Single-cell and bulk transcriptional profiling of mouse ovaries reveals novel genes and pathways associated with DNA damage response in oocytes.

Immature oocytes enclosed in primordial follicles stored in female ovaries are under constant threat of DNA damage induced by endogenous and exogenous factors. Checkpoint kinase 2 (CHEK2) is a key mediator of the DNA damage response in all cells. Genetic studies have shown that CHEK2 and its downstream targets, p53 and TAp63, regulate primordial follicle elimination in response to DNA damage, however the mechanism leading to their demise is still poorly characterized.

In Vitro and In Vivo Evaluation of Bioactive Compounds from Berries for Wound Healing.

Managing chronic wounds can be challenging and have a major impact on the quality of life, due to the significant financial and psychosocial burden on the affected individuals and their families. The need for safe, effective, and cost-efficient wound healing remedies has led to the identification of naturally occurring bioactive compounds with positive effects on tissue regeneration. Berry fruits are a promising source of such compounds and may therefore prove distinctively beneficial.

The Eye as the Window to the Heart: Optical Coherence Tomography Angiography Biomarkers as Indicators of Cardiovascular Disease.

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism.

Endothelial IL17RD promotes Western diet-induced aortic myeloid cell infiltration.

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor) belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent leukocyte adhesion.

Color-Flu Fluorescent Reporter Influenza A Viruses Allow for In Vivo Studies of Innate Immune Function in Zebrafish.

Influenza virus infection can cause severe respiratory disease and is estimated to cause millions of illnesses annually. Studies on the contribution of the innate immune response to influenza A virus (IAV) to viral pathogenesis may yield new antiviral strategies. Zebrafish larvae are useful models for studying the innate immune response to pathogens, including IAV, in vivo.

High-throughput drug screen identifies calcium and calmodulin inhibitors that reduce JCPyV infection.

JC polyomavirus (JCPyV) is a nonenveloped, double-stranded DNA virus that infects the majority of the population. Immunocompetent individuals harbor infection in their kidneys, while severe immunosuppression can result in JCPyV spread to the brain, causing the neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Due to a lack of approved therapies to treat JCPyV and PML, the disease results in rapid deterioration, and is often fatal.

Standardization of zebrafish drug testing parameters for muscle diseases.

Skeletal muscular diseases predominantly affect skeletal and cardiac muscle, resulting in muscle weakness, impaired respiratory function and decreased lifespan. These harmful outcomes lead to poor health-related quality of life and carry a high healthcare economic burden. The absence of promising treatments and new therapies for muscular disorders requires new methods for candidate drug identification and advancement in animal models.

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

Introduction: MODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models.

Methods: We created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age.

Genetic context drives age-related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits.

The disconnection of neuronal circuitry through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through maintenance or vulnerability of synaptic connections remains unknown. Previous work using rodent and primate models leveraged various techniques to imply that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus.

Centromere innovations within a mouse species.

Mammalian centromeres direct faithful genetic inheritance and are typically characterized by regions of highly repetitive and rapidly evolving DNA. We focused on a mouse species, that we found has evolved to house centromere-specifying centromere protein-A (CENP-A) nucleosomes at the nexus of a satellite repeat that we identified and termed π-satellite (π-sat), a small number of recruitment sites for CENP-B, and short stretches of perfect telomere repeats. One chromosome, however, houses a radically divergent centromere harboring ~6 mega-base pairs of a homogenized π-sat-related repeat, π-sat, that contains >20,000 functional CENP-B boxes.

Multi-spectral Fluorescent Reporter Influenza A Viruses Allow for Studies of Innate Immune Function in Zebrafish.

Influenza virus infection can cause severe respiratory disease and is estimated to cause millions of illnesses annually. Studies of the contribution of the innate immune response to influenza A virus (IAV) to viral pathogenesis may yield new antiviral strategies. Zebrafish larvae are useful models to study the innate immune response to pathogens, including IAV, .

Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.

To our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention.

Notch Signaling Regulates Mouse Perivascular Adipose Tissue Function via Mitochondrial Pathways.

Perivascular adipose tissue (PVAT) regulates vascular function by secreting vasoactive substances. In mice, Notch signaling is activated in the PVAT during diet-induced obesity, and leads to the loss of the thermogenic phenotype and adipocyte whitening due to increased lipid accumulation. We used the Adiponectin-Cre () strain to activate a ligand-independent Notch1 intracellular domain transgene () to drive constitutive Notch signaling in the adipose tissues ().

A CRISPR Screen Identifies the E3 Ubiquitin Ligase Rfwd2 as a Negative Regulator of Glucose Uptake in Brown Adipocytes.

Brown adipose tissue activation increases energy expenditure and has been shown to improve glucose tolerance, making it a promising target for the treatment of obesity and type 2 diabetes. Brown adipocytes differentiate into cells with multilocular lipid droplets, which can efficiently absorb and oxidize glucose; however, the mechanisms regulating these processes are not completely understood. We conducted a genome-wide loss-of-function screen using a CRISPR-based approach to identify genes that promote or inhibit adipogenesis and glucose uptake in brown adipocytes.

Cardiovascular sex-differences: insights via physiology-based modeling and potential for noninvasive sensing via ballistocardiography.

In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal.

Homocysteine Reduction for Stroke Prevention: Regarding the Recent AHA/ASA 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.

Reduction of secondary ischemic stroke risk following an initial stroke is an important goal. The 2021 Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack assembles opportunities for up to 80% secondary stroke reduction. Homocysteine reduction was not included in the recommendations.

Removal of Free Liquid Layer from Liquid-Infused Catheters Reduces Silicone Loss into the Environment while Maintaining Adhesion Resistance.

Silicone urinary catheters infused with silicone liquid offer an effective alternative to antibiotic coatings, reducing microbial adhesion while decreasing bladder colonization and systemic dissemination. However, loss of free silicone liquid from the surface into the host system is undesirable. To reduce the potential for liquid loss, free silicone liquid was removed from the surface of liquid-infused catheters by either removing excess liquid from fully infused samples or by partial infusion.

Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models.

The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for a century. However, laboratory mice capture a narrow subset of the genetic variation found in wild mouse populations. This consideration inherently restricts the scope of potential discovery in laboratory models and narrows the pool of potentially identified phenotype-associated variants and pathways.

Ex-chitin-g news on drug-induced fungal epitope unmasking.

The microbial cell wall is an essential cellular organelle commonly targeted by antimicrobials. It is also a battleground of innate immune recognition where microbes can evade immune recognition by masking essential cell wall components. A recent study (A.

Purification of functional mouse skeletal muscle mitochondria using percoll density gradient centrifugation.

Objective: Our goal was to isolate purified mitochondria from mouse skeletal muscle using a Percoll density gradient and to assess bioenergetic function and purity via Seahorse Extracellular Flux (XF) Analyses and mass spectrometry.

Results: Mitochondria isolated from murine quadriceps femoris skeletal muscle using a Percoll density gradient method allowed for minimally contaminated preparations with time from tissue harvest to mitochondrial isolation and quantification in about 3-4 h. Percoll purification from 100 to 200 mg fresh tissue yielded ~ 200-400 ug protein.

Primary cilia are critical for tracheoesophageal septation.

Introduction: Primary cilia play pivotal roles in the patterning and morphogenesis of a wide variety of organs during mammalian development. Here we examined murine foregut septation in the cobblestone mutant, a hypomorphic allele of the gene encoding the intraflagellar transport protein IFT88, a protein essential for normal cilia function.

Results: We reveal a crucial role for primary cilia in foregut division, since their dramatic decrease in cilia in both the foregut endoderm and mesenchyme of mutant embryos resulted in a proximal tracheoesophageal septation defects and in the formation of distal tracheo(broncho)esophageal fistulae similar to the most common congenital tracheoesophageal malformations in humans.

Control of hippocampal synaptic plasticity by microglia-dendrite interactions depends on genetic context in mouse models of Alzheimer's disease.

Introduction: Human data suggest susceptibility and resilience to features of Alzheimer's disease (AD) such as microglia activation and synaptic dysfunction are under genetic control. However, causal relationships between these processes, and how genomic diversity modulates them remain systemically underexplored in mouse models.

Methods: AD-vulnerable hippocampal neurons were virally labeled in inbred (C57BL/6J) and wild-derived (PWK/PhJ) APP/PS1 and wild-type mice, and brain microglia depleted from 4 to 8 months of age.

Variation in the CENP-A sequence association landscape across diverse inbred mouse strains.

Centromeres are crucial for chromosome segregation, but their underlying sequences evolve rapidly, imposing strong selection for compensatory changes in centromere-associated kinetochore proteins to assure the stability of genome transmission. While this co-evolution is well documented between species, it remains unknown whether population-level centromere diversity leads to functional differences in kinetochore protein association. Mice (Mus musculus) exhibit remarkable variation in centromere size and sequence, but the amino acid sequence of the kinetochore protein CENP-A is conserved.