that in addition to avoiding spleen removal, other factors related to CD36-mediated sequestration are beneficial for parasite growth. These results reveal for the first time the importance of sequestration to a malaria infection, with implications for the development of strategies aimed at reducing pathology by inhibiting tissue sequestration.Host-parasite interactio