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| 2. |
- Al-Smadi, Derar, 1983-, et al.
(author)
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Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di-, and Tri-Hydroxypentanones
- 2019
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In: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 84:11, s. 6982-6991
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Journal article (peer-reviewed)abstract
- Polyhydroxylated compounds are building blocks for the synthesis of carbohydrates and other natural products. Their synthesis is mainly achieved by different synthetic versions of aldol-coupling reactions, catalyzed either by organocatalysts, enzymes or metal-organic catalysts. We have investigated the formation of 1,4-substituted 2,3-dihydroxybutan-1-one derivatives from para- and meta-substituted phenylacetaldehydes by three distinctly different strategies. The first involved a direct aldol reaction with hydroxyacetone, dihydroxyacetone or 2-hydroxyacetophenone, catalyzed by the cinchona derivative cinchonine. The second was reductive cross-coupling with methyl or phenyl glyoxal promoted by SmI2 resulting in either 5-substituted 3,4-dihydroxypentan-2-ones or 1,4 bis-phenyl substituted butanones, respectively. Finally, in the third case, aldolase catalysis was employed for synthesis of the corresponding 1,3,4-trihydroxylated pentan-2-one derivatives. The organocatalytic route with cinchonine generated distereomerically enriched syn products (de = 60−99 %), with moderate enantiomeric excesses (ee = 43−56%), but did not produce aldols with either hydroxyacetone or dihydroxyacetone as donor ketones. The SmI2-promoted reductive cross-coupling generated product mixtures with diastereomeric and enantiomeric ratios close to unity. This route allowed for the production of both 1-methyl- and 1-phenylsubstituted 2,3-dihydroxybutanones, at yields between 40−60%. Finally, the biocatalytic approach resulted in enantiopure syn (3R,4S) 1,3,4-trihydroxypentan-2-ones.
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| 3. |
- Al-Smadi, Derar, 1983-, et al.
(author)
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Synthesis of substrates for aldolase-catalyzed reactions : A comparison of methods for the synthesis of substituted phenylacetaldehydes
- 2018
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In: Synlett. - : Georg Thieme Verlag KG. - 0936-5214 .- 1437-2096. ; 29:9, s. 1187-1190
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Journal article (peer-reviewed)abstract
- Methods for the synthesis of phenylacetaldehydes (oxidation, one-carbon chain extension) were compared by using the synthesis of 4-methoxyphenylacetaldehyde as a model example. Oxidations of 4-methoxyphenylethanol with activated DMSO (Swern oxidation) or manganese dioxide gave unsatisfactory results; whereas oxidation with 2-iodoxybenzoic add (IBX) produced 4-methoxyphenylacetaldehyde in reasonable (75%) yield. However, Wittig-type one-carbon chain extension with methoxymethylene-triphenylphosphine followed by hydrolysis gave an excellent (81% overall) yield of 4-methoxyphenylacetaldehyde from 4-methoxybenzaldehyde (a cheap starting material). This approach was subsequently used to synthesise a set of 10 substituted phenylacetaldehydes in good to excellent yields.
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| 4. |
- Allard, Christina, et al.
(author)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Other publication (pop. science, debate, etc.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 5. |
- Anthony, Niklas
(author)
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Laser Interaction with Minerals Common on Asteroids
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Asteroids are worth studying for three reasons: planetary protection, industrial applications, and scientific knowledge. It is critical we develop technologies capable of diverting objects on collision courses with our planet. We can use the same technology to move or process asteroids and comets for materials to build structures or refuel in Low-Earth Orbit. Asteroids are also windows into the past; they were formed in the early Solar System, and could potentially have been the source of water and/or life on Earth. There are unique challenges to manipulating an asteroid or asteroid materials, which means that much of what we know about material processing needs to be revamped to fit the situation. One of the motivating drives of this research was that a laser would be an excellent tool to perform many tasks at an asteroid.One process of interest is laser drilling. The surface composition of asteroids is altered by aeons of space weathering; by studying the subsurface composition we can ascertain just how much it is altered and possibly by which processes. It is possible that hydrated minerals or ices exist below the surface as well, which are of great economic interest in asteroid mining. One of the greatest challenges to get under the surface of an asteroid is the low gravity: any forces or torques generated by a sampling mechanism may tip the spacecraft or launch it into deep space. A laser does not generate any significant forces, and can even be used without having to land; lasers do use a lot of electric power so the laser parameters need to be optimized to minimize the size and power requirements of the spacecraft. We found that nearly 1-cm deep holes can be made with as little as 18~J of energy using a 300-W laser.Laser ablation has been studied as a mechanism to redirect asteroids, but it is not particularly energy efficient at material removal. If the idea is to create a momentum exchange by removing surface material beyond an object's gravitational pull, then there could perhaps be more energy efficient mechanisms. One mechanism we investigated was spallation, where the shock wave of a laser pulse breaks off a relatively large chunk of material without having to melt and vaporize it. We found that spallation may be many times more energy efficient than ablation.Laser welding of metals has been of industrial interest for decades, though the welding of two different materials is still a challenge. We sought to develop a laser-based wire-attachment mechanism that can be used to anchor spacecraft to the surface of a small body or to maneuver boulders or small asteroids. When attempting to follow a traditional welding process, it was found that the two melt pools would not mix, and if it did, it was very weak. Instead, we used the laser to drill a hole and melt a wire while inserting it into the hole. This produced a solid anchor with a hold strength of up to 120~N.
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| 6. |
- Bergstrand, Sofie, et al.
(author)
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Biallelic mutations in WRAP53 result in dysfunctional telomeres, Cajal bodies and DNA repair, thereby causing Hoyeraal-Hreidarsson syndrome
- 2020
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In: Cell Death and Disease. - : Nature Publishing Group. - 2041-4889. ; 11:4
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Journal article (peer-reviewed)abstract
- Approximately half of all cases of Hoyeraal-Hreidarsson syndrome (HHS), a multisystem disorder characterized by bone marrow failure, developmental defects and very short telomeres, are caused by germline mutations in genes related to telomere biology. However, the varying symptoms and severity of the disease indicate that additional mechanisms are involved. Here, a 3-year-old boy with HHS was found to carry biallelic germline mutations in WRAP53 (WD40 encoding RNA antisense to p53), that altered two highly conserved amino acids (L283F and R398W) in the WD40 scaffold domain of the protein encoded. WRAP53 beta (also known as TCAB1 or WDR79) is involved in intracellular trafficking of telomerase, Cajal body functions and DNA repair. We found that both mutations cause destabilization, mislocalization and faulty interactions of WRAP53 beta, defects linked to misfolding by the TRiC chaperonin complex. Consequently, WRAP53 beta HHS mutants cannot elongate telomeres, maintain Cajal bodies or repair DNA double-strand breaks. These findings provide a molecular explanation for the pathogenesis underlying WRAP53 beta-associated HHS and highlight the potential contribution of DNA damage and/or defects in Cajal bodies to the early onset and/or severity of this disease.
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| 7. |
- Blazic, Marija, et al.
(author)
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High-throughput selection of (new) enzymes : phage display-mediated isolation of alkyl halide hydrolases from a library of active-site mutated epoxide hydrolases
- 2024
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In: Faraday discussions. - : Royal Society of Chemistry. - 1359-6640 .- 1364-5498.
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Journal article (peer-reviewed)abstract
- Epoxide hydrolase StEH1, from potato, is similar in overall structural fold and catalytic mechanism to haloalkane dehalogenase DhlA from Xanthobacter autotrophicus. StEH1 displays low (promiscuous) hydrolytic activity with (2-chloro)- and (2-bromo)ethanebenzene producing 2-phenylethanol. To investigate possibilities to amplify these very low dehalogenase activities, StEH1 was subjected to targeted randomized mutagenesis at five active-site amino acid residues and the resulting protein library was challenged for reactivity towards a bait chloride substrate. Enzymes catalyzing the first half-reaction of a hydrolytic cycle were isolated following monovalent phage display of the mutated proteins. Several StEH1 derived enzymes were identified with enhanced dehalogenase activities.
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| 8. |
- Bolte, S., et al.
(author)
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The Roots of Autism and ADHD Twin Study in Sweden (RATSS)
- 2014
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In: Twin Research and Human Genetics. - Stockholm : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 17:3, s. 164-176
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Journal article (peer-reviewed)abstract
- Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.
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| 9. |
- Chahtane, Hicham, et al.
(author)
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LEAFY activity is post-transcriptionally regulated by BLADE ON PETIOLE2 and CULLIN3 in Arabidopsis
- 2018
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In: New Phytologist. - : Wiley-Blackwell. - 0028-646X .- 1469-8137. ; 220:2, s. 579-592
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Journal article (peer-reviewed)abstract
- The Arabidopsis LEAFY (LFY) transcription factor is a key regulator of floral meristem emergence and identity. LFY interacts genetically and physically with UNUSUAL FLORAL ORGANS, a substrate adaptor of CULLIN1-RING ubiquitin ligase complexes (CRL1). The functionally redundant genes BLADE ON PETIOLE1 (BOP1) and -2 (BOP2) are potential candidates to regulate LFY activity and have recently been shown to be substrate adaptors of CULLIN3 (CUL3)-RING ubiquitin ligases (CRL3). We tested the hypothesis that LFY activity is controlled by BOPs and CUL3s in plants and that LFY is a substrate for ubiquitination by BOP-containing CRL3 complexes. When constitutively expressed, LFY activity is fully dependent on BOP2 as well as on CUL3A and B to regulate target genes such as APETALA1 and to induce ectopic flower formation. We also show that LFY and BOP2 proteins interact physically and that LFY-dependent ubiquitinated species are produced invitro in a reconstituted cell-free CRL3 system in the presence of LFY, BOP2 and CUL3. This new post-translational regulation of LFY activity by CRL3 complexes makes it a unique transcription factor subjected to a positive dual regulation by both CRL1 and CRL3 complexes and suggests a novel mechanism for promoting flower development.
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| 10. |
- Cornelius Chukwu, Eugenia, et al.
(author)
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Engineered Aldolases Catalyzing Stereoselective Aldol Reactions Between Aryl-Substituted Ketones and Aldehydes
- 2023
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In: Catalysis Science & Technology. - : Royal Society of Chemistry. - 2044-4753 .- 2044-4761.
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Journal article (peer-reviewed)abstract
- An A129G/R134V/S166G triple mutant of fructose 6-phosphate aldolase (FSA) from Escherichia coli was further engineered with the goal to generate new enzyme variants capable of catalyzing aldol reactions between aryl substituted ketones and aldehydes. Residues L107 and L163 were subjected to saturation mutagenesis and the resulting library of FSA variants was screened for catalytic activity with 2-hydroxyacetophenone and phenylacetaldehyde as substrates. A selection of aldolase variants was identified that catalyze the synthesis of 2,3-dihydroxy-1,4-diphenylbutanone. The most active enzyme variants contained an L163C substitution. An L107C/L163C variant was further tested for activity with substituted phenylacetaldehydes, and was shown to afford the production of the corresponding diphenyl substituted butanones with good diastereoselectivities (anti : syn dr of 10 to 30) and reasonable to good enantioselectivities of syn enantiomers (er of 5 to 25).
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