Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception.

Chemical platforms that facilitate both the identification and elucidation of new areas for therapeutic development are necessary but lacking. Activity-based protein profiling (ABPP) leverages active site-directed chemical probes as target discovery tools that resolve activity from expression and immediately marry the targets identified with lead compounds for drug design. However, this approach has traditionally focused on predictable and intrinsic enzyme functionality.

AIBP regulates TRPV1 activation in chemotherapy-induced peripheral neuropathy by controlling lipid raft dynamics and proximity to TLR4 in dorsal root ganglion neurons.

Nociceptive afferent signaling evoked by inflammation and nerve injury is mediated by the opening of ligand-gated and voltage-gated receptors or channels localized to cholesterol-rich lipid raft membrane domains. Dorsal root ganglion (DRG) nociceptors express high levels of toll-like receptor 4 (TLR4), which also localize to lipid rafts. Genetic deletion or pharmacologic blocking of TLR4 diminishes pain associated with chemotherapy-induced peripheral neuropathy (CIPN).

mTORC2 Inhibition Improves Morphological Effects of PTEN Loss, But Does Not Correct Synaptic Dysfunction or Prevent Seizures.

Hyperactivation of PI3K/PTEN-mTOR signaling during neural development is associated with focal cortical dysplasia (FCD), autism, and epilepsy. mTOR can signal through two major hubs, mTORC1 and mTORC2, both of which are hyperactive following PTEN loss of function (LOF). Here, we tested the hypothesis that genetic inactivation of the mTORC2 complex via deletion of is sufficient to rescue morphologic and electrophysiological abnormalities in the dentate gyrus caused by PTEN loss, as well as generalized seizures.

Traffic crash changes following transitions between daylight saving time and standard time in the United States: New evidence for public policy making.

Introduction: This study examined the impact of daylight saving time changes on traffic crashes in the United States. Using a data-driven regression analysis approach, the study analyzed 2014-2016 crash data from six states spanning all four major time zones in the contiguous United States.

Method: The researchers developed regression models for a number of analysis scenarios and by days of week separately.

Structural Equation Models Suggest That On-Farm Noncrop Vegetation Removal Is Not Associated with Improved Food Safety Outcomes but Is Linked to Impaired Water Quality.

While growers have reported pressures to minimize wildlife intrusion into produce fields through noncrop vegetation (NCV) removal, NCV provides key ecosystem services. To model food safety and environmental tradeoffs associated with NCV removal, published and publicly available food safety and water quality data from the Northeastern United States were obtained. Because data on NCV removal are not widely available, forest-wetland cover was used as a proxy, consistent with previous studies.

Obstacle clearance performance in individuals with high body mass index.

The objective of this study was to quantify performance in an obstacle clearance task among individuals with excess body weight or body mass index (BMI). Task performance was operationalized as the maximum obstacle height cleared, four duration measures of successful task completion and compensatory movements used in the process of task completion. Eighteen participants with a BMI exceeding 30 kg/m completed a laboratory experiment that required stepping over seven lightweight obstacles.

Reinforcer efficacy of grain for horses.

Positive reinforcement is becoming more common in horse training. Identifying effective reinforcers is critical for training success. The aim of this study was to determine relative reinforcer efficacy of different grains.

Joint Inversion of GNSS and GRACE for Terrestrial Water Storage Change in California.

Global Navigation Satellite System (GNSS) vertical displacements measuring the elastic response of Earth's crust to changes in hydrologic mass have been used to produce terrestrial water storage change (∆TWS) estimates for studying both annual ∆TWS as well as multi-year trends. However, these estimates require a high observation station density and minimal contamination by nonhydrologic deformation sources. The Gravity Recovery and Climate Experiment (GRACE) is another satellite-based measurement system that can be used to measure regional TWS fluctuations.

Using Random Forest, a machine learning approach to predict nitrogen, phosphorus, and sediment event mean concentrations in urban runoff.

Estimating pollutant loads from developed watersheds is vitally important to reduce nonpoint source pollution from urban areas, as a key tool in meeting water quality goals is the implementation of Stormwater Control Measures (SCMs). SCMs are selected and sized based on influent pollutant loads. A common method used to estimate pollutant loads in urban runoff is the Event Mean Concentration (EMC) method.

Designing Patient-Driven, Tissue-Engineered Models of Primary and Metastatic Breast Cancer.

The rising survival rate for early-stage breast cancer in the United States has created an expanding population of women in remission at risk for distant recurrence, with metastatic spread to the brain demonstrating an especially poor prognosis. The current standard of care for breast cancer brain metastases is not well defined or differentiated from the treatment of brain metastases from other primary sites. Here, we present tissue-engineered models of the primary and brain metastatic breast cancer microenvironments informed by analysis of patient tumor resections.

Liberation extension: building capacities for civilizational transition.

COVID 19 has exacerbated and underscored structural inequalities and endemic vulnerabilities in food, economic, and social systems, compounding concerns about environmental sustainability and racial and economic justice. Convergent crises have amplified a growing chorus of voices and movements calling for new thinking and new practices to adapt to these shifts, mitigate their impact, and address their root causes through far reaching changes in social and economic life and values, including breaking with the free market paradigm. In the face of a historic choice between transition or multiple systems collapse that deepen injustice and threaten planetary survival, I make the case for expanding on liberatory tendencies in Extension programs to build capacities for response-ability to transition toward more just and sustainable futures.

Long-read metagenomic sequencing reveals shifts in associations of antibiotic resistance genes with mobile genetic elements from sewage to activated sludge.

Background: There is concern that the microbially rich activated sludge environment of wastewater treatment plants (WWTPs) may contribute to the dissemination of antibiotic resistance genes (ARGs). We applied long-read (nanopore) sequencing to profile ARGs and their neighboring genes to illuminate their fate in the activated sludge treatment by comparing their abundance, genetic locations, mobility potential, and bacterial hosts within activated sludge relative to those in influent sewage across five WWTPs from three continents.

Results: The abundances (gene copies per Gb of reads, aka gc/Gb) of all ARGs and those carried by putative pathogens decreased 75-90% from influent sewage (192-605 gc/Gb) to activated sludge (31-62 gc/Gb) at all five WWTPs.

Herbivorous Caterpillars and the Green Leaf Volatile (GLV) Quandary.

Several herbivorous caterpillars contain effectors in their oral secretions that alter the emission of green leaf volatiles (GLVs) produced by the plants upon which the caterpillars are feeding. These effectors include an isomerase, a fatty acid dehydratase (FHD), and a heat-stable hexenal trapping (HALT) molecule. GLVs serve as signaling compounds in plant-insect interactions and inter-and intra-plant communication.

A Role for Inositol Pyrophosphates in the Metabolic Adaptations to Low Phosphate in .

Phosphate is a major plant macronutrient and low phosphate availability severely limits global crop productivity. In , a key regulator of the transcriptional response to low phosphate, phosphate starvation response 1 (PHR1), is modulated by a class of signaling molecules called inositol pyrophosphates (PP-InsPs). Two closely related diphosphoinositol pentakisphosphate enzymes ( and ) are responsible for the synthesis and turnover of InsP, the most implicated molecule.

Sex differences in neuroimmune and glial mechanisms of pain.

Pain is the primary motivation for seeking medical care. Although pain may subside as inflammation resolves or an injury heals, it is increasingly evident that persistency of the pain state can occur with significant regularity. Chronic pain requires aggressive management to minimize its physiological consequences and diminish its impact on quality of life.

Chronic pain and COVID-19: The association of delay discounting with perceived stress and pain severity.

The coronavirus disease pandemic of 2019 (COVID-19) is a worldwide threat to public health that has significantly affected the United States. The pandemic poses a variety of health risks including stressful disruptions in social and economic activity. Understanding the pandemic's effects on already vulnerable populations, such as individuals with chronic pain, may inform healthcare preparation for future catastrophic events.

Narrative theory IV: Within-subject effects of active and control scarcity narratives on delay discounting in alcohol use disorder.

Imagining narratives involving sudden economic scarcity has been shown to increase delay discounting rates. However, previous studies have only compared active and control narratives between groups. Moreover, an investigation of the quantitative effects of different narrative scenario types has not been conducted.

Evaluating the success of treatments that slow spread of an invasive insect pest.

Background: Treatments for the suppression and eradication of insect populations undergo substantial testing to ascertain their efficacy and safety, but the generally limited spatial and temporal scope of such studies limit knowledge of how contextual factors encountered in operational contexts shape the relative success of pest management treatments. These contextual factors potentially include ecological characteristics of the treated area, or the timing of treatments relative to pest phenology and weather events. We used an extensive database on over 1000 treatments of nascent populations of Lymantria dispar (L.

Refining Pheromone Lures for the Invasive Halyomorpha halys (Hemiptera: Pentatomidae) Through Collaborative Trials in the United States and Europe.

Brown marmorated stink bug, Halyomorpha halys, is native to Asia and has invaded North America and Europe inflicting serious agricultural damage to specialty and row crops. Tools to monitor the spread of H. halys include traps baited with the two-component aggregation pheromone (PHER), (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol, and pheromone synergist, methyl (2E,4E,6Z)-decatrienoate (MDT).

Development of a High-Throughput Method to Study the Inhibitory Effect of Phytochemicals on Trimethylamine Formation.

Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter.

Translating the Transcriptome: Sex Differences in the Mechanisms of Depression and Stress, Revisited.

The past decade has produced a plethora of studies examining sex differences in the transcriptional profiles of stress and mood disorders. As we move forward from accepting the existence of extensive molecular sex differences in the brain to exploring the purpose of these sex differences, our approach must become more systemic and less reductionist. Earlier studies have examined specific brain regions and/or cell types.