Theileria annulata and Theileria lestoquardi are deadly tick-borne parasites of cattle and sheep, respectively. These parasites are transmitted by Hyalomma ticks, and their geographical distributions partially overlap, with T. annulata having a wider range.
View Article and Find Full Text PDFis the causative agent of East Coast fever and Corridor disease, which are fatal, economically important diseases of cattle in eastern, central and southern Africa. Improved methods of control of the diseases are urgently required. The parasite transforms host lymphocytes, resulting in a rapid, clonal expansion of infected cells.
View Article and Find Full Text PDFCorridor disease (CD) is a fatal condition of cattle caused by buffalo-derived . Unlike the related condition, East Coast fever, which results from infection with cattle-derived , CD has not been extensively studied. We describe in detail the clinical and laboratory findings in cattle naturally infected with buffalo-derived .
View Article and Find Full Text PDFNeglected parasitic diseases remain a major public health issue worldwide, especially in tropical and subtropical areas. Human parasite diversity is very large, ranging from protozoa to worms. In most cases, more effective and new drugs are urgently needed.
View Article and Find Full Text PDFThe CD4/CD8 ratio is used as a marker of the immune regulation of T cell balance. When the ratio in peripheral blood is less than 1, this is considered an indication of immune suppression in an individual. Previous work on bovine Peripheral Blood Mononuclear Cells (PBMC) has consistently reported a ratio ≥1 as seen in other mammalian hosts, i.
View Article and Find Full Text PDFConstitutive c-Jun N-terminal kinase (JNK) activity characterizes bovine T and B cells infected with Theileria parva, and B cells and macrophages infected with Theileria annulata. Here, we show that T. annulata infection of macrophages manipulates JNK activation by recruiting JNK2 and not JNK1 to the parasite surface, whereas JNK1 is found predominantly in the host cell nucleus.
View Article and Find Full Text PDFOne powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets.
View Article and Find Full Text PDFChristian de Duve first coined the expression "autophagy" during his seminal work on the discovery of lysosomes, which led to him being awarded the Nobel Prize in Physiology or Medicine in 1974. The term was adopted to distinguish degradation of intracellular components from the uptake and degradation of extracellular substances that he called "heterophagy". Studies until the 1990s were largely observational/morphological-based until in 1993 Yoshinori Oshumi described a genetic screen in yeast undergoing nitrogen deprivation that led to the isolation of autophagy-defective mutants now better known as ATG (AuTophaGy-related) genes.
View Article and Find Full Text PDFApicomplexan parasites are responsible for a number of important human pathologies. Obviously, as Eukaryotes they share a number of cellular features and pathways with their respective host cells. One of them is autophagy, a process involved in the degradation of the cell's own components.
View Article and Find Full Text PDFOriginally described as a TGF-β-inducible gene, tsc-22 (Transforming growth factor-beta Stimulated Clone 22) encodes a transcriptional regulator affecting biological processes such as cell growth, differentiation, or apoptosis. Along with GILZ (Glucocorticoid-Induced Leucine Zipper), TSC-22 belongs to the evolutionary conserved TSC-22 Domain family. We previously showed that, in T-lymphocytes, GILZ expression was induced upon IL-2 withdrawal, delaying apoptosis through down-regulation of the pro-apoptotic protein BIM expression.
View Article and Find Full Text PDFThe GILZ (glucocorticoid-induced leucine zipper) protein has first been identified as a glucocorticoid-responsive gene and is now presented as a major regulator of inflammation. Expanding literature documents a role for GILZ as a mediator of the immuno-modulatory and anti-inflammatory effects of glucocorticoids, mainly through interference with key signal transduction pathways such as nuclear factor-kappa B (NF-kB) or activated protein-1 (AP-1). The TSC-22 (TGF-β-stimulated clone-22) protein is described as an apoptosis modulator and as a new tumor suppressor gene.
View Article and Find Full Text PDFSF-1 (NR5A1) overexpression can induce adrenocortical tumor formation in transgenic mice and is associated with more severe prognosis in patients with adrenocortical cancer. In this study we have identified Vanin-1 (Vnn1), a SF-1 target gene, as a novel modulator of the tumorigenic effect of Sf-1 overexpression in the adrenal cortex. Vanin-1 is endowed with pantetheinase activity, releasing cysteamine in tissues and regulating cell response to oxidative stress by modulating the production of glutathione.
View Article and Find Full Text PDFSteroidogenic Factor-1 (SF-1) is a nuclear receptor transcription factor that has an essential role in the development of adrenal glands and gonads and in the regulation of steroidogenic gene expression. Recent studies using genomic approaches have revealed that SF-1 also has an important role in regulating proliferation of adrenocortical cells and have revealed its role in the control of a variety of biological processes as diverse as angiogenesis, adhesion to the extracellular matrix, cytoskeleton dynamics, transcriptional and post-transcriptional regulation of gene expression and apoptosis in the adrenal cortex. The identification of the complete set of SF-1 target genes will be of great importance to open new avenues for therapeutic intervention in adrenal diseases.
View Article and Find Full Text PDFAdrenocortical tumors in children are usually diagnosed because of signs of virilization and their prognosis is poor. They possess several distinct pathological features compared to adrenocortical tumors in adults and have an exceptional prevalence in southern Brazil, where they are nearly invariably linked to the presence of a germline specific TP53 (R337H) mutation. Other important factors in childhood adrenocortical tumor pathogenesis are overexpression of the Steroidogenic Factor-1 transcription factor and imprinting defects in the 11p15 genomic region, causing overexpression of Insulin-like Growth Factor-2.
View Article and Find Full Text PDFGILZ (glucocorticoid-induced leucine zipper) is an ubiquitous protein whose expression is induced by glucocorticoids in lymphoid cells. We previously showed that GILZ expression is rapidly induced upon interleukin 2 deprivation in T-cells, protecting cells from apoptosis induced by forkhead box subgroup O3 (FOXO3). The aim of this work is to elucidate the molecular mechanism of FOXO factor inhibition by GILZ.
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