| 1. |
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| 2. |
- Achberger, Christine, 1968, et al.
(författare)
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State of the Climate in 2011
- 2012
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 93:7
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale climate patterns influenced temperature and weather patterns around the globe in 2011. In particular, a moderate-to-strong La Nina at the beginning of the year dissipated during boreal spring but reemerged during fall. The phenomenon contributed to historical droughts in East Africa, the southern United States, and northern Mexico, as well the wettest two-year period (2010-11) on record for Australia, particularly remarkable as this follows a decade-long dry period. Precipitation patterns in South America were also influenced by La Nina. Heavy rain in Rio de Janeiro in January triggered the country's worst floods and landslides in Brazil's history. The 2011 combined average temperature across global land and ocean surfaces was the coolest since 2008, but was also among the 15 warmest years on record and above the 1981-2010 average. The global sea surface temperature cooled by 0.1 degrees C from 2010 to 2011, associated with cooling influences of La Nina. Global integrals of upper ocean heat content for 2011 were higher than for all prior years, demonstrating the Earth's dominant role of the oceans in the Earth's energy budget. In the upper atmosphere, tropical stratospheric temperatures were anomalously warm, while polar temperatures were anomalously cold. This led to large springtime stratospheric ozone reductions in polar latitudes in both hemispheres. Ozone concentrations in the Arctic stratosphere during March were the lowest for that period since satellite records began in 1979. An extensive, deep, and persistent ozone hole over the Antarctic in September indicates that the recovery to pre-1980 conditions is proceeding very slowly. Atmospheric carbon dioxide concentrations increased by 2.10 ppm in 2011, and exceeded 390 ppm for the first time since instrumental records began. Other greenhouse gases also continued to rise in concentration and the combined effect now represents a 30% increase in radiative forcing over a 1990 baseline. Most ozone depleting substances continued to fall. The global net ocean carbon dioxide uptake for the 2010 transition period from El Nino to La Nina, the most recent period for which analyzed data are available, was estimated to be 1.30 Pg C yr(-1), almost 12% below the 29-year long-term average. Relative to the long-term trend, global sea level dropped noticeably in mid-2010 and reached a local minimum in 2011. The drop has been linked to the La Nina conditions that prevailed throughout much of 2010-11. Global sea level increased sharply during the second half of 2011. Global tropical cyclone activity during 2011 was well-below average, with a total of 74 storms compared with the 1981-2010 average of 89. Similar to 2010, the North Atlantic was the only basin that experienced above-normal activity. For the first year since the widespread introduction of the Dvorak intensity-estimation method in the 1980s, only three tropical cyclones reached Category 5 intensity level-all in the Northwest Pacific basin. The Arctic continued to warm at about twice the rate compared with lower latitudes. Below-normal summer snowfall, a decreasing trend in surface albedo, and above-average surface and upper air temperatures resulted in a continued pattern of extreme surface melting, and net snow and ice loss on the Greenland ice sheet. Warmer-than-normal temperatures over the Eurasian Arctic in spring resulted in a new record-low June snow cover extent and spring snow cover duration in this region. In the Canadian Arctic, the mass loss from glaciers and ice caps was the greatest since GRACE measurements began in 2002, continuing a negative trend that began in 1987. New record high temperatures occurred at 20 m below the land surface at all permafrost observatories on the North Slope of Alaska, where measurements began in the late 1970s. Arctic sea ice extent in September 2011 was the second-lowest on record, while the extent of old ice (four and five years) reached a new record minimum that was just 19% of normal. On the opposite pole, austral winter and spring temperatures were more than 3 degrees C above normal over much of the Antarctic continent. However, winter temperatures were below normal in the northern Antarctic Peninsula, which continued the downward trend there during the last 15 years. In summer, an all-time record high temperature of -12.3 degrees C was set at the South Pole station on 25 December, exceeding the previous record by more than a full degree. Antarctic sea ice extent anomalies increased steadily through much of the year, from briefly setting a record low in April, to well above average in December. The latter trend reflects the dispersive effects of low pressure on sea ice and the generally cool conditions around the Antarctic perimeter.
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| 3. |
- Emile-Geay, J., et al.
(författare)
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Data Descriptor: A global multiproxy database for temperature reconstructions of the Common Era
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature-sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850-2014. Global temperature composites show a remarkable degree of coherence between high-and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python. Since the pioneering work of D'Arrigo and Jacoby1-3, as well as Mann et al. 4,5, temperature reconstructions of the Common Era have become a key component of climate assessments6-9. Such reconstructions depend strongly on the composition of the underlying network of climate proxies10, and it is therefore critical for the climate community to have access to a community-vetted, quality-controlled database of temperature-sensitive records stored in a self-describing format. The Past Global Changes (PAGES) 2k consortium, a self-organized, international group of experts, recently assembled such a database, and used it to reconstruct surface temperature over continental-scale regions11 (hereafter, ` PAGES2k-2013'). This data descriptor presents version 2.0.0 of the PAGES2k proxy temperature database (Data Citation 1). It augments the PAGES2k-2013 collection of terrestrial records with marine records assembled by the Ocean2k working group at centennial12 and annual13 time scales. In addition to these previously published data compilations, this version includes substantially more records, extensive new metadata, and validation. Furthermore, the selection criteria for records included in this version are applied more uniformly and transparently across regions, resulting in a more cohesive data product. This data descriptor describes the contents of the database, the criteria for inclusion, and quantifies the relation of each record with instrumental temperature. In addition, the paleotemperature time series are summarized as composites to highlight the most salient decadal-to centennial-scale behaviour of the dataset and check mutual consistency between paleoclimate archives. We provide extensive Matlab code to probe the database-processing, filtering and aggregating it in various ways to investigate temperature variability over the Common Era. The unique approach to data stewardship and code-sharing employed here is designed to enable an unprecedented scale of investigation of the temperature history of the Common Era, by the scientific community and citizen-scientists alike.
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| 4. |
- de Graauw, Th., et al.
(författare)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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| 5. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 6. |
- Yaghootkar, Hanieh, et al.
(författare)
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Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:12, s. 2806-2818
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Tidskriftsartikel (refereegranskat)abstract
- Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Sabo, Robert D., et al.
(författare)
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Phosphorus Inventory for the Conterminous United States (2002-2012)
- 2021
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Ingår i: Journal of Geophysical Research - Biogeosciences. - : John Wiley & Sons. - 2169-8953 .- 2169-8961. ; 126:4
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Tidskriftsartikel (refereegranskat)abstract
- Published reports suggest efforts designed to prevent the occurrence of harmful algal blooms and hypoxia by reducing non‐point and point source phosphorus (P) pollution are not delivering water quality improvements in many areas. Part of the uncertainty in evaluating watershed responses to management practices is the lack of standardized estimates of phosphorus inputs and outputs. To assess P trends across the conterminous United States, we compiled an inventory using publicly available datasets of agricultural P fluxes, atmospheric P deposition, human P demand and waste, and point source discharges for 2002, 2007 and 2012 at the scale of the 8‐digit Hydrologic Unit Code subbasin (∼1800 km2). Estimates of agricultural legacy P surplus accumulated from 1945‐2001 were also developed. Fertilizer and manure inputs were found to continue exceed crop removal rates by up to 50% in many agricultural regions. This excess in inputs has led to the continued accumulation of legacy P in agricultural lands. Atmospheric P deposition increased throughout the Rockies, potentially contributing to reported increases in surface water P concentrations in undisturbed watersheds. In some urban areas, P fluxes associated with human waste and non‐farm fertilizer use has declined despite population growth, likely due, in part, to various sales bans on P‐containing detergents and fertilizers. Although regions and individual subbasins have different contemporary and legacy P sources, a standardized method of accounting for large and small fluxes and ready to use inventory numbers are essential for coordinated and targeted interventions to reduce P concentrations in the nation's waters.
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| 13. |
- Bergström, Anders, et al.
(författare)
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Grey wolf genomic history reveals a dual ancestry of dogs
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 607:7918, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.
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| 14. |
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| 15. |
- Melani, Rafael D., et al.
(författare)
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The Blood Proteoform Atlas : A reference map of proteoforms in human hematopoietic cells
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6579, s. 411-
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Tidskriftsartikel (refereegranskat)abstract
- Human biology is tightly linked to proteins, yet most measurements do not precisely determine alternatively spliced sequences or posttranslational modifications. Here, we present the primary structures of similar to 30,000 unique proteoforms, nearly 10 times more than in previous studies, expressed from 1690 human genes across 21 cell types and plasma from human blood and bone marrow. The results, compiled in the Blood Proteoform Atlas (BPA), indicate that proteoforms better describe protein-level biology and are more specific indicators of differentiation than their corresponding proteins, which are more broadly expressed across cell types. We demonstrate the potential for clinical application, by interrogating the BPA in the context of liver transplantation and identifying cell and proteoform signatures that distinguish normal graft function from acute rejection and other causes of graft dysfunction.
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| 16. |
- Campana, Pietro Elia, et al.
(författare)
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Suitable and optimal locations for implementing photovoltaic water pumping systems for grassland irrigation in China
- 2017
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Ingår i: APPLIED ENERGY. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 185, s. 1879-1889
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Tidskriftsartikel (refereegranskat)abstract
- Grassland plays a key role for the food security of China because of the large number of livestock raised in those areas. Thus, grassland degradation due to climate change and overgrazing is considered as one of the most severe environmental and economic threat for the future sustainable development of China. Photovoltaic water pumping systems for irrigation can play a fundamental role for the conservation of grassland areas. This paper investigates the geospatial distribution of the technically suitable grassland locations for the implementation of photovoltaic water pumping systems. The technically suitable grassland areas were taken as starting point to assess the optimal locations. The assessment of the optimal locations was conducted using a spatially explicit optimization model of renewable energy systems based on the cost minimization of the whole forage supply chain. The results indicate that the photovoltaic water pumping systems provide high potential for improving forage productivity, contributing to meet the local demand. The optimal areas are highly sensitive to several environmental and economic parameters such as increased forage potential yield, forage management costs, forage water requirements, ground water depth, forage price and CO2 price. Most of the optimal areas are selected when the market forage price ranges from 300 to 500 $/tonne DM, indicating that the forage produced using PVWP technology for irrigation is already competitive compared to the imported forage.
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| 17. |
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| 18. |
- Deng, JY, et al.
(författare)
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Everolimus and plicamycin specifically target chemoresistant colorectal cancer cells of the CMS4 subtype
- 2021
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:11, s. 978-
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancers (CRC) can be classified into four consensus molecular subtypes (CMS), among which CMS1 has the best prognosis, contrasting with CMS4 that has the worst outcome. CMS4 CRC is notoriously resistant against therapeutic interventions, as demonstrated by preclinical studies and retrospective clinical observations. Here, we report the finding that two clinically employed agents, everolimus (EVE) and plicamycin (PLI), efficiently target the prototypic CMS4 cell line MDST8. As compared to the prototypic CMS1 cell line LoVo, MDST8 cells treated with EVE or PLI demonstrated stronger cytostatic and cytotoxic effects, increased signs of apoptosis and autophagy, as well as a more pronounced inhibition of DNA-to-RNA transcription and RNA-to-protein translation. Moreover, nontoxic doses of EVE and PLI induced the shrinkage of MDST8 tumors in mice, yet had only minor tumor growth-reducing effects on LoVo tumors. Altogether, these results suggest that EVE and PLI should be evaluated for their clinical activity against CMS4 CRC.
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| 19. |
- Dumontet, Charles, et al.
(författare)
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Clinical characteristics and outcome of 318 families with familial monoclonal gammopathy : A multicenter Intergroupe Francophone du Myélome study
- 2023
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609 .- 1096-8652. ; 98:2, s. 264-271
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Tidskriftsartikel (refereegranskat)abstract
- Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Humeau, J, et al.
(författare)
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Phosphorylation of eukaryotic initiation factor-2α (eIF2α) in autophagy
- 2020
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:6, s. 433-
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Tidskriftsartikel (refereegranskat)abstract
- The integrated stress response is characterized by the phosphorylation of eukaryotic initiation factor-2α (eIF2α) on serine 51 by one out of four specific kinases (EIF2AK1 to 4). Here we provide three series of evidence suggesting that macroautophagy (to which we refer to as autophagy) induced by a variety of distinct pharmacological agents generally requires this phosphorylation event. First, the induction of autophagic puncta by various distinct compounds was accompanied by eIF2α phosphorylation on serine 51. Second, the modulation of autophagy by >30 chemically unrelated agents was partially inhibited in cells expressing a non-phosphorylable (S51A) mutant of eIF2α or lacking all four eIF2α kinases, although distinct kinases were involved in the response to different autophagy inducers. Third, inhibition of eIF2α phosphatases was sufficient to stimulate autophagy. In synthesis, it appears that eIF2α phosphorylation is a central event for the stimulation of autophagy.
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| 24. |
- Karlson, Agnes M. L., et al.
(författare)
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Large Infaunal Bivalves Determine Community Uptake of Macroalgal Detritus and Food Web Pathways
- 2021
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Ingår i: Ecosystems (New York. Print). - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; :24, s. 384-402
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Tidskriftsartikel (refereegranskat)abstract
- Human activities alter biodiversity, influencing bottom-up and top-down control on food webs which can affect ecosystem functioning. In marine ecosystems, large bivalves play a critical role in benthic-pelagic coupling including nutrient cycling; however, their influence on the uptake of detrital organic matter by benthic communities is less understood. In a replicated factorial field experiment, we examined how the presence or absence (overharvesting scenario) of a large suspension-feeding clam on an intertidal sandflat and the addition of isotopically enriched macroalgal (Ulva sp.) detritus (eutrophication scenario) influenced infaunal biodiversity, and how changes in trophic interactions influenced key ecosystem functions (nutrient cycling and benthic metabolism and primary production). Both clams and Ulva increased community metabolism, but only clams had an effect on nutrient regeneration. We used the C-13- and N-15-enriched Ulva to quantify the effect of clams on detritus uptake in fauna and recovery in sediment. Due to their large biomass, nitrogen incorporation by clams constituted one-third of the infaunal community uptake after 14 days. Clam uptake likely resulted from ingestion of resuspended microphytobentos which had utilized N-15 leaking out from decomposing Ulva. In plots without Ulva addition, the effect of clams on the overall resource utilization by the benthic community using natural abundance isotope niche metrics were tested. In plots without clams, the isotope niche of the community was reduced, and less carbon of pelagic origin was channelled into the infaunal food web. Our results imply that the loss of clams changes trophic pathways and reduces community uptake of macroalgal detritus, potentially exacerbating eutrophication.
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| 25. |
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| 26. |
- Latacz, Emily, et al.
(författare)
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Histopathological growth patterns of liver metastasis : updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights
- 2022
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127:6, s. 988-1013
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Forskningsöversikt (refereegranskat)abstract
- The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.
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| 27. |
- LeDuc, Richard D., et al.
(författare)
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Proteomics Standards Initiative's ProForma 2.0 : Unifying the Encoding of Proteoforms and Peptidoforms br
- 2022
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:4, s. 1189-1195
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Tidskriftsartikel (refereegranskat)abstract
- It is important for the proteomics community to have a standardizedmanner to represent all possible variations of a protein or peptide primary sequence,including natural, chemically induced, and artifactual modifications. The HumanProteome Organization Proteomics Standards Initiative in collaboration with severalmembers of the Consortium for Top-Down Proteomics (CTDP) has developed astandard notation called ProForma 2.0, which is a substantial extension of the originalProForma notation developed by the CTDP. ProForma 2.0 aims to unify therepresentation of proteoforms and peptidoforms. ProForma 2.0 supports use casesneeded for bottom-up and middle-/top-down proteomics approaches and allows theencoding of highly modified proteins and peptides using a human- and machine-readable string. ProForma 2.0 can be used to represent protein modifications in a specified or ambiguous location, designated bymass shifts, chemical formulas, or controlled vocabulary terms, including cross-links (natural and chemical) and atomic isotopes.Notational conventions are based on public controlled vocabularies and ontologies. The most up-to-date full specification documentand information about software implementations are available athttp://psidev.info/proforma.
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| 28. |
- LeDuc, Stephen D., et al.
(författare)
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Nitrogen and Sulfur Deposition Reductions Projected to Partially Restore Forest Soil Conditions in the US Northeast, While Understory Composition Continues to Shift with Future Climate Change
- 2022
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Ingår i: Water, Air and Soil Pollution. - : Springer Science and Business Media LLC. - 0049-6979 .- 1573-2932. ; 233:9
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Tidskriftsartikel (refereegranskat)abstract
- Human activities have dramatically increased nitrogen (N) and sulfur (S) deposition, altering forest ecosystem function and structure. Anticipating how changes in deposition and climate impact forests can inform decisions regarding these environmental stressors. Here, we used a dynamic soil-vegetation model (ForSAFE-Veg) to simulate responses to future scenarios of atmospheric deposition and climate change across 23 Northeastern hardwood stands. Specifically, we simulated soil percent base saturation, acid neutralizing capacity (ANC), nitrate (NO3−) leaching, and understory composition under 13 interacting deposition and climate change scenarios to the year 2100, including anticipated deposition reductions under the Clean Air Act (CAA) and Intergovernmental Panel on Climate Change–projected climate futures. Overall, deposition affected soil responses more than climate did. Soils recovered to historic conditions only when future deposition returned to pre-industrial levels, although anticipated CAA deposition reductions led to a partial recovery of percent base saturation (60 to 72%) and ANC (65 to 71%) compared to historic values. CAA reductions also limited NO3− leaching to 30 to 66% above historic levels, while current levels of deposition resulted in NO3− leaching 150 to 207% above historic values. In contrast to soils, understory vegetation was affected strongly by both deposition and climate. Vegetation shifted away from historic and current assemblages with increasing deposition and climate change. Anticipated CAA reductions could maintain current assemblages under current climate conditions or slow community shifts under increased future changes in temperature and precipitation. Overall, our results can inform decision-makers on how these dual stressors interact to affect forest health, and the efficacy of deposition reductions under a changing climate.
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| 29. |
- Natarajan, K., et al.
(författare)
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Potential expansion of second generation Fischer Tropsch biodiesel production in Finland
- 2012
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Ingår i: NWBC 2012 - 4th Nordic Wood Biorefinery Conference. - : VTT Technical Research Centre of Finland. ; , s. 277-278
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Konferensbidrag (refereegranskat)abstract
- The Finnish biofuel industry is undergoing a major change in particular second generation Fischer Tropsch (FT) biodiesel production. However, efficient geographical energy planning is essential to optimally allocate the limited natural resources between biomass based industries. Therefore, a decision tool was formulated which includes three different models: (1) a spatial model that estimates the amount of biomass supply and industrial residues available for energy production, (2) an energy demand model calculates the amount of heat and transport fuel that can be delivered to the customers, (3) an optimization model that minimizes the complete costs of biodiesel supply chain from biomass supply to biodiesel delivery at the fuel stations to determine the optimal location, size and configurations of FT biodiesel production plants in Finland. Model results show that five cost-optimal biodiesel production plant locations of 390 MWfeedstock are needed to be built to meet the 2020 renewable energy share in transport (25.2 PJ). The unit cost of FT biodiesel produced in Finland could range between 1.1 and 1.4 €/l2011 without heat sales. © NWBC 2012.All rights reserved.
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| 31. |
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| 33. |
- Tian, AL, et al.
(författare)
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Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response
- 2021
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:1, s. 6-
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Tidskriftsartikel (refereegranskat)abstract
- The integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.
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| 34. |
- Wu, Q, et al.
(författare)
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IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms
- 2021
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological autophagy enhancement constitutes a preclinically validated strategy for preventing or treating most major age-associated diseases. Driven by this consideration, we performed a high-content/high-throughput screen on 65 000 distinct compounds on a robotized fluorescence microscopy platform to identify novel autophagy inducers.ResultsHere, we report the discovery of picropodophyllin (PPP) as a potent inducer of autophagic flux that acts on-target, as an inhibitor of the tyrosine kinase activity of the insulin-like growth factor-1 receptor (IGF1R). Thus, PPP lost its autophagy-stimulatory activity in cells engineered to lack IGF1R or to express a constitutively active AKT serine/threonine kinase 1 (AKT1) mutant. When administered to cancer-bearing mice, PPP improved the therapeutic efficacy of chemoimmunotherapy with a combination of immunogenic cytotoxicants and programmed cell death 1 (PDCD1, better known as PD-1) blockade. These PPP effects were lost when tumors were rendered PPP-insensitive or autophagy-incompetent. In combination with chemotherapy, PPP enhanced the infiltration of tumors by cytotoxic T lymphocytes, while reducing regulatory T cells. In human triple-negative breast cancer patients, the activating phosphorylation of IGF1R correlated with inhibited autophagy, an unfavorable local immune profile, and poor prognosis.ConclusionAltogether, these results suggest that IGF1R may constitute a novel and druggable therapeutic target for the treatment of cancer in conjunction with chemoimmunotherapies.
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| 35. |
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| 36. |
- Zhang, SY, et al.
(författare)
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Squaramide-based synthetic chloride transporters activate TFEB but block autophagic flux
- 2019
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 10:3, s. 242-
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis is a disease caused by defective function of a chloride channel coupled to a blockade of autophagic flux. It has been proposed to use synthetic chloride transporters as pharmacological agents to compensate insufficient chloride fluxes. Here, we report that such chloride anionophores block autophagic flux in spite of the fact that they activate the pro-autophagic transcription factor EB (TFEB) coupled to the inhibition of the autophagy-suppressive mTORC1 kinase activity. Two synthetic chloride transporters (SQ1 and SQ2) caused a partially TFEB-dependent relocation of the autophagic marker LC3 to the Golgi apparatus. Inhibition of TFEB activation using a calcium chelator or calcineurin inhibitors reduced the formation of LC3 puncta in cells, yet did not affect the cytotoxic action of SQ1 and SQ2 that could be observed after prolonged incubation. In conclusion, the squaramide-based synthetic chloride transporters studied in this work (which can also dissipate pH gradients) are probably not appropriate for the treatment of cystic fibrosis yet might be used for other indications such as cancer.
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| 37. |
- Zhou, H, et al.
(författare)
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Oncolysis with DTT-205 and DTT-304 generates immunological memory in cured animals
- 2018
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:11, s. 1086-
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Tidskriftsartikel (refereegranskat)abstract
- Oncolytic peptides and peptidomimetics are being optimized for the treatment of cancer by selecting agents with high cytotoxic potential to kill a maximum of tumor cells as well as the capacity to trigger anticancer immune responses and hence to achieve long-term effects beyond therapeutic discontinuation. Here, we report on the characterization of two novel oncolytic peptides, DTT-205 and DTT-304 that both selectively enrich in the lysosomal compartment of cancer cells yet differ to some extent in their cytotoxic mode of action. While DTT-304 can trigger the aggregation of RIP3 in ripoptosomes, coupled to the phosphorylation of MLKL by RIP3, DTT-205 fails to activate RIP3. Accordingly, knockout of either RIP3 or MLKL caused partial resistance against cell killing by DTT-304 but not DTT-205. In contrast, both agents shared common features in other aspects of pro-death signaling in the sense that their cytotoxic effects were strongly inhibited by both serum and antioxidants, partially reduced by lysosomal inhibition with bafilomycin A1 or double knockout of Bax and Bak, yet totally refractory to caspase inhibition. Both DTT-304 and DTT-205 caused the exposure of calreticulin at the cell surface, as well as the release of HMGB1 from the cells. Mice bearing established subcutaneous cancers could be cured by local injection of DTT-205 or DTT-304, and this effect depended on T lymphocytes, as it led to the establishment of a long-term memory response against tumor-associated antigens. Thus, mice that had been cured from cancer by the administration of DTT compounds were refractory against rechallenge with the same cancer type several months after the disappearance of the primary lesion. In summary, DTT-205 and DTT-304 both have the capacity to induce immunotherapeutic oncolysis.
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| 38. |
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