The Sugar-Coated Truth of Alcohol-Associated Liver Disease: Galectins as Multifaceted Regulators of Alcohol-Induced Liver Injury.

Alcohol-associated diver disease is a major driver of end-stage liver diseases globally. Alcohol functions as a hepatotoxin by overwhelming cell stress response pathways and deregulating hepatocellular protein, amino acid, and lipid metabolism. In addition, alcohol alters innate and adaptive inflammatory immune responses and acts on extrahepatic organs to flood the liver with pro-inflammatory stimuli.

Distributed Temporal Coding of Visual Memory Categories in Human Hippocampal Neurons Revealed by an Interpretable Decoding Model.

The hippocampus is crucial for forming new episodic memories. While its role in encoding spatial and temporal information (where and when) is well understood, how it encodes objects (what) remains unclear due to the high dimensionality of object space. Rather than encoding each object separately, the hippocampus may encode object categories to reduce complexity.

Tumor site influences efficacy of MEKi and immunotherapy combinations in a preclinical model of cholangiocarcinoma.

Background And Aims: Although chemotherapy and anti-PD-L1 antibodies are the standard of care for cholangiocarcinoma (CCA), resistance is common and limits durable benefits for patients. This hurdle underscores the urgent need to innovate combination approaches that promote durable immunity in patients. MEK inhibitors (MEKi) have shown potential to enhance immunotherapy in CCA models, but early clinical trials combining MEKi with anti-PD-L1 therapy have yielded suboptimal results.

The Microbial Metabolite δ-Valerobetaine Strengthens the Gut Epithelial Barrier.

Metabolic processes within gut microbes generate bioactive metabolites that impact intestinal epithelial barrier function. Herein, gnotobiotic mice and mass spectrometry-based metabolomics were used to identify novel metabolites in host tissues of microbial origin. Of those detected, the gut microbe-generated metabolite δ-valerobetaine (δ-VB) is a potent inhibitor of l-carnitine biosynthesis and a modulator of fatty acid oxidation by mitochondria in liver cells.

Distributed Temporal Coding of Visual Memory Categories in Human Hippocampal Neurons.

The hippocampus is crucial for forming new episodic memories. While the encoding of spatial and temporal information (where and when) in the hippocampus is well understood, the encoding of objects (what) remains less clear due to the high dimensions of object space. Rather than encoding each individual object separately, the hippocampus may instead encode categories of objects to reduce this dimensionality.

Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent.

Oxidative stress mediates end-organ damage in a novel model of acetaminophen-toxicity in Drosophila.

Acetaminophen is the most common cause of acute drug-induced liver injury in the United States. However, research into the mechanisms of acetaminophen toxicity and the development of novel therapeutics is hampered by the lack of robust, reproducible, and cost-effective model systems. Herein, we characterize a novel Drosophila-based model of acetaminophen toxicity.

Corrigendum: Patterned hippocampal stimulation facilitates memory in patients with a history of head impact and/or brain injury.

[This corrects the article DOI: 10.3389/fnhum.2022.

Patterned Hippocampal Stimulation Facilitates Memory in Patients With a History of Head Impact and/or Brain Injury.

Rationale: Deep brain stimulation (DBS) of the hippocampus is proposed for enhancement of memory impaired by injury or disease. Many pre-clinical DBS paradigms can be addressed in epilepsy patients undergoing intracranial monitoring for seizure localization, since they already have electrodes implanted in brain areas of interest. Even though epilepsy is usually not a memory disorder targeted by DBS, the studies can nevertheless model other memory-impacting disorders, such as Traumatic Brain Injury (TBI).

Online learning for orientation estimation during translation in an insect ring attractor network.

Insect neural systems are a promising source of inspiration for new navigation algorithms, especially on low size, weight, and power platforms. There have been unprecedented recent neuroscience breakthroughs with Drosophila in behavioral and neural imaging experiments as well as the mapping of detailed connectivity of neural structures. General mechanisms for learning orientation in the central complex (CX) of Drosophila have been investigated previously; however, it is unclear how these underlying mechanisms extend to cases where there is translation through an environment (beyond only rotation), which is critical for navigation in robotic systems.

Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response.

Background & Aims: In colorectal cancer, approximately 95% of patients are refractory to immunotherapy because of low antitumor immune responses. Therefore, there is an exigent need to develop treatments that increase antitumor immune responses and decrease tumor burden to enhance immunotherapy.

Methods: The gut microbiome has been described as a master modulator of immune responses.

Accelerating Estimation of a Multi-Input Multi-Output Model of the Hippocampus with a Parallel Computing Strategy.

To build hippocampal memory prosthesis for restoring memory functions, we previously developed and implemented a multi-input multi-output (MIMO) nonlinear dynamic model of the hippocampus. This model can successfully predict hippocampal output spike activities based on input spike activities, and thus be used to drive microstimulation to bypass the damaged hippocampal region. Building such a MIMO model involves estimations of a large number of model coefficients, which typically takes hundreds of hours using a single personal computer.

Proline-Rich Acidic Protein 1 (PRAP1) Protects the Gastrointestinal Epithelium From Irradiation-Induced Apoptosis.

Background & Aims: The intestinal epithelium must be resilient to physiochemical stress to uphold the physiological barrier separating the systemic compartment from the microbial and antigenic components of the gut lumen. Identifying proteins that mediate protection and enhancing their expression is therefore a clear approach to promote intestinal health. We previously reported that oral ingestion of the probiotic Lactobacillus rhamnosus GG not only induced the expression of several recognized cytoprotective factors in the murine colon, but also many genes with no previously described function, including the gene encoding proline-rich acidic protein 1 (PRAP1).

Galectin-9 Is a Novel Regulator of Epithelial Restitution.

Increasingly, the ß-galactoside binding lectins, termed galectins, are being recognized as critical regulators of cell function and organismal homeostasis. Within the context of the mucosal surface, galectins are established regulators of innate and adaptive immune responses, microbial populations, and several critical epithelial functions, including cell migration, proliferation, and response to injury. However, given their complex tissue distribution and expression patterns, their role within specific processes remains poorly understood.

Gut-Resident Lactobacilli Activate Hepatic Nrf2 and Protect Against Oxidative Liver Injury.

Many studies have suggested a role for gut-resident microbes (the "gut microbiome") in modulating host health; however, the mechanisms by which they impact systemic physiology remain largely unknown. In this study, metabolomic and transcriptional profiling of germ-free and conventionalized mouse liver revealed an upregulation of the Nrf2 antioxidant and xenobiotic response in microbiome-replete animals. Using a Drosophila-based screening assay, we identified members of the genus Lactobacillus capable of stimulating Nrf2.

Lactococcus lactis Subspecies cremoris Elicits Protection Against Metabolic Changes Induced by a Western-Style Diet.

Background & Aims: A Western-style diet, which is high in fat and sugar, can cause significant dyslipidemia and nonalcoholic fatty liver disease; the diet has an especially strong effect in women, regardless of total calorie intake. Dietary supplementation with beneficial microbes might reduce the detrimental effects of a Western-style diet. We assessed the effects of Lactococcus lactis subspecies (subsp) cremoris on weight gain, liver fat, serum cholesterol, and insulin resistance in female mice on a high-fat, high-carbohydrate diet.

The Sweet-Side of Leukocytes: Galectins as Master Regulators of Neutrophil Function.

Among responders to microbial invasion, neutrophils represent one of the earliest and perhaps most important factors that contribute to initial host defense. Effective neutrophil immunity requires their rapid mobilization to the site of infection, which requires efficient extravasation, activation, chemotaxis, phagocytosis, and eventual killing of potential microbial pathogens. Following pathogen elimination, neutrophils must be eliminated to prevent additional host injury and subsequent exacerbation of the inflammatory response.

Anemia induces gut inflammation and injury in an animal model of preterm infants.

Background: While very low birth weight (VLBW) infants often require multiple red blood cell transfusions, efforts to minimize transfusion-associated risks have resulted in more restrictive neonatal transfusion practices. However, whether restrictive transfusion strategies limit transfusions without increasing morbidity and mortality in this population remains unclear. Recent epidemiologic studies suggest that severe anemia may be an important risk factor for the development of necrotizing enterocolitis (NEC).

Lactococcus Lactis Subsp. cremoris Is an Efficacious Beneficial Bacterium that Limits Tissue Injury in the Intestine.

The use of beneficial bacteria to promote health is widely practiced. However, experimental evidence corroborating the efficacy of bacteria promoted with such claims remains limited. We address this gap by identifying a beneficial bacterium that protects against tissue damage and injury-induced inflammation in the gut.

VopA Is a Potent Inhibitor of Cell Migration and Apoptosis in the Intestinal Epithelium of .

Animal models have played a key role in providing an understanding of the mechanisms that govern the pathophysiology of intestinal diseases. To expand on the repertoire of organisms available to study enteric diseases, we report on the use of the model to identify a novel function of an effector protein secreted by , which is an enteric pathogen found in contaminated seafood. During pathogenesis, secretes effector proteins that usurp the host's innate immune signaling pathways, thus allowing the bacterium to evade detection by the innate immune system.

Proteomic analysis of microbial induced redox-dependent intestinal signaling.

Intestinal homeostasis is regulated in-part by reactive oxygen species (ROS) that are generated in the colonic mucosa following contact with certain lactobacilli. Mechanistically, ROS can modulate protein function through the oxidation of cysteine residues within proteins. Recent advances in cysteine labeling by the Isotope Coded Affinity Tags (ICATs) technique has facilitated the identification of cysteine thiol modifications in response to stimuli.

Organic Solute Transporter α-β Protects Ileal Enterocytes From Bile Acid-Induced Injury.

Background & Aims: Ileal bile acid absorption is mediated by uptake via the apical sodium-dependent bile acid transporter (ASBT), and export via the basolateral heteromeric organic solute transporter α-β (OSTα-OSTβ). In this study, we investigated the cytotoxic effects of enterocyte bile acid stasis in mice, including the temporal relationship between intestinal injury and initiation of the enterohepatic circulation of bile acids.

Methods: Ileal tissue morphometry, histology, markers of cell proliferation, gene, and protein expression were analyzed in male and female wild-type and mice at postnatal days 5, 10, 15, 20, and 30.

Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall.

Objective: We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient's own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval.

Approach: We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory.