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2021 ◽  
Author(s):  
Julia K. Gundersen ◽  
David A. Menassa ◽  
Thomas R. Wood ◽  
Lars Walløe ◽  
Marianne Thoresen

We study the effect of hypothermia (HT) following hypoxic-ischemic (HI) brain injury in postnatal day 7 (P7) rats. In 2015, new European Union animal transport regulations prompted a change in practice at the breeding facility, which henceforth crossfostered P3 litters to P8 older lactating dam prior to transportation. It is generally assumed that crossfostering does not significantly affect the experimental results. The aim of this study was to examine whether crossfostering affects our model consistency by modifying injury susceptibility and hypothermic neuroprotection. We analysed 219 pups (56 litters) from 11 experiments conducted between 2013 and 2015: 73 non-crossfostered and 146 crossfostered pups. At P7, all pups underwent unilateral common carotid artery ligation followed by 50min of hypoxia (8% O2, 36°C). Immediately after this mild insult, the pups were randomised to post-insult normothermia (NT) or HT treatment. Pups were culled at P14. Injury was assessed by area loss of the ipsilateral hemisphere and histopathology scoring of hippocampus, cortex, thalamus, and basal ganglia. Crossfostered pups had double the injury compared to non-crossfostered pups irrespective of treatment group. Hypothermic neuroprotection was statistically significant, but with a smaller and less consistent effect in crossfostered pups (relative neuroprotection 16% vs. 31% in non-crossfostered). These results demonstrate hypothermic neuroprotection following a mild HI insult. A representative subset of 41 animals were also assessed for evidence of microglial reactivity, however no detectable difference in microglial reactivity was observed between any of the groups. In conclusion, crossfostering alters outcomes in our established model through reduced insult tolerance and variable neuroprotection. Crossfostering as a common breeding practice is a largely unexplored variable in animal research that may result in invalid research conclusions if inadequately adjusted for by larger group sizes. As a result, crossfostering is likely to be inconsistent with the principles of replacement, reduction, and refinement.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12496
Author(s):  
Kévin Fontaine ◽  
Céline Fourrier-Jeandel ◽  
Andrew D. Armitage ◽  
Anne-Laure Boutigny ◽  
Manuela Crépet ◽  
...  

Leaf blotch caused by Alternaria spp. is a common disease in apple-producing regions. The disease is usually associated with one phylogenetic species and one species complex, Alternaria alternata and the Alternaria arborescens species complex (A. arborescens SC), respectively. Both taxa may include the Alternaria apple pathotype, a quarantine or regulated pathogen in several countries. The apple pathotype is characterized by the production of a host-selective toxin (HST) which is involved in pathogenicity towards the apple. A cluster of genes located on conditionally dispensable chromosomes (CDCs) is involved in the production of this HST (namely AMT in the case of the apple pathotype). Since 2016, leaf blotch and premature tree defoliation attributed to Alternaria spp. have been observed in apple-producing regions of central and south-eastern France. Our study aimed to identify the Alternaria species involved in apple tree defoliation and assess the presence of the apple pathotype in French orchards. From 2016 to 2018, 166 isolates were collected and identified by multi-locus sequence typing (MLST). This analysis revealed that all these French isolates belonged to either the A. arborescens SC or A. alternata. Specific PCR detection targeting three genes located on the CDC did not indicate the presence of the apple pathotype in France. Pathogenicity was assessed under laboratory conditions on detached leaves of Golden Delicious and Gala apple cultivars for a representative subset of 28 Alternaria isolates. All the tested isolates were pathogenic on detached leaves of cultivars Golden Delicious and Gala, but no differences were observed between the pathogenicity levels of A. arborescens SC and A. alternata. However, the results of our pathogenicity test suggest that cultivar Golden Delicious is more susceptible than Gala to Alternaria leaf blotch. Implications in the detection of the Alternaria apple pathotype and the taxonomic assignment of Alternaria isolates involved in Alternaria leaf blotch are discussed.


Author(s):  
Buo-Fu Chen ◽  
Christopher A. Davis ◽  
Ying-Hwa Kuo

AbstractIdealized numerical studies have suggested that in addition to vertical wind shear (VWS) magnitude, the VWS profile also affects tropical cyclone (TC) development. A way to further understand the VWS profile’s effect is to examine the interaction between a TC and various shear-relative low-level mean flow (LMF) orientations. This study mainly uses the ERA5 reanalysis to verify that, consistent with idealized simulations, boundary-layer processes associated with different shear-relative LMF orientations affect real-world TC’s intensity and size. Based on analyses of 720 TCs from multiple basins during 2004–2016, a TC affected by an LMF directed toward downshear-left in the Northern Hemisphere favors intensification, whereas an LMF directed toward upshear-right is favorable for expansion. Furthermore, physical processes associated with shear-relative LMF orientation may also partly explain the relationship between the VWS direction and TC development, as there is a correlation between the two variables.The analysis of reanalysis data provides other new insights. The relationship between shear-relative LMF and intensification is not significantly modified by other factors [inner-core sea surface temperature (SST), VWS magnitude, and relative humidity (RH)]. However, the relationship regarding expansion is partly attributed to environmental SST and RH variations for various LMF orientations. Moreover, SST is critical to the basin-dependent variability of the relationship between the shear-relative LMF and intensification. For Atlantic TCs, the relationship between LMF orientation and intensification is inconsistent with all-basin statistics unless the analysis is restricted to a representative subset of samples associated with generally favorable conditions.


Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1315
Author(s):  
Foteini Vasilopoulou ◽  
Carmen Escolano ◽  
Mercè Pallàs ◽  
Christian Griñán-Ferré

I2-IR have been found dysregulated in patients with neurodegenerative diseases, such as Alzheimer’s disease (AD), in which the importance of neuroinflammation in the establishment and maintenance of cognitive decline is well-documented. To research the implication of I2-IR in neuroinflammatory pathways altered in AD, we determined the expression profile of genes associated with inflammation in the 5XFAD model treated with LSL60101, a well-established I2-IR ligand. Thus, we performed a qPCR array containing 84 inflammation-related genes. Hierarchical clustering analysis revealed three gene clusters, suggesting that treatment with LSL60101 affects the gene expression associated with inflammation in the 5XFAD model. Furthermore, we evaluated the functions of the three clusters; thereby performing a pathway enrichment analysis using the GO database. As we expected, clusters 2 and 3 showed alterations in the inflammatory response, chemotaxis and the chemokine-mediated signaling pathway, among others. To validate previous results from the gene profiling analysis, the expression levels of a representative subset of mRNAs were selected according to the intensity of the observed changes and their biological relevance. Interestingly, changes induced by LSL60101 in the 5XFAD model were validated for several genes. These results suggest that treatment with LSL60101 in the 5XFAD model reverses the inflammatory process during the development of AD.


2021 ◽  
Vol 5 (ICFP) ◽  
pp. 1-30
Author(s):  
Joshua Yanovski ◽  
Hoang-Hai Dang ◽  
Ralf Jung ◽  
Derek Dreyer

The Rust language offers a promising approach to safe systems programming based on the principle of aliasing XOR mutability : a value may be either aliased or mutable, but not both at the same time. However, to implement pointer-based data structures with internal sharing, such as graphs or doubly-linked lists, we need to be able to mutate aliased state. To support such data structures, Rust provides a number of APIs that offer so-called interior mutability : the ability to mutate data via method calls on a shared reference. Unfortunately, the existing APIs sacrifice flexibility, concurrent access, and/or performance, in exchange for safety. In this paper, we propose a new Rust API called GhostCell which avoids such sacrifices by separating permissions from data : it enables the user to safely synchronize access to a collection of data via a single permission. GhostCell repurposes an old trick from typed functional programming: branded types (as exemplified by Haskell’s ST monad), which combine phantom types and rank-2 polymorphism to simulate a lightweight form of state-dependent types. We have formally proven the soundness of GhostCell by adapting and extending RustBelt, a semantic soundness proof for a representative subset of Rust, mechanized in Coq.


Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1233
Author(s):  
Alemayehu Teressa Negawo ◽  
Meki S. Muktar ◽  
Yilikal Assefa ◽  
Jean Hanson ◽  
Alieu M. Sartie ◽  
...  

Rhodes grass (Chloris gayana Kunth) is one of the most important forage grasses used throughout the tropical and subtropical regions of the world. Enhancing the conservation and use of genetic resources requires the development of knowledge and understanding about the existing global diversity of the species. In this study, 104 Rhodes grass accessions, held in trust in the ILRI forage genebank, were characterized using DArTSeq markers to evaluate the genetic diversity and population structure, and to develop representative subsets, of the collection. The genotyping produced 193,988 SNP and 142,522 SilicoDArT markers with an average polymorphic information content of 0.18 and 0.26, respectively. Hierarchical clustering using selected informative markers showed the presence of two and three main clusters using SNP and SilicoDArT markers, respectively, with a cophenetic correction coefficient of 82%. Bayesian population structure analysis also showed the presence of two main subpopulations using both marker types indicating the existence of significant genetic variation in the collection. A representative subset, containing 21 accessions from diverse origins, was developed using the SNP markers. In general, the results revealed substantial genetic diversity in the Rhodes grass collection, and the generated molecular information, together with the developed subset, should help enhance the management, use and improvement of Rhodes grass germplasm in the future.


Author(s):  
Byunggook Na ◽  
Jisoo Mok ◽  
Hyeokjun Choe ◽  
Sungroh Yoon

Despite the increasing interest in neural architecture search (NAS), the significant computational cost of NAS is a hindrance to researchers. Hence, we propose to reduce the cost of NAS using proxy data, i.e., a representative subset of the target data, without sacrificing search performance. Even though data selection has been used across various fields, our evaluation of existing selection methods for NAS algorithms offered by NAS-Bench-1shot1 reveals that they are not always appropriate for NAS and a new selection method is necessary. By analyzing proxy data constructed using various selection methods through data entropy, we propose a novel proxy data selection method tailored for NAS. To empirically demonstrate the effectiveness, we conduct thorough experiments across diverse datasets, search spaces, and NAS algorithms. Consequently, NAS algorithms with the proposed selection discover architectures that are competitive with those obtained using the entire dataset. It significantly reduces the search cost: executing DARTS with the proposed selection requires only 40 minutes on CIFAR-10 and 7.5 hours on ImageNet with a single GPU. Additionally, when the architecture searched on ImageNet using the proposed selection is inversely transferred to CIFAR-10, a state-of-the-art test error of 2.4% is yielded. Our code is available at https://github.com/nabk89/NAS-with-Proxy-data.


2021 ◽  
Author(s):  
Aaron Wacholder ◽  
Omer Acar ◽  
Anne-Ruxandra Carvunis

Ribosome profiling experiments demonstrate widespread translation of eukaryotic genomes outside of annotated protein-coding genes. However, it is unclear how much of this "noncanonical" translation contributes biologically relevant microproteins rather than insignificant translational noise. Here, we developed an integrative computational framework (iRibo) that leverages hundreds of ribosome profiling experiments to detect signatures of translation with high sensitivity and specificity. We deployed iRibo to construct a reference translatome in the model organism S. cerevisiae. We identified ~19,000 noncanonical translated elements outside of the ~5,400 canonical yeast protein-coding genes. Most (65%) of these non-canonical translated elements were located on transcripts annotated as non-coding, or entirely unannotated, while the remainder were located on the 5' and 3' ends of mRNA transcripts. Only 14 non-canonical translated elements were evolutionarily conserved. In stark contrast with canonical protein-coding genes, the great majority of the yeast noncanonical translatome appeared evolutionarily transient and showed no signatures of selection. Yet, we uncovered phenotypes for 53% of a representative subset of evolutionarily transient translated elements. The iRibo framework and reference translatome described here provide a foundation for further investigation of a largely unexplored, but biologically significant, evolutionarily transient translatome.


Crops ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 54-67
Author(s):  
Alexey Morgounov ◽  
Fatih Özdemir ◽  
Mesut Keser ◽  
Beyhan Akin ◽  
Abdelfattah A. Dababat ◽  
...  

Collection of wheat landraces (WLR) was conducted in Afghanistan, Iran, and Turkey in 2010–2014. A representative subset of this collection was used in the current study and included 45 bread wheat landraces from Turkey, 19 from Iran, and 20 from Afghanistan. This material was supplemented by 73 modern cultivars and breeding lines adapted to semiarid conditions and irrigated conditions. Overall, 157 genotypes were tested in Turkey in 2018 and 2019 and in Afghanistan and Iran in 2019 under rainfed conditions to compare performance of WLR and modern material. The germplasm was genotyped using a high density Illumina Infinium 25K wheat SNP array and KASP markers for agronomic traits. The average grain yield ranged between 2.2 and 4.0 t/ha depending on the site and year. Three groups of landraces demonstrated similar average grain yield, though Afghanistan material was slightly higher yielding not only in Afghanistan but also in Turkey. Modern material outyielded the landraces in two environments out of four. The highest yielding landraces were competitive with the best modern germplasm. Frequency of gene Sus2-2B affecting 1000 kernel weight was 64% in WLR and only 3% in modern material. Presence of positive allele of Sus2-2B increased 1000 kernel weight by nearly 4%. Breeding strategy to improved landraces and modern cultivars is discussed.


Author(s):  
Alemayehu Teressa Negawo ◽  
Meki S. Muktar ◽  
Yilikal Assefa ◽  
Jean Hanson ◽  
Alieu M. Sartie ◽  
...  

Rhodes grass (Chloris gayana Kunth) is one of the most important forage grasses used throughout the tropical and subtropical regions of the world. Enhancing the conservation and use of genetic resources requires the development of knowledge and understanding about the existing global diversity of the species. In this study, 104 Rhodes grass accessions, held in trust in the ILRI forage genebank, were characterized using DArTSeq markers to evaluate the genetic diversity and population structure, and to develop representative subsets, of the collection. The genotyping produced 193,988 SNP and 142,522 SilicoDArT markers with an average polymorphic information content of 0.18 and 0.26, respectively. Hierarchical clustering using selected informative markers showed the presence of two and three main clusters using SNP and SilicoDArT markers, respectively, with a cophenetic correction coefficient of 82 %. Bayesian population structure analysis also showed the presence of two main subpopulations using both marker types indicating the existence of significant genetic variation in the collection. A representative subset, containing 21 accessions from diverse origins, was developed using the SNP markers. In general, the results revealed substantial genetic diversity in the Rhodes grass collection and the generated molecular information, together with the developed subset, should help enhance the management, use and improvement of Rhodes grass germplasm in the future.


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