Many cellular functions are compartmentalized within the optimized environments of organelles. However, processing or storage of metabolites from the same pathway can occur in multiple organelles. Thus, spatially separated organelles need to cooperate functionally.
View Article and Find Full Text PDFProduction of hard X-ray via inverse Compton scattering at photon energies below 100 keV range aimed at potential applications in medicine and material research is reported. Experiments have been performed at the Brookhaven National Laboratory, Accelerator Test Facility, employing the counter collision of a 70 MeV, 0.3 nC electron beam with a near infra-red Nd: YAG laser (1064 nm wavelength) pulse containing ~ 100 mJ in a single shot basis.
View Article and Find Full Text PDFCoordinated spatio-temporal regulation of the determination and differentiation of neural stem cells is essential for brain development. Failure to integrate multiple factors leads to defective brain structures or tumour formation. Previous studies suggest changes of chromatin state are needed to direct neural stem cell differentiation, but the mechanisms are unclear.
View Article and Find Full Text PDFDrosophila melanogaster is a proven metazoan model to investigate the fundamentals of human genetic diseases including peroxisome-related disorders. Drosophila have facile cell and animal culture but with a relatively simpler genome and organ morphology compared to vertebrates. Drosophila Schneider 2 (S2) cells have been used extensively as a platform for investigating peroxisome functions like transport along the cytoskeleton via their amenability to RNA-interference (RNAi)-based gene knockdown.
View Article and Find Full Text PDFBoth peroxisomes and lipid droplets regulate cellular lipid homeostasis. Direct inter-organellar contacts as well as novel roles for proteins associated with peroxisome or lipid droplets occur when cells are induced to liberate fatty acids from lipid droplets. We have shown a non-canonical role for a subset of peroxisome-assembly [Peroxin (Pex)] proteins in this process in Drosophila.
View Article and Find Full Text PDFPhagocytosis, signal transduction, and inflammatory responses require changes in lipid metabolism. Peroxisomes have key roles in fatty acid homeostasis and in regulating immune function. We find that Drosophila macrophages lacking peroxisomes have perturbed lipid profiles, which reduce host survival after infection.
View Article and Find Full Text PDFPeroxisome biogenesis disorders (PBDs) are a group of metabolic developmental diseases caused by mutations in one or more genes encoding peroxisomal proteins. Zellweger syndrome spectrum (PBD-ZSS) results from metabolic dysfunction caused by damaged or non-functional peroxisomes and manifests as a multi-organ syndrome with significant morbidity and mortality for which there is no current drug therapy. Mild PBD-ZSS patients can exhibit a more progressive disease course and could benefit from the identification of drugs to improve the quality of life and extend the lifespan of affected individuals.
View Article and Find Full Text PDFResearch using the fruit fly has traditionally focused on understanding how mutations affecting gene regulation or function affect processes linked to animal development. Accordingly, flies have become an essential foundation of modern medical research through repeated contributions to our fundamental understanding of how their homologs of human genes function. Peroxisomes are organelles that metabolize lipids and reactive oxygen species like peroxides.
View Article and Find Full Text PDFThere is increasing interest in understanding potential impacts of complex pollutant profiles to long-lived species such as the green sea turtle (Chelonia mydas), a threatened megaherbivore resident in north Australia. Dietary ingestion may be a key exposure route for metals in these animals and marine plants can accumulate metals at higher concentrations than the surrounding environment. We investigated concentrations of 19 metals and metalloids in C.
View Article and Find Full Text PDFAging is characterized by a chronic, low-grade inflammation, which is a major risk factor for cardiovascular diseases. It remains poorly understood whether pro-inflammatory factors released from non-cardiac tissues contribute to the non-autonomous regulation of age-related cardiac dysfunction. Here, we report that age-dependent induction of cytokine unpaired 3 (upd3) in Drosophila oenocytes (hepatocyte-like cells) is the primary non-autonomous mechanism for cardiac aging.
View Article and Find Full Text PDFPeroxisomes are organelles in eukaryotic cells responsible for processing several types of lipids and management of reactive oxygen species. A conserved family of peroxisome biogenesis (, ) genes encode proteins essential to peroxisome biogenesis or function. In yeast and mammals, PEROXIN7 (PEX7) acts as a cytosolic receptor protein that targets enzymes containing a peroxisome targeting signal 2 (PTS2) motif for peroxisome matrix import.
View Article and Find Full Text PDFMultiple mechanisms tightly regulate mRNAs during their transcription, translation, and degradation. Of these, the physical localization of mRNAs to specific cytoplasmic regions is relatively easy to detect; however, linking localization to functional regulatory roles has been more difficult to establish. Historically, is a highly effective model to identify localized mRNAs and has helped identify roles for this process by regulating various cell activities.
View Article and Find Full Text PDFPeroxisomes are ubiquitous membrane-enclosed organelles involved in lipid processing and reactive oxygen detoxification. Mutations in human peroxisome biogenesis genes (, , or ) cause developmental disabilities and often early death. Pex5 and Pex7 are receptors that recognize different peroxisomal targeting signals called PTS1 and PTS2, respectively, and traffic proteins to the peroxisomal matrix.
View Article and Find Full Text PDFAs a laboratory animal, Drosophila melanogaster has made extensive contributions to understanding many areas of fundamental biology as well as being an effective model for human disease. Until recently, there was relatively little known about fly peroxisomes. There were early studies that examined the role of peroxisome enzymes during development of organs like the eye.
View Article and Find Full Text PDFThe gut has a central role in digestion and nutrient absorption, but it also serves in defending against pathogens, engages in mutually beneficial interactions with commensals, and is a major source of endocrine signals. Gut homeostasis is necessary for organismal health and changes to the gut are associated with conditions like obesity and diabetes and inflammatory illnesses like Crohn's disease. We report that peroxisomes, organelles involved in lipid metabolism and redox balance, are required to maintain gut epithelium homeostasis and renewal in Drosophila and for survival and development of the organism.
View Article and Find Full Text PDFAn intact actomyosin network is essential for anchoring polarity proteins to the cell cortex and maintaining cell size asymmetry during asymmetric cell division of neuroblasts (NBs). However, the mechanisms that control changes in actomyosin dynamics during asymmetric cell division remain unclear. We find that the actin-binding protein, Moesin, is essential for NB proliferation and mitotic progression in the developing brain.
View Article and Find Full Text PDFThe innate immune response is critical for animal homeostasis and is conserved from invertebrates to vertebrates. This response depends on specialized cells that recognize, internalize, and destroy microbial invaders through phagocytosis. This is coupled to autonomous or non-autonomous cellular signaling via reactive oxygen species (ROS) and cytokine production.
View Article and Find Full Text PDFThe Drosophila vestigial gene is required for proliferation and differentiation of the adult wing and for differentiation of larval and adult muscle identity. Vestigial is part of a multi-protein transcription factor complex, which includes Scalloped, a TEAD-class DNA binding protein. Binding Scalloped is necessary for translocation of Vestigial into the nucleus.
View Article and Find Full Text PDFPeroxisomes are membrane-bound organelles found in almost all eukaryotic cells. They perform specialized biochemical functions that vary with organism, tissue or cell type. Mutations in human genes required for the assembly of peroxisomes result in a spectrum of diseases called the peroxisome biogenesis disorders.
View Article and Find Full Text PDFMammalian DDX1 has been implicated in RNA trafficking, DNA double-strand break repair and RNA processing; however, little is known about its role during animal development. Here, we report phenotypes associated with a null Ddx1 (Ddx1(AX)) mutation generated in Drosophila melanogaster. Ddx1 null flies are viable but significantly smaller than control and Ddx1 heterozygous flies.
View Article and Find Full Text PDFHuman peroxisome biogenesis disorders are lethal genetic diseases in which abnormal peroxisome assembly compromises overall peroxisome and cellular function. Peroxisomes are ubiquitous membrane-bound organelles involved in several important biochemical processes, notably lipid metabolism and the use of reactive oxygen species for detoxification. Using cultured cells, we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins; required for peroxisome assembly and linked to peroxisome biogenesis disorders), and confirmed that at least 13 of them are required for normal peroxisome assembly.
View Article and Find Full Text PDFDrosophila melanogaster is used extensively as a model system to uncover genetic and molecular pathways that regulate various cellular activities. There are five members of the Argonaute protein family in Drosophila. Argonautes have been found to be localized to cytoplasmic ribonucleoprotein containing structures in both cultured Drosophila cells and developing embryos.
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