Showing papers by "University of California, Irvine published in 2023"

Single-Cell Transcriptional Changes in Hypothalamic Corticotropin-Releasing Factor–Expressing Neurons After Early-Life Adversity Inform Enduring Alterations in Vulnerabilities to Stress

Abstract: Mental health and vulnerabilities to neuropsychiatric disorders involve the interplay of genes and environment, particularly during sensitive developmental periods. Early-life adversity (ELA) and stress promote vulnerabilities to stress-related affective disorders, yet it is unknown how transient ELA dictates lifelong neuroendocrine and behavioral reactions to stress. The population of hypothalamic corticotropin-releasing factor (CRF)–expressing neurons that regulate stress responses is a promising candidate to mediate the long-lasting influences of ELA on stress-related behavioral and hormonal responses via enduring transcriptional and epigenetic mechanisms. Capitalizing on a well-characterized model of ELA, we examined ELA-induced changes in gene expression profiles of CRF-expressing neurons in the hypothalamic paraventricular nucleus of developing male mice. We used single-cell RNA sequencing on isolated CRF-expressing neurons. We determined the enduring functional consequences of transcriptional changes on stress reactivity in adult ELA mice, including hormonal responses to acute stress, adrenal weights as a measure of chronic stress, and behaviors in the looming shadow threat task. Single-cell transcriptomics identified distinct and novel CRF-expressing neuronal populations, characterized by both their gene expression repertoire and their neurotransmitter profiles. ELA-provoked expression changes were selective to specific subpopulations and affected genes involved in neuronal differentiation, synapse formation, energy metabolism, and cellular responses to stress and injury. Importantly, these expression changes were impactful, apparent from adrenal hypertrophy and augmented behavioral responses to stress in adulthood. We uncover a novel repertoire of stress-regulating CRF cell types differentially affected by ELA and resulting in augmented stress vulnerability, with relevance to the origins of stress-related affective disorders.

Continuous time graph processes with known ERGM equilibria: contextual review, extensions, and synthesis

Abstract: Graph processes that unfold in continuous time are of obvious theoretical and practical interest. Particularly useful are those whose long-term behavior converges to a graph distribution of known form. Here, we review some of the conditions for such convergence, and provide examples of novel and/or known processes that do so. These include subfamilies of the well-known stochastic actor-oriented models, as well as continuum extensions of temporal and separable temporal exponential family random graph models. We also comment on some related threads in the broader work on network dynamics, which provide additional context for the continuous time case.

2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors

Abstract: 2,4-Di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. We asked whether 2,4-DTBP is a potential obesogen. Using a human mesenchymal stem cell adipogenesis assay, we found that exposure to 2,4-DTBP led to increased lipid accumulation and expression of adipogenic marker genes. Antagonist assays revealed that 2,4-DTBP increased lipid accumulation by activating the peroxisome proliferator-activated receptor (PPAR) γ-retinoid X receptor (RXR) heterodimer. 2,4-DTBP likely activated the PPARγ/RXRα heterodimer by activating RXRα but not directly binding to PPARγ. We confirmed that 2,4-DTBP directly bound to RXRα by solving the crystal structure of this complex, then predicted and demonstrated that related compounds could also activate RXRα. Our study demonstrated that 2,4-DTBP and related chemicals could act as obesogens and endocrine disruptors via RXRs. These data showed that 2,4-DTBP belongs to a family of compounds whose endocrine-disrupting and obesogenic effects can be strongly modulated by their chemical composition. Structure-activity studies such as the present one could help guide the rational development of safer antioxidants that do not interact with important nuclear receptors having broad effects on human development and physiology.

Recognition of Oculofacial Plastic Surgery: Past, Present, and Future Directions

Abstract: Tao, Jeremiah M.D., F.A.C.S.*; Lelli, Gary M.D.†; Chambers, Christopher M.D.‡; Fante, Robert M.D., F.A.C.S.§ Author Information

Spectrally dispersed kernel phase interferometry with SCExAO/CHARIS: proof of concept and calibration strategies

Abstract: Kernel phase interferometry (KPI) is a data processing technique that allows for the detection of asymmetries (such as companions or disks) in high-Strehl images, close to and within the classical diffraction limit. We show that KPI can successfully be applied to hyperspectral image cubes generated from integral field spectrographs (IFSs). We demonstrate this technique of spectrally-dispersed kernel phase by recovering a known binary with the SCExAO/CHARIS IFS in high-resolution K-band mode. We also explore a spectral differential imaging (SDI) calibration strategy that takes advantage of the information available in images from multiple wavelength bins. Such calibrations have the potential to mitigate high-order, residual systematic kernel phase errors, which currently limit the achievable contrast of KPI. The SDI calibration presented here is applicable to searches for line emission or sharp absorption features, and is a promising avenue toward achieving photon-noise-limited kernel phase observations. The high angular resolution and spectral coverage provided by dispersed kernel phase offers novel opportunities for science observations which would have been challenging to achieve otherwise.

Network Hamiltonian Models for Unstructured Protein Aggregates, with Application to γD-Crystallin

Abstract: Network Hamiltonian models (NHMs) are a framework for topological coarse-graining of protein–protein interactions, in which each node corresponds to a protein, and edges are drawn between nodes representing proteins that are noncovalently bound. Here, this framework is applied to aggregates of γD-crystallin, a structural protein of the eye lens implicated in cataract disease. The NHMs in this study are generated from atomistic simulations of equilibrium distributions of wild-type and the cataract-causing variant W42R in solution, performed by Wong, E. K.; Prytkova, V.; Freites, J. A.; Butts, C. T.; Tobias, D. J. Molecular Mechanism of Aggregation of the Cataract-Related γD-Crystallin W42R Variant from Multiscale Atomistic Simulations. Biochemistry2019, 58 (35), 3691–3699. Network models are shown to successfully reproduce the aggregate size and structure observed in the atomistic simulation, and provide information about the transient protein–protein interactions therein. The system size is scaled from the original 375 monomers to a system of 10000 monomers, revealing a lowering of the upper tail of the aggregate size distribution of the W42R variant. Extrapolation to higher and lower concentrations is also performed. These results provide an example of the utility of NHMs for coarse-grained simulation of protein systems, as well as their ability to scale to large system sizes and high concentrations, reducing computational costs while retaining topological information about the system.

A Systematic Review of Research Examining Teachers’ Competence-Related Beliefs About ICT Use: Frameworks and Related Measures

Abstract: Existing measures of teachers’ ICT-related competences and competence beliefs vary broadly across studies. This systematic review provides a summary of competence dimensions and assigned competences across different theoretical conceptualizations of teacher competence regarding ICT use, both basic and professional pedagogical competence. Guided by this summary, existing measures of teacher competence-related beliefs about ICT use are reviewed, described, and compared. A total of 45 studies published between 2016 and early 2021 are included in this rapid systematic review (databases: ERIC, ScienceDirect, tandfonline). Across all included studies, teachers’ competence-related beliefs about ICT use were assessed in 49 different ways. The majority of measures were designed to assess competence-related beliefs about professional pedagogical ICT use (n = 46) rather than competence-related beliefs about basic ICT use (n = 25). In addition to the large variability of assessed competence dimensions and assigned competences across the reviewed instruments, the labels used, the theoretical background, and the number of items used in the measures also vary. Thus, our systematic review points to a high diversity of measures of teachers’ competence-related beliefs about ICT use.

Transformed primal-dual methods for nonlinear saddle point systems

Abstract: Abstract A transformed primal-dual (TPD) flow is developed for a class of nonlinear smooth saddle point system. The flow for the dual variable contains a Schur complement which is strongly convex. Exponential stability of the saddle point is obtained by showing the strong Lyapunov property. Several TPD iterations are derived by implicit Euler, explicit Euler, implicit-explicit and Gauss-Seidel methods with accelerated overrelaxation of the TPD flow. Generalized to the symmetric TPD iterations, linear convergence rate is preserved for convex-concave saddle point systems under assumptions that the regularized functions are strongly convex. The effectiveness of augmented Lagrangian methods can be explained as a regularization of the non-strongly convexity and a preconditioning for the Schur complement. The algorithm and convergence analysis depends crucially on appropriate inner products of the spaces for the primal variable and dual variable. A clear convergence analysis with nonlinear inexact inner solvers is also developed.

Grounding Zone of Amery Ice Shelf, Antarctica, From Differential Synthetic‐Aperture Radar Interferometry

Abstract: We employ a time series of Sentinel-1 differential radar interferometry data from 2018 to detect the variability in grounding line position of the Fisher, Mellor, and Lambert glaciers, which drain about 47 billion tons of ice per year from East Antarctica. We observe kilometer-scale tidal migration, two orders of magnitude larger than expected for ice flowing over a hard bed. The migration is not in phase with changes in oceanic tide. In two estuaries underlaid by subglacial channels, we observe two states of migration that switch on and off over time scales of several weeks. The range of vertical motion reveals a water column thickness of 2–20 cm. Such intrusions of seawater over wide grounding zones are not accounted for in physical models. Including them will add vigorous melting of grounded ice that will enhance the sensitivity of glaciers to ocean warming and increase projections of mass loss.

The Door Is Still Open

Abstract: As COVID-19 threatened the lives of those incarcerated, compassionate release motions emerged as a critical mechanism to seek the release of those individuals most vulnerable to severe illness or death. But today, as the urgency of the pandemic diminishes and the grounds justifying release is limited in some Circuits, some may fear that compassionate release has returned to its flawed roots of being available only to a very few. This Article argues that the historical categories related to an individual’s age and health need not, and should not, be so narrowly viewed. Rather, these existing categories for compassionate release can be approached more expansively, by grounding them in an understanding of how an elderly individual’s health deteriorates in prison, and by calling attention to the inability of an incarcerated individual to access specialized and necessary medical care. Framing these categories in this way ultimately encompasses many elderly individuals in prison and those younger individuals with serious medical conditions who are receiving inadequate medical care. Given the rapidly aging federal prison population and the thousands of prisoners who suffer from significant medical conditions, many of whom have already served many years in prison and demonstrate compelling rehabilitation, these categories remain viable—and even promising— avenues for release.

Thanks and response to RC1 with a query

Abstract: Abstract. The NASA Atmospheric Tomography (ATom) Mission completed four seasonal deployments (August 2016, February 2017, October 2017, May 2018), each with regular 0.2–12 km profiling through transecting the remote Pacific and Atlantic Ocean basins. Additional data are acquired also for the Southern Ocean and Artic basin, as well as two flights over Antarctica. ATom in situ measurements provide a near-complete chemical characterization of the ~140,000 10-second (80 m by 2 km) air parcels measured along the flight path. This paper presents the Modeling Data Stream (MDS), a continuous gap-filled record of the 10-s parcels containing the chemical species needed to initialize a gas-phase chemistry model for the budgets of tropospheric ozone and methane. Global 3D models have been used to calculate the Reactivity Data Stream (RDS), which is comprised of the chemical reactivities (production and loss) for methane, ozone, and carbon monoxide, through 24-hour integration of the 10-s parcels. These parcels accurately sample tropospheric heterogeneity and allow us to partially deconstruct the spatial scales and variability that defines tropospheric chemistry from composition to reactions. This paper provides a first look and analysis of the up-to-date MDS and RDS data including all four deployments (Prather et al., 2023, https://doi.org/10.7280/D1B12H). ATom's regular profiling of the ocean basins allows for weighted averages to build probability densities for key species and reactivities presented here. These statistics provide climatological metrics for global chemistry models, for example, the large-scale pattern of ozone and methane loss in the lower troposphere, and the more sporadic hot spots of ozone production in the upper troposphere. The profiling curtains of reactivity also identify meteorologically variable and hence deployment-specific hot spots of photochemical activity. Added calculations of the sensitivities of the production and loss terms relative to each species emphasize the few dominant species that control the ozone and methane budgets, and whose statistical patterns should be key model-measurement metrics. From the sensitivities, we also derive linearized lifetimes of ozone and methane on a parcel-by-parcel basis and average over the basins, providing an observational basis for these previously model-only diagnostics. We had found that most model differences in the ozone and methane budgets are caused by the models calculating different climatologies for the key species such as O₃, CO, H₂O, NOx, CH₄ plus T, and thus these ATom measurements provide a substantial contribution to the understanding of model differences and even identifying model errors in global tropospheric chemistry.

Improved estimates of smoke exposure during Australia fire seasons: Importance of quantifying plume injection heights

Abstract: Abstract. Wildfires can have a significant impact on air quality in Australia during severe burning seasons, but incomplete knowledge of the injection heights of smoke plumes poses a challenge for quantifying smoke exposure. In this study, we use two approaches to quantify the fractions of fire emissions injected above the planetary boundary layer (PBL), and we further investigate the impact of plume injection fractions on daily mean surface concentrations of fine particulate matter (PM2.5) from wildfire smoke in key cities over northern and southeastern Australia from 2009 to 2020. For the first method, we rely on climatological, monthly mean vertical profiles of smoke emissions from the Integrated Monitoring and Modelling System for wildland fires (IS4FIRES), together with assimilated PBL heights from NASA Modern-Era Retrospective analysis for Research and Application (MERRA) version 2. For the second method, we develop a novel approach based on the Multi-angle Imaging Spectro-Radiometer (MISR) observations and a random forest, machine-learning model that allows us to directly predict the daily plume injection fractions above the PBL in each grid cell. We apply the resulting plume injection fractions quantified by the two methods to smoke PM2.5 concentrations simulated by the Stochastic Time-Inverted Lagrangian Transport (STILT) model in target cities. We find that characterization of the plume injection heights greatly affects estimates of surface daily smoke PM2.5, especially during severe wildfire seasons, when intense heat from fires can loft smoke high in the troposphere. However, using climatological injection profiles cannot capture well the spatiotemporal variability of plume injection fractions, resulting in a 63 % underestimate of daily fire emission fluxes injected above the PBL. Our random forest model successfully reproduces the daily injected fire emission fluxes against MISR observations (R2 = 0.88, normalized mean bias = 10 %), which predicts that 27 % and 45 % of total fire emissions rise above the PBL in northern and southeastern Australia, respectively, from 2009 to 2020. Using the plume behavior predicted by the random forest method also leads to the best model agreement with observed surface PM2.5 in several key cities, with smoke PM2.5 accounting for 5 % to 52 % of total PM2.5 during fire seasons from 2009 to 2020.

Mpox Masquerading as Secondary Syphilis

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The WIMP paradigm: Theme and variations

Abstract: WIMPs, weakly-interacting massive particles, have been leading candidates for particle dark matter for decades, and they remain a viable and highly motivated possibility. In these lectures, I describe the basic motivations for WIMPs, beginning with the WIMP miracle and its under-appreciated cousin, the discrete WIMP miracle. I then give an overview of some of the basic features of WIMPs and how to find them. These lectures conclude with some variations on the WIMP theme that have by now become significant topics in their own right and illustrate the richness of the WIMP paradigm.

Estimating Individual Tree Mortality in the Sierra Nevada Using Lidar and Multispectral Reflectance Data

Abstract: Widespread tree mortality events occur during periods of severe drought in temperate conifer forests and are expected to become more frequent in many areas due to climate change. Improved mapping of individual tree mortality is needed to identify risk factors and design effective conservation strategies. In this study, we used National Ecological Observatory Network (NEON) lidar and multispectral reflectance airborne observations to map individual tree mortality over a 160 km2 area during and after the 2012-2016 drought for two sites in California’s Sierra National Forest. We used NEON lidar to derive tree locations and crown perimeters and multispectral data to map tree mortality for more than one million trees. We found that 25.4% of the trees in our study area died between 2013 and 2017, with considerably higher mortality at the lower-elevation Soaproot Saddle site. Between 2017 and 2019, an additional 2.0-2.8% of the trees died each year. Two wildfires in 2020 and 2021 increased tree mortality within burned area perimeters by 49-89% between 2019 and 2021. Consistent with previous work, we found that tree mortality risk increased as a function of tree height. Tree mortality was positively associated with distance from rivers, trees per hectare, and decreasing slope at the lower elevation site. In contrast, increasing slope was positively associated with tree mortality at the higher elevation site. Our approach and dataset provide a means to study the combined effects of drought and wildfire on tree mortality and may improve projections of forest resilience under a changing climate.

Life in Groups

Abstract: Abstract Life in Groups: How We Think, Feel, and Act Together comprises thirteen essays by the author relating to human life in groups, together with a substantial introduction and concluding discussion. The essays continue the development and application of the author’s perspective on collective beliefs, emotions, and actions, arguing that these and other central social phenomena are grounded in a joint commitment of the parties. This commitment unifies them, guides their actions going forward, and determines their relations to one another in important ways. In particular, it grounds in each of the parties a set of rights and obligations of a particular kind. The introduction serves both to introduce joint commitment to those unfamiliar with it and to advance discussion in light of questions that have been raised. Several of the essays respond to comments on particular aspects of the author’s work. These include an essay that addresses some central questions about a joint commitment approach to the problem of political obligation

Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat

Abstract: Neural communication networks form the fundamental basis for brain function. These communication networks are enabled by emitted ligands such as neurotransmitters, which activate receptor complexes to facilitate communication. Thus, neural communication is fundamentally dependent on the transcriptome. Here we develop NeuronChat, a method and package for the inference, visualization and analysis of neural-specific communication networks among pre-defined cell groups using single-cell expression data. We incorporate a manually curated molecular interaction database of neural signaling for both human and mouse, and benchmark NeuronChat on several published datasets to validate its ability in predicting neural connectivity. Then, we apply NeuronChat to three different neural tissue datasets to illustrate its functionalities in identifying interneural communication networks, revealing conserved or context-specific interactions across different biological contexts, and predicting communication pattern changes in diseased brains with autism spectrum disorder. Finally, we demonstrate NeuronChat can utilize spatial transcriptomics data to infer and visualize neural-specific cell-cell communication.

Data from Survival of Middle Eastern and North African Individuals Diagnosed with Colorectal Cancer: A Population-Based Study in California

Abstract: <div>AbstractBackground:<p>Literature on colorectal cancer outcomes in individuals of Middle Eastern and North African (MENA) descent is limited. To address this gap, we estimated five-year colorectal cancer–specific survival by race and ethnicity, including MENA individuals, in a diverse, population-based sample in California.</p>Methods:<p>We identified adults (ages 18–79 years) diagnosed with a first or only colorectal cancer in 2004 to 2017 using the California Cancer Registry (CCR), including non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and MENA individuals. For each racial/ethnic group, we calculated five-year colorectal cancer–specific survival and used Cox proportional hazards regression models to examine the association of race/ethnicity and survival, adjusting for clinical and socio demographic factors.</p>Results:<p>Of 110,192 persons diagnosed with colorectal cancer, five-year colorectal cancer–specific survival was lowest in Black (61.0%) and highest in MENA (73.2%) individuals. Asian (72.2%) individuals had higher survival than White (70.0%) and Hispanic (68.2%) individuals. In adjusted analysis, MENA [adjusted HR (aHR), 0.82; 95% confidence interval (CI), 0.76–0.89], Asian (aHR, 0.86; 95% CI, 0.83–0.90), and Hispanic (aHR, 0.94; 95% CI, 0.91–0.97) race/ethnicity were associated with higher, and Black (aHR, 1.13; 95% CI, 1.09–1.18) race/ethnicity was associated with lower survival compared with non-Hispanic White race/ethnicity.</p>Conclusions:<p>To our knowledge, this is the first study to report colorectal cancer survival in MENA individuals in the United States. We observed higher survival of MENA individuals compared with other racial/ethnic groups, adjusting for sociodemographic and clinical factors.</p>Impact:<p>Future studies are needed to identify factors contributing to cancer outcomes in this unique population.</p></div>