| 61. |
- Andreassen, Anna H., et al.
(författare)
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Brain dysfunction during warming is linked to oxygen limitation in larval zebrafish
- 2022
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:39
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the physiological mechanisms that limit animal thermal tolerance is crucial in predicting how animals will respond to increasingly severe heat waves. Despite their importance for understanding climate change impacts, these mechanisms underlying the upper thermal tolerance limits of animals are largely unknown. It has been hypothesized that the upper thermal tolerance in fish is limited by the thermal tolerance of the brain and is ultimately caused by a global brain depolarization. In this study, we developed methods for measuring the upper thermal limit (CTmax) in larval zebrafish (Danio rerio) with simultaneous recordings of brain activity using GCaMP6s calcium imaging in both free-swimming and agar-embedded fish. We discovered that during warming, CTmax precedes, and is therefore not caused by, a global brain depolarization. Instead, the CTmax coincides with a decline in spontaneous neural activity and a loss of neural response to visual stimuli. By manipulating water oxygen levels both up and down, we found that oxygen availability during heating affects locomotor-related neural activity, the neural response to visual stimuli, and CTmax. Our results suggest that the mechanism limiting the upper thermal tolerance in zebrafish larvae is insufficient oxygen availability causing impaired brain function.
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| 62. |
- Angeletti, Davide, 1984, et al.
(författare)
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Outflanking immunodominance to target subdominant broadly neutralizing epitopes
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 116:27, s. 13474-13479
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Tidskriftsartikel (refereegranskat)abstract
- A major obstacle to vaccination against antigenically variable viruses is skewing of antibody responses to variable immunodominant epitopes. For influenza virus hemagglutinin (HA), the immunodominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immunogenicity is enhanced by immunizing with stem-only constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, coimmunization of full-length HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance, with important implications for human vaccination. © 2019 National Academy of Sciences. All rights reserved.
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| 63. |
- Antonelli, Alexandre, 1978, et al.
(författare)
-
Amazonia is the primary source of Neotropical biodiversity
- 2018
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 115:23, s. 6034-6039
-
Tidskriftsartikel (refereegranskat)abstract
- The American tropics (the Neotropics) are the most species-rich realm on Earth, and for centuries, scientists have attempted to understand the origins and evolution of their biodiversity. It is now clear that different regions and taxonomic groups have responded differently to geological and climatic changes. However, we still lack a basic understanding of how Neotropical biodiversity was assembled over evolutionary timescales. Here we infer the timing and origin of the living biota in all major Neotropical regions by performing a cross-taxonomic biogeographic analysis based on 4,450 species from six major clades across the tree of life (angiosperms, birds, ferns, frogs, mammals, and squamates), and integrate > 1.3 million species occurrences with large-scale phylogenies. We report an unprecedented level of biotic interchange among all Neotropical regions, totaling 4,525 dispersal events. About half of these events involved transitions between major environmental types, with a predominant directionality from forested to open biomes. For all taxonomic groups surveyed here, Amazonia is the primary source of Neotropical diversity, providing > 2,800 lineages to other regions. Most of these dispersal events were to Mesoamerica (similar to 1,500 lineages), followed by dispersals into open regions of northern South America and the Cerrado and Chaco biomes. Biotic interchange has taken place for > 60 million years and generally increased toward the present. The total amount of time lineages spend in a region appears to be the strongest predictor of migration events. These results demonstrate the complex origin of tropical ecosystems and the key role of biotic interchange for the assembly of regional biotas.
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| 64. |
- Antonelli, Alexandre, 1978, et al.
(författare)
-
Tracing the impact of the Andean uplift on Neotropical plant evolution
- 2009
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 106:24, s. 9749-9754
-
Tidskriftsartikel (refereegranskat)abstract
- Recent phylogenetic studies have revealed the major role played by the uplift of the Andes in the extraordinary diversification of the Neotropical flora. These studies, however, have typically considered the Andean uplift as a single, time-limited event fostering the evolution of highland elements. This contrasts with geological reconstructions indicating that the uplift occurred in discrete periods from west to east and that it affected different regions at different times. We introduce an approach for integrating Andean tectonics with biogeographic reconstructions of Neotropical plants, using the coffee family (Rubiaceae) as a model group. The distribution of this family spans highland and montane habitats as well as tropical lowlands of Central and South America, thus offering a unique opportunity to study the influence of the Andean uplift on the entire Neotropical flora. Our results suggest that the Rubiaceae originated in the Paleotropics and used the boreotropical connection to reach South America. The biogeographic patterns found corroborate the existence of a long-lasting dispersal barrier between the Northern and Central Andes, the "Western Andean Portal.'' The uplift of the Eastern Cordillera ended this barrier, allowing dispersal of boreotropical lineages to the South, but gave rise to a huge wetland system ("Lake Pebas'') in western Amazonia that prevented in situ speciation and floristic dispersal between the Andes and Amazonia for at least 6 million years. Here, we provide evidence of these events in plants.
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| 65. |
- Antonelli, A, et al.
(författare)
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Tracing the impact of the Andean uplift on Neotropical plant evolution : evidence from the coffee family
- 2009
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:24, s. 9749-9754
-
Tidskriftsartikel (refereegranskat)abstract
- Recent phylogenetic studies have revealed the major role played by the uplift of the Andes in the extraordinary diversification of the Neotropical flora. These studies, however, have typically considered the Andean uplift as a single, time-limited event fostering the evolution of highland elements. This contrasts with geological reconstructions indicating that the uplift occurred in discrete periods from west to east and that it affected different regions at different times. We introduce an approach for integrating Andean tectonics with biogeographic reconstructions of Neotropical plants, using the coffee family (Rubiaceae) as a model group. The distribution of this family spans highland and montane habitats as well as tropical lowlands of Central and South America, thus offering a unique opportunity to study the influence of the Andean uplift on the entire Neotropical flora. Our results suggest that the Rubiaceae originated in the Paleotropics and used the boreotropical connection to reach South America. The biogeographic patterns found corroborate the existence of a long-lasting dispersal barrier between the Northern and Central Andes, the "Western Andean Portal.'' The uplift of the Eastern Cordillera ended this barrier, allowing dispersal of boreotropical lineages to the South, but gave rise to a huge wetland system ("Lake Pebas'') in western Amazonia that prevented in situ speciation and floristic dispersal between the Andes and Amazonia for at least 6 million years. Here, we provide evidence of these events in plants
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| 66. |
- Antonucci, Laura, et al.
(författare)
-
Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress.
- 2015
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:45
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic acinar cells possess very high protein synthetic rates as they need to produce and secrete large amounts of digestive enzymes. Acinar cell damage and dysfunction cause malnutrition and pancreatitis, and inflammation of the exocrine pancreas that promotes development of pancreatic ductal adenocarcinoma (PDAC), a deadly pancreatic neoplasm. The cellular and molecular mechanisms that maintain acinar cell function and whose dysregulation can lead to tissue damage and chronic pancreatitis are poorly understood. It was suggested that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis, but it is unknown whether impaired autophagy is a cause or a consequence of pancreatitis. To address this question, we generated Atg7Δpan mice that lack the essential autophagy-related protein 7 (ATG7) in pancreatic epithelial cells. Atg7Δpan mice exhibit severe acinar cell degeneration, leading to pancreatic inflammation and extensive fibrosis. Whereas ATG7 loss leads to the expected decrease in autophagic flux, it also results in endoplasmic reticulum (ER) stress, accumulation of dysfunctional mitochondria, oxidative stress, activation of AMPK, and a marked decrease in protein synthetic capacity that is accompanied by loss of rough ER. Atg7Δpan mice also exhibit spontaneous activation of regenerative mechanisms that initiate acinar-to-ductal metaplasia (ADM), a process that replaces damaged acinar cells with duct-like structures.
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| 67. |
- Antzutkin, Oleg, et al.
(författare)
-
Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer's β-amyloid fibrils
- 2000
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 97:24, s. 13045-13050
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Tidskriftsartikel (refereegranskat)abstract
- Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue β-amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended β-sheet structure for Alzheimer's β-amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the β-sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils. Here we report solid-state NMR measurements, using a multiple quantum (MQ) 13C NMR technique, that probe the β-sheet organization in fibrils formed by the full-length, 40-residue β-amyloid peptide (Aβ1-40). Although an antiparallel β-sheet organization often is assumed and is invoked in recent structural models for full-length β-amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length β-amyloid fibrils and applies MQNMR to a significant problem in structural biology.
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| 68. |
- Aparicio, S, et al.
(författare)
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Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.
- 1995
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 92:5, s. 1684-1688
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Tidskriftsartikel (refereegranskat)abstract
- Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.
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| 69. |
- Arapan, S., et al.
(författare)
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Prediction of incommensurate crystal structure in Ca at high pressure
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:52, s. 20627-20630
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Tidskriftsartikel (refereegranskat)abstract
- Ca shows an interesting high-pressure phase transformation sequence, but, despite similar physical properties at high pressure and affinity in the electronic structure with its neighbors in the periodic table, no complex phase has been identified for Ca so far. We predict an incommensurate high-pressure phase of Ca from first principle calculations and describe a procedure of estimating incommensurate structure parameters by means of electronic structure calculations for periodic crystals. Thus, by using the ab initio technique for periodic structures, one can get not only reliable information about the electronic structure and structural parameters of an incommensurate phase, but also identify and predict such phases in new elements.
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| 70. |
- Arbiser, JL, et al.
(författare)
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Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways
- 1997
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 94:3, s. 861-866
-
Tidskriftsartikel (refereegranskat)abstract
- The switch from a quiescent tumor to an invasive tumor is accompanied by the acquisition of angiogenic properties. This phenotypic change likely requires a change in the balance of angiogenic stimulators and angiogenic inhibitors. The nature of the angiogenic switch is not known. Here, we show that introduction of activated H-ras into immortalized endothelial cells is capable of activating the angiogenic switch. Angiogenic switching is accompanied by up-regulation of vascular endothelial growth factor and matrix metalloproteinase (MMP) bioactivity and down-regulation of tissue inhibitor of MMP. Furthermore, we show that inhibition of phosphatidylinositol-3-kinase leads to partial inhibition of tumor angiogenesis, thus demonstrating that activated H-ras activates tumor angiogenesis through two distinct pathways. Finally, we show evidence for two forms of tumor dormancy.
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