TheClockgene is an essential regulator of circadian rhythms. It encodes a member of the basic helix-loop-helix/PER-ARNT-SIM family of transcription factors known to play a central role in the control ...of diverse cellular events. Previously we described the functional identification and molecular isolation of theClockgene in the mouse, its interaction with the BMAL1 protein, and the role of this complex as a transcriptional activator in the circadian pacemaker. Here, we report the cloning, exon organization, chromosomal location, and mRNA expression of the humanCLOCKgene. The coding sequence of humanCLOCKextends for 2538 bp and is 89% identical to its mouse ortholog; its deduced amino acid sequence is 846 residues long and is 96% identical to mouse CLOCK. Radiation hybrid mapping localized humanCLOCKto the long arm of human chromosome 4 (4q12). Direct sequencing of a genomicCLOCKclone indicated that the coding sequence of humanCLOCKextends over 20 exons and that its intron/exon organization is identical to that of the mouse ortholog. Northern blot analysis indicated widespread expression of two major transcripts of 8 and 10 kb, andin situhybridization of human brain tissue revealed elevated expression ofCLOCKmRNA in the suprachiasmatic nuclei, the locus of circadian control in mammals, and in the cerebellum. Comparison of cDNA clones revealed two single nucleotide polymorphisms in noncoding sequence flanking theCLOCKopen reading frame. The central role ofClockin the organization of circadian rhythms suggests that it will be a useful candidate gene for genetic analyses of disorders associated with dysfunction of the circadian system.
We used positional cloning to identify the circadian Clock gene in mice. Clock is a large transcription unit with 24 exons spanning ∼100,000 bp of DNA from which transcript classes of 7.5 and ∼10 kb ...arise. Clock encodes a novel member of the bHLH–PAS family of transcription factors. In the Clock mutant allele, an A→T nucleotide transversion in a splice donor site causes exon skipping and deletion of 51 amino acids in the CLOCK protein. Clock is a unique gene with known circadian function and with features predicting DNA binding, protein dimerization, and activation domains. CLOCK represents the second example of a PAS domain–containing clock protein (besides Drosophila PERIOD), which suggests that this motif may define an evolutionarily conserved feature of the circadian clock mechanism.
Alien hand syndrome and dystonia in a pediatric patient Soman, Teesta; Steeves, Thomas D L; Lang, Anthony E
Movement disorders : official journal of the Movement Disorder Society,
07/2009, Letnik:
24, Številka:
10
Report
While microplastics have been recently detected in human blood and the placenta, their impact on human health is not well understood. Using a mouse model of environmental exposure during pregnancy, ...our group has previously reported that exposure to polystyrene micro- and nanoplastics throughout gestation results in fetal growth restriction. While polystyrene is environmentally relevant, polyethylene is the most widely produced plastic and amongst the most commonly detected microplastic in drinking water and human blood. In this study, we investigated the effect of maternal exposure to polyethylene micro- and nanoplastics on fetal growth and placental function. Healthy, pregnant CD-1 dams were divided into three groups: 10
ng/L of 740-4990 nm polyethylene with surfactant in drinking water (n = 12), surfactant alone in drinking water (n = 12) or regular filtered drinking water (n = 11). At embryonic day 17.5, high-frequency ultrasound was used to investigate the placental and fetal hemodynamic responses following exposure. While maternal exposure to polyethylene did not impact fetal growth, there was a significant effect on placental function with a 43% increase in umbilical artery blood flow in the polyethylene group compared to controls (p < 0.01). These results suggest polyethylene has the potential to cause adverse pregnancy outcomes through abnormal placental function.
Mosquitoes are important vectors for human and animal diseases. Genetic markers, like the mitochondrial COI gene, can facilitate the taxonomic classification of disease vectors, vector-borne disease ...surveillance, and prevention. Within the control region (CR) of the mitochondrial genome, there exists a highly variable and poorly studied non-coding AT-rich area that contains the origin of replication. Although the CR hypervariable region has been used for species differentiation of some animals, few studies have investigated the mosquito CR. In this study, we analyze the mosquito mitogenome CR sequences from 125 species and 17 genera. We discovered four conserved motifs located 80 to 230 bp upstream of the 12S rRNA gene. Two of these motifs were found within all 392 Anopheles (An.) CR sequences while the other two motifs were identified in all 37 Culex (Cx.) CR sequences. However, only 3 of the 304 non-Culicidae Dipteran mitogenome CR sequences contained these motifs. Interestingly, the short motif found in all 37 Culex sequences had poly-A and poly-T stretch of similar length that is predicted to form a stable hairpin. We show that supervised learning using the frequency chaos game representation of the CR can be used to differentiate mosquito genera from their dipteran relatives.
Globally, the production of marine bivalves has been steadily increasing over the past several decades. As the effects of human population growth are magnified, bivalves help provide food security as ...a source of inexpensive protein. However, as climate change alters sea surface temperatures (SST), the physiology, and thus the survival, growth, and distribution of bivalves are being altered. Challenges with managing bivalves may become more pronounced, as the uncertainty associated with climate change makes it difficult to predict future production levels. Modelling techniques, applied to both climate change and bivalve bioenergetics, can be used to predict and explore the impacts of changing ocean temperatures on bivalve physiology, and concomitantly on aquaculture production. This study coupled a previously established high resolution climate model and two dynamic energy budget models to explore the future growth and distribution of two economically and ecologically important species, the eastern oyster (Crassotrea virginica), and the blue mussel (Mytilus edulis) along the Atlantic coast of Canada. SST was extracted from the climate model and used as a forcing variable in the bioenergetic models. This approach was applied across three discreet time periods: the past (1986-1990), the present (2016-2020), and the future (2046-2050), thus permitting a comparison of bivalve performance under different temporal scenarios. Results show that the future growth is variable both spatially and interspecifically. Modelling outcomes suggest that warming ocean temperatures will cause an increase in growth rates of both species as a result of their ectothermic nature. However, as the thermal tolerance of C. virginica is higher than M. edulis, oysters will generally outperform mussels. The predicted effects of temperature on bivalve physiology also provided insight into vulnerabilities (e.g. mortality) under future SST scenarios. Such information is useful for adapting future management strategies for both farmed and wild shellfish. Although this study focused on a geographically specific area, the approach of coupling bioenergetic and climate models is valid for species and environments across the globe.
Poly- and perfluoroalkyl substances (PFAS) are a group of compounds with uses in industry and many consumer products. Concerns about the potential health effects of these compounds resulted in ...regulation by the Stockholm Convention on the use of three of the most common PFAS, including perfluorooctanoic acid (PFOA). Thousands of PFAS remain in production that are unregulated and for which their toxicity is unknown. Our group recently identified a new class of PFAS, fluorotelomer ethoxylates (FTEOs), in indoor dust and industrial wastewater. In this study, we investigated the effect of PFAS on placental metabolism by exposing healthy, pregnant CD-1 mice to PFOA or FTEOs at one of three concentrations (0 ng/L (controls), 5 ng/L, 100 ng/L) (n = 7–8/group). While PFOA is banned and PFOA concentrations in human blood are decreasing, we hypothesize that FTEOs will cause adverse pregnancy outcomes similar to PFOA, the compounds they were meant to replace. Placental tissue samples were collected at embryonic day 17.5 and 1H solid-state magic angle spinning nuclear magnetic resonance spectroscopy was used to determine the relative concentration of placental metabolites (n = 18–20/group). At the highest concentration, the relative concentrations of glucose and threonine were increased and the relative concentration of creatine was decreased in the PFOA-exposed placentas compared to controls (p < 0.05). In contrast, the relative concentrations of asparagine and lysine were decreased and the relative concentration of creatine was increased in the FTEOs-exposed placentas compared to controls (p < 0.05). Partial least squares - discriminant analysis showed the FTEOs-exposed and control groups were significantly separated (p < 0.005) and pathway analysis found four biochemical pathways were perturbed following PFOA exposure, while one pathway was altered following FTEOs exposure. Maternal exposure to PFOA and FTEOs had a significant impact on the placental metabolome, with the effect depending on the pollutant. This work motivates further studies to determine exposure levels and evaluate associations with adverse outcomes in human pregnancies.
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•Fluorotelomer ethoxylates (FTEOs) were previously found to be environmentally persistent.•The health impacts of FTEOs are unknown.•Exposure of pregnant mice to FTEOs results in abnormal placental metabolism.
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