| 1. |
- Gallego-Sala, Angela V., et al.
(författare)
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Latitudinal limits to the predicted increase of the peatland carbon sink with warming
- 2018
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:10, s. 907-
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Tidskriftsartikel (refereegranskat)abstract
- The carbon sink potential of peatlands depends on the balance of carbon uptake by plants and microbial decomposition. The rates of both these processes will increase with warming but it remains unclear which will dominate the global peatland response. Here we examine the global relationship between peatland carbon accumulation rates during the last millennium and planetary-scale climate space. A positive relationship is found between carbon accumulation and cumulative photosynthetically active radiation during the growing season for mid- to high-latitude peatlands in both hemispheres. However, this relationship reverses at lower latitudes, suggesting that carbon accumulation is lower under the warmest climate regimes. Projections under Representative Concentration Pathway (RCP)2.6 and RCP8.5 scenarios indicate that the present-day global sink will increase slightly until around AD 2100 but decline thereafter. Peatlands will remain a carbon sink in the future, but their response to warming switches from a negative to a positive climate feedback (decreased carbon sink with warming) at the end of the twenty-first century.
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| 2. |
- Ades, M., et al.
(författare)
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Global Climate : in State of the climate in 2019
- 2020
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Ades, M., et al.
(författare)
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GLOBAL CLIMATE
- 2020
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Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 5. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 6. |
- Cain, Peter, et al.
(författare)
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A novel extended family of stromal thioredoxins
- 2009
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Ingår i: Plant Molecular Biology. - : Springer. - 0167-4412 .- 1573-5028. ; 70:3, s. 273-281
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Tidskriftsartikel (refereegranskat)abstract
- Thioredoxins play key regulatory roles in chloroplasts by linking photosynthetic light reactions to a series of plastid functions. In addition to the established groups of thioredoxins, f, m, x, and y, novel plant thioredoxins were also considered to include WCRKC motif proteins, CDSP32, the APR proteins, the lilium proteins and HCF164. Despite their important roles, the subcellular locations of many novel thioredoxins has remained unknown. Here, we report a study of their subcellular location using the cDNA clone resources of TAIR. In addition to filling all gaps in the subcellular map of the established chloroplast thioredoxins f, m, x and y, we show that the members of the WCRKC family are targeted to the stroma and provide evidence for a stromal location of the lilium proteins. The combined data from this and related studies indicate a consistent stromal location of the known Arabidopsis chloroplast thioredoxins except for thylakoid-bound HCF164.
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| 7. |
- Crosby, Jacy, et al.
(författare)
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Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
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Tidskriftsartikel (refereegranskat)abstract
- Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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| 8. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 9. |
- Gaziano, Liam, et al.
(författare)
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Mild-to-moderate kidney dysfunction and cardiovascular disease : Observational and mendelian randomization analyses
- 2022
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 146:20, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.
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| 10. |
- Hanna, Stephanie J., et al.
(författare)
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Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans
- 2023
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded T-cells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified gold-specific clones were CD8+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans.
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| 11. |
- Hill, Rebecca M., et al.
(författare)
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Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease
- 2015
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 27:1, s. 72-84
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.
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| 12. |
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| 13. |
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| 14. |
- Jabado, Rima W., et al.
(författare)
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Troubled waters : Threats and extinction risk of the sharks, rays and chimaeras of the Arabian Sea and adjacent waters
- 2018
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Ingår i: Fish and Fisheries. - : Wiley-Blackwell. - 1467-2960 .- 1467-2979. ; 19:6, s. 1043-1062
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Tidskriftsartikel (refereegranskat)abstract
- The extinction risk of sharks, rays and chimaeras is higher than that for most other vertebrates due to low intrinsic population growth rates of many species and the fishing intensity they face. The Arabian Sea and adjacent waters border some of the most important chondrichthyan fishing and trading nations globally, yet there has been no previous attempt to assess the conservation status of species occurring here. Using IUCN Red List of Threatened Species Categories and Criteria and their guidelines for application at the regional level, we present the first assessment of extinction risk for 153 species of sharks, rays and chimaeras. Results indicate that this region, home to 15% of described chondrichthyans including 30 endemic species, has some of the most threatened chondrichthyan populations in the world. Seventy-eight species (50.9%) were assessed as threatened (Critically Endangered, Endangered or Vulnerable), and 27 species (17.6%) as Near Threatened. Twenty-nine species (19%) were Data Deficient with insufficient information to assess their status. Chondrichthyan populations have significantly declined due to largely uncontrolled and unregulated fisheries combined with habitat degradation. Further, there is limited political will and national and regional capacities to assess, manage, conserve or rebuild stocks. Outside the few deepsea locations that are lightly exploited, the prognosis for the recovery of most species is poor in the near-absence of management. Concerted national and regional management measures are urgently needed to ensure extinctions are avoided, the sustainability of more productive species is secured, and to avoid the continued thinning of the regional food security portfolio.
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| 15. |
- Jensen, Poul Erik, et al.
(författare)
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Structure, function and regulation of plant photosystem I.
- 2007
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 0005-2728. ; 1767:5, s. 335-52
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Tidskriftsartikel (refereegranskat)abstract
- Photosystem I (PSI) is a multisubunit protein complex located in the thylakoid membranes of green plants and algae, where it initiates one of the first steps of solar energy conversion by light-driven electron transport. In this review, we discuss recent progress on several topics related to the functioning of the PSI complex, like the protein composition of the complex in the plant Arabidopsis thaliana, the function of these subunits and the mechanism by which nuclear-encoded subunits can be inserted into or transported through the thylakoid membrane. Furthermore, the structure of the native PSI complex in several oxygenic photosynthetic organisms and the role of the chlorophylls and carotenoids in the antenna complexes in light harvesting and photoprotection are reviewed. The special role of the ‘red’ chlorophylls (chlorophyll molecules that absorb at longer wavelength than the primary electron donor P700) is assessed. The physiology and mechanism of the association of the major light-harvesting complex of photosystem II (LHCII) with PSI during short term adaptation to changes in light quality and quantity is discussed in functional and structural terms. The mechanism of excitation energy transfer between the chlorophylls and the mechanism of primary charge separation is outlined and discussed. Finally, a number of regulatory processes like acclimatory responses and retrograde signalling is reviewed with respect to function of the thylakoid membrane. We finish this review by shortly discussing the perspectives for future research on PSI.
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| 16. |
- Jerjes, Waseem K., et al.
(författare)
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The future of medical diagnostics: review paper
- 2011
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Ingår i: Head & Neck Oncology. - : Springer Science and Business Media LLC. - 1758-3284. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation. Their accuracy, expressed as sensitivity and specificity, are reported in a number of studies suggests that they have a potential for cost effective, real-time, in situ diagnosis. We review the Third Scientific Meeting of the Head and Neck Optical Diagnostics Society held in Congress Innsbruck, Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual Scientific Meeting was held in association with the International Photodynamic Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The aim was to enhance the interdisciplinary aspects of optical diagnostics and other photodynamic applications. The meeting included 2 sections: oral communication sessions running in parallel to the IPA programme and poster presentation sessions combined with the IPA and EPPM posters sessions.
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| 17. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 18. |
- Pisareva, Tatiana, 1978-
(författare)
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A model for membrane organization and protein sorting in the cyanobacterium Synechocystis sp. PCC 6803
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cyanobacteria constitute a unique group of eubacteria, possessing outer and plasma membranes as well as internal thylakoid membranes, the site for both photosynthesis and respiration. The combination of sucrose density centrifugation and two-phase partitioning methods leads to purification of different membranes from the cyanobacterium Synechocystis sp. PCC 6803 (referred to as Synechocystis). The standard proteomics methods, based on 1D- and 2D-gel electrophoresis, followed by protein digestion and MALDI-TOF MS, led to identification of 76 thylakoid and 51 plasma membrane proteins. In order to increase the number of identified proteins a shotgun proteomics approach was employed. Proteins were digested in complex mixtures, followed by LC separation of obtained peptides coupled to MS/MS. This approach led to identification of 379 different thylakoid and plasma membrane proteins, of which 124 were integral membrane proteins. The complex membrane organization of Synechocystis requires a unique system for transport and sorting of proteins into extracytosolic cell compartments. Obtained gel-based and shotgun proteomics data as well as results of the multivariate sequence analysis of both soluble and integral membrane proteins allowed to suggest a new mechanism for membrane organization and protein sorting in Synechocystis. The plasma and thylakoid membranes are proposed to be dynamically connected and both soluble and integral membrane proteins are inserted into connection points. The Synechocystis genome possesses two genes encoding leader peptidases. Proteomic studies revealed that Sll0716 is localized in the thylakoid membrane (LepT), whereas Slr1377 in the plasma membrane (LepP). The BN/SDS-PAGE of the total membranes from mutant LepT revealed that LepT is directly involved in the processing of several photosynthetic and lumenal subunits, required for the assembly and function of PSI and maintaining of the thylakoid membrane organization in Synechocystis.
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| 19. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 20. |
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| 21. |
- Tarrason Risa, Gabriel, et al.
(författare)
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The proteasome controls ESCRT-III-mediated cell division in an archaeon
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 369:6504
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Tidskriftsartikel (refereegranskat)abstract
- Sulfolobus acidocaldarius is the closest experimentally tractable archaeal relative of eukaryotes and, despite lacking obvious cyclin-dependent kinase and cyclin homologs, has an ordered eukaryote-like cell cycle with distinct phases of DNA replication and division. Here, in exploring the mechanism of cell division in S. acidocaldarius, we identify a role for the archaeal proteasome in regulating the transition from the end of one cell cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homolog, CdvB, as a key target of the proteasome and show that its degradation triggers division by allowing constriction of the CdvB1:CdvB2 ESCRT-III division ring. These findings offer a minimal mechanism for ESCRT-III-mediated membrane remodeling and point to a conserved role for the proteasome in eukaryotic and archaeal cell cycle control.
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| 22. |
- Thidholm, Ellinor, et al.
(författare)
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Novel approach reveals localisation and assembly pathway of the PsbS and PsbW proteins into the photosystem II dimer
- 2002
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Ingår i: FEBS LETTERS. - 0014-5793 .- 1873-3468. ; 513:2-3, s. 217-22
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Tidskriftsartikel (refereegranskat)abstract
- A blue-native gel electrophoresis system was combined with an in organello import assay to specifically analyse the location and assembly of two nuclear-encoded photosystem 11 (PSII) subunits. With this method we were able to show that initially the low molecular mass PsbW protein is not associated with the monomeric form of PSII. Instead a proportion of newly imported PsbW is directly assembled in dimeric PSH super-complexes with very fast kinetics; its negatively charged N-terminal domain is essential for this process. The chlorophyll-binding PsbS protein, which is involved in energy dissipation, is first detected in the monomeric PSII subcomplexes, and only at later time points in the dimeric form of PSII. It seems to be bound tighter to the PSII core complex than to light harvesting complex II. These data point to radically different assembly pathways for different PSII subunits. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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| 23. |
- Upile, Tahwinder, et al.
(författare)
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At the frontiers of surgery: review
- 2011
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Ingår i: Head & Neck Oncology. - : Springer Science and Business Media LLC. - 1758-3284. ; 3
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Forskningsöversikt (refereegranskat)abstract
- The complete surgical removal of disease is a desirable outcome particularly in oncology. Unfortunately much disease is microscopic and difficult to detect causing a liability to recurrence and worsened overall prognosis with attendant costs in terms of morbidity and mortality. It is hoped that by advances in optical diagnostic technology we could better define our surgical margin and so increase the rate of truly negative margins on the one hand and on the other hand to take out only the necessary amount of tissue and leave more unaffected non-diseased areas so preserving function of vital structures. The task has not been easy but progress is being made as exemplified by the presentations at the 2nd Scientific Meeting of the Head and Neck Optical Diagnostics Society (HNODS) in San Francisco in January 2010. We review the salient advances in the field and propose further directions of investigation.
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| 24. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 25. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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