Two types of cannabinoid receptor have been discovered so far, CB(1) (2.1: CBD:1:CB1:), cloned in 1990, and CB(2) (2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on ...differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the other receptor type. Cannabinoid receptors CB(1) and CB(2) exhibit 48% amino acid sequence identity. Both receptor types are coupled through G proteins to adenylyl cyclase and mitogen-activated protein kinase. CB(1) receptors are also coupled through G proteins to several types of calcium and potassium channels. These receptors exist primarily on central and peripheral neurons, one of their functions being to inhibit neurotransmitter release. Indeed, endogenous CB(1) agonists probably serve as retrograde synaptic messengers. CB(2) receptors are present mainly on immune cells. Such cells also express CB(1) receptors, albeit to a lesser extent, with both receptor types exerting a broad spectrum of immune effects that includes modulation of cytokine release. Of several endogenous agonists for cannabinoid receptors identified thus far, the most notable are arachidonoylethanolamide, 2-arachidonoylglycerol, and 2-arachidonylglyceryl ether. It is unclear whether these eicosanoid molecules are the only, or primary, endogenous agonists. Hence, we consider it premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. Although pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging, other kinds of supporting evidence are still lacking.
Recent measurements over the Northern Hemisphere indicate that the long‐term decline in the atmospheric burden of ethane (C2H6) has ended and the abundance increased dramatically between 2010 and ...2014. The rise in C2H6 atmospheric abundances has been attributed to oil and natural gas extraction in North America. Existing global C2H6 emission inventories are based on outdated activity maps that do not account for current oil and natural gas exploitation regions. We present an updated global C2H6 emission inventory based on 2010 satellite‐derived CH4 fluxes with adjusted C2H6 emissions over the U.S. from the National Emission Inventory (NEI 2011). We contrast our global 2010 C2H6 emission inventory with one developed for 2001. The C2H6 difference between global anthropogenic emissions is subtle (7.9 versus 7.2 Tg yr−1), but the spatial distribution of the emissions is distinct. In the 2010 C2H6 inventory, fossil fuel sources in the Northern Hemisphere represent half of global C2H6 emissions and 95% of global fossil fuel emissions. Over the U.S., unadjusted NEI 2011 C2H6 emissions produce mixing ratios that are 14–50% of those observed by aircraft observations (2008–2014). When the NEI 2011 C2H6 emission totals are scaled by a factor of 1.4, the Goddard Earth Observing System Chem model largely reproduces a regional suite of observations, with the exception of the central U.S., where it continues to underpredict observed mixing ratios in the lower troposphere. We estimate monthly mean contributions of fossil fuel C2H6 emissions to ozone and peroxyacetyl nitrate surface mixing ratios over North America of ~1% and ~8%, respectively.
Key Points
We present a global C2H6 emission inventory and simulate C2H6 abundances for the year 2010 by using the GEOS‐Chem model
Northern Hemisphere fossil fuel sources represent 95% of global fossil fuel emissions and half of total global C2H6 emissions
NEI 2011 C2H6 emissions produce C2H6 mixing ratios that are 14–50% of those observed by recent aircraft observations across the U.S.
Cyclin C: The Story of a Non-Cycling Cyclin Ježek, Jan; Smethurst, Daniel G J; Stieg, David C ...
Biology (Basel, Switzerland),
01/2019, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle ...progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit transcriptional coactivator complex, the Mediator, to modulate RNA polymerase II-dependent transcription. Apart from its transcriptional regulatory function, recent research has revealed a novel signaling role for cyclin C at the mitochondria. Upon oxidative stress, cyclin C leaves the nucleus and directly activates the guanosine 5'-triphosphatase (GTPase) Drp1, or Dnm1 in yeast, to induce mitochondrial fragmentation. Importantly, cyclin C-induced mitochondrial fission was found to increase sensitivity of both mammalian and yeast cells to apoptosis. Here, we review and discuss the biology of cyclin C, focusing mainly on its transcriptional and non-transcriptional roles in tumor promotion or suppression.
Integration of high throughput DNA genotyping and RNA-sequencing data allows for the identification of genomic regions that control gene expression, known as expression quantitative trait loci ...(eQTL), on a whole genome scale. Intramuscular fat (IMF) content and carcass composition play important roles in metabolic and physiological processes in mammals because they influence insulin sensitivity and consequently prevalence of metabolic diseases such as obesity and type 2 diabetes. However, limited information is available on the genetic variants and mechanisms associated with IMF deposition in mammals. Thus, our hypothesis was that eQTL analyses could identify putative regulatory regions and transcription factors (TFs) associated with intramuscular fat (IMF) content traits.
We performed an integrative eQTL study in skeletal muscle to identify putative regulatory regions and factors associated with intramuscular fat content traits. Data obtained from skeletal muscle samples of 192 animals was used for association analysis between 461,466 SNPs and the transcription level of 11,808 genes. This yielded 1268 cis- and 10,334 trans-eQTLs, among which we identified nine hotspot regions that each affected the expression of > 119 genes. These putative regulatory regions overlapped with previously identified QTLs for IMF content. Three of the hotspots respectively harbored the transcription factors USF1, EGR4 and RUNX1T1, which are known to play important roles in lipid metabolism. From co-expression network analysis, we further identified modules significantly correlated with IMF content and associated with relevant processes such as fatty acid metabolism, carbohydrate metabolism and lipid metabolism.
This study provides novel insights into the link between genotype and IMF content as evident from the expression level. It thereby identifies genomic regions of particular importance and associated regulatory factors. These new findings provide new knowledge about the biological processes associated with genetic variants and mechanisms associated with IMF deposition in mammals.
Abstract A hierarchy of cellular stemness exists in certain cancers, and any successful strategy to treat such cancers would have to eliminate the self-renewing tumor-initiating cells at the apex of ...the hierarchy. The cellular microenvironment, in particular the extracellular matrix (ECM), is believed to have a role in regulating stemness. In this work, U251 glioblastoma cells are cultured on electrospun polystyrene (ESPS) scaffolds coated with an array of 7 laminin isoforms to provide a 3D model for stem cell-related genes and proteins expression studies. We observed collaboration between 3D context and laminins in promoting glioma stemness. Depending on the laminin isoform presented, U251 cells cultured on ESPS scaffolds (3D) exhibited increased expression of stemness markers compared to those cultured on tissue culture polystyrene (2D). Our results indicate the influence of 3D (versus 2D) context on integrin expression, specifically, the upregulation of the laminin-binding integrins alpha 6 and beta 4. By a colony forming assay, we showed enhanced clonogenicity of cells grown on ESPS scaffolds in collaboration with laminins 411, 421, 511 and 521. Evaluation of patient glioma databases demonstrated significant enrichment of integrin and ECM pathway networks in tumors of worse prognosis, consistent with our observations. The present results demonstrate how 3D versus 2D context profoundly affects ECM signaling, leading to stemness.
Objective
We aimed to identify generic measures of self-regulation and to examine the degree to which these measures fit a recently developed conceptual model of self-regulation in a rehabilitation ...context.
Data sources
Pubmed, Embase, PsycInfo, and CINAHL were searched.
Review methods
Articles were included if they were published between January 2015 and August 2020 and reported on empirical studies (trials and observational studies) using a measure of self-regulation or a related concept, in an adult rehabilitation population. Main content was analysed by linking all items of the selected measures to one or more of the six sub-themes of self-regulation: (1) insight into physical and cognitive impairments, (2) insight into the consequences of the impairments, (3) insight into abilities, (4) to be able to communicate limitations, (5) trust in body and functioning, and (6) make use of abilities.
Results
Two reviewers independently screened 7808 abstracts, resulting in the inclusion of 236 articles. In these articles, 80 different measures were used to assess self-regulation or related concept. Nineteen of these measures met the inclusion criteria and were included for the content analyses. Nine of these were self-efficacy measures. No measures covered four or more of the six sub-themes of self-regulation. The three sub-themes on gaining insights were covered less compared to the sub-domains ‘trust’ and ‘make use of abilities’.
Conclusions
Many measures on self-regulation exist None of these measures cover all six sub-themes of self-regulation considered important to measure self-regulation as a rehabilitation outcome.
In recent years the usage of machine learning techniques within data-intensive sciences in general and high-energy physics in particular has rapidly increased, in part due to the availability of ...large datasets on which such algorithms can be trained, as well as suitable hardware, such as graphic or tensor processing units, which greatly accelerate the training and execution of such algorithms. Within the HEP domain, the development of these techniques has so far relied on resources external to the primary computing infrastructure of the WLCG (Worldwide LHC Computing Grid). In this paper we present an integration of hardware-accelerated workloads into the Grid through the declaration of dedicated queues with access to hardware accelerators and the use of Linux container images holding a modern data science software stack. A frequent use-case in the development of machine learning algorithms is the optimization of neural networks through the tuning of their Hyper Parameters (HP). For this often a large range of network variations must be trained and compared, which for some optimization schemes can be performed in parallel - a workload well suited for Grid computing. An example of such a hyper-parameter scan on Grid resources for the case of flavor tagging within ATLAS is presented.
The need for the optimal use of land, without a yield penalty, in urban and peri-urban (UP) settlements is vital. This study investigated the effect of intercropping madumbe and rice with respect to ...yield and land productivity when irrigated with anaerobic baffled reactor (ABR) effluent under different irrigation water management techniques. It was hypothesized that intercropping under different irrigation water management techniques has no effect on the yield and land productivity. Field trials were conducted in the 2017 and 2018 cropping seasons with ABR effluent (without fertilizer) at the Newlands Mashu Experimental Site, Newlands East, Durban, South Africa. A randomized complete block design with 3 replications; cropping treatments of sole madumbe, sole rice and madumbe + rice (intercrop) and irrigation treatments of alternate wetting and drying (AWD), continuous flood irrigation (CFI) and wetting without flooding (WWF) was used. Growth and yield parameters at harvest were determined. Thereafter, land equivalent ratio (LER) was calculated to evaluate the productivity of the intercrop. The effect of intercropping was significant (P < 0.05) on the total number of irrigation events and total water use. There was a significant reduction (P < 0.05) in plant heights of both madumbe and rice at intercrop. However, the effect on plant height for treatment CFI was positive but not significant (P > 0.05) for both seasons. A significant (P < 0.05) reduction also occurred in the number of madumbe leaves/plant, and panicles/plant and tillers/plant for rice. Intercropping significantly reduced (P < 0.05) madumbe corm and rice grain yield over the two seasons relative to sole cropping. LER showed that intercropping madumbe with rice was not more productive (LER < 1) than sole cropping of madumbe. It was concluded that over the two-season period, intercropping madumbe and rice do not yield appreciably under any of the three irrigation management techniques applied and the study hypothesis is thus rejected.
Leaf-cutter ants perform a series of specialized behaviors in preparing plant substrates for their symbiotic fungus. This process may be related to contamination of workers by substances such as ...insecticides, leading us to hypothesize that substances are spread among workers through behaviors they perform to grow the fungus. To test this hypothesis, we analyzed the behavioral acts of workers during the processing of the pellets by using a fat-soluble tracing dye, since the active ingredient that composes toxic baits, used for control of leaf-cutter ants, is fat-soluble. The frequencies of performed behaviors were recorded and the number of dyed workers was assessed after fungus cultivation. The most frequent behavior is allogrooming and corresponds to 45.87% of the contamination process in workers, followed by holding, licking, and cutting pellets, which account for 40.22% of the process. After pellet processing, the workers had their external and internal morphological structures marked by the tracing dye—93.75% and 79.25%, respectively. These results confirm that behaviors performed during fungus cultivation contribute to dispersing substances such as insecticides, causing the contamination of workers.
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