Placental transcriptome analysis of hypertensive pregnancies identifies distinct gene expression profiles of preeclampsia superimposed on chronic hypertension.

Background: The pathogenesis of preeclampsia superimposed on chronic hypertension (SI) is poorly understood relative to preeclampsia (PreE) occurring in pregnant people without chronic hypertension. Placental transcriptomes in pregnancies complicated by PreE and SI have not been previously compared.

Methods: We identified pregnant people in the University of Michigan Biorepository for Understanding Maternal and Pediatric Health with hypertensive disorders affecting singleton, euploid gestations (N = 36) along with non-hypertensive control subjects (N = 12).

Mediation effects of DNA methylation and hydroxymethylation on birth outcomes after prenatal per- and polyfluoroalkyl substances (PFAS) exposure in the Michigan mother-infant Pairs cohort.

Background: Per- and polyfluoroalkyl substances (PFAS) are chemicals that are resistant to degradation and ubiquitous in our environments. PFAS may impact the developing epigenome, but current human evidence is limited to assessments of total DNA methylation. We assessed associations between first trimester PFAS exposures with newborn DNA methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC).

Machine intelligence for radiation science: summary of the Radiation Research Society 67th annual meeting symposium.

The era of high-throughput techniques created big data in the medical field and research disciplines. Machine intelligence (MI) approaches can overcome critical limitations on how those large-scale data sets are processed, analyzed, and interpreted. The 67 Annual Meeting of the Radiation Research Society featured a symposium on MI approaches to highlight recent advancements in the radiation sciences and their clinical applications.

Deep Learning Based Automated Orthotopic Lung Tumor Segmentation in Whole-Body Mouse CT-Scans.

Lung cancer is the leading cause of cancer related deaths worldwide. The development of orthotopic mouse models of lung cancer, which recapitulates the disease more realistically compared to the widely used subcutaneous tumor models, is expected to critically aid the development of novel therapies to battle lung cancer or related comorbidities such as cachexia. However, follow-up of tumor take, tumor growth and detection of therapeutic effects is difficult, time consuming and requires a vast number of animals in orthotopic models.

Discovering and Applying the Urban Rules of Life to Design Sustainable and Healthy Cities.

The city and its urban biome provides an extreme laboratory for studying fundamental biological questions and developing best practices for sustaining biodiverse and well-functioning ecological communities within anthropogenic built environments. We propose by studying urban organisms, urban biotic communities, the urban biome, and the interactions between the urban biome and peri-urban built and natural environments, we can (1) discover new "rules of life" for the structure, function, interaction, and evolution of organisms; (2) use these discoveries to understand how novel emerging biotic communities affect and are affected by anthropogenic environmental changes in climate and other environmental factors; and (3) apply what we have learned to engage residents of the urban biome, and design cities that are more biologically diverse, are provided with more and better ecosystem services, and are more equitable and healthier places to live. The built environment of the urban biome is a place that reflects history, economics, technology, governance, culture, and values of the human residents; research on and applications of the rules of life in the urban biome can be used by all residents in making choices about the design of the cities where they live.

An Amphipathic Alpha-Helix Domain from Poliovirus 2C Protein Tubulate Lipid Vesicles.

Positive-strand RNA viruses universally remodel host intracellular membranes to form membrane-bound viral replication complexes, where viral offspring RNAs are synthesized. In the majority of cases, viral replication proteins are targeted to and play critical roles in the modulation of the designated organelle membranes. Many viral replication proteins do not have transmembrane domains, but contain single or multiple amphipathic alpha-helices.

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia.

Background: Cachexia, highly prevalent in patients with non-small cell lung cancer (NSCLC), impairs quality of life and is associated with reduced tolerance and responsiveness to cancer therapy and decreased survival. MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in post-transcriptional gene regulation. Changes in intramuscular levels of miRNAs have been implicated in muscle wasting conditions.

Rapid expansion of Greenland's low-permeability ice slabs.

In recent decades, meltwater runoff has accelerated to become the dominant mechanism for mass loss in the Greenland ice sheet. In Greenland's high-elevation interior, porous snow and firn accumulate; these can absorb surface meltwater and inhibit runoff, but this buffering effect is limited if enough water refreezes near the surface to restrict percolation. However, the influence of refreezing on runoff from Greenland remains largely unquantified.

The Mitochondrial Peptide Humanin Targets but Does Not Denature Amyloid Oligomers in Type II Diabetes.

Mitochondrially derived peptides (MDPs) such as humanin (HN) have shown a remarkable ability to modulate neurological amyloids and apoptosis-associated proteins in cells and animal models. Recently, we found that humanin-like peptides also inhibit amyloid formation outside of neural environments in islet amyloid polypeptide (IAPP) fibrils and plaques, which are hallmarks of Type II diabetes. However, the biochemical basis for regulating amyloids through endogenous MDPs remains elusive.

E46K-like α-synuclein mutants increase lipid interactions and disrupt membrane selectivity.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, and both genetic and histopathological evidence have implicated the ubiquitous presynaptic protein α-synuclein (αSyn) in its pathogenesis. Recent work has investigated how disrupting αSyn's interaction with membranes triggers trafficking defects, cellular stress, and apoptosis. Special interest has been devoted to a series of mutants exacerbating the effects of the E46K mutation (associated with autosomal dominant PD) through homologous Glu-to-Lys substitutions in αSyn's N-terminal region ( E35K and E61K).

Hospital contribution to variation in rates of vaginal birth after cesarean.

Objective: To determine the influence of delivery hospital on the rate of vaginal birth after cesarean (VBAC).

Study Design: This retrospective cohort study used claims data from Blue Cross and Blue Shield of Michigan. Women with a prior cesarean and a singleton livebirth between 2012 and 2016 were included.

Directed Supramolecular Organization of N-BAR Proteins through Regulation of H0 Membrane Immersion Depth.

Many membrane remodeling events rely on the ability of curvature-generating N-BAR membrane proteins to organize into distinctive supramolecular configurations. Experiments have revealed a conformational switch in N-BAR proteins resulting in vesicular or tubular membrane shapes, with shallow membrane immersion of the H0 amphipathic helices of N-BAR proteins on vesicles but deep H0 immersion on tubes. We develop here a minimal elastic model of the local thinning of the lipid bilayer resulting from H0 immersion.

Direct measurements of meltwater runoff on the Greenland ice sheet surface.

Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.

Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies.

Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with ¹⁸F-Fluoroazomycin Arabinoside and ¹⁵O-H₂O PET.

Unlabelled: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) is a PET tracer of tumor hypoxia. However, as hypoxia often is associated with decreased perfusion, the delivery of (18)F-FAZA may be compromised, potentially disturbing the association between tissue hypoxia and (18)F-FAZA uptake. The aim of this study was to gain insight into the relationship between tumor perfusion and (18)F-FAZA uptake.

O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease.

Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear.

Membrane Curvature-sensing and Curvature-inducing Activity of Islet Amyloid Polypeptide and Its Implications for Membrane Disruption.

Islet amyloid polypeptide (IAPP) is a 37-amino acid amyloid protein intimately associated with pancreatic islet β-cell dysfunction and death in type II diabetes. In this study, we combine spectroscopic methods and microscopy to investigate α-helical IAPP-membrane interactions. Using light scattering and fluorescence microscopy, we observe that larger vesicles become smaller upon treatment with human or rat IAPP.

A Game of Hide and Seek: Expectations of Clumpy Resources Influence Hiding and Searching Patterns.

Resources are often distributed in clumps or patches in space, unless an agent is trying to protect them from discovery and theft using a dispersed distribution. We uncover human expectations of such spatial resource patterns in collaborative and competitive settings via a sequential multi-person game in which participants hid resources for the next participant to seek. When collaborating, resources were mostly hidden in clumpy distributions, but when competing, resources were hidden in more dispersed (random or hyperdispersed) patterns to increase the searching difficulty for the other player.

Mutualistic root endophytism is not associated with the reduction of saprotrophic traits and requires a noncompromised plant innate immunity.

During a compatible interaction, the sebacinoid root-associated fungi Piriformospora indica and Sebacina vermifera induce modification of root morphology and enhance shoot growth in Arabidopsis thaliana. The genomic traits common in these two fungi were investigated and compared with those of other root-associated fungi and saprotrophs. The transcriptional responses of the two sebacinoid fungi and of Arabidopsis roots to colonization at three different symbiotic stages were analyzed by custom-designed microarrays.

Experimental observation of a generalized Gibbs ensemble.

The description of the non-equilibrium dynamics of isolated quantum many-body systems within the framework of statistical mechanics is a fundamental open question. Conventional thermodynamical ensembles fail to describe the large class of systems that exhibit nontrivial conserved quantities, and generalized ensembles have been predicted to maximize entropy in these systems. We show experimentally that a degenerate one-dimensional Bose gas relaxes to a state that can be described by such a generalized ensemble.

Are College Students' Assessments of Threat Shaped by the Dangers of Their Childhood Environment?

Humans internalize environmental cues of mortality risk at an early age, which influences subsequent risk perceptions and behavior. In this respect, an individual's current risk assessment may be viewed as an adaptive response to the dangers present within his or her early local environment. Here we examine the relationship between several variables indicating threat within an individual's early environment (e.

The compromised recognition of turnip crinkle virus1 subfamily of microrchidia ATPases regulates disease resistance in barley to biotrophic and necrotrophic pathogens.

MORC1 and MORC2, two of the seven members of the Arabidopsis (Arabidopsis thaliana) Compromised Recognition of Turnip Crinkle Virus1 subfamily of microrchidia Gyrase, Heat Shock Protein90, Histidine Kinase, MutL (GHKL) ATPases, were previously shown to be required in multiple layers of plant immunity. Here, we show that the barley (Hordeum vulgare) MORCs also are involved in disease resistance. Genome-wide analyses identified five MORCs that are 37% to 48% identical on the protein level to AtMORC1.

Hydration dynamics as an intrinsic ruler for refining protein structure at lipid membrane interfaces.

Knowing the topology and location of protein segments at water-membrane interfaces is critical for rationalizing their functions, but their characterization is challenging under physiological conditions. Here, we debut a unique spectroscopic approach by using the hydration dynamics gradient found across the phospholipid bilayer as an intrinsic ruler for determining the topology, immersion depth, and orientation of protein segments in lipid membranes, particularly at water-membrane interfaces. This is achieved through the site-specific quantification of translational diffusion of hydration water using an emerging tool, (1)H Overhauser dynamic nuclear polarization (ODNP)-enhanced NMR relaxometry.

Relaxation and prethermalization in an isolated quantum system.

Understanding relaxation processes is an important unsolved problem in many areas of physics. A key challenge is the scarcity of experimental tools for the characterization of complex transient states. We used measurements of full quantum mechanical probability distributions of matter-wave interference to study the relaxation dynamics of a coherently split one-dimensional Bose gas and obtained comprehensive information about the dynamical states of the system.

Mortality of inherited arrhythmia syndromes: insight into their natural history.

Background: For most arrhythmia syndromes, the risk of sudden cardiac death for asymptomatic mutation carriers is ill defined. Data on the natural history of these diseases, therefore, are essential. The family tree mortality ratio method offers the unique possibility to study the natural history at a time when the disease was not known and patients received no treatment.