557 research outputs found
Translational Regulation of the DOUBLETIME/CKIĪ“/Īµ Kinase by LARK Contributes to Circadian Period Modulation
Full text linkThe Drosophila homolog of Casein Kinase I Ī“/Īµ, DOUBLETIME (DBT), is required for Wnt, Hedgehog, Fat and Hippo signaling as well as circadian clock function. Extensive studies have established a critical role of DBT in circadian period determination. However, how DBT expression is regulated remains largely unexplored. In this study, we show that translation of dbt transcripts are directly regulated by a rhythmic RNA-binding protein (RBP) called LARK (known as RBM4 in mammals). LARK promotes translation of specific alternative dbt transcripts in clock cells, in particular the dbt-RC transcript. Translation of dbt-RC exhibits circadian changes under free-running conditions, indicative of clock regulation. Translation of a newly identified transcript, dbt-RE, is induced by light in a LARK-dependent manner and oscillates under light/dark conditions. Altered LARK abundance affects circadian period length, and this phenotype can be modified by different dbt alleles. Increased LARK delays nuclear degradation of the PERIOD (PER) clock protein at the beginning of subjective day, consistent with the known role of DBT in PER dynamics. Taken together, these data support the idea that LARK influences circadian period and perhaps responses of the clock to light via the regulated translation of DBT. Our study is the first to investigate translational control of the DBT kinase, revealing its regulation by LARK and a novel role of this RBP in Drosophila circadian period modulation
The Drosophila FMRP and LARK RNA-binding proteins function together to regulate eye development and circadian behavior
Get PDFFragile X syndrome (FXS) is the most common form of hereditary mental retardation. FXS patients have a deficit for the fragile X mental retardation protein (FMRP) that results in abnormal neuronal dendritic spine morphology and behavioral phenotypes, including sleep abnormalities. In a Drosophila model of FXS, flies lacking the dfmr1 protein (dFMRP) have abnormal circadian rhythms apparently as a result of altered clock output. In this study, we present biochemical and genetic evidence that dFMRP interacts with a known clock output component, the LARK RNA-binding protein. Our studies demonstrate physical interactions between dFMRP and LARK, that the two proteins are present in a complex in vivo, and that LARK promotes the stability of dFMRP. Furthermore, we show genetic interactions between the corresponding genes indicating that dFMRP and LARK function together to regulate eye development and circadian behavior
Vibrio cholerae Infection of Drosophila melanogaster Mimics the Human Disease Cholera
Get PDFCholera, the pandemic diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, continues to be a major public health challenge in the developing world. Cholera toxin, which is responsible for the voluminous stools of cholera, causes constitutive activation of adenylyl cyclase, resulting in the export of ions into the intestinal lumen. Environmental studies have demonstrated a close association between V. cholerae and many species of arthropods including insects. Here we report the susceptibility of the fruit fly, Drosophila melanogaster, to oral V. cholerae infection through a process that exhibits many of the hallmarks of human disease: (i) death of the fly is dependent on the presence of cholera toxin and is preceded by rapid weight loss; (ii) flies harboring mutant alleles of either adenylyl cyclase, GsĪ±, or the Gardos K(+) channel homolog SK are resistant to V. cholerae infection; and (iii) ingestion of a K(+) channel blocker along with V. cholerae protects wild-type flies against death. In mammals, ingestion of as little as 25 Ī¼g of cholera toxin results in massive diarrhea. In contrast, we found that ingestion of cholera toxin was not lethal to the fly. However, when cholera toxin was co-administered with a pathogenic strain of V. cholerae carrying a chromosomal deletion of the genes encoding cholera toxin, death of the fly ensued. These findings suggest that additional virulence factors are required for intoxication of the fly that may not be essential for intoxication of mammals. Furthermore, we demonstrate for the first time the mechanism of action of cholera toxin in a whole organism and the utility of D. melanogaster as an accurate, inexpensive model for elucidation of host susceptibility to cholera
Sources of Airborne Endotoxins in Ambient Air and Exposure of Nearby CommunitiesāA Review
Get PDFEndotoxin is a bioaerosol component that is known to cause respiratory effects in exposed populations. To date, most research focused on occupational exposure, whilst much less is known about the impact of emissions from industrial operations on downwind endotoxin concentrations. A review of the literature was undertaken, identifying studies that reported endotoxin concentrations in both ambient environments and around sources with high endotoxin emissions. Ambient endotoxin concentrations in both rural and urban areas are generally below 10 endotoxin units (EU) mā3; however, around significant sources such as compost facilities, farms, and wastewater treatment plants, endotoxin concentrations regularly exceeded 100 EU mā3. However, this is affected by a range of factors including sampling approach, equipment, and duration. Reported downwind measurements of endotoxin demonstrate that endotoxin concentrations can remain above upwind concentrations. The evaluation of reported data is complicated due to a wide range of different parameters including sampling approaches, temperature, and site activity, demonstrating the need for a standardised methodology and improved guidance. Thorough characterisation of ambient endotoxin levels and modelling of endotoxin from pollution sources is needed to help inform future policy and support a robust health-based risk assessment process
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