Investigating the role of Wnt3a and Wnt5a as critical factors of hepatic stellate cell activation in acute toxicant-induced liver injury.

Toxicant exposure can lead to acute liver injury, characterized by hepatic reprogramming and wound healing. Hepatic stellate cells (HSC) play a key role in liver regeneration during wound healing by secreting fibrogenic factors and production of extracellular matrix (ECM). However, repetitive injury to the liver can lead to extensive scarring and liver fibrosis, indicating HSCs coordinate both regeneration and disease.

AQUILA: A laboratory facility for the irradiation of astrochemical ice analogs by keV ions.

The detection of various molecular species, including complex organic molecules relevant to biochemical and geochemical processes, in astronomical settings, such as the interstellar medium or the outer solar system, has led to the increased need for a better understanding of the chemistry occurring in these cold regions of space. In this context, the chemistry of ices prepared and processed at cryogenic temperatures has proven to be of particular interest due to the fact that many interstellar molecules are believed to originate within the icy mantles adsorbed on nano- and micro-scale dust particles. The chemistry leading to the formation of such molecules may be initiated by ionizing radiation in the form of galactic cosmic rays or stellar winds, and thus, there has been an increased interest in commissioning experimental setups capable of simulating and better characterizing this solid-phase radiation astrochemistry.

Impact of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality based active shooter training drill.

Ingestion of L-theanine and L-tyrosine has been shown to reduce salivary stress biomarkers and improve aspects of cognitive performance in response to stress. However, there have been no studies to concurrently examine the impact of both L-theanine and L-tyrosine ingestion during a mental stress challenge (MSC) involving a brief cognitive challenge and a virtual reality based active shooter training drill. Thus, the purpose of this study was to determine the impact of ingestion of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality active shooter drill and cognitive challenge.

Emerging concepts in alcohol, infection & immunity: A summary of the 2023 alcohol and immunology research interest group (AIRIG) meeting.

On December 8th 2023, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The 2023 meeting focused broadly on how acute and chronic alcohol exposure leads to immune dysregulation, and how this contributes to damage in multiple tissues and organs. These include impaired lung immunity, intestinal dysfunction, autoimmunity, the gut-Central Nervous System (CNS) axis, and end-organ damage.

NF-κB/NLRP3 Translational Inhibition by Nanoligomer Therapy Mitigates Ethanol and Advanced Age-Related Neuroinflammation.

Binge alcohol use is increasing among aged adults (>65 years). Alcohol-related toxicity in aged adults is associated with neurodegeneration, yet the molecular underpinnings of age-related sensitivity to alcohol are not well described. Studies utilizing rodent models of neurodegenerative disease reveal heightened activation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Nod like receptor 3 (NLRP3) mediate microglia activation and associated neuronal injury.

Lactoylglutathione promotes inflammatory signaling in macrophages through histone lactoylation.

Chronic, systemic inflammation is a pathophysiological manifestation of metabolic disorders. Inflammatory signaling leads to elevated glycolytic flux and a metabolic shift towards aerobic glycolysis and lactate generation. This rise in lactate corresponds with increased generation of lactoylLys modifications on histones, mediating transcriptional responses to inflammatory stimuli.

Binge ethanol exposure in advanced age elevates neuroinflammation and early indicators of neurodegeneration and cognitive impairment in female mice.

Binge drinking is rising among aged adults (>65 years of age), however the contribution of alcohol misuse to neurodegenerative disease development is not well understood. Both advanced age and repeated binge ethanol exposure increase neuroinflammation, which is an important component of neurodegeneration and cognitive dysfunction. Surprisingly, the distinct effects of binge ethanol exposure on neuroinflammation and associated degeneration in the aged brain have not been well characterized.

Lactoylglutathione promotes inflammatory signaling in macrophages.

Chronic, systemic inflammation is a pathophysiological manifestation of metabolic disorders. Inflammatory signaling leads to elevated glycolytic flux and a metabolic shift towards aerobic glycolysis and lactate generation. This rise in lactate corresponds with increased generation of lactoylLys modifications on histones, mediating transcriptional responses to inflammatory stimuli.

A systematic mid-infrared spectroscopic study of thermally processed SO ices.

The use of mid-infrared spectroscopy to characterise the chemistry of icy interstellar and Solar System environments will be exploited in the near future to better understand the chemical processes and molecular inventories in various astronomical environments. This is, in part, due to observational work made possible by the recently launched as well as forthcoming missions to the outer Solar System that will observe in the mid-infrared spectroscopic region (, the and the missions). However, such spectroscopic characterisations are crucially reliant upon the generation of laboratory data for comparative purposes.

Alcohol and Immunology: Mechanisms of multi-organ damage. Summary of the 2022 alcohol and Immunology research interest group (AIRIG) meeting.

On October 26th, 2022 the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Hawaii. The 2022 meeting focused broadly on the immunological consequences of acute, chronic, and prenatal alcohol exposure and how these contribute to damage in multiple organs and tissues. These included alcohol-induced neuroinflammation, impaired lung immunity, intestinal dysfunction, and decreased anti-microbial and anti-viral responses.

Per- and polyfluoroalkyl substances (PFAS) inhibit cytochrome P450 CYP3A7 through direct coordination to the heme iron and water displacement.

Per- and polyfluoroalkyl substances (PFAS) are a chemical class of highly stable, fluorinated compounds popular for use in a variety of consumer products. PFAS environmental persistence in drinking water contributes to acute exposure in humans and subsequent bioaccumulation of the compounds in the liver and lung tissue. Prenatal PFAS exposure has been associated with lowered birth weight, premature birth, and developmental defects including cranio-facial abnormalities.

Oxidized low density lipoprotein in the liver causes decreased permeability of liver lymphatic- but not liver sinusoidal-endothelial cells VEGFR-3 regulation of VE-Cadherin.

The lymphatic vasculature of the liver is vital for liver function as it maintains fluid and protein homeostasis and is important for immune cell transport to the lymph node. Chronic liver disease is associated with increased expression of inflammatory mediators including oxidized low-density lipoprotein (oxLDL). Intrahepatic levels of oxLDL are elevated in nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C infection (HCV), alcohol-associated liver disease (ALD), and cholestatic liver diseases.

Energetic electron irradiations of amorphous and crystalline sulphur-bearing astrochemical ices.

Laboratory experiments have confirmed that the radiolytic decay rate of astrochemical ice analogues is dependent upon the solid phase of the target ice, with some crystalline molecular ices being more radio-resistant than their amorphous counterparts. The degree of radio-resistance exhibited by crystalline ice phases is dependent upon the nature, strength, and extent of the intermolecular interactions that characterise their solid structure. For example, it has been shown that crystalline CHOH decays at a significantly slower rate when irradiated by 2 keV electrons at 20 K than does the amorphous phase due to the stabilising effect imparted by the presence of an extensive array of strong hydrogen bonds.

Profiling the oxylipidome in aged mice after chronic ethanol feeding: Identifying lipid metabolites as drivers of hepatocyte stress.

The global population of people over the age of 65 is increasing and expected to reach 1.5 billion by 2050. While aging is associated with a number of chronic illnesses including dementia, the underlying contribution of alcohol misuse in the elderly is understudied.

Ozone production in electron irradiated CO:O ices.

The detection of ozone (O) in the surface ices of Ganymede, Jupiter's largest moon, and of the Saturnian moons Rhea and Dione, has motivated several studies on the route of formation of this species. Previous studies have successfully quantified trends in the production of O as a result of the irradiation of pure molecular ices using ultraviolet photons and charged particles (, ions and electrons), such as the abundances of O formed after irradiation at different temperatures or using different charged particles. In this study, we extend such results by quantifying the abundance of O as a result of the 1 keV electron irradiation of a series of 14 stoichiometrically distinct CO:O astrophysical ice analogues at 20 K.

New insights into the mechanism of alcohol-mediated organ damage via its impact on immunity, metabolism, and repair pathways: A summary of the 2021 Alcohol and Immunology Research Interest Group (AIRIG) meeting.

On November 19th, 2021, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at Loyola University Chicago Health Sciences Campus in Maywood, Illinois. The 2021 meeting focused on how alcohol misuse is linked to immune system derangements, leading to tissue and organ damage, and how this research can be translated into improving treatment of alcohol-related disease. This meeting was divided into three plenary sessions: the first session focused on how alcohol misuse affects different parts of the immune system, the second session presented research on mechanisms of organ damage from alcohol misuse, and the final session highlighted research on potential therapeutic targets for treating alcohol-mediated tissue damage.

Comparative electron irradiations of amorphous and crystalline astrophysical ice analogues.

Laboratory studies of the radiation chemistry occurring in astrophysical ices have demonstrated the dependence of this chemistry on a number of experimental parameters. One experimental parameter which has received significantly less attention is that of the phase of the solid ice under investigation. In this present study, we have performed systematic 2 keV electron irradiations of the amorphous and crystalline phases of pure CHOH and NO astrophysical ice analogues.

Proteomic analysis of alcohol-associated hepatitis reveals glycoprotein NMB (GPNMB) as a novel hepatic and serum biomarker.

Alcohol consumption remains a leading cause of liver disease worldwide, resulting in a complex array of hepatic pathologies, including steatosis, steatohepatitis, and cirrhosis. Individuals who progress to a rarer form of alcohol-associated liver disease (ALD), alcohol-associated hepatitis (AH), require immediate life-saving intervention in the form of liver transplantation. Rapid onset of AH is poorly understood and the metabolic mechanisms contributing to the progression to liver failure remain undetermined.

The Ice Chamber for Astrophysics-Astrochemistry (ICA): A new experimental facility for ion impact studies of astrophysical ice analogs.

The Ice Chamber for Astrophysics-Astrochemistry (ICA) is a new laboratory end station located at the Institute for Nuclear Research (Atomki) in Debrecen, Hungary. The ICA has been specifically designed for the study of the physico-chemical properties of astrophysical ice analogs and their chemical evolution when subjected to ionizing radiation and thermal processing. The ICA is an ultra-high-vacuum compatible chamber containing a series of IR-transparent substrates mounted on a copper holder connected to a closed-cycle cryostat capable of being cooled down to 20 K, itself mounted on a 360° rotation stage and a z-linear manipulator.

Plant hormone signaling: Is upside down right side up?

Since the early days of plant biology, small molecule hormones have held a central place in our understanding of development. A key feature of plant hormone action is the ability to regulate multiple developmental processes. Despite this pleiotropy, decades of genetic and molecular studies have shown that plant hormone signaling is often canalized through a core pathway.