IMPORTANCE: Severe coronavirus disease 2019 (COVID-19) can occur in younger, predominantly male, patients without preexisting medical conditions. Some individuals may have primary immunodeficiencies ...that predispose to severe infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: To explore the presence of genetic variants associated with primary immunodeficiencies among young patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Case series of pairs of brothers without medical history meeting the selection criteria of young (age <35 years) brother pairs admitted to the intensive care unit (ICU) due to severe COVID-19. Four men from 2 unrelated families were admitted to the ICUs of 4 hospitals in the Netherlands between March 23 and April 12, 2020. The final date of follow-up was May 16, 2020. Available family members were included for genetic variant segregation analysis and as controls for functional experiments. EXPOSURE: Severe COVID-19. MAIN OUTCOME AND MEASURES: Results of rapid clinical whole-exome sequencing, performed to identify a potential monogenic cause. Subsequently, basic genetic and immunological tests were performed in primary immune cells isolated from the patients and family members to characterize any immune defects. RESULTS: The 4 male patients had a mean age of 26 years (range, 21-32), with no history of major chronic disease. They were previously well before developing respiratory insufficiency due to severe COVID-19, requiring mechanical ventilation in the ICU. The mean duration of ventilatory support was 10 days (range, 9-11); the mean duration of ICU stay was 13 days (range, 10-16). One patient died. Rapid clinical whole-exome sequencing of the patients and segregation in available family members identified loss-of-function variants of the X-chromosomal TLR7. In members of family 1, a maternally inherited 4-nucleotide deletion was identified (c.2129_2132del; p.Gln710Argfs*18); the affected members of family 2 carried a missense variant (c.2383G>T; p.Val795Phe). In primary peripheral blood mononuclear cells from the patients, downstream type I interferon (IFN) signaling was transcriptionally downregulated, as measured by significantly decreased mRNA expression of IRF7, IFNB1, and ISG15 on stimulation with the TLR7 agonist imiquimod as compared with family members and controls. The production of IFN-γ, a type II IFN, was decreased in patients in response to stimulation with imiquimod. CONCLUSIONS AND RELEVANCE: In this case series of 4 young male patients with severe COVID-19, rare putative loss-of-function variants of X-chromosomal TLR7 were identified that were associated with impaired type I and II IFN responses. These preliminary findings provide insights into the pathogenesis of COVID-19.
In this work, we present a novel quantitative geographical information system-based procedure to obtain the magnitude (area) and frequency of medium to large first-time shallow slope failures. The ...procedure has been set up at the Barcedana Valley, in the Tremp Basin (Eastern Pyrenees). First, pixel-based susceptibility classes were defined using a slope stability index obtained with the physically based model SINMAP. The frequency calculated from the number of first-time failures recorded during the last 60 years was then assigned to each susceptibility class. We devised a procedure to estimate the size of potential failures by means of the aggregation of pixels within the boundaries of morphological slope units, optimized for the purpose. Finally, the landslide hazard was prepared using the magnitude-frequency matrix. Results show that a proper pixel clustering has been carried which avoids the generation of small groups of pixels with different susceptibility degrees within the same slope unit. For a given hill slope, the area of the cluster of pixels depends on the size of the slope unit, which is not unique as it depends on the criterion used to delineate them. Therefore, the latter is a key factor in the final results. In this study, we validated our results with the size distribution of the observed landslides. The methodology presented in this work can be applied using any susceptibility assessment method with a pixel-based output.
Slopes undergoing deep-seated gravitational deformation create surface landforms that, if trenched and dated, yield critical data on slope kinematics. The northern slope of Pic d'Encampadana descends ...steeply 800 m down into the glaciated Valira d'Orient of Andorra and has long been known for its numerous antislope scarps (sackungen), indicative of deep-seated gravitational slope deformation (DSGSD). We excavated three trenches across antislope scarps and their adjacent troughs to date the deformation structures and to infer slope kinematics. Trough deposits have been disrupted by normal and reverse faulting, with the largest fault zone underlying the antislope scarp and dipping into the slope at 40°-80°. Trenches in the troughs expose fining-upward sequences of strata from which we interpret several cycles of: (1) episodic downdropping along graben faults and deepening of the topographic trough, (2) filling the trough with marginal colluvial and axial sag-pond sediments, followed by (3) a hiatus of soil profile development. The average time between deformation events in any one trench in the past 12–15 ka is about 3–3.5 ka. Deformation seems to have begun first in the lower part of the northern slope (1935 m elevation) about 15.3 ka, and had spread to the upper parts of the slope (2320 m) by 11.6 ka. Deformation in the lower slope ceased after 5.5 ka, but continued higher on the slope into the mid-late Holocene. The youngest deformation dated (1.4–1.6 ka) occurred in the highest trench on the slope. This pattern of younger deformation with increasing elevation has been documented at several other sites and has been ascribed to an upslope-migrating extensional stress field which originated at the base of the slope from glacial oversteepening and end-glacial debuttressing.
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•Reconstruction of a deep slope failure movement chronology by trenching•Trenches were in closed depressions (troughs) formed by antislope scarps•Slope deformation episodes represented by faulting/folding of trough deposits•Deformation episodes began immediately post-LGM and recur every 3 to 3.5 kyr•3D geometry of weak and strong rock units underlying the slope controls the style of deformation
Rockfalls are ubiquitous diffuse hazard in mountain regions, cliffs, and cutslopes, with the potential of causing victims and severely damaging buildings and infrastructures. A vast majority of ...detached rock masses break up when impacting the ground, generating multiple trajectories of rock fragments. In this paper, we present the quantitative risk analysis (QRA) of fragmental rockfalls. Fragmentation in rockfalls requires the redefinition of the probability of reach and the evaluation of the effect of multiple rock blocks trajectories on the exposure. An example of QRA was carried out at the Monasterio de Piedra, Spain, using RockGIS, a rockfall propagation model that takes fragmentation into account (Matas et al. Landslides 14:1565–1578,
2017
). The results show that fragmentation has a significant but contrasting effect in the calculation of risk. The risk is reduced if the slope where blocks propagate is sufficiently long and gentle. The reason for this is that, compared to the unfragmented rock masses, the new fragments generated travel shorter distances with lesser kinetic energy. The effect disappears in case of large rockfalls. Conversely, the risk increases if the rock fragments propagate over steep slopes. The reason is that few blocks stop along the way while the generation of a cone of fragments increases the exposure. Our simulations also show that assuming a continuous flow of visitors or segregating the flow in groups of different number of people has only a minor influence on the results. Finally, we observed that the capability of the protection barriers to stop rockfalls of up to a few tens of cubic meters increases with fragmentation.
This first overview of large-scale rock slope failure (RSF) in the yrenees addresses the eastern third of the range. Around 30 principal RSFs greater than 0.25 km
2
and 20 lesser or uncertain cases ...have been identified from remote imagery and groundtruthing. Compared with other European mountain ranges, RSF incidence is relatively sparse, displays no obvious regional trend or spatial clustering, and occurs across diverse landscape types, if mainly on metamorphic rocks. A transition is observed from paraglacial RSFs in formerly glaciated valleys to what are here termed 'parafluvial' RSFs, within wholly or mainly fluvial valleys but where slope failure is not directly provoked by or linked to river erosion. RSFs are particularly found in three topographic settings: at cirque and trough-head thresholds (transition zones of elevated instability between cirque and main glaciated trough walls); near the upper or outer periphery of the ice field, where glacial adaptation of fluvial valleys is incomplete; and in fluvial valleys beyond glacial limits where incision is locally intense. RSF is absent from the range divide, from within cirques, and from most main valleys. In the montane areas, RSF is strongly associated with vestiges of preglacial summit surfaces, confirming that plateau ridges are less stable than sharpened crests and horns. RSF is contributing significantly to the progressive destruction of this paleic relief. The overall sparsity of RSF indicates insufficient rock mass stresses, including rebound after concentrated bedrock erosion. This may reflect a relatively weak imprint of glacial erosion, including breaching, in a context of relatively low mean rates of neotectonic uplift, possibly signalling overall that eastern yrenees landscapes are close to dynamic equilibrium.
New advances in high-throughput technologies have allowed for the massive analysis of genomic data, providing new opportunities for the characterization of the transcriptome architectures. Recent ...studies in pigs have employed RNA-Seq to explore the transcriptome of different tissues in a reduced number of animals. The main goal of this study was the identification of differentially-expressed genes in the liver of Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition using RNA-Seq.
The liver transcriptomes of two female groups (H and L) with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L) and 270 (H) lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96), as well as between microarrays and RNA-Seq (r=0.72). A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism.
In the present study RNA-Seq was used as a tool to explore the liver transcriptome of pigs with extreme phenotypes for intramuscular fatty acid composition. The differential gene expression analysis showed potential gene networks which affect lipid and fatty acid metabolism. These results may help in the design of selection strategies to improve the sensorial and nutritional quality of pork meat.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
El texto reflexiona sobre tres ejes claves: la necesidad de considerar la memoria y sus espacios físicos y simbólicos como patrimonio colectivo en nuestros espacios de residencia; la necesidad y reto ...de transmitir y resinificar estos lugares como lugares de resistencia y como patrimonio transformador de valores actuales y contemporáneos; y la voluntad más actual de hacerlo de forma transnacional, comparada y en red. De ahí que el texto aborda una parte más reflexiva conceptual y teórica y otra parte habla de casos estudiados a modo de ejemplo sobre los debates y conflictos actuales que pueden ser modelos de trabajo y análisis. Conceptos como la memoria múltiple, las memorias nostálgicas, resistentes, incómodas e incluso conflictivas son tratados como conceptos, pero el autor los intenta vincular a casos prácticos a través de la interpretación, transmisión cultural y turística de la memoria. Metodologicamente el texto combina la reflexión teórica con los casos prácticos de análisis concretos de espacios de memoria.
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