Publications by authors named "RT Cox"

Drosophila oogenesis has long been an important model for understanding myriad cellular processes controlling development, RNA biology and patterning. Flies are easily fed drugs to disrupt various molecular pathways. However, this is often done under poor nutrient conditions that adversely affect oogenesis, thus making analysis challenging.

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As hubs of metabolism, mitochondria contribute critical processes to coordinate and optimize energy and intermediate metabolites. Drosophila Clueless (Clu) and vertebrate CLUH are ribonucleoproteins critical for supporting mitochondrial function; yet do so in multiple ways. Clu-CLUH bind mRNAs, and CLUH regulates mRNA localization and translation of mRNAs encoding proteins destined for mitochondrial import.

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oogenesis has long been an important model for understanding myriad cellular processes controlling development, RNA biology, and patterning. Flies are easily fed drugs to disrupt various molecular pathways. However, this is often done under poor nutrient conditions that adversely affect oogenesis, thus making analysis challenging.

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The cytoplasm is populated with many ribonucleoprotein (RNP) particles that post-transcriptionally regulate mRNAs. These membraneless organelles assemble and disassemble in response to stress, performing functions such as sequestering stalled translation pre-initiation complexes or mRNA storage, repression and decay. Clueless (Clu) is a conserved multi-domain ribonucleoprotein essential for mitochondrial function that forms dynamic particles within the cytoplasm.

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Mitochondria contain their own DNA, mitochondrial DNA, which encodes thirteen proteins. However, mitochondria require thousands of proteins encoded in the nucleus to carry out their many functions. Identifying the definitive mitochondrial proteome has been challenging as methods isolating mitochondrial proteins differ and different tissues and organisms may have specialized proteomes.

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In this study, we examine the cause and progression of mitochondrial diseases linked to the loss of mtRNase P, a three-protein complex responsible for processing and cleaving mitochondrial transfer RNAs (tRNA) from their nascent transcripts. When mtRNase P function is missing, mature mitochondrial tRNA levels are decreased, resulting in mitochondrial dysfunction. mtRNase P is composed of Mitochondrial RNase P Protein (MRPP) 1, 2, and 3.

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Unlabelled: There is a worldwide trend for women to have their first pregnancy later in life. However, as oocyte quality declines with maternal aging, this trend leads to an increase in subfertility. The cellular mechanisms underlying this decline in oocyte competence are poorly understood.

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Over a thousand nucleus-encoded mitochondrial proteins are imported from the cytoplasm; however, mitochondrial (mt) DNA encodes for a small number of critical proteins and the entire suite of mt:tRNAs responsible for translating these proteins. Mitochondrial RNase P (mtRNase P) is a three-protein complex responsible for cleaving and processing the 5'-end of mt:tRNAs. Mutations in any of the three proteins can cause mitochondrial disease, as well as mutations in mitochondrial DNA.

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Live imaging of Drosophila melanogaster ovaries has been instrumental in understanding a variety of basic cellular processes during development, including ribonucleoprotein particle movement, mRNA localization, organelle movement, and cytoskeletal dynamics. There are several methods for live imaging that have been developed. Due to the fact that each method involves dissecting individual ovarioles placed in media or halocarbon oil, cellular damage due to hypoxia and/or physical manipulation will inevitably occur over time.

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Drosophila Clueless (Clu) is a ribonucleoprotein that directly affects mitochondrial function. Loss of clu causes mitochondrial damage, and Clu associates with proteins on the mitochondrial outer membrane. Clu's subcellular pattern is diffuse throughout the cytoplasm, but Clu also forms large mitochondria-associated particles.

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Mitochondrial diseases are a prevalent, heterogeneous class of diseases caused by defects in oxidative phosphorylation, whose severity depends upon particular genetic mutations. These diseases can be difficult to diagnose, and current therapeutics have limited efficacy, primarily treating only symptoms. Because mitochondria play a pivotal role in numerous cellular functions, especially ATP production, their diminished activity has dramatic physiological consequences.

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Proteins encoded by mitochondrial DNA are translated using mitochondrially encoded tRNAs and rRNAs. As with nuclear encoded tRNAs, mitochondrial tRNAs must be processed to become fully functional. The mitochondrial form of ribonuclease P (mt:RNase P) is responsible for 5'-end maturation and is comprised of three proteins; mitochondrial RNase P protein (MRPP) 1 and 2 together with proteinaceous RNase P (PRORP).

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Mitochondrial function is tied to the nucleus, in that hundreds of proteins encoded by nuclear genes must be imported into mitochondria. While post-translational import is fairly well understood, emerging evidence supports that mitochondrial site-specific import, or co-translational import, also occurs. However, the mechanism and the extent to which it is used are not fully understood.

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Histone deacetylase inhibitors (HDIs) are under investigation for the treatment of a number of human health problems. HDIs have proven therapeutic value in refractory cases of cutaneous T-cell lymphoma. Electrocardiographic ST segment morphological changes associated with HDIs were observed during development.

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Cystic fibrosis (CF) is due to mutations in the CFTR gene, which prevents correct folding, trafficking and function of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. The dysfunctional effect of CFTR mutations, principally the F508del-CFTR mutant, is further manifested by hypersecretion of the pro-inflammatory chemokine interleukin-8 into the airway lumen, which further contributes to morbidity and mortality. We have hypothesized that microRNA (miR)-based therapeutics could rescue the dysfunctional consequences of mutant CFTR.

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Article Synopsis
  • Mitochondrial dysfunction is linked to neurodegenerative diseases like Parkinson's, but the exact processes leading to neuron death are still unclear.
  • PTEN-induced putative kinase 1 (PINK1) and Parkin (Park) are critical proteins that, when mutated, cause early-onset Parkinson's and are involved in targeting damaged mitochondria for destruction.
  • The study identifies the protein Clueless (Clu) as a significant player in mitochondrial function, showing it interacts with PINK1 and Parkin and may act as a negative regulator within the PINK1-Park pathway, thus playing a key role in maintaining mitochondrial quality control.
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Article Synopsis
  • There is a significant connection between heart disease and how heart cells use energy, with previous research showing that palmitate decreases heart cell contraction.
  • In this study, sodium acetate was found to temporarily reduce the contraction ability of isolated mouse heart cells while increasing the length of diastolic sarcomeres, without affecting the action potential duration.
  • The study concluded that acetate boosts calcium uptake in mitochondria, which indirectly influences the contraction of heart cells.
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Antigens obtained from the intestinal tract of filarial nematodes have been proposed as potential safe and effective vaccine candidates. Because they may be 'hidden' from the immune response during natural infection, yet accessible by antibodies induced by vaccination, intestinal antigens may have a low potential for eliciting allergic responses when vaccinating previously infected individuals. Despite prior promising data, vaccination with intestinal antigens has yet to be tested in a permissive model of filariasis.

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Mitochondria are critical for neuronal function due to the high demand of ATP in these cell types. During Drosophila development, neuroblasts in the larval brain divide asymmetrically to populate the adult central nervous system. While many of the proteins responsible for maintaining neuroblast cell fate and asymmetric cell divisions are known, little is know about the role of metabolism and mitochondria in neuroblast division and maintenance.

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We report the experimental realization of coherent electron spin flip in a modulation-doped CdTe quantum well. Coherent spin rotation is realized with an off-resonant laser pulse, which induces a polarization-dependent optical Stark shift in the trion resonance. Complete electron spin flip is made possible by a laser pulse designed to avoid excessive excitations of nearby exciton resonances and minimizes detrimental many-body effects.

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Parkinson's disease has been linked to altered mitochondrial function. Mutations in parkin (park), the Drosophila ortholog of a human gene that is responsible for many familial cases of Parkinson's disease, shorten life span, abolish fertility and disrupt mitochondrial structure. However, the role played by Park in mitochondrial function remains unclear.

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We report a remarkable enhancement of the magnetic moments of excitons as a result of their motion. This surprising result, which we have observed in magneto-optical studies of three distinct zinc-blende semiconductors, GaAs, CdTe, and ZnSe, becomes significant as the kinetic energy of the exciton becomes comparable with its Rydberg energy and is attributed to motionally induced changes in the internal structure of the exciton. The enhancement of the magnetic moment as a function of the exciton translational wave vector can be represented by a universal equation.

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Mitochondria in many species enter the young oocyte en mass from interconnected germ cells to generate the large aggregate known as the Balbiani body. Organelles and germ plasm components frequently associate with this structure. Balbiani body mitochondria are thought to populate the germ line, ensuring that their genomes will be inherited preferentially.

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