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  • 1
    Publication Date: 2013-04-19
    Description: Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howe, Kerstin -- Clark, Matthew D -- Torroja, Carlos F -- Torrance, James -- Berthelot, Camille -- Muffato, Matthieu -- Collins, John E -- Humphray, Sean -- McLaren, Karen -- Matthews, Lucy -- McLaren, Stuart -- Sealy, Ian -- Caccamo, Mario -- Churcher, Carol -- Scott, Carol -- Barrett, Jeffrey C -- Koch, Romke -- Rauch, Gerd-Jorg -- White, Simon -- Chow, William -- Kilian, Britt -- Quintais, Leonor T -- Guerra-Assuncao, Jose A -- Zhou, Yi -- Gu, Yong -- Yen, Jennifer -- Vogel, Jan-Hinnerk -- Eyre, Tina -- Redmond, Seth -- Banerjee, Ruby -- Chi, Jianxiang -- Fu, Beiyuan -- Langley, Elizabeth -- Maguire, Sean F -- Laird, Gavin K -- Lloyd, David -- Kenyon, Emma -- Donaldson, Sarah -- Sehra, Harminder -- Almeida-King, Jeff -- Loveland, Jane -- Trevanion, Stephen -- Jones, Matt -- Quail, Mike -- Willey, Dave -- Hunt, Adrienne -- Burton, John -- Sims, Sarah -- McLay, Kirsten -- Plumb, Bob -- Davis, Joy -- Clee, Chris -- Oliver, Karen -- Clark, Richard -- Riddle, Clare -- Elliot, David -- Threadgold, Glen -- Harden, Glenn -- Ware, Darren -- Begum, Sharmin -- Mortimore, Beverley -- Kerry, Giselle -- Heath, Paul -- Phillimore, Benjamin -- Tracey, Alan -- Corby, Nicole -- Dunn, Matthew -- Johnson, Christopher -- Wood, Jonathan -- Clark, Susan -- Pelan, Sarah -- Griffiths, Guy -- Smith, Michelle -- Glithero, Rebecca -- Howden, Philip -- Barker, Nicholas -- Lloyd, Christine -- Stevens, Christopher -- Harley, Joanna -- Holt, Karen -- Panagiotidis, Georgios -- Lovell, Jamieson -- Beasley, Helen -- Henderson, Carl -- Gordon, Daria -- Auger, Katherine -- Wright, Deborah -- Collins, Joanna -- Raisen, Claire -- Dyer, Lauren -- Leung, Kenric -- Robertson, Lauren -- Ambridge, Kirsty -- Leongamornlert, Daniel -- McGuire, Sarah -- Gilderthorp, Ruth -- Griffiths, Coline -- Manthravadi, Deepa -- Nichol, Sarah -- Barker, Gary -- Whitehead, Siobhan -- Kay, Michael -- Brown, Jacqueline -- Murnane, Clare -- Gray, Emma -- Humphries, Matthew -- Sycamore, Neil -- Barker, Darren -- Saunders, David -- Wallis, Justene -- Babbage, Anne -- Hammond, Sian -- Mashreghi-Mohammadi, Maryam -- Barr, Lucy -- Martin, Sancha -- Wray, Paul -- Ellington, Andrew -- Matthews, Nicholas -- Ellwood, Matthew -- Woodmansey, Rebecca -- Clark, Graham -- Cooper, James D -- Tromans, Anthony -- Grafham, Darren -- Skuce, Carl -- Pandian, Richard -- Andrews, Robert -- Harrison, Elliot -- Kimberley, Andrew -- Garnett, Jane -- Fosker, Nigel -- Hall, Rebekah -- Garner, Patrick -- Kelly, Daniel -- Bird, Christine -- Palmer, Sophie -- Gehring, Ines -- Berger, Andrea -- Dooley, Christopher M -- Ersan-Urun, Zubeyde -- Eser, Cigdem -- Geiger, Horst -- Geisler, Maria -- Karotki, Lena -- Kirn, Anette -- Konantz, Judith -- Konantz, Martina -- Oberlander, Martina -- Rudolph-Geiger, Silke -- Teucke, Mathias -- Lanz, Christa -- Raddatz, Gunter -- Osoegawa, Kazutoyo -- Zhu, Baoli -- Rapp, Amanda -- Widaa, Sara -- Langford, Cordelia -- Yang, Fengtang -- Schuster, Stephan C -- Carter, Nigel P -- Harrow, Jennifer -- Ning, Zemin -- Herrero, Javier -- Searle, Steve M J -- Enright, Anton -- Geisler, Robert -- Plasterk, Ronald H A -- Lee, Charles -- Westerfield, Monte -- de Jong, Pieter J -- Zon, Leonard I -- Postlethwait, John H -- Nusslein-Volhard, Christiane -- Hubbard, Tim J P -- Roest Crollius, Hugues -- Rogers, Jane -- Stemple, Derek L -- 095908/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 1 R01 DK55377-01A1/DK/NIDDK NIH HHS/ -- P01 HD022486/HD/NICHD NIH HHS/ -- P01 HD22486/HD/NICHD NIH HHS/ -- R01 GM085318/GM/NIGMS NIH HHS/ -- R01 OD011116/OD/NIH HHS/ -- R01 RR010715/RR/NCRR NIH HHS/ -- R01 RR020833/RR/NCRR NIH HHS/ -- England -- Nature. 2013 Apr 25;496(7446):498-503. doi: 10.1038/nature12111. Epub 2013 Apr 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23594743" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromosomes/genetics ; Conserved Sequence/*genetics ; Evolution, Molecular ; Female ; Genes/genetics ; Genome/*genetics ; Genome, Human/genetics ; Genomics ; Humans ; Male ; Meiosis/genetics ; Molecular Sequence Annotation ; Pseudogenes/genetics ; Reference Standards ; Sex Determination Processes/genetics ; Zebrafish/*genetics ; Zebrafish Proteins/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1995-01-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogel, H -- New York, N.Y. -- Science. 1995 Jan 27;267(5197):437.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7824939" target="_blank"〉PubMed〈/a〉
    Keywords: *Aggression ; Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases/deficiency/genetics ; *Drama ; *Fear ; Humans ; *Literature, Modern ; Male ; Mice ; Mice, Knockout
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-08-15
    Description: CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192026/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Nostrand, Jeanine L -- Brady, Colleen A -- Jung, Heiyoun -- Fuentes, Daniel R -- Kozak, Margaret M -- Johnson, Thomas M -- Lin, Chieh-Yu -- Lin, Chien-Jung -- Swiderski, Donald L -- Vogel, Hannes -- Bernstein, Jonathan A -- Attie-Bitach, Tania -- Chang, Ching-Pin -- Wysocka, Joanna -- Martin, Donna M -- Attardi, Laura D -- 1F31CA167917-01/CA/NCI NIH HHS/ -- F31 CA167917/CA/NCI NIH HHS/ -- R01 CA140875/CA/NCI NIH HHS/ -- R01 DC009410/DC/NIDCD NIH HHS/ -- R01 GM095555/GM/NIGMS NIH HHS/ -- R01 HL118087/HL/NHLBI NIH HHS/ -- R01HL121197/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Oct 9;514(7521):228-32. doi: 10.1038/nature13585. Epub 2014 Aug 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA (C.A.B.); Department of Medicine, University of Central Florida, Orlando, Florida 32827, USA (M.M.K.); Department of Emergency Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA (T.M.J.). ; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Otolaryngology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Departement de Genetique, Hopital Necker-Enfants Malades, APHP, 75015 Paris, France [2] Unite INSERM U1163, Universite Paris Descartes-Sorbonne Paris Cite, Institut Imagine, 75015 Paris, France. ; Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. ; 1] Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA. ; 1] Department of Pediatrics, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Human Genetics, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; 1] Department of Radiation Oncology, Division of Radiation and Cancer Biology, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119037" target="_blank"〉PubMed〈/a〉
    Keywords: Abnormalities, Multiple/genetics/*metabolism ; Alleles ; Animals ; Apoptosis/genetics ; CHARGE Syndrome/*genetics/*metabolism ; Cell Cycle Checkpoints/genetics ; Craniofacial Abnormalities/genetics/metabolism ; DNA-Binding Proteins/deficiency/genetics/metabolism ; Ear/abnormalities ; Embryo, Mammalian/abnormalities/metabolism ; Female ; Fibroblasts ; Gene Deletion ; Heterozygote ; Humans ; Male ; Mice ; Mutant Proteins/metabolism ; *Phenotype ; Promoter Regions, Genetic/genetics ; Tumor Suppressor Protein p53/*genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    ISSN: 1432-1041
    Keywords: pirenzepine ; hepatic insufficiency ; hepato-renal insufficiency ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in patients with chronic liver disease and others with combined chronic liver disease and renal sufficiency. The plasma clearance (CL) of Pirenzepine, steady-state plasma concentration Cmin(ss) and dominant half life t1/2γ were not significantly altered in the chronic liver disease group. In patients with renal and hepatic insufficiency, CL was reduced, t1/2γ was prolonged from 11.1 to 19.4 h and Cmin(ss) was elevated from 36 ng/ml to 66 ng/ml compared to healthy controls. Plasma concentrations remained in the therapeutic range and the dosage regimen was well tolerated. Adjustment of the dose of pirenzepine need be considered only in cases of severe impairment of both renal and hepatic elimination.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 75-78 
    ISSN: 1432-1041
    Keywords: pirenzepine ; renal insufficiency ; haemodialysis ; steady-state pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady-state intravenous pharmacokinetics of pirenzepine has been investigated in 57 subjects whose renal function ranged from normal to chronic failure requiring regular haemodialysis. Pirenzepine renal clearance, total clearance and terminal (dominant) half-life were found to be correlated with the creatinine clearance (CLCR), but this was not the case for the volume of distribution and the nonrenal clearance. The therapeutic regimen was well tolerated by all subjects. Haemodialysis did not significantly contribute to the elimination of pirenzepine. Dosage adjustment need only be considered in patients with CLCR〈25 ml/min in order to reduce the frequency of minor side-effects.
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  • 6
    Publication Date: 2020-02-12
    Description: Here we present a tephrostratigraphic record (core Co1202) recovered from the northeastern part of Lake Ohrid (Republics of Macedonia and Albania) reaching back to Marine Isotope Stage (MIS) 6. Overall ten horizons (OT0702-1 to OT0702-10) containing volcanic tephra have been recognised throughout the 14.94 m long sediment succession. Four tephra layers were visible at macroscopic inspection (OT0702-4, OT0702-6, OT0702-8 and OT0702-9), while the remaining six are cryptotephras (OT0702-1, OT0702-2, OT0702-3, OT0702-5, OT0702-7 and OT0702-10) identified from peaks in K, Zr and Sr intensities, magnetic susceptibility measurements, and washing and sieving of the sediments. Glass shards of tephra layers and cryptotephras were analysed with respect to their major element composition, and correlated to explosive eruptions of Italian volcanoes. The stratigraphy and the major element composition of tephra layers and cryptotephras allowed the correlation of OT0702-1 to AD 472 or AD 512 eruptions of Somma-Vesuvius, OT0702-2 to the FL eruption of Mount Etna, OT0702-3 to the Mercato from Somma-Vesuvius, OT0702-4 to SMP1-e/Y-3 eruption from the Campi Flegrei caldera, OT0702-5 to the Codola eruption (Somma-Vesuvius or Campi Flegrei), OT0702-6 to the Campanian Ignimbrite/Y-5 from the Campi Flegrei caldera, OT0702-7 to the Green Tuff/Y-6 eruption from Pantelleria Island, OT0702-8 to the X-5 eruption probably originating from the Campi Flegrei caldera, OT0702-9 to the X-6 eruption of generic Campanian origin, and OT0702-10 to the P-11 eruption from Pantelleria Island. The fairly well-known ages of these tephra layers and parent eruptions provide new data on the dispersal and deposition of these tephras and, furthermore, allow the establishment of a chronological framework for core Co1202 for a first interpretation of major sedimentological changes.
    Keywords: 550 - Earth sciences
    Type: info:eu-repo/semantics/article
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  • 7
    Publication Date: 2020-02-12
    Description: The reliability of Arctic climate predictions is currently hampered by insufficient knowledge of natural climate variability in the past. A sediment core from Lake El’gygytgyn (NE Russia) provides a continuous high-resolution record from the Arctic spanning the past 2.8 Ma. The core reveals numerous “super interglacials” during the Quaternary, with maximum summer temperatures and annual precipitation during marine benthic isotope stages (MIS) 11c and 31 ~4-5°C and ~300 mm higher than those of MIS 1 and 5e. Climate simulations show these extreme warm conditions are difficult to explain with greenhouse gas and astronomical forcing alone, implying the importance of amplifying feedbacks and far field influences. The timing of Arctic warming relative to West Antarctic Ice Sheet retreats implies strong interhemispheric climate connectivity.
    Keywords: 550 - Earth sciences
    Type: info:eu-repo/semantics/article
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  • 8
    Publication Date: 2020-02-12
    Description: Rock magnetic, biochemical and inorganic records of the sediment cores PG1351 and Lz1024 from Lake El'gygytgyn, Chukotka peninsula, Far East Russian Arctic, were subject to a hierarchical agglomerative cluster analysis in order to refine and extend the pattern of climate modes as defined by Melles et al. (2007). Cluster analysis of the data obtained from both cores yielded similar results, differentiating clearly between the four climate modes warm, peak warm, cold and dry, and cold and moist. In addition, two transitional phases were identified, representing the early stages of a cold phase and slightly colder conditions during a warm phase. The statistical approach can thus be used to resolve gradual changes in the sedimentary units as an indicator of available oxygen in the hypolimnion in greater detail. Based upon cluster analyses on core Lz1024, the published succession of climate modes in core PG1351, covering the last 250 ka, was modified and extended back to 350 ka. Comparison to the marine oxygen isotope (δ18O) stack LR04 (Lisiecki and Raymo, 2005) and the summer insolation at 67.5° N, with the extended Lake El'gygytgyn parameter records of magnetic susceptibility (κLF), total organic carbon content (TOC) and the chemical index of alteration (CIA; Minyuk et al., 2007), revealed that all stages back to marine isotope stage (MIS) 10 and most of the substages are clearly reflected in the pattern derived from the cluster analysis.
    Keywords: 550 - Earth sciences
    Type: info:eu-repo/semantics/article
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  • 9
    Publication Date: 2020-02-12
    Description: To date, terrestrial archives of long-term climatic change within the Arctic have widely been restricted to ice cores from Greenland and, more recently, sediments from Lake El’gygytgyn in northeast Arctic Russia. Sedi- ments from this lake contain a paleoclimate record of glacial- interglacial cycles during the last three million years. Low- resolution studies at this lake have suggested that changes observed during Transition IV (the transition from marine isotope stage (MIS) 10 to MIS 9) are of greater amplitude than any observed since. In this study, geochemical param- eters are used to infer past climatic conditions thus provid- ing the first high-resolution analyses of Transition IV from a terrestrial Arctic setting. These results demonstrate that a significant shift in climate was subsequently followed by a rapid increase in biogenic silica (BSi) production. Follow- ing this sharp increase, bioproductivity remained high, but variable, for over a thousand years. This study reveals differ- ences in the timing and magnitude of change within the ratio of silica to titanium (Si/Ti) and BSi records that would not be apparent in lower resolution studies. This has significant implications for the increasingly common use of Si/Ti data as an alternative to traditional BSi measurements.
    Keywords: 550 - Earth sciences
    Type: info:eu-repo/semantics/article
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  • 10
    Publication Date: 2020-02-12
    Description: The Last Interglacial Period (LIP) is often regarded as a good analogue for potential climatic conditions under predicted global warming scenarios. Despite this, there is still debate over the nature, duration and frequency of climatic changes during this period. One particularly contentious issue has been the apparent evidence of climatic instability identified in many marine cores but seemingly lacking from many terrestrial archives, especially within the Arctic, a key region for global climate change research. In this paper, geochemical records from Lake El’gygytgyn, north-eastern Russia, are used to infer past climatic changes during the LIP from within the high Arctic. With a sampling resolution of ~ 20 - ~ 90 years, these records offer the potential for detailed, high-resolution paleoclimate reconstruction. This study shows that the LIP commenced in central Chukotka ~ 129 thousand years ago (ka), with the warmest climatic conditions occurring between ~ 128-127 ka before being interrupted by a short-lived cold reversal. Mild climatic conditions then persisted until ~ 122 ka when a marked reduction in the sedimentation rate suggests a decrease in precipitation. A further climatic deterioration at ~ 118 ka marks the return to glacial conditions. This study highlights the value of incorporating several geochemical proxies when inferring past climatic conditions, thus providing the potential to identify signals related to environmental change within the catchment. We also demonstrate the importance of considering how changes in sedimentation rate influence proxy records, in order to develop robust paleoenvironmental reconstructions.
    Keywords: 550 - Earth sciences
    Type: info:eu-repo/semantics/article
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