ORCID Profile
0000-0002-6126-2966
Current Organisations
Valdospan Pharmaceuticals
,
University of California, San Diego
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Publisher: Wiley
Date: 11-10-2022
Abstract: The question of how RNA, as the principal carrier of genetic information evolved is fundamentally important for our understanding of the origin of life. The RNA molecule is far too complex to have formed in one evolutionary step, suggesting that ancestral proto‐RNAs (first ancestor of RNA) may have existed, which evolved over time into the RNA of today. Here we show that isoxazole nucleosides, which are quickly formed from hydroxylamine, cyanoacetylene, urea and ribose, are plausible precursors for RNA. The isoxazole nucleoside can rearrange within an RNA‐strand to give cytidine, which leads to an increase of pairing stability. If the proto‐RNA contains a canonical seed‐nucleoside with defined stereochemistry, the seed‐nucleoside can control the configuration of the anomeric center that forms during the in‐RNA transformation. The results demonstrate that RNA could have emerged from evolutionarily primitive precursor isoxazole ribosides after strand formation.
Publisher: Wiley
Date: 07-12-2022
Abstract: Biorthogonal labelling with fluorescent small molecules is an indispensable tool for diagnostic and biomedical applications. In dye‐based 5‐ethynyl‐2′‐deoxyuridine (EdU) cell proliferation assays, augmentation of the fluorescent signal entails an overall enhancement in the sensitivity and quality of the method. To this end, a rapid, ergent synthetic procedure that provides ready‐to‐click pH‐insensitive rhodamine dyes exhibiting outstanding brightness was established. Compared to the shortest available synthesis of related high quantum‐yielding rhodamines, two fewer synthetic steps are required. In a head‐to‐head imaging comparison involving copper(I)‐catalyzed azide alkyne cycloaddition reactions with in vitro administered EdU, our new 3,3‐difluoroazetidine rhodamine azide outperformed the popular 5‐TAMRA‐azide, making it among the best available choices when it comes to fluorescent imaging of DNA. In a further exploration of the fluorescence properties of these dyes, a set of bis‐MPA dendrons carrying multiple fluorescein or rhodamine units was prepared by branching click chemistry. Fluorescence self‐quenching of fluorescein‐ and rhodamine‐functionalized dendrons limited the suitability of the dyes as labels in EdU‐based experiments but provided new insights into these effects.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-02-2022
Abstract: To determine the impact of genetic variants on the brain, we used genetically informed brain atlases in genome-wide association studies of regional cortical surface area and thickness in 39,898 adults and 9136 children. We uncovered 440 genome-wide significant loci in the discovery cohort and 800 from a post hoc combined meta-analysis. Loci in adulthood were largely captured in childhood, showing signatures of negative selection, and were linked to early neurodevelopment and pathways associated with neuropsychiatric risk. Opposing gradations of decreased surface area and increased thickness were associated with common inversion polymorphisms. Inferior frontal regions, encompassing Broca’s area, which is important for speech, were enriched for human-specific genomic elements. Thus, a mixed genetic landscape of conserved and human-specific features is concordant with brain hierarchy and morphogenetic gradients.
Publisher: Wiley
Date: 17-04-2018
Publisher: Wiley
Date: 30-10-2019
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-10-2019
Abstract: In the absence of biological catalysts and metabolism, can atmospheric and geochemical processes provide the substrates and conditions required for production of biological molecules? Becker et al. devised an abiotic synthetic scheme that allows for accumulation of both purine and pyrimidine nucleoside mono- and diphosphates (see the Perspective by Hud and Fialho). A key starting material for this chemistry, hydroxylamine and/or hydroxylamine disulfonate, can form under plausible early atmospheric conditions. Cycles between wet and dry conditions provide the environments necessary to complete formation of purine and pyrimidine bases essentially in one pot. Science , this issue p. 76 see also p. 32
Publisher: Wiley
Date: 30-10-2019
Publisher: CSIRO Publishing
Date: 28-07-2021
DOI: 10.1071/CH21140
Abstract: Certain cyclic sulfates (e.g. 23) together with various of their precursor sulfites (e.g. 21 and 22) have been prepared from the corresponding chiral, non-racemic bicyclo[2.2.2]octane-2,3-diols (e.g. 20). Such diols are obtained by engaging the corresponding enzymatically derived and enantiomerically enriched or homochiral cis-1,2-dihydrocatechol (e.g. 10) or certain derivatives in either inter- or intra-molecular Diels–Alder cycloaddition reactions. Other functionalities present within the title compounds can be chemoselectively manipulated without adversely affecting the associated sulfate residues.
Publisher: Wiley
Date: 05-11-2020
Publisher: eLife Sciences Publications, Ltd
Date: 15-06-2018
DOI: 10.7554/ELIFE.38297
Abstract: An artificially evolved ribozyme can catalyse the synthesis of RNA by using trinucleotide triphosphates as building blocks.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2018
DOI: 10.1038/S41467-017-02639-1
Abstract: The molecules of life were created by a continuous physicochemical process on an early Earth. In this hadean environment, chemical transformations were driven by fluctuations of the naturally given physical parameters established for ex le by wet–dry cycles. These conditions might have allowed for the formation of (self)-replicating RNA as the fundamental biopolymer during chemical evolution. The question of how a complex multistep chemical synthesis of RNA building blocks was possible in such an environment remains unanswered. Here we report that geothermal fields could provide the right setup for establishing wet–dry cycles that allow for the synthesis of RNA nucleosides by continuous synthesis. Our model provides both the canonical and many ubiquitous non-canonical purine nucleosides in parallel by simple changes of physical parameters such as temperature, pH and concentration. The data show that modified nucleosides were potentially formed as competitor molecules. They could in this sense be considered as molecular fossils.
Publisher: Cold Spring Harbor Laboratory
Date: 06-08-2021
DOI: 10.1101/2021.08.04.455143
Abstract: Despite their increasing application, the genetic and environmental etiology of global predicted brain ageing (PBA) indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown. We analyzed data from 734 men from the Vietnam Era Twin Study of Aging with repeated MRI assessments between the ages 52 to 72 years. Biometrical genetic analyses revealed significant and highly correlated estimates of additive genetic heritability ranging from 59% to 75%. Multivariate longitudinal modelling revealed that covariation between PBA at different timepoints could be explained by a single latent factor with 73% heritability. Our results suggest that genetic influences on PBA are detectable in midlife or earlier, are longitudinally very stable, and are largely explained by common genetic influences.
Publisher: Proceedings of the National Academy of Sciences
Date: 12-10-2020
Abstract: As the prevalence of pediatric obesity continues to rise, determining neurobiological mechanisms underlying longitudinal childhood weight gain is critically important for informing early intervention and prevention strategies. We use an MRI technique to probe nucleus accumbens (NAcc) tissue microstructure and predict waist circumference after 1 y. We find that increased cell density in the NAcc is strongly associated with obesity in a large cohort of children and predicts future weight gain independent of waist circumference at baseline. These results extend animal studies showing a vicious cycle in which diet-induced neuroinflammation leads to disruption of the brain’s reward circuitry and subsequently promotes further unhealthy eating and weight gain.
Publisher: Public Library of Science (PLoS)
Date: 09-01-2018
Publisher: American Chemical Society (ACS)
Date: 26-09-2022
DOI: 10.1021/ACS.BIOCONJCHEM.2C00353
Abstract: Here we describe the development of a novel click chemistry-based method for the generation and lification of full-length cDNA libraries from total RNA, while avoiding the need for problematic template-switching (TS) reactions. Compared with prior efforts, our method involves neither random priming nor stochastic cDNA termination, thus enabling lification of transcripts that were previously inaccessible via related click chemistry-based RNA sequencing techniques. A key modification involving the use of PCR primers containing two overhanging 3'-nucleotides substantially improved the read-through compatibility of the 1,4-disubstituted 1,2,3-triazole-containing cDNA, where such modifications typically hinder lification. This allowed us to more than double the possible insert size compared with the state-of-the art click chemistry-based technique, PAC-seq. Furthermore, our method performed on par with a commercially available PCR-cDNA RNA sequencing kit, as determined by Oxford Nanopore sequencing. Given the known advantages of PAC-seq, namely, suppression of PCR artifacts, we anticipate that our contribution could enable erse applications including improved analyses of mRNA splicing variants and fusion transcripts.
Publisher: Springer Science and Business Media LLC
Date: 12-12-2018
DOI: 10.1038/S41467-018-07222-W
Abstract: Prebiotic chemistry, driven by changing environmental parameters provides canonical and a multitude of non-canonical nucleosides. This suggests that Watson-Crick base pairs were selected from a erse pool of nucleosides in a pre-Darwinian chemical evolution process.
Publisher: Wiley
Date: 14-10-2020
Publisher: Wiley
Date: 08-2019
Publisher: Wiley
Date: 17-04-2018
Abstract: The RNA-world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional ersity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.
Publisher: Wiley
Date: 10-10-2022
Abstract: Die Frage, wie sich die RNA als ein Träger der genetischen Information entwickelt hat, ist von grundlegender Bedeutung für unser Verständnis des Ursprungs des Lebens. Das RNA‐Molekül ist viel zu komplex, als das es in einem einzigen Evolutionsschritt hat entstehen können, was darauf hindeutet, dass es Proto‐RNAs (erste Vorläufer der RNA) gegeben haben könnte, die sich im Laufe der Zeit zu der heutigen RNA entwickelt haben. Hier zeigen wir, dass Isoxazol‐Nukleoside, die aus Hydroxylamin, Cyanoacetylen, Harnstoff und Ribose gebildet werden, plausible Vorläufer für RNA sind. Das Isoxazol‐Nukleosid kann sich innerhalb eines RNA‐Strangs zu Cytidin umlagern, was zu einer Erhöhung der Paarungsstabilität führt. Wenn die Proto‐RNA ein kanonisches seed‐Nukleosid mit definierter Stereochemie enthält, kann das seed‐Nukleosid die Konfiguration des anomeren Zentrums kontrollieren, das sich, während der in‐RNA‐Umwandlung bildet. Die Ergebnisse zeigen, dass sich die RNA nach der Strangbildung aus evolutionär primitiven Vorläufern wie Isoxazol‐Ribosiden entwickelt haben könnte.
Publisher: Springer Science and Business Media LLC
Date: 15-01-2019
DOI: 10.1038/S41467-019-08340-9
Abstract: The original version of this Article contained errors in the citations in the second, third and fourth sentences of the first paragraph of the ‘Life and LUCA’ section, which incorrectly read ‘Its development is explained by Darwinian evolution, which must have begun with rudimentary “living” vesicles that at some point transitioned into what we call the last universal common ancestor (LUCA) 2 . LUCA is a hypothetical life form obtained from phylogenetic analysis from which all three kingdoms of life originated 3 . To our understanding, LUCA already possessed the capacity to synthesize specific building blocks such as amino acids, nucleotides and lipids 2 .’ The correct version states ‘(LUCA) 1 ’ in place of ‘(LUCA) 2 ’, ‘originated 2 ’ instead of ‘originated 3 ’ and ‘lipids 1 ’ rather than ‘lipids 2 ’. This has been corrected in both the PDF and HTML versions of the Article.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 20-03-2020
Abstract: The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 in iduals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. We identified 369 nominally genome-wide significant loci ( P 5 × 10 −8 ) associated with cortical structure in a discovery s le of 33,992 participants of European ancestry. Of the 360 loci for which replication data were available, 241 loci influencing surface area and 66 influencing thickness remained significant after replication, with 237 loci passing multiple testing correction ( P 8.3 × 10 −10 187 influencing surface area and 50 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness surface area and thickness showed a negative genetic correlation ( r G = −0.32, SE = 0.05, P = 6.5 × 10 −12 ), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain s les, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on in idual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 46 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function. ( A ) Measurement of cortical surface area and thickness from MRI. ( B ) Genomic locations of common genetic variants that influence global and regional cortical structure. ( C ) Our results support the radial unit hypothesis that the expansion of cortical surface area is driven by proliferating neural progenitor cells. ( D ) Cortical surface area shows genetic correlation with psychiatric and cognitive traits. Error bars indicate SE. IMAGE CREDITS: (A) K. COURTNEY (C) M. R. GLASS
Publisher: Elsevier BV
Date: 06-2020
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/CH15340
Abstract: A short review of the literature on palladium-catalysed intramolecular Alder-ene reactions of C-, N-, and O-linked 1,6-enynes is provided with a particular focus on the use of the latter two processes in the authors’ laboratories for the purposes of constructing various alkaloids.
Publisher: Wiley
Date: 18-07-2019
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
Location: United States of America
No related grants have been discovered for Anders Dale.