| 1. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 4. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 5. |
- Bentham, James, et al.
(författare)
-
A century of trends in adult human height
- 2016
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
|
|
| 6. |
|
|
| 7. |
- Adam, A, et al.
(författare)
-
Abstracts from Hydrocephalus 2016.
- 2017
-
Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
-
Tidskriftsartikel (refereegranskat)
|
|
| 8. |
- Cruz, Raquel, et al.
(författare)
-
Novel genes and sex differences in COVID-19 severity
- 2022
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
-
Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
|
|
| 9. |
- ter Steege, Hans, et al.
(författare)
-
Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
-
Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
|
|
| 10. |
- Householder, John Ethan, et al.
(författare)
-
One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
-
Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
-
Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
|
|
| 11. |
- Luize, Bruno Garcia, et al.
(författare)
-
Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
-
Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
|
|
| 12. |
- Santangelo, James S., et al.
(författare)
-
Global urban environmental change drives adaptation in white clover
- 2022
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
-
Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
|
|
| 13. |
- Peripato, Vinicius, et al.
(författare)
-
More than 10,000 pre-Columbian earthworks are still hidden throughout Amazonia
- 2023
-
Ingår i: Science (New York, N.Y.). - 1095-9203. ; 382:6666, s. 103-109
-
Tidskriftsartikel (refereegranskat)abstract
- Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.
|
|
| 14. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 15. |
- Flores-Figueroa, Jose, et al.
(författare)
-
Patterns of illness in travelers visiting Mexico and Central America : the GeoSentinel experience.
- 2011
-
Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press. - 1537-6591. ; 53:6, s. 523-531
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mexico and Central America are important travel destinations for North American and European travelers. There is limited information on regional differences in travel related morbidity. METHODS: We describe the morbidity among 4779 ill travelers returned from Mexico and Central America who were evaluated at GeoSentinel network clinics during December 1996 to February 2010. RESULTS: The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. A higher proportion of ill travelers from the United States had acute diarrhea, compared with their Canadian and European counterparts (odds ratio, 1.9; P < .0001). During the 2009 H1N1 influenza outbreak from March 2009 through February 2010, the proportionate morbidity (PM) associated with respiratory illnesses in ill travelers increased among those returned from Mexico, compared with prior years (196.0 cases per 1000 ill returned travelers vs 53.7 cases per 1000 ill returned travelers; P < .0001); the PM remained constant in the rest of Central America (57.3 cases per 1000 ill returned travelers). We identified 50 travelers returned from Mexico and Central America who developed influenza, including infection due to 2009 H1N1 strains and influenza-like illness. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (PM, 2.2 cases per 1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis. CONCLUSIONS: Travel medicine practitioners advising and treating travelers visiting these regions should dedicate special attention to vaccine-preventable illnesses and should consider the uncommon occurrence of acute hepatitis A, leptospirosis, neurocysticercosis, acute Chagas disease, onchocerciasis, mucocutaneous leishmaniasis, neurocysticercosis, HIV, malaria, and brucellosis.
|
|
| 16. |
- Hoang, Oanh N, et al.
(författare)
-
Mucins MUC5AC and MUC5B Are Variably Packaged in the Same and in Separate Secretory Granules.
- 2022
-
Ingår i: American journal of respiratory and critical care medicine. - 1073-449X .- 1535-4970. ; 206:9, s. 1081-1095
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: MUC5AC (mucin 5AC, oligomeric gel-forming) and MUC5B (mucin 5B, oligomeric gel-forming) are the predominant secreted polymeric mucins in mammalian airways. They contribute differently to the pathogenesis of various muco-obstructive and interstitial lung diseases, and their genes are separately regulated, but whether they are packaged together or in separate secretory granules is not known. Objectives: To determine the packaging of MUC5AC and MUC5B within individual secretory granules in mouse and human airways under varying conditions of inflammation and along the proximal-distal axis. Methods: Lung tissue was obtained from mice stimulated to upregulate mucin production by the cytokines IL-1β and IL-13 or by porcine pancreatic elastase. Human lung tissue was obtained from donated normal lungs, biopsy samples of transplanted lungs, and explanted lungs from subjects with chronic obstructive pulmonary disease. MUC5AC and MUC5B were labeled with antibodies from different animal species or, in mice only, by transgenic chimeric mucin-fluorescent proteins and imaged using widefield deconvolution or Airyscan fluorescence microscopy. Measurements and Main Results: In both mouse and human airways, most secretory granules contained both mucins interdigitating within the granules. Smaller numbers of granules contained MUC5B alone, and even fewer contained MUC5AC alone. Conclusions: MUC5AC and MUC5B are variably stored both in the same and in separate secretory granules of both mice and humans. The high fraction of granules containing both mucins under a variety of conditions makes it unlikely that their secretion can be differentially controlled as a therapeutic strategy. This work also advances knowledge of the packaging of mucins within secretory granules to understand mechanisms of epithelial stress in the pathogenesis of chronic lung diseases.
|
|
| 17. |
|
|
| 18. |
- Acuna, Lillian G., et al.
(författare)
-
Architecture and Gene Repertoire of the Flexible Genome of the Extreme Acidophile Acidithiobacillus caldus
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Acidithiobacillus caldus is a sulfur oxidizing extreme acidophile and the only known mesothermophile within the Acidithiobacillales. As such, it is one of the preferred microbes for mineral bioprocessing at moderately high temperatures. In this study, we explore the genomic diversity of A. caldus strains using a combination of bioinformatic and experimental techniques, thus contributing first insights into the elucidation of the species pangenome. Principal Findings: Comparative sequence analysis of A. caldus ATCC 51756 and SM-1 indicate that, despite sharing a conserved and highly syntenic genomic core, both strains have unique gene complements encompassing nearly 20% of their respective genomes. The differential gene complement of each strain is distributed between the chromosomal compartment, one megaplasmid and a variable number of smaller plasmids, and is directly associated to a diverse pool of mobile genetic elements (MGE). These include integrative conjugative and mobilizable elements, genomic islands and insertion sequences. Some of the accessory functions associated to these MGEs have been linked previously to the flexible gene pool in microorganisms inhabiting completely different econiches. Yet, others had not been unambiguously mapped to the flexible gene pool prior to this report and clearly reflect strain-specific adaption to local environmental conditions. Significance: For many years, and because of DNA instability at low pH and recurrent failure to genetically transform acidophilic bacteria, gene transfer in acidic environments was considered negligible. Findings presented herein imply that a more or less conserved pool of actively excising MGEs occurs in the A. caldus population and point to a greater frequency of gene exchange in this econiche than previously recognized. Also, the data suggest that these elements endow the species with capacities to withstand the diverse abiotic and biotic stresses of natural environments, in particular those associated with its extreme econiche.
|
|
| 19. |
- Collantes, Edward Ryan A., et al.
(författare)
-
EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma
- 2022
-
Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:2, s. 240-252
-
Tidskriftsartikel (refereegranskat)abstract
- Juvenile open-angle glaucoma (JOAG) is a severe type of glaucoma with onset before age 40 and dominant inheritance. Using exome sequencing we identified 3 independent families from the Philippines with novel EFEMP1 variants (c.238A>T, p.Asn80Tyr; c.1480T>C, p.Ter494Glnext*29; and c.1429C>T, p.Arg477Cys) co-segregating with disease. Affected variant carriers (N = 34) exhibited severe disease with average age of onset of 16 years and with 76% developing blindness. To investigate functional effects, we transfected COS7 cells with vectors expressing the three novel EFEMP1 variants and showed that all three variants found in JOAG patients caused significant intracellular protein aggregation and retention compared to wild type and also compared to EFEMP1 variants associated with other ocular phenotypes including an early-onset form of macular degeneration, Malattia Leventinese/Doyne's Honeycomb retinal dystrophy. These results suggest that rare EFEMP1 coding variants can cause JOAG through a mechanism involving protein aggregation and retention, and that the extent of intracellular retention correlates with disease phenotype. This is the first report of EFEMP1 variants causing JOAG, expanding the EFEMP1 disease spectrum. Our results suggest that EFEMP1 mutations appear to be a relatively common cause of JOAG in Filipino families, an ethnically diverse population.
|
|
| 20. |
- Flores, Jose-Abel, et al.
(författare)
-
Distribution of large Emiliania huxleyi in the Central and Northeast Atlantic as a tracer of surface ocean dynamics during the last 25,000 years
- 2010
-
Ingår i: Marine Micropaleontology. - : Elsevier BV. - 0377-8398 .- 1872-6186. ; 76:3-4, s. 53-66
-
Tidskriftsartikel (refereegranskat)abstract
- The coccolithophore species Emiliania huxleyi is characterized by a wide range of sizes. which can be easily distinguished in the light microscope. In this study we have quantified the abundance of large (coccoliths >4 mu m in maximum length) E. huxleyi specimens during the last 25 kyr in sedimentary records from eleven cores and drill sites in the NE Atlantic and W Mediterranean Sea, to prove its usefulness in the reconstruction of water mass dynamics and biostratigraphic potential. During the Last Glacial Maximum this large form, a cold-water indicator, was common in the NE Atlantic and Mediterranean, and its regional variation in abundance indicates a displacement of the climatic zones southwards in agreement with the development of ice sheets and sea ice in the Northern Hemisphere during this period. On the other hand, the gradient between northern and southern surface water masses in the Subtropical Gyre appears to have been more pronounced than at present, while the Portugal and Canary Currents were more intense. In the western Mediterranean basin temperatures were cooler than in the adjacent Atlantic, provoking a quasi-endemism of these specimens until the end of Heinrich Event 1. This may have been due to a restriction in the communication between the Atlantic and Mediterranean through the Strait of Gibraltar, the arrival of cold surface water and the amplification of cooling after the development of ice sheets in the Northern Hemisphere. During the deglaciation, large E. huxleyi specimens decreased in abundance at medium and low latitudes, but were still numerous close to the Subarctic region during the Holocene. In transitional waters this decrease to present day abundances occurred after Termination lb. The abrupt change in abundance of this large E. huxleyi form is proposed as a new biostratigraphic event to characterize the Holocene in mid- to low-latitude water masses in the North Atlantic, although this horizon seems to be diachronous by 5 kyr from tropical to subarctic regions, in agreement with the gradual onset of warm conditions.
|
|
| 21. |
- Flores-Morales, Amilcar, et al.
(författare)
-
Proteogenomic characterization of patient-derived xenografts highlights the role of REST in neuroendocrine differentiation of castration-resistant prostate cancer
- 2019
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 25:2, s. 595-608
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: An increasing number of castration-resistant prostate cancer (CRPC) tumors exhibit neuroendocrine (NE) features. NE prostate cancer (NEPC) has poor prognosis, and its development is poorly understood. Experimental Design: We applied mass spectrometry–based proteomics to a unique set of 17 prostate cancer patient–derived xenografts (PDX) to characterize the effects of castration in vivo, and the proteome differences between NEPC and prostate adenocarcinomas. Genome-wide profiling of REST-occupied regions in prostate cancer cells was correlated to the expression changes in vivo to investigate the role of the transcriptional repressor REST in castration-induced NEPC differentiation. Results: An average of 4,881 proteins were identified and quantified from each PDX. Proteins related to neurogenesis, cell-cycle regulation, and DNA repair were found upregulated and elevated in NEPC, while the reduced levels of proteins involved in mitochondrial functions suggested a prevalent glycolytic metabolism of NEPC tumors. Integration of the REST chromatin bound regions with expression changes indicated a direct role of REST in regulating neuronal gene expression in prostate cancer cells. Mechanistically, depletion of REST led to cell-cycle arrest in G1, which could be rescued by p53 knockdown. Finally, the expression of the REST-regulated gene secretagogin (SCGN) correlated with an increased risk of suffering disease relapse after radical prostatectomy. Conclusions: This study presents the first deep characterization of the proteome of NEPC and suggests that concomitant inhibition of REST and the p53 pathway would promote NEPC. We also identify SCGN as a novel prognostic marker in prostate cancer.
|
|
| 22. |
- Matuozzo, Daniela, et al.
(författare)
-
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
- 2023
-
Ingår i: Genome medicine. - 1756-994X. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in~80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1×10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1×10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4×10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7×10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68×10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.
|
|
| 23. |
- Pitcher, Grant C., et al.
(författare)
-
System controls of coastal and open ocean oxygen depletion
- 2021
-
Ingår i: Progress in Oceanography. - : Elsevier BV. - 0079-6611. ; 197
-
Forskningsöversikt (refereegranskat)abstract
- The epoch of the Anthropocene, a period during which human activity has been the dominant influence on climate and the environment, has witnessed a decline in oxygen concentrations and an expansion of oxygen-depleted environments in both coastal and open ocean systems since the middle of the 20th century. This paper provides a review of system-specific drivers of low oxygen in a range of case studies representing marine systems in the open ocean, on continental shelves, in enclosed seas and in the coastal environment. Identification of similar and contrasting responses within and across system types and corresponding oxygen regimes is shown to be informative both in understanding and isolating key controlling processes and provides a sound basis for predicting change under anticipated future conditions. Case studies were selected to achieve a balance in system diversity and global coverage. Each case study describes system attributes, including the present-day oxygen environment and known trends in oxygen concentrations over time. Central to each case study is the identification of the physical and biogeochemical processes that determine oxygen concentrations through the tradeoff between ventilation and respiration. Spatial distributions of oxygen and time series of oxygen data provide the opportunity to identify trends in oxygen availability and have allowed various drivers of low oxygen to be distinguished through correlative and causative relationships. Deoxygenation results from a complex interplay of hydrographic and biogeochemical processes and the superposition of these processes, some additive and others subtractive, makes attribution to any particular driver challenging. System-specific models are therefore required to achieve a quantitative understanding of these processes and of the feedbacks between processes at varying scales.
|
|
| 24. |
|
|
| 25. |
- Tavares, Julia, et al.
(författare)
-
Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests
- 2023
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 617:7959, s. 111-117
-
Tidskriftsartikel (refereegranskat)abstract
- Tropical forests face increasing climate risk(1,2), yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, ?(50)) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk(3-5), little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters ?(50) and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both ?(50) and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM(50 )forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon(6,7), with strong implications for the Amazon carbon sink.
|
|
| 26. |
|
|
