Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain.

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes anteriorly past the left.

Preservation of Cardiac Xenografts in a Model of Infant Human Cardiac Transplantation.

Introduction: There is no standard protocol for management of organ preservation for orthotopic, life-sustaining cardiac xenotransplantation, particularly for hearts from pediatric sized donors. Standard techniques and solutions successful in human allotransplantation are not viable. We theorized that a solution commonly used in reparative cardiac surgery in human children would suffice by exploiting the advantages inherent to xenotransplantation, namely the ability to reduce organ ischemic times by co-locating the donor and recipient.

Early Results of an Infant Model of Orthotopic Cardiac Xenotransplantation.

Background: Genetically engineered porcine hearts may have an application for infants in need of a bridge to cardiac allotransplantation. The current animal model that resulted in 2 human applications has been validated in adult non-human primates only. We sought to create an infant animal model of life sustaining cardiac xenotransplantation to understand limitations specific to this age group.

Application of Microsponge Drug Platform to Enhance Methotrexate Administration in Rheumatoid Arthritis Therapy.

Background/objectives: This study aimed to develop a novel nanotechnological slow-release drug delivery platform based on hyaluronic acid Microsponge (MSP) for the subcutaneous administration of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). RA is a chronic autoimmune disease characterized by joint inflammation and damage, while MTX is a common disease-modifying antirheumatic drug (DMARD), the conventional use of which is limited by adverse effects and the lack of release control.

Methods: MSP were synthesized as freeze-dried powder to increase their stability and allow for a facile reconstitution prior to administration and precise MTX dosing.

Diet therapy abates mutant APC and KRas effects by reshaping plasma membrane cholesterol nanodomains.

Cholesterol-enriched plasma membrane domains are known to serve as signaling platforms in a diverse array of cellular processes. However, the link between cholesterol homeostasis and mutant APC-KRas-associated colorectal tumorigenesis remains to be established. Thus, we investigated the impact of Apc-Kras on (i) colonocyte plasma membrane cholesterol homeostasis, order, and receptor nanoclustering, (ii) colonocyte cell proliferation, and (iii) whether these effects are modulated by select membrane active dietaries (MADs).

Long term impacts of early social environment on chimpanzee white matter.

Early adverse rearing conditions are known to have deleterious consequences on social behavior, cognition, and brain development of both human and nonhuman primates. We analyzed archival diffusion tensor imaging (DTI) data from mother- (MR) or nursery-reared (NR) chimpanzees and used support vector machine learning to determine whether we could retrospectively classify chimpanzees as MR or NR based on white matter fractional anisotropy (FA) decades after their rearing experiences. A significant proportion of chimpanzees were correctly classified as MR and NR based on white matter fractional anisotropy (76.

The primate gut microbiota contributes to interspecific differences in host metabolism.

Because large brains are energetically expensive, they are associated with metabolic traits that facilitate energy availability across vertebrates. However, the biological underpinnings driving these traits are not known. Given its role in regulating host metabolism in disease studies, we hypothesized that the gut microbiome contributes to variation in normal cross-vertebrate species differences in metabolism, including those associated with the brain's energetic requirements.

Fungal symbiont transmitted by free-living mice promotes type 2 immunity.

The gut mycobiota is crucial for intestinal homeostasis and immune function. Yet its variability and inconsistent fungal colonization of laboratory mice hinders the study of the evolutionary and immune processes that underpin commensalism. Here, we show that Kazachstania pintolopesii is a fungal commensal in wild urban and rural mice, with an exceptional ability to colonize the mouse gastrointestinal tract and dominate the gut mycobiome.

Serial 'deep-sampling' PCR of fragmented DNA reveals the wide range of burden among chronically infected hosts and allows accurate monitoring of parasite load following treatment.

Infection with the protozoan parasite is generally well-controlled by host immune responses, but appears to be rarely eliminated. The resulting persistent, low-level infection results in cumulative tissue damage with the greatest impact generally in the heart in the form of chagasic cardiomyopathy. The relative success in immune control of infection usually averts acute phase death but has the negative consequence that the low-level presence of in hosts is challenging to detect unequivocally.

ECG Features in Orthotopic Cardiac Xenotransplantation: Comparisons With Published Literature.

Introduction: Although there is a plethora of literature on electrocardiographic changes following cardiac allotransplantation, there is little in the field of cardiac xenotransplantation. The only published literature to date is that of the first pig-to-human cardiac xenotransplantation. Here we take a close look at the electrocardiographic parameters in four non-human primate recipients of orthotopic cardiac xenotransplantation to develop baseline metrics for comparison.

An antimicrobial blue light prototype device controls infected wounds in a preclinical porcine model.

We developed a translational prototype antimicrobial blue light (ABL) device for treating skin wounds with ABL. Partial-thickness surgical wounds were created in live swine, an animal whose skin is considered the most like human skin, then heavily contaminated and left untreated for 24 hours with methicillin-resistant Staphylococcus aureus (MRSA). ABL treatment stabilized and reduced MRSA infection by greater than four orders of magnitude (>99.

Sex-dependent differences in hematopoietic stem cell aging and leukemogenic potential.

Sex influences many biological outcomes, but how sex affects hematopoietic stem cell (HSC) aging and hematological disorders is poorly understood. The widespread use of young animal models to study age-related diseases further complicates these matters. Using aged and long-lived BALB/c mouse models, we discovered that aging mice exhibit sex-dependent disparities, mirroring aging humans, in developing myeloid skewing, anemia, and leukemia.

An autonomous implantable device for the prevention of death from opioid overdose.

Opioid overdose accounts for nearly 75,000 deaths per year in the United States, now a leading cause of mortality among young people aged 18 to 45 years. At overdose levels, opioid-induced respiratory depression becomes fatal without the administration of naloxone within minutes. Currently, overdose survival relies on bystander intervention, requiring a nearby person to find the overdosed individual and have immediate access to naloxone to administer.

The role of vector-borne pathogens and cardiac Striatin genotype on survival in boxer dogs with arrhythmogenic right ventricular cardiomyopathy.

Introduction/objectives: Risk factors for severe disease in boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC) are not well understood. This study's objective was to determine whether Striatin genotype or canine vector-borne pathogen (CVBP) exposure/infection in boxer dogs with ARVC was associated with disease severity or survival.

Animals: Sixty-four client-owned, adult boxer dogs with ARVC were included in the study.

Implementation of automated cognitive testing systems for socially housed rhesus (Macaca mulatta) and squirrel (Saimiri spp.) monkeys: Age differences in learning.

Utilizing Automated Cognitive Testing Systems (ACTS) with group-housed nonhuman primates offers a number of advantages over manual testing and computerized testing of singly housed subjects. To date, ACTS usage has been limited to great apes or African monkeys. Here, we detail what we have learned while implementing ACTS with socially housed squirrel monkeys and rhesus macaques and provide information about the training process.

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus.

Peripheral-derived regulatory T cells contribute to tumor-mediated immune suppression in a nonredundant manner.

Identifying tumor-mediated mechanisms that impair immunity is instrumental for the design of new cancer therapies. Regulatory T cells (Tregs) are a key component of cancer-derived immune suppression; however, these lymphocytes are necessary to prevent systemic autoimmunity in mice and humans, and thus, direct targeting of Tregs is not a clinical option for cancer patients. We have previously demonstrated that excising transcription factor Kruppel-like factor 2 () within the T cell lineage blocks the generation of peripheral-derived Tregs (pTregs) without impairing production of thymic-derived Tregs.

The uniqueness of human vulnerability to brain aging in great ape evolution.

Aging is associated with progressive gray matter loss in the brain. This spatially specific, morphological change over the life span in humans is also found in chimpanzees, and the comparison between these great ape species provides a unique evolutionary perspective on human brain aging. Here, we present a data-driven, comparative framework to explore the relationship between gray matter atrophy with age and recent cerebral expansion in the phylogeny of chimpanzees and humans.