| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 3. |
- Deventer, Marie H., et al.
(författare)
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In vitro cannabinoid activity profiling of generic ban-evading brominated synthetic cannabinoid receptor agonists and their analogs
- 2024
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Ingår i: Drug Testing and Analysis. - : WILEY. - 1942-7603 .- 1942-7611. ; 16:6, s. 616-628
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Tidskriftsartikel (refereegranskat)abstract
- Following the enactment of a generic ban in China in 2021, the synthetic cannabinoid market has been evolving, now encompassing even wider structural diversity. Compounds carrying a brominated core such as ADB-5 Br-BUTINACA (ADMB-B-5Br-INACA) and tail-less analogs, such as ADB-5 Br-INACA (ADMB-5Br-INACA), MDMB-5 Br-INACA, and ADB-INACA (ADMB-INACA), have been detected since late 2021. This study investigated the cannabinoid receptor (CB) activation potential of synthesized (S)-enantiomers of these substances, as well as of two predicted analogs MDMB-5 Br-BUTINACA (MDMB-B-5Br-INACA) and ADB-5 F-BUTINACA (ADMB-B-5F-INACA), using CB1 and CB2 beta-arrestin 2 recruitment assays and a CB1 intracellular calcium release assay. Surprisingly, the tail-less (S)-ADB-5 Br-INACA and (S)-MDMB-5 Br-INACA retained CB activity, albeit with a decreased potency compared to their tailed counterparts (S)-ADB-5 Br-BUTINACA and (S)-MDMB-5 Br-BUTINACA, respectively, which were potent and efficacious CB1 agonists. Also, at CB2, tail-less analogs showed a lower potency but increased efficacy. Removing the bromine substitution ((S)-ADB-INACA) resulted in a reduced activity at CB1; however, this effect was less prominent at CB2. Looking at tailed analogs, replacing the bromine with a fluorine substitution ((S)-ADB-5 F-BUTINACA) resulted in an increased potency and efficacy at both receptors. Furthermore, as ADB-5 Br-INACA and MDMB-5 Br-INACA have been frequently detected together in Scottish prisons, this study also evaluated the CB1 receptor activation potential of different mixtures of their respective reference standards, showing no unexpected cannabimimetic effect of combining both substances. Lastly, two powders seized by Belgian Customs and confirmed to contain ADB-5 Br-INACA and MDMB-5 Br-INACA, respectively, were assessed for CB activity. Based on the comparison with their reference standards, varying degrees of purity were suspected. The enactment of the Chinese generic ban (2021) has majorly impacted the SCRA market, exemplified by the recent emergence of tail-less compounds and substances with a brominated core. CB1 and CB2 cannabinoid activity of six analogs was assessed using beta arr2 recruitment and Ca2+ release assays. Absence of a tail moiety still yielded cannabinoid activity albeit with lower potency, whereas tailed analogs were highly efficacious.image
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| 4. |
- Ji, Qinglei, et al.
(författare)
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A Modular Microfluidic Device via Multimaterial 3D Printing for Emulsion Generation
- 2018
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- 3D-printing (3DP) technology has been developing rapidly. However, limited studies on the contribution of 3DP technology, especially multimaterial 3DP technology, to droplet-microfluidics have been reported. In this paper, multimaterial 3D-printed devices for the pneumatic control of emulsion generation have been reported. A 3D coaxial flexible channel with other rigid structures has been designed and printed monolithically. Numerical and experimental studies have demonstrated that this flexible channel can be excited by the air pressure and then deform in a controllable way, which can provide the active control of droplet generation. Furthermore, a novel modular microfluidic device for double emulsion generation has been designed and fabricated, which consists of three modules: function module, T-junction module, and co-flow module. The function module can be replaced by (1) Single-inlet module, (2) Pneumatic Control Unit (PCU) module and (3) Dual-inlet module. Different modules can be easily assembled for different double emulsion production. By using the PCU module, double emulsions with different number of inner droplets have been successfully produced without complicated operation of flow rates of different phases. By using single and dual inlet module, various double emulsions with different number of encapsulated droplets or encapsulated droplets with different compositions have been successfully produced, respectively.
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| 5. |
- Lichti, Cheryl F., et al.
(författare)
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Integrated Chromosome 19 Transcriptomic and Proteomic Data Sets Derived from Glioma Cancer Stem-Cell Lines
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:1, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- One subproject within the global Chromosome 19 Consortium is to define chromosome 19 gene and protein expression in glioma-derived cancer stem cells (GSCs). Chromosome 19 is notoriously linked to glioma by 1p/19q codeletions, and clinical tests are established to detect that specific aberration. GSCs are tumor-initiating cells and are hypothesized to provide a repository of cells in tumors that can self-replicate and be refractory to radiation and chemotherapeutic agents developed for the treatment of tumors. In this pilot study, we performed RNA-Seq, label-free quantitative protein measurements in six GSC lines, and targeted transcriptomic analysis using a chromosome 19-specific microarray in an additional six GSC lines. The data have been deposited to the ProteomeXchange with identifier PXD000563. Here we present insights into differences in GSC gene and protein expression, including the identification of proteins listed as having no or low evidence at the protein level in the Human Protein Atlas, as correlated to chromosome 19 and GSC subtype. Furthermore, the upregulation of proteins downstream of adenovirus-associated integration site 1 (AAVS1) in GSC11 in response to oncolytic adenovirus treatment was demonstrated. Taken together, our results may indicate new roles for chromosome 19, beyond the 1p/19q codeletion, in the future of personalized medicine for glioma patients.
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| 6. |
- Nilsson, C. L., et al.
(författare)
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Chromosome 19 Annotations with Disease Speciation: A First Report from the Global Research Consortium
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 134-149
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Tidskriftsartikel (refereegranskat)abstract
- A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC–MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks.
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| 7. |
- Niu, Guoxiang, et al.
(författare)
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Subtropical forest macro-decomposers rapidly transfer litter carbon and nitrogen into soil mineral-associated organic matter
- 2024
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Ingår i: Forest Ecosystems. - 2095-6355. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Forest soils in tropical and subtropical areas store a significant amount of carbon. Recent frameworks to assess soil organic matter (SOM) dynamics under evolving global conditions suggest that dividing bulk SOM into particulate and mineral-associated organic matter (POM vs. MAOM) is a promising method for identifying how SOM contributes to reducing global warming. Soil macrofauna, earthworms, and millipedes have been found to play an important role in facilitating SOM processes. However, how these two co-existing macrofaunae impact the litter decomposition process and directly impact the formation of POM and MAOM remains unclear. Methods: Here, we set up a microcosm experiment, which consisted of 20 microcosms with four treatments: earthworm and litter addition (E), millipedes and litter addition (M), earthworm, millipedes, and litter addition (E+M), and control (only litter addition) in five replicates. The soil and litter were sterilized prior to beginning the incubation experiment to remove any existing microbes. After incubating the samples for 42 days, the litter properties (mass, C, and N contents), soil physicochemical properties, as well as the C and N contents, and POM and MAOM 13C abundance in the 0–5 and 5–10 cm soil layers were measured. Finally, the relative influences of soil physicochemical and microbial properties on the distribution of C and N in the soil fractions were analyzed. Results: The litter mass, C, and N associated with all four treatments significantly decreased after incubation, especially under treatment E+M (litter mass: −58.8%, litter C: −57.0%, litter N: −75.1%, respectively), while earthworm biomass significantly decreased under treatment E. Earthworm or millipede addition alone showed no significant effects on the organic carbon (OC) and total nitrogen (TN) content in the POM fraction, but joint addition of both significantly increased OC and TN regardless of soil depth. Importantly, all three macrofauna treatments increased the OC and TN content and decreased the 13C abundance in the MAOM fraction. More than 65% of the total variations in the distribution of OC and TN throughout the two fractions can be explained by a combination of soil physicochemical and microbial properties. Changes in the OC distribution in the 0–5 cm soil layer are likely due to a decrease in soil pH and an increase in arbuscular mycorrhizal fungi (AMF), while those in the 5–10 cm layer are probably caused by increases in soil exchangeable Ca and Mg, in addition to fungi and gram-negative (GN) bacteria. The observed TN distribution changes in the 0–5 cm soil likely resulted from a decrease in soil pH and increases in AMF, GN, and gram-negative (GP) bacteria, while TN distribution changes in the 5–10 cm soil could be explained by increases in exchangeable Mg and GN bacteria. Conclusions: The results indicate that the coexistence of earthworms and millipedes can accelerate the litter decomposition process and store more C in the MAOM fractions. This novel finding helps to unlock the processes by which complex SOM systems serve as C sinks in tropical forests and addresses the importance of soil macrofauna in maintaining C-neutral atmospheric conditions under global climate change.
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| 8. |
- Norman, Caitlyn, et al.
(författare)
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Detection in seized samples, analytical characterization, and in vitro metabolism of the newly emerged 5-bromo-indazole-3-carboxamide synthetic cannabinoid receptor agonists
- 2023
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Ingår i: Drug Testing and Analysis. - : WILEY. - 1942-7603 .- 1942-7611.
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances (NPS) and new structural scaffolds have emerged on the recreational drug market since the enactment of Chinese SCRA analog controls in 2021. This study reports the first SCRAs to be detected with a bromide at the 5 position (5 ' Br) on the phenyl ring of the indazole core and without a tail moiety. ADB-5 ' Br-INACA (ADMB-5 ' Br-INACA) and MDMB-5 ' Br-INACA were detected in seized samples from Scottish prisons, Belgian customs, and US forensic casework. The brominated analog with a tail moiety, ADB-5 ' Br-BUTINACA (ADMB-5 ' Br-BUTINACA), was also detected in Scottish prisons and US forensic casework. The metabolites of these compounds and the predicted compound MDMB-5 ' Br-BUTINACA were identified through incubation with primary human hepatocytes to aid in their toxicological identification. The bromide on the indazole remains intact on metabolites, allowing these compounds to be easily distinguished in toxicological samples from their non-brominated analogs. Glucuronidation was more common for tail-less analogs than their butyl tail-containing counterparts. Forensic toxicologists are advised to update their analytical methods with the characteristic ions for these compounds, as well as their anticipated urinary markers: amide hydrolysis and monoOH at tert-butyl metabolites (after beta-glucuronidase treatment) for ADB-5 ' Br-INACA; monoOH at tert-butyl and amide hydrolysis metabolites for ADB-5 ' Br-BUTINACA; and ester hydrolysis metabolites with additional metabolites for MDMB-5 ' Br-INACA and MDMB-5 ' Br-BUTINACA. Toxicologists should remain vigilant to the emergence of new SCRAs with halogenation of the indazole core and tail-less analogs, which have already started to emerge. This study reports the detection of the new synthetic cannabinoids ADB-5 ' Br-INACA and MDMB-5 ' Br-INACA in Scotland, Belgium, and the US, and ADB-5 ' Br-BUTINACA in Scotland and the US. These compounds, along with the predicted compound MDMB-5 ' Br-BUTINACA, were incubated with primary human hepatocytes to examine metabolic pathways and aid in toxicological identification.image
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| 9. |
- Wallgren, Jakob, et al.
(författare)
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Concise Synthesis of Potential 4-Hydroxy-5-fluoropentyl Side-Chain Metabolites of Four Synthetic Cannabinoids
- 2020
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Ingår i: Synlett. - : GEORG THIEME VERLAG KG. - 0936-5214 .- 1437-2096. ; 31:5, s. 517-520
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic cannabinoids are a group of compounds that act on the CB1 receptor and are used illicitly as substitutes for cannabis. Given the rapid and extensive metabolism of synthetic cannabinoids, urinary biomarkers are essential if proof of drug intake is to be obtained in forensic laboratories. To identify good biomarker candidates, the metabolism of synthetic cannabinoids must be studied and reference standards need to be acquired. Studies on the metabolism of synthetic cannabinoids containing a terminally fluorinated pentyl side chain have shown that hydroxylation can occur at the four position of the side chain. This makes the 4-hydroxy-5-fluoropentyl side-chain metabolite a good urinary biomarker for proving intake of the corresponding parent drug, as this compound cannot be formed from its nonfluorinated analogue. Here, a concise synthetic route to the 4-hydroxy-5-fluoropentyl side-chain metabolites of the synthetic cannabinoids STS-135, MAM-2201, AM-2201, and XLR-11 is reported.
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| 10. |
- Zhang, Jia Ming, et al.
(författare)
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An integrated micro-millifluidic processing system.
- 2018
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Ingår i: Lab on a chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 18:22, s. 3393-3404
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Tidskriftsartikel (refereegranskat)abstract
- The development of integrated microfluidic systems/platforms concerns many fields. Current remarkable integrated systems based on stacking multi-layer polydimethylsiloxane (PDMS) require complicated fabrication and operation and still remain challenging. We propose a novel micro-millifluidic processing system (MPS) comprising three core modules: a motherboard, a control panel and microfluidic chips. Fluids are handled in sub-millichannels in a motherboard and functional operations occur in microchannels in microfluidic chips. A motherboard with versatile functional units for fluid handling was monolithically fabricated via multimaterial 3D printing, which avoids multi-layer structures, and the major disadvantage of current 3D printing, i.e. low resolution, has been overcome by integrating novel microfluidic chips based on our developed maskless lithography platform. Both numerical and experimental studies were conducted to validate our system. Potential applications such as droplet generation and distribution, microfluidic mixing and simple bacterial resistance tests have been demonstrated via our MPS.
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