928 resultados para Variant in site acceptor splicing consensus
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The tobiano white-spotting pattern is one of several known depigmentation phenotypes in horses and is desired by many horse breeders and owners. The tobiano spotting phenotype is inherited as an autosomal dominant trait. Horses that are heterozygous or homozygous for the tobiano allele (To) are phenotypically indistinguishable. A SNP associated with To had previously been identified in intron 13 of the equine KIT gene and was used for an indirect gene test. The test was useful in several horse breeds. However, genotyping this sequence variant in the Lewitzer horse breed revealed that 14% of horses with the tobiano pattern did not show the polymorphism in intron 13 and consequently the test was not useful to identify putative homozygotes for To within this breed. Speculations were raised that an independent mutation might cause the tobiano spotting pattern in this breed. Recently, the putative causative mutation for To was described as a large chromosomal inversion on equine chromosome 3. One of the inversion breakpoints is approximately 70 kb downstream of the KIT gene and probably disrupts a regulatory element of the KIT gene. We obtained genotypes for the intron 13 SNP and the chromosomal inversion for 204 tobiano spotted horses and 24 control animals of several breeds. The genotyping data confirmed that the chromosomal inversion was perfectly associated with the To allele in all investigated horses. Therefore, the new test is suitable to discriminate heterozygous To/+ and homozygous To/To horses in the investigated breeds.
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Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re-sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration.
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Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10-20 cases and 10-20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted re-sequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-of-concept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrl änder dogs. To our knowledge, this is the first time this family trio WGS-approach, has successfully been used to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrl änder dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G>C (p.R52P) was found to be concordant in eight additional cases and 16 healthy Kromfohrl änder dogs.
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In order to propose a role for internucleosomal high mobility group proteins (HMGs), and HI histone variants study of their levels and synthesis in a system of development and differentiation--rat spermatogenesis--was undertaken. HMG1, 2, 14, and 17 were isolated from rat testes and found to be very similar to calf thymus HMGs. Testis levels of HMGs, relative to DNA, were equivalent to other rat tissues for HMG1 (13 ug/mg DNA), HMG14 (2 ug/mg DNA), and HMG17 (5 ug/mg DNA). HMG2 levels were different among rat tissues, with three groups observed: (1) nonproliferating tissues (1-5 ug/mg DNA); (2) proliferating tissues (8-13 ug/mg DNA); and (3) the testis (32 ug/mg DNA). Other species (toad, opposum, mouse, dog, and monkey) showed the same testis-specific increase of HMG2. Populations of purified testis cell types were separated by centrifugal elutriation and density gradient centrifugation from adult and immature rat testes. Pachytene spermatocytes and early spermatids (56 and 47 ug/mg DNA, respectively) caused the testis-specific increase of HMG2 levels. Cell types preceding pachytenes (types A and B spermatogonia, mixtures of spermatogonia and early primary spermatocytes, and early pachytenes contained HMG2 levels similar to proliferating tissues (12 ug/mg DNA). Late spermatids did not contain HMGs. Somatic Sertoli and Leydig cells (2 ug/mg DNA) exhibited HMG2 levels similar to nonproliferating tissues. HMGs synthesized in spermatogonia and spermatocytes had similar specific activities, but early spermatids did not synthesize HMGs. Germ cells also contained an HMG2 species (on acid-urea gels) not found in somatic tissues. Other investigators have shown that HMGs may be associated with transcriptional or replicative processes. Thus, it is proposed that HMG2 plays a role in modulatable gene expression, while HMG1 is associated with housekeeping functions.^ HI histone variants were also studied throughout spermatogenesis. The minor somatic variant, HIa, is the predominant variant in spermatogonia and early primary spermatocytes. In early pachytenes, the testis-specific variant, HIt, is first synthesized and appears, largely replacing somatic variants HIbcd and e by late pachytene stage. Early spermatids contain the same HI composition as pachytenes, but do not synthesize HI histones. HI('0) is present in low amounts in all germ cells. These results suggest that expression of HI variants is developmentally controlled.^
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Analysis of the human genome has revealed that more than 74% of human genes undergo alternative RNA splicing. Aberrations in alternative RNA splicing have been associated with several human disorders, including cancer. ^ We studied the aberrant expression of alternative RNA splicing isoforms of the Fibroblast Growth Factor Receptor 1 (FGFR1) gene in a human glioblastoma cancer model. Normal glial cells express the FGFR1α, which contains three extracellular domains. In tumors the most abundant isoform is the FGFR1β, which lacks the first extracellular domain due to the skipping of a single exon, termed alpha. The skipping of the α-exon is regulated by two intronic silencing sequences within the precursor mRNA. Since we observed no mutations on these elements in tumor cells, we hypothesized that the over-expression of regulatory proteins that recognize these sequences is responsible for the aberrant expression of splicing isoforms. Hence, we blocked the formation of protein complexes on the ISS using antisense RNA oligonucleotides in vitro. We also evaluated the impact of the ISS antisense oligonucleotides on the endogenous FGFR1 splicing, in a glioblastoma cell model. By targeting intronic regulatory elements we were able to increase the level of alpha exon inclusion up to 90% in glioblastoma cells. The effect was dose dependent, sequence specific and reproducible in glioblastoma and other cancer cells, which also exhibit an alpha exon skipping phenotype. Targeting FGFR1 endogenous ISS1 and ISS2 sequences did not have an additive or synergistic effect, which suggest a regulatory splicing mechanism that requires the interaction of complexes formed on these elements. An increase in the levels of the FGFR1α isoform resulted in a reduction in cell invasiveness. Also, a significant increase in the levels of caspase 3/7 activities, which is indicative of an elevation in apoptosis levels, suggests that expression of FGFR1β might be relevant for tumor survival. These studies demonstrate that it is possible to prevent aberrant expression of exon skipping events through the targeting of intronic regulatory elements, providing an important new therapeutic tool for the correction of human disease caused by alternative RNA splicing. ^
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The Drosophila Transformer-2 (Tra2) protein activates the splicing of doublesex and fruitless pre-mRNA and represses M1 intron splicing in its own RNA in male germline. The M1 retention is part of negative feedback mechanism that controls Tra2 protein synthesis. However it is not known how the M1 intron is repressed or why Tra2 activates splicing of some RNAs while repressing splicing in others. Here we show that Tra2 and SR protein Rbp1 function together to specifically repress M1 splicing in vitro through the same intronic silencer by binding independently to distinct sites. The role of Rbp1 in M1 repression in vivo was validated by the finding that increased expression of Rbp1 in S2 cells promotes M1 retention. Furthermore, Tra2 blocks prespliceosomal A complex formation, a step corresponding to U2 snRNP recruitment to the branchpoint. High levels of Tra2 repression require an upstream enhancer. Together, we propose that the complex formed by Tra2 and Rbp1 on the silencer achieves splicing repression by blocking the recognition of the branchpoint or antagonizing enhancer function. ^ In addition, both splicing regulatory activities of Tra2 are essential developmental events, doublesex splicing is the key for Drosophila sex determination in the soma, while M1 retention occurs in the male germline and is necessary for spermatogenesis. However, active Tra2 is expressed ubiquitously. So another issue we have studied is how Tra2 accomplishes negative and positive splicing regulation in a tissue-specific fashion. Surprisingly, we found that nuclear extract from somatically-derived S2 cells support M1 repression in vitro. This led us to hypothesize that no germline specific factor is required and that high levels of Tra2 expression in the male germline is sufficient to trigger M1 retention. To test it, I examined whether increased expression of Tra2 could promote M1 retention in cells outside male germline. My results show that increased Tra2 expression promotes M1 retention in somatically-derived S2 cells as well as in the somatic tissues of living flies. These results show that somatic tissues are capable of supporting M1 repression but do not normally do so because the low levels of Tra2 do not trigger negative feedback regulation. ^
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This research study offers a critical assessment of NIH's Consensus Development Program (CDP), focusing upon its historical and valuative bases and its institutionalization in response to social and political forces. The analysis encompasses systems-level, as well as interpersonal factors in the adoption of consensus as the mechanism for resolving scientific controversies in clinical practice application. Further, the evolution of the CDP is also considered from an ecological perspective as a reasoned adaptation by NIH to pressures from its supporters and clients for translating biomedical research into medical practice. The assessment examines federal science policy and institutional designs for the inclusion of the public interest and democratic deliberation.^ The study relies on three distinct approaches to social research. Conventional historical methods were utilized in the interpretation of social and political influences across eras on the evolution of the National Institutes of Health and its response to demands for accountability and relevance through its Consensus Development Program. An embedded single-case study was utilized for an empirical examination of the CDP mechanism through five exemplar conferences. Lastly, a sociohistorical approach was taken to the CDP in order to consider its responsiveness to the values of the eras which created and shaped it. An exploration of organizational behavior with considerations for institutional reform as a response to continuing political and social pressure, it is a study of organizational birth, growth, and response to demands from its environment. The study has explanatory import in its attempt to account for the creation, timing, and form of the CDP, relative to political, institutional, and cultural pressures, and predictive import thorough its historical view which provides a basis for informed speculation on the playing out of tensions between extramural and intermural scientists and the current demands for health care reform. ^
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Atherosclerosis is widely accepted as a complex genetic phenotype and is the usual cause of cardiovascular disease, the world’s leading killer. Genetic factors have been proven to be important risk contributors for atherosclerosis and much work has been done to identify promising candidates that might play a role in the development of atherosclerosis. It is well known that many independent replications are needed to unequivocally establish a valid genotype-phenotype association across different populations before the findings are extended to clinical settings and to the expensive follow-up studies designed to identify causal genetic variants. Aiming to replicate the association with atherosclerosis in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we assessed the relationship of 32 atherosclerosis candidate SNPs to atherosclerosis in the PDAY cohort, consisting of AA and EA young people aged 15-34 years who died of non-medical causes. Two association studies, a whole sample study and a 1:1 matched case control study were performed by use of multiple linear regression and logistic regression analyses, respectively. For the whole sample association study, 32 SNPs among 2,650 individuals (1,369 AA and 1,281 EA) were tested for the association with six early atherosclerosis phenotypes: abdominal aorta fatty streaks, abdominal aorta raised lesions, right coronary artery fatty streaks, right coronary artery raised lesions, thoracic aorta fatty streaks, and thoracic aorta raised lesions. For the matched case-control association study, 337 case-control paired samples were included; cases were chosen with the highest total raised lesion scores from the studied population, while controls were randomly selected from individuals that had no raised lesions and matched to cases by age, gender and race. Sixteen SNPs in 13 genes were found to be significantly associated with atherosclerosis in at least one of the PDAY association studies. Among these 16 findings: eight SNPs (rs9579646, rs6053733, rs3849150, rs10499903, rs2148079, rs5073691, rs10116277, and rs17228212) successfully replicated previous results, six SNPs (rs17222814, rs10811661, rs7028570, rs7291467, rs16996148 and rs10401969) were reported as new findings exclusive to our study, the last two of the 16 SNPs, rs501120 and rs6922269, showed either intriguing or conflicting result. SNP rs17222814 in ALOX5AP and SNP rs3849150 in LRRC18 were consistently associated with atherosclerosis in both prior and the two PDAY association studies. SNP rs3849150 was also identified to be highly correlated with a non-synonymous coding SNP, rs17772611, which may damage the protein (polyphen score = 0.996), suggesting that SNP rs17772611 may be the causal functional variant.^ In conclusion, our study added more support for the association of these candidate genes with atherosclerosis. SNPs rs3849150 and rs17772611 of LRRC18, as well as SNP rs17222814 of ALOX5AP, were the most significant findings from our study, and may be ranked among the best for further study.^
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Multiple Endocrine Neoplasia type 1 (MEN1) is a hereditary cancer syndrome characterized by tumors of the endocrine system. Tumors most commonly develop in the parathyroid glands, pituitary gland, and the gastro-entero pancreatic tract. MEN1 is a highly penetrant condition and age of onset is variable. Most patients are diagnosed in early adulthood; however, rare cases of MEN1 present in early childhood. Expert consensus opinion is that predictive genetic testing should be offered at age 5 years, however there are no evidence-based studies that clearly establish that predictive genetic testing at this age would be beneficial since most symptoms do not present until later in life. This study was designed to explore attitudes about the most appropriate age for predictive genetic testing from individuals at risk of having a child with MEN1. Participants who had an MEN1 mutation were invited to complete a survey and were asked to invite their spouses to participate as well. The survey included several validated measures designed to assess participants’ attitudes about predictive testing in minors. Fifty-eight affected participants and twenty-two spouses/partners completed the survey. Most participants felt that MEN1 genetic testing was appropriate in healthy minors. Younger age and increased knowledge of MEN1 genetics and inheritance predicted genetic testing at a younger age. Additionally, participants who saw more positive than negative general outcomes from genetic testing were more likely to favor genetic testing at younger ages. Overall, participants felt genetic testing should be offered at a younger age than most adult onset conditions and most felt the appropriate time for testing was when a child could understand and participate in the testing process. Psychological concerns seemed to be the primary focus of participants who favored later ages for genetic testing, while medical benefits were more commonly cited for younger age. This exploratory study has implications for counseling patients whose children are at risk of developing MEN1 and illustrates issues that are important to patients and their spouses when considering testing in children.
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Total organic carbon, amino compounds, and carbohydrates were measured in pore waters and sediments of Pliocene to Pleistocene age from Sites 723 and 724 (ODP Leg 117) to evaluate (1) relationships between organic matter in the sediment and in the pore water, (2) the imprint of lithological variations on the abundance and contribution of organic substances, (3) degradation of amino compounds and carbohydrates with time and/or depth, and (4) the dependence of the ammonia concentration in the pore water on the degradation of amino compounds in the sediment. Total organic carbon concentrations (TOC) of the investigated sediment samples range from 0.9% to 8.7%, and total nitrogen concentrations (TN) from 0.1% to 0.5%. Up to 4.9% of the TOC is contributed by hydrolyzable amino acids (THAA) which are present in amounts between 1.1 and 21.3 µmol/g dry sediment and decrease strongly downhole. Hydrolyzable carbohydrates (THCHO) were found in concentrations from 1.3 to 6.6 ?mol/g sediment constituting between 0.1% and 2.0% of the TOC. Differences between the distribution patterns of monomers in Sites 723 and 724 indicate higher terrigenous influence for Site 724 and, furthermore, enhanced input of organic matter that is relatively resistant to microbial degradation. Lithologically distinct facies close to the Pliocene/Pleistocene boundary yield different organic matter compositions. Laminated horizons seem to correspond with enhanced amounts of biogenic siliceous material and minor microbiological degradation. Total amounts of dissolved organic carbon (DOC) in pore waters vary between 11 and 131 mg/L. Concentrations of DOC as well as of dissolved amino compounds and carbohydrates appear to be related to microbial activity and/or associated redox zones and not so much to the abundance of organic matter in the sediments. Distributions of amino acids and monosaccharides in pore waters show a general enrichment in relatively stable components in comparison to those of the sediments. Nevertheless, the same trend appears between amino acids present in the sediments from Sites 723 and 724 as well as between amino acids in pore waters from these two sites, indicating a direct relation between the dissolved and the sedimentary organic fractions. Different ammonia concentrations in the pore waters of Sites 723 and 724 seem to be related to enhanced release of ammonia from degradation of amino compounds in Site 723.
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C2-C8 hydrocarbon concentrations (about 35 compounds identified, including saturated, aromatic, and olefinic compounds) from 38 shipboard sealed, deep-frozen core samples of Deep Sea Drilling Project Sites 585 (East Mariana Basin) and 586 (Ontong-Java Plateau) were determined by a gas stripping-thermovaporization method. Total concentrations, which represent the hydrocarbons dissolved in the pore water and adsorbed on the mineral surfaces of the sediment, vary from 20 to 630 ng/g of rock at Site 585 (sub-bottom depth range 332-868 m). Likewise, organic-carbon normalized yields range from 3*10**4 to 9*10**5 ng/g Corg, indicating that the organic matter is still in the initial, diagenetic evolutionary stage. The highest value (based on both rock weight and organic carbon) is measured in an extremely organic-carbon-poor sample of Lithologic Subunit VB (Core 585-30). In this unit (504-550 m) several samples with elevated organic-carbon contents and favorable kerogen quality including two thin "black-shale" layers deposited at the Cenomanian/Turonian boundary (not sampled for this study) were encountered. We conclude from a detailed comparison of light hydrocarbon compositions that the Core 585-30 sample is enriched in hydrocarbons of the C2-C8 molecular range, particularly in gas compounds, which probably migrated from nearby black-shale source layers. C2-C8 hydrocarbon yields in Site 586 samples (sub-bottom depth range 27-298 m) did not exceed 118 ng/g of dry sediment weight (average 56 ng/g), indicating the immaturity of these samples.
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The Br/Cl, Li/Cl and B/Cl ratios and boron isotope compositions of hypersaline pore fluids from DSDP Sites 372 and 374 were measured in an attempt to evaluate the origin of the brines. In Site 374 the relationships between the Cl concentrations (up to 5000 mM) and Br/Cl (~0.012), Na/Cl (as low as 0.1), B/Cl (0.0025), and d11B values (43-55?) of the deep pore water between 380 and 405 mbsf, located within the Messinian sediments, reflect remnants of ~65-fold evaporated sea water. The original evaporated sea water was modified by: (1) dilution with overlying or less saline water by about 30%; and (2) slight dissolution of NaCl evaporites. The variations in d11B show a continuous increase in d11B values with depth in Site 374, up to 66.7? at a depth of 300 mbsf (Upper Pliocene marl sediments). The conspicuous 11B enrichment trend is consistent with elemental boron depletion, which was calculated from the expected boron concentrations of evaporated sea water with corresponding Br/Cl and Na/Cl ratios. Li/Cl variations also show a depletion of Li relative to evaporated sea water. The apparent depletions of B and Li, as well as the 11B enrichment, reflect uptake of these elements by clay minerals at low water/sediment ratios.
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Early Miocene to Quaternary benthic foraminifers have been quantitatively studied (>63 ?m size fraction) in a southwest Pacific traverse of DSDP sites at depths from about 1300 to 3200 m down the Lord Howe Rise (Site 590,1299 m; Site 591, 2131 m; Site 206, 3196 m). Benthic foraminiferal species smaller than 150 µm are by far dominant in the samples, averaging from 78 to 89% of the total benthic foraminiferal assemblages in the three sites examined. Although about 150 benthic foraminiferal species or taxonomic groups have been identified, only a few species dominate the assemblages. These dominant species include Epistominella exigua, E. rotunda, and Globocassidulina subglobosa, which prevail in the three sites, and Oridorsalis umbonatus, E. umbonifera, and Cassidulina carinata, which occur usually in frequencies of between 10 and 30%. Faunal changes in Neogene benthic foraminiferal assemblages are not similar in each of the three sites, but faunal successions are most similar between the two shallowest sites. The deepest site differs in composition and distribution of dominant species. There are three intervals during which the most important changes occur in benthic foraminiferal assemblages: the early middle Miocene (14 Ma; the Orbulina suturalis Zone and the Globorotalia fohsi s.l. Zone); the late Miocene (6 Ma; the Globigerina nepenthes Zone) and near the Pliocene/Pleistocene boundary at about 2 Ma. A Q-mode factor analysis of the faunal data has assisted in recognizing assemblage changes during the Neogene at each of the sites. Early Miocene assemblages were dominated by Globocassidulina subglobosa at Site 590 (1299 m), by G. subglobosa and Oridorsalis umbonatus at Site 591 (2131 m), and by G. subglobosa, E. exigua, and Bolivina pusilla at Site 206 (3196 m). In the early middle Miocene at Sites 590 and 591, a marked increase occurred in the frequencies of E. exigua. Epistominella exigua reached maximum abundance in the early Miocene in the deeper Site 206, and in the middle and early late Miocene in the shallower Sites 590 and 591. In the late Miocene, a spike occurred in the frequencies of E. umbonifera in Site 206, whereas the dominant species changed from E. exigua to E. rotunda at Site 590. Latest Miocene to late Pliocene assemblages were dominated by E. rotunda at Site 590, by E. exigua at Site 591, and by G. subglobosa-E. exigua (early Pliocene) and E. rotunda-E. exigua (late Pliocene) at Site 206. At the Pliocene/Pleistocene boundary, E. exigua temporarily diminished in importance at Sites 591 and 206. Quaternary assemblages were dominated by E. rotunda and Cassidulina carinata at Site 590, by E. rotunda at Site 591, and by E. exigua at Site 206. These major faunal changes are all associated with known major paleoceanographic events-the middle Miocene development of the Antarctic ice sheet; the latest Miocene global cooling and increased polar glaciation; and the onset of quasiperiodic glaciation of the Northern Hemisphere. These major paleoceanographic events undoubtedly had a profound effect on the intermediate and deep water mass structure of the Tasman Sea as recorded by changes in benthic foraminiferal assemblages.
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We determined changes in equatorial Pacific phosphorus (µmol P/g) and barite (BaSO4; wt%) concentrations at high resolution (2 cm) across the Paleocene/Eocene (P/E) boundary in sediments from Ocean Drilling Program (ODP) Leg 199 Site 1221 (153.40 to 154.80 meters below seafloor [mbsf]). Oxide-associated, authigenic, and organic P sequentially extracted from bulk sediment were used to distinguish reactive P from detrital P. We separated barite from bulk sediment and compared its morphology with that of modern unaltered biogenic barite to check for diagenesis. On a CaCO3-free basis, reactive P concentrations are relatively constant and high (323 µmol P/g or ~1 wt%). Barite concentrations range from 0.05 to 5.6 wt%, calculated on a CaCO3-free basis, and show significant variability over this time interval. Shipboard measurements of P and Ba in bulk sediments are systematically lower (by ~25%) than shore-based concentrations and likely indicate problems with shipboard standard calibrations. The presence of Mn oxides and the size, crystal morphology, and sulfur isotopes of barite imply deposition in sulfate-rich pore fluids. Relatively constant reactive P, organic C, and biogenic silica concentrations calculated on a CaCO3-free basis indicate generally little variation in organic C, reactive P, and biogenic opal burial across the P/E boundary, whereas variable barite concentrations indicate significant changes in export productivity. Low barite Ba/reactive P ratios before and immediately after the Benthic Extinction Event (BEE) may indicate efficient nutrient burial, and, if nutrient burial and organic C burial are linked, high relative organic C burial that could temporarily drawdown CO2 at this site. This interpretation requires postdepositional oxidation of organic C because organic C to reactive P ratios are low throughout the section. After the BEE, higher barite Ba/reactive P ratios combined with higher barite Ba concentrations may imply that higher export productivity was coupled with unchanged reactive P burial, indicating efficient nutrient and possibly also organic C recycling in the water column. If the nutrient recycling is decoupled from organic C, the high export production could be indicative of drawdown of CO2. However, the observation that organic C burial is not high where barite burial is high may imply that either C sequestration was restricted to the deep ocean and thus occurred only on timescales of the deep ocean mixing or that postdepositional oxidation (burn down) of organic matter affected the sediments. The decoupling of barite and opal may result from low opal preservation or production that is not diatom based.