Measuring excitation-inhibition balance through spectral components of local field potentials.

The balance between excitation and inhibition is critical to brain functioning, and dysregulation of this balance is a hallmark of numerous psychiatric conditions. Measuring this excitation-inhibition (E:I) balance has remained difficult, but theoretical models have proposed that characteristics of local field potentials (LFP) may provide an accurate proxy. To establish a conclusive link between LFP and E:I balance, we recorded single units and LFP from the prefrontal cortex (mPFC) of rats during decision making.

Bona fide dendritic cells are pivotal precursors for osteoclasts.

Objectives: Osteoclasts (OCs) are myeloid-derived multinucleated cells uniquely able to degrade bone. However, the exact nature of their myeloid precursors is not yet defined.

Methods: CD11c-diphtheria toxin receptor (CD11cDTR) transgenic mice were treated with diphtheria toxin (DT) or phosphate buffered saline (PBS) during serum transfer arthritis (STA) and human tumour necrosis factor transgenic (hTNFtg) arthritis and scored clinically and histologically.

Differential processing of decision information in subregions of rodent medial prefrontal cortex.

Decision-making involves multiple cognitive processes requiring different aspects of information about the situation at hand. The rodent medial prefrontal cortex (mPFC) has been hypothesized to be central to these abilities. Functional studies have sought to link specific processes to specific anatomical subregions, but past studies of mPFC have yielded controversial results, leaving the precise nature of mPFC function unclear.

Design and synthesis of astatinated benzothiazole compounds for their potential use in Targeted Alpha Therapy (TAT) strategies to treat Alzheimer's disease-associated amyloid plaques.

Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer.

Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration.

Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity.

Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer.

Inflammatory bowel disease (IBD) is a chronic life-long inflammatory disease affecting almost 2 million Americans. Although new biologic therapies have been developed, the standard medical treatment fails to selectively control the dysregulated immune pathways involved in chronic colonic inflammation. Further, IBD patients with uncontrolled colonic inflammation are at a higher risk for developing colorectal cancer (CRC).

Culturable Microbial Population From the Upper Respiratory Tract of 1,010 Clinically Healthy Horses in Southern Brazil.

Microbiological diagnosis of equine respiratory infections is essential for disease management. However, reliable diagnosis can be a challenge due to colonization of the upper respiratory tract (URT) by a diverse microbial population, and because there is a lack of studies with samples from healthy animals. Aiming to guide adequate URT culture, this work reports culturable microbial population from the URT of 1,010 apparently healthy horses from 341 farms in Southern Brazil and identifies the putative presence of pathogenic microorganisms.

Interleukin-1β secretion induced by mucosa-associated gut commensal bacteria promotes intestinal barrier repair.

The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal isolate, GDAR2-2, that protects mice from infection and dextran sulfate sodium-induced colitis.

T cells in harmony: Aligning the TCR repertoire pool to identify microbiota recognizing T cells.

Microbiota-specific T cell responses have been identified for select microbes, but individual T cell receptor repertoire differences make characterizing responses across populations difficult. In this issue of Immunity, Muschaweck et al. establish a system allowing for reproducible responses between individual mice, a powerful tool for characterizing microbiota directed immunity.

Thymic development of gut-microbiota-specific T cells.

Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection. Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen while limiting inflammatory anti-commensal responses. Antigen-specific recognition of intestinal microorganisms by T cells has previously been described.

Healthy Intestinal Function Relies on Coordinated Enteric Nervous System, Immune System, and Epithelium Responses.

During both health and disease, a coordinated response between the epithelium, immune system, and enteric nervous system is required for proper intestinal function. While each system responds to a number of common stimuli, their coordinated responses support digestion as well as responses and recovery following injury or pathogenic infections. In this review, we discuss how individual responses to common signals work together to support these critical functions.

Serologic evidence of West Nile virus and Saint Louis encephalitis virus in horses from Southern Brazil.

Flaviviruses as West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilhéus virus (ILHV), and Rocio virus (ROCV) are previously reported in different Brazilian regions, but studies in Southern Brazil are still scarce. To improve the information regarding flaviviruses in Southern Brazil, horse serum samples were analyzed using RT-qPCR and a commercial ELISA-Ab against WNV followed by PRNT. All 1000 samples analyzed by real-time RT-PCR resulted negative.

Potential roles of the rodent medial prefrontal cortex in conflict resolution between multiple decision-making systems.

Mammalian decision-making is mediated by the interaction of multiple, neurally and computationally separable decision systems. Having multiple systems requires a mechanism to manage conflict and converge onto the selection of singular actions. A long history of evidence has pointed to the prefrontal cortex as a central component in processing the interactions between distinct decision systems and resolving conflicts among them.

Adherent-invasive E. coli metabolism of propanediol in Crohn's disease regulates phagocytes to drive intestinal inflammation.

Adherent-invasive E. coli (AIEC) are enriched in the intestinal microbiota of patients with Crohn's disease (CD) and promote intestinal inflammation. Yet, how AIEC metabolism of nutrients impacts intestinal homeostasis is poorly defined.

Intestinal Microbes in Autoimmune and Inflammatory Disease.

Autoimmune diseases and chronic inflammatory disorders are characterized by dysregulated immune responses resulting in excessive and uncontrolled tissue inflammation. Multiple factors including genetic variation, environmental stimuli, and infection are all thought to contribute to continued inflammation and pathology. Current evidence supports the microbiota as one such factor with emerging data linking commensal organisms to the onset and progression of disease.

Cyclotron Production and Separation of Scandium Radionuclides from Natural Titanium Metal and Titanium Dioxide Targets.

Theranostic strategies involve select radionuclides that allow diagnostic imaging and tailored radionuclide therapy in the same patient. An example of a Food and Drug Administration-approved theranostic pair is the Ga- and Lu-labeled DOTATATE peptides, which are used to image neuroendocrine tumors, predict treatment response, and treat disease. However, when using radionuclides of 2 different elements, differences in the pharmacokinetic and pharmacodynamic profile of the agent can occur.

Spatial encoding in primate hippocampus during free navigation.

The hippocampus comprises two neural signals-place cells and θ oscillations-that contribute to facets of spatial navigation. Although their complementary relationship has been well established in rodents, their respective contributions in the primate brain during free navigation remains unclear. Here, we recorded neural activity in the hippocampus of freely moving marmosets as they naturally explored a spatial environment to more explicitly investigate this issue.

Intestinal microbes direct CXCR1 cells to balance intestinal immunity.

Intestinal damage driven by unrestricted immune responses against the intestinal microbiota can lead to the development of inflammatory diseases including inflammatory bowel disease. How such breakdown in tolerance occurs alongside the mechanisms to reinforce homeostasis with the microbiota are a focus of many studies. Our recent work demonstrates coordinated interactions between intact microbiota and CXCR1 expressing intestinal antigen presenting cells (APCs) that limits T helper 1 cell responses and promotes differentiation of regulatory T cells (Treg) against intestinal antigens including pathogens, soluble proteins and the microbiota itself.

Cigarette smoke-induced reduction of C1q promotes emphysema.

Alteration of innate immune cells in the lungs can promote loss of peripheral tolerance that leads to autoimmune responses in cigarette smokers. Development of autoimmunity in smokers with emphysema is also strongly linked to the expansion of autoreactive T helper (Th) cells expressing interferon gamma (Th1), and interleukin 17A (Th17). However, the mechanisms responsible for enhanced self-recognition and reduced immune tolerance in smoker with emphysema remain less clear.

Cigarette Smoke Induces Intestinal Inflammation via a Th17 Cell-Neutrophil Axis.

Epidemiological evidence finds cigarette smoking is a common risk factor for a number of diseases, not only in the lung but also in other tissues, such as the gastrointestinal tract. While it is well-documented that smoking directly drives lung inflammatory disease, how it promotes disease in peripheral tissues is incompletely understood. In this study, we utilized a mouse model of short-term smoke exposure and found increased Th17 cells and neutrophilia in the lung as well as in the circulation.

Skin IL-17-Producing T Cells Support Repair 2!

In a recent study, Harrison et al. (Science 2019;363;eaat6280) report that RORγt-expressing skin commensal-specific T cells rapidly respond to tissue wounding by producing type 2 T helper cell (Th2) cytokines in mice. The cells constitutively coexpress GATA-3 and type 2 cytokine mRNAs that are translated after injury.

Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis.

Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A is not known. Here, we found that adherent IBD-associated microbiota induced TL1A release from CX3CR1 mononuclear phagocytes (MNPs).