Project description:COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85-0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6-28) vs. 4 days for the rest (IQR: 3-7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.
Project description:Soil creeps imperceptibly but relentlessly downhill, shaping landscapes and the human and ecological communities that live within them. What causes this granular material to 'flow' at angles well below repose? The unchallenged dogma is churning of soil by (bio)physical disturbances. Here we experimentally render slow creep dynamics down to micron scale, in a laboratory hillslope where disturbances can be tuned. Surprisingly, we find that even an undisturbed sandpile creeps indefinitely, with rates and styles comparable to natural hillslopes. Creep progressively slows as the initially fragile pile relaxes into a lower energy state. This slowing can be enhanced or reversed with different imposed disturbances. Our observations suggest a new model for soil as a creeping glass, wherein environmental disturbances maintain soil in a perpetually fragile state.
Project description:Acquired genetic or cytogenetic alterations in a blood stem cell that confer clonal fitness promote its relative expansion leading to clonal hematopoiesis (CH). Despite a largely intact hematopoietic output, CH is associated with a heightened risk of progression to hematologic malignancies and with non-hematologic health manifestations, including cardiovascular disease and overall mortality. We focus on the evidence for the role of inflammation in establishing, maintaining and reciprocally being affected by CH. We describe the known pro-inflammatory signals associated with CH and preclinical studies that elucidated the cellular mechanisms involved. We review the evolving literature on early-onset CH in germline predisposition conditions and the possible role of immune dysregulation in this context.
Project description:Representation of the environment by hippocampal populations is known to drift even within a familiar environment, which could reflect gradual changes in single-cell activity or result from averaging across discrete switches of single neurons. Disambiguating these possibilities is crucial, as they each imply distinct mechanisms. Leveraging change point detection and model comparison, we find that CA1 population vectors decorrelate gradually within a session. In contrast, individual neurons exhibit predominantly step-like emergence and disappearance of place fields or sustained changes in within-field firing. The changes are not restricted to particular parts of the maze or trials and do not require apparent behavioral changes. The same place fields emerge, disappear, and reappear across days, suggesting that the hippocampus reuses pre-existing assemblies, rather than forming new fields de novo. Our results suggest an internally driven perpetual step-like reorganization of the neuronal assemblies.
Project description:Noncoding RNAs have emerged as mediators of transgenerational epigenetic inheritance (TEI) in a number of organisms. A robust example of such RNA-directed TEI is the inheritance of gene-silencing states following RNA interference (RNAi) in the metazoan C. elegans. During RNAi inheritance, gene silencing is transmitted by a self-perpetuating cascade of siRNA-directed poly(UG) tailing of mRNA fragments (pUGylation), followed by siRNA synthesis from poly(UG)-tailed mRNA templates (termed pUG RNA/siRNA cycling). Despite the self-perpetuating nature of pUG RNA/siRNA cycling, RNAi inheritance is finite, suggesting that systems likely exist to prevent indefinite RNAi-triggered gene silencing. Here we show that, in the absence of Piwi-interacting RNAs (piRNAs), an animal-specific class of small noncoding RNA, RNAi-based gene silencing can become essentially permanent, lasting at near 100% penetrance for more than 5 years and hundreds of generations. This perpetual gene silencing is mediated by continuous pUG RNA/siRNA cycling. Further, we find that piRNAs coordinate endogenous RNAi pathways to prevent germline-expressed genes, which are not normally subjected to TEI, from entering a state of continual and irreversible epigenetic silencing also mediated by continuous maintenance of pUG RNA/siRNA cycling. Together, our results show that one function of C. elegans piRNAs is to insulate germline-expressed genes from aberrant and runaway inactivation by the pUG RNA/siRNA epigenetic inheritance system.
Project description:The floral repressor APETALA2 (AP2) in Arabidopsis regulates flowering through the age pathway. The AP2 ortholog in the alpine perennial Arabis alpina, PERPETUAL FLOWERING 2 (PEP2), was previously reported to control flowering through the vernalization pathway via enhancing the expression of another floral repressor PERPETUAL FLOWERING 1 (PEP1), the ortholog of Arabidopsis FLOWERING LOCUS C (FLC). However, PEP2 also regulates flowering independently of PEP1. To characterize the function of PEP2, we analyzed the transcriptomes of pep2 and pep1 mutants. The majority of differentially expressed genes were detected between pep2 and the wild type or between pep2 and pep1, highlighting the importance of the PEP2 role that is independent of PEP1. Here, we demonstrate that PEP2 activity prevents the up-regulation of the A. alpina floral meristem identity genes FRUITFUL (AaFUL), LEAFY (AaLFY), and APETALA1 (AaAP1), ensuring floral commitment during vernalization. Young pep2 seedlings respond to vernalization, suggesting that PEP2 regulates the age-dependent response to vernalization independently of PEP1. The major role of PEP2 through the PEP1-dependent pathway takes place after vernalization, when it facilitates PEP1 activation both in the main shoot apex and in axillary branches. These multiple roles of PEP2 in the vernalization response contribute to the A. alpina life cycle.
Project description:Nature conservation is underresourced, requiring managers to prioritize where, when, and how to spend limited funds. Prioritization methods identify the subset of actions that provide the most benefit to an actor's objective. However, spending decisions by conservation actors are often misaligned with their objectives. Although this misalignment is frequently attributed to poor choices by the actors, we argue that it can also be a byproduct of working alongside other organizations. Using strategic analyses of multi-actor systems in conservation, we show how interactions among multiple conservation actors can create misalignment between the spending and objectives of individual actors and why current uncoordinated prioritizations lead to fewer conservation objectives achieved for individual actors. We draw three conclusions from our results. First, that misalignment is an unsuitable metric for evaluating spending, because it may be necessary to achieve actors' objectives. Second, that current prioritization methods cannot identify optimal decisions (as they purport to do), because they do not incorporate other actors' decisions. Third, that practical steps can be taken to move actors in the direction of coordination and thereby better achieve their conservation objectives.
Project description:In our quest to leverage the capabilities of the emerging single-atom catalysts (SACs) for wastewater purification, we confronted fundamental challenges related to electron scarcity and instability. Through meticulous theoretical calculations, we identified optimal placements for nitrogen vacancies (Nv) and iron (Fe) single-atom sites, uncovering a dual-site approach that significantly amplified visible-light absorption and charge transfer dynamics. Informed by these computational insights, we cleverly integrated Nv into the catalyst design to boost electron density around iron atoms, yielding a potent and flexible photoactivator for benign peracetic acid. This exceptional catalyst exhibited remarkable stability and effectively degraded various organic contaminants over 20 cycles with self-cleaning properties. Specifically, the Nv sites captured electrons, enabling their swift transfer to adjacent Fe sites under visible light irradiation. This mechanism accelerated the reduction of the formed "peracetic acid-catalyst" intermediate. Theoretical calculations were used to elucidate the synergistic interplay of dual mechanisms, illuminating increased adsorption and activation of reactive molecules. Furthermore, electron reduction pathways on the conduction band were elaborately explored, unveiling the production of reactive species that enhanced photocatalytic processes. A six-flux model and associated parameters were also applied to precisely optimize the photocatalytic process, providing invaluable insights for future photocatalyst design. Overall, this study offers a molecule-level insight into the rational design of robust SACs in a photo-Fenton-like system, with promising implications for wastewater treatment and other high-value applications.