Mechanistic roles for many lncRNAs are poorly understood, in part because their direct interactions with genomic loci and proteins are difficult to assess. Using a method to purify endogenous RNAs ...and their associated factors, we mapped the genomic binding sites for two highly expressed human lncRNAs, NEAT1 and MALAT1. We show that NEAT1 and MALAT1 localize to hundreds of genomic sites in human cells, primarily over active genes. NEAT1 and MALAT1 exhibit colocalization to many of these loci, but display distinct gene body binding patterns at these sites, suggesting independent but complementary functions for these RNAs. We also identified numerous proteins enriched by both lncRNAs, supporting complementary binding and function, in addition to unique associated proteins. Transcriptional inhibition or stimulation alters localization of NEAT1 on active chromatin sites, implying that underlying DNA sequence does not target NEAT1 to chromatin, and that localization responds to cues involved in the transcription process.
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•High-resolution genomic binding sites for the human lncRNAs NEAT1 and MALAT1•NEAT1 and MALAT1 exhibit distinct colocalized binding at active chromatin•Transcription impacts NEAT1 localization patterns•CHART-MS identifies proteins associated with endogenous RNAs in vivo
NEAT1 and MALAT1 are two of the most abundant mammalian lncRNAs. West et al. map the genomic binding of NEAT1 and MALAT1 and identify interacting proteins via RNA pull-down followed by mass spectrometry, showing these RNAs play a synergistic role in nuclear organization linking active genes and nuclear subdomains.
Self‐concealment, secrecy, and guilt Davis, Christopher G.
Journal of personality,
April 2024, 2024-Apr, 2024-04-00, 20240401, Volume:
92, Issue:
2
Journal Article
Peer reviewed
Open access
Objective
Individuals with a tendency to conceal unflattering information about themselves are more likely to be preoccupied by their secrets and tend to report more negative affect. According to ...theory, this negative affect is due to self‐concealers' conflicting motivation to be authentic in their relationship but fear the negative consequences should they reveal their secrets, which promotes ill‐fated attempts to suppress. The purpose of the current study was to test a central component of this model.
Methods
Two studies of adults who were in a romantic relationship and keeping a secret from their partner (combined N = 635; 67.2% women; Mage = 39.6, SD = 11.9) were surveyed on four biweekly occasions. Multilevel mediation analyses were conducted to test whether preoccupation and suppression mediated the link between self‐concealing and negative affect and guilt.
Results
The data support the hypotheses. Self‐concealers were more preoccupied with and prone to suppress their secret than those low on the trait, which, in turn, predicted greater negative affect and guilt.
Conclusion
The findings suggest that self‐concealers' insecurities and fear of the relational consequences of disclosure set the stage for the debilitating cycle of suppression and preoccupation that leaves them feeling anxious and guilty.
The upscale aggregation of convection is used to understand the emergence of rotating, coherent midtropospheric structures and the subsequent process of tropical cyclone formation. The Cloud Model, ...version 1 (CM1), is integrated on an f plane with uniform sea surface temperature (SST) and prescribed uniform background flow. Deep convection is maintained by surface fluxes from an ocean with uniform surface temperature. Convection begins to organize simultaneously into moist and dry midtropospheric patches after 10 days. After 20 days, the patches begin to rotate on relatively small scales. Moist cyclonic vortices merge, eventually forming a single dominant vortex that subsequently forms a tropical cyclone on a realistic time scale of about 5 days. Radiation that interacts with clouds and water vapor aids in forming coherent rotating structures. Using the path to genesis provided by the aggregated solution, the relationship between thermodynamic changes within the vortex and changes in the character of convection prior to genesis is explored. Consistent with previous studies, the approach to saturation within the midtropospheric vortex accelerates the genesis process. A novel result is that, prior to genesis, downdrafts become widespread and somewhat stronger. The increased downdraft mass flux leads to stronger and larger surface cold pools. Shear-cold pool dynamics promote the organization of lower-tropospheric updrafts that spin up the surface vortex. It is inferred that the observed inconsistency between convective intensity and thermodynamic stabilization prior to genesis results from sampling limitations of the observations wherein the important cold pool gradients are unresolved.
Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are ...central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core proteins, including one from the CBX family. These complexes have been shown previously to reside in membraneless organelles called Polycomb bodies, leading to speculation that canonical PRC1 might be found in a separate phase from the rest of the nucleus. We show here that reconstituted PRC1 readily phase-separates into droplets in vitro at low concentrations and physiological salt conditions. This behavior is driven by the CBX2 subunit. Point mutations in an internal domain of
eliminate phase separation. These same point mutations eliminate the formation of puncta in cells and have been shown previously to eliminate nucleosome compaction in vitro and generate axial patterning defects in mice. Thus, the domain of CBX2 that is important for phase separation is the same domain shown previously to be important for chromatin compaction and proper development, raising the possibility of a mechanistic or evolutionary link between these activities.
Abstract Aims Self-reports remain the most common means of assessing alcohol consumption despite concern for their validity. The objective of this research is to assess the extent to which social ...desirability biases relate to self-reported consumption, hazardous use, and harms. Methods In each of two studies presented, undergraduate students ( N = 391 and N = 177) who reported that they had consumed alcohol in the past year completed online confidential surveys. Results Both studies show consistent associations between impression management bias and self-reported consumption such that high impression managers report 20 to 33% less consumption and are about 50% less likely to report risky drinking. No significant correlations involving consumption were found for self-deception bias. Study 2 also indicated that high impression managers report 30–50% fewer acute harms following a drinking episode, and that these effects are maintained after controlling statistically for trait impulsivity/constraint. Conclusions Impression management bias represents a significant threat to the validity of self-reported alcohol use and harms. Such bias may lead to misspecification of models and under-estimates of harmful or hazardous use.
This is a comprehensive survey, in both its theory and its practice, of the Tabwa who live on the western shore of Lake Tanganyika in the Democratic Republic of Congo (fomerly Zaire). The following ...topics are covered: concepts of the body and of illness, illness categories and approaches to diagnosis, divination and the meaning of illness in the life-histories of individuals and lineage groups. Moving to a broader perspective, it embraces therapies both of bodily events ('medicine') and of social circumstances ('magic' and 'religion'), and relates them to the cosmological beliefs which link and underwrite all three. Based on nearly four years of fieldwork, Dr Davis' book is the most complete study so far of an African therapeutic system. In contrast to most ethnographies of medicine, which take social structures as primary and treat medical knowledge as an extension or reflection of it, this study focuses on the medical system itself. When medicine is thus considered first as an indigenous or vernacular science, it is soon seen that much of what passes for an inderstanding of ritual, magic and religion in Africa is thin and misconceived. Summary reprinted by permission of Edinburgh University Press
Abstract
A major open issue in tropical meteorology is how and why some tropical cyclones intensify under moderate vertical wind shear. This study tackles that issue by diagnosing physical processes ...of tropical cyclone intensification in a moderately sheared environment using a 20-member ensemble of idealized simulations. Consistent with previous studies, the ensemble shows that the onset of intensification largely depends on the timing of vortex tilt reduction and symmetrization of precipitation. A new contribution of this work is a process-based analysis following a shear-induced midtropospheric vortex with its associated precipitation. This analysis shows that tilt reduction and symmetrization precede intensification because those processes are associated with a substantial increase in near-surface vertical mass fluxes and equivalent potential temperature. A vorticity budget demonstrates that the increased near-surface vertical mass fluxes aid intensification via near-surface stretching of absolute vorticity and free-tropospheric tilting of horizontal vorticity. Importantly, tilt reduction happens because of a vortex merger process—not because of advective vortex alignment—that yields a single closed circulation over a deep layer. Vortex merger only happens after the midtropospheric vortex reaches upshear left, where the flow configuration favors near-surface vortex stretching, deep updrafts, and a substantial reduction of low-entropy fluxes. These results lead to the hypothesis that intensification under moderate shear happens if and when a “restructuring” process is completed, after which a closed circulation favors persistent vorticity spinup and recirculating warm, moist air parcels.
High altitude illness encompasses a spectrum of clinical entities to include: acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. These illnesses occur as a ...result of a hypobaric hypoxic environment. Although a mild case of acute mountain sickness may be self-limited, high altitude cerebral edema and high altitude pulmonary edema represent critical emergencies that require timely intervention. This article reviews recent advances in the prevention and treatment of high altitude illness, including new pharmacologic strategies for prophylaxis and revised treatment guidelines.
Complex, highly-computational, individual-based models are abundant in epidemiology. For epidemics such as macro-parasitic diseases, detailed modelling of human behaviour and pathogen life-cycle are ...required in order to produce accurate results. This can often lead to models that are computationally-expensive to analyse and perform model fitting, and often require many simulation runs in order to build up sufficient statistics. Emulation can provide a more computationally-efficient output of the individual-based model, by approximating it using a statistical model. Previous work has used Gaussian processes (GPs) in order to achieve this, but these can not deal with multi-modal, heavy-tailed, or discrete distributions. Here, we introduce the concept of a mixture density network (MDN) in its application in the emulation of epidemiological models. MDNs incorporate both a mixture model and a neural network to provide a flexible tool for emulating a variety of models and outputs. We develop an MDN emulation methodology and demonstrate its use on a number of simple models incorporating both normal, gamma and beta distribution outputs. We then explore its use on the stochastic SIR model to predict the final size distribution and infection dynamics. MDNs have the potential to faithfully reproduce multiple outputs of an individual-based model and allow for rapid analysis from a range of users. As such, an open-access library of the method has been released alongside this manuscript.
Macrophages take advantage of the antibacterial properties of copper ions in the killing of bacterial intruders. However, despite the importance of copper for innate immune functions, coordinated ...efforts to exploit copper ions for therapeutic interventions against bacterial infections are not yet in place. Here we report a novel high-throughput screening platform specifically developed for the discovery and characterization of compounds with copper-dependent antibacterial properties toward methicillin-resistant Staphylococcus aureus (MRSA). We detail how one of the identified compounds, glyoxal-bis(N4-methylthiosemicarbazone) (GTSM), exerts its potent strictly copper-dependent antibacterial properties on MRSA. Our data indicate that the activity of the GTSM-copper complex goes beyond the general antibacterial effects of accumulated copper ions and suggest that, in contrast to prevailing opinion, copper complexes can indeed exhibit species- and target-specific activities. Based on experimental evidence, we propose that copper ions impose structural changes upon binding to the otherwise inactive GTSM ligand and transfer antibacterial properties to the chelate. In turn, GTSM determines target specificity and utilizes a redox-sensitive release mechanism through which copper ions are deployed at or in close proximity to a putative target. According to our proof-of-concept screen, copper activation is not a rare event and even extends to already established drugs. Thus, copper-activated compounds could define a novel class of anti-MRSA agents that amplify copper-dependent innate immune functions of the host. To this end, we provide a blueprint for a high-throughput drug screening campaign which considers the antibacterial properties of copper ions at the host-pathogen interface.
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