Forearc deformation along the peruvian margin and the effects of changes in subduction style: quantifying the rates of Quaternary deformation using in situ produced cosmogenic 10Be and 26Al.

The Andes are one ofthe world's two highest mountain ranges and together wíth the westem cordillera of North America they forro an almost a continuous mountaín chain from the tip of Patagonia to the Alaskan peninsula. Common to all the cordillera of westem North and South America is the ín:fluence oflong-lived subduction. Indeed, the style of this subduction process has profoundly modified the margin of both continents. For example, following relatively normal subduction in the Jurassíc and the Cretaceous, the Laramide orogeny of North America is thought to have been produced from effects of extremely flat subduction

Adverse Life Trajectories Are a Risk Factor for SARS-CoV-2 IgA Seropositivity.

Asymptomatic individuals, called "silent spreaders" spread SARS-CoV-2 efficiently and have complicated control of the ongoing COVID-19 pandemic. As seen in previous influenza pandemics, socioeconomic and life-trajectory factors are important in disease progression and outcome. The demographics of the asymptomatic SARS-CoV-2 carriers are unknown. We used the CON-VINCE cohort of healthy, asymptomatic, and oligosymptomatic individuals that is statistically representative of the overall population of Luxembourg for age, gender, and residency to characterise this population. Gender (male), not smoking, and exposure to early-life or adult traumatic experiences increased the risk of IgA seropositivity, and the risk associated with early-life exposure was a dose-dependent metric, while some other known comorbidities of active COVID-19 do not impact it. As prior exposure to adversity is associated with negative psychobiological reactions to external stressors, we recorded psychological wellbeing during the study period. Exposure to traumatic events or concurrent autoimmune or rheumatic disease were associated with a worse evolution of anxiety and depressive symptoms throughout the lockdown period. The unique demographic profile of the "silent spreaders" highlights the role that the early-life period plays in determining our lifelong health trajectory and provides evidence that the developmental origins of health and disease is applicable to infectious diseases

T cell immunosenescence after early life adversity: association with cytomegalovirus infection.

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts

Single-nucleotide Polymorphisms in the p53 Signaling Pathway

The p53 tumor suppressor pathway is central both in reducing cancer frequency in vertebrates and in mediating the response of commonly used cancer therapies. This article aims to summarize and discuss a large body of evidence suggesting that the p53 pathway harbors functional inherited single-nucleotide polymorphisms (SNPs) that affect p53 signaling in cells, resulting in differences in cancer risk and clinical outcome in humans. The insights gained through these studies into how the functional p53 pathway SNPs could help in the tailoring of cancer therapies to the individual are discussed. Moreover, recent work is discussed that suggests that many more functional p53 pathway SNPs are yet to be fully characterized and that a thorough analysis of the functional human genetics of this important tumor suppressor pathway is required

Endothelin B receptors targeted by iron oxide nanoparticles functionalized with a specific antibody: toward immunoimaging of brain tumors

International audienc

Epigenetic regulation of the glucocorticoid receptor promoter 1 7 in adult rats

Regulation of glucocorticoid receptor (GR) levels is an important stress adaptation mechanism. Transcription factor Nfgi-a and environmentally induced Gr promoter 1(7) methylation have been implicated in fine-tuning the expression of Gr 1(7) transcripts. Here, we investigated Gr promoter 1(7) methylation and Gr 1(7) expression in adult rats exposed to either acute or chronic stress paradigms. A strong negative correlation was observed between the sum of promoter-wide methylation levels and Gr 1(7) transcript levels, independent of the stressor. Methylation of individual sites did not, however, correlate with transcript levels. This suggested that promoter 1(7) was directly regulated by promoter-wide DNA methylation. Although acute stress increased Ngfi-a expression in the hypothalamic paraventricular nucleus (PVN), Gr 1(7) transcript levels remained unaffected despite low methylation levels. Acute stress had little effect on these low methylation levels, except at four hippocampal CpGs. Chronic stress altered the corticosterone response to an acute stressor. In the adrenal and pituitary glands, but not in the brain, this was accompanied by an increase in methylation levels in orchestrated clusters rather than individual CpGs. PVN methylation levels, unaffected by acute or chronic stress, were significantly more variable within- than between-groups, suggesting that they were instated probably during the perinatal period and represent a pre-established trait. Thus, in addition to the known perinatal programming, the Gr 1(7) promoter is epigenetically regulated by chronic stress in adulthood, and retains promoter-wide tissue-specific plasticity. Differences in methylation susceptibility between the PVN in the perinatal period and the peripheral HPA axis tissues in adulthood may represent an important “trait” vs. “state” regulation of the Gr gene

Long-term slip rate of the southern San Andreas Faultfrom 10Be-26Al surface exposure dating of an offset alluvial fan

International audience[1] We determine the long-term slip rate of the southern San Andreas Fault in the southeastern Indio Hills using 10 Be and 26 Al isotopes to date an offset alluvial fan surface. Field mapping complemented with topographic data, air photos and satellite images allows precise determination of piercing points across the fault zone that are used to measure an offset of 565 ± 80 m. A total of 26 quartz-rich cobbles from three different fan surfaces were collected and dated. The tight cluster of nuclide concentrations from 19 samples out of 20 from the offset fan surface implies a simple exposure history, negligible prior exposure and erosion, and yields an age of 35.5 ± 2.5 ka. The long-term slip rate of the San Andreas Fault south of Biskra Palms is thus 15.9 ± 3.4 mm/yr. This rate is about 10 mm/yr slower than geological (0–14 ka) and short-term geodetic estimates for this part of the San Andreas Fault, implying changes in slip rate or in faulting behavior. This result puts new constraints on the slip rate of the San Jacinto and on the Eastern California Shear Zone for the last 35 kyr. Our study shows that more sites along the major faults of southern California need to be targeted to better constrain the slip rates over different timescales