Biology subjects

Veith, A.

Publications and source records attributed to Veith, A..

5 recordsLinked to original sources

bioRxiv2025

Circadian rhythms in sexual behavior and their influence on reproductive outcomes in mice

Circadian clocks coordinate mammalian reproductive physiology, and circadian misalignment (resulting from shift work, jet lag, etc.) is known to impair fertility. Despite the well-established links between clock function and reproductive success, it remains unclear whether male and female mice maintained under standard ad libitum feeding conditions exhibit circadian rhythms in the propensity for sexual behavior, and to what degree such timing influences reproductive outcomes. Using standardized mating paradigms in C57BL/6J mice, we identified a circadian rhythm in sexual behavior in both sexes, with peak sexual activity most often occurring at circadian time (CT) 13-16 and a trough at CT4-7. To test the functional significance of these rhythms, we conducted 1-hour mating trials across four cohorts of C57BL/6J mice with pairs of mice having either aligned (e.g. male CT16 peak and female CT16 peak) or misaligned (e.g. male CT16 peak and female CT4 nadir) sexual behavior phases and monitored mating outcomes via ultrasound. While pregnancies were almost as frequent across all four cohorts, the numbers of live offspring were significantly more frequent when both the male and female mated at their peak phases than when both mice mated at their troughs. Notably, mating specifically during the males behavioral peak increased the likelihood of successful delivery of pups, suggesting that male circadian phase is a key determinant of miscarriage vs successful birth. These findings establish a circadian rhythm in the propensity for sexual behavior under standard feeding and housing conditions and indicate that mating time--particularly relative to the males circadian peak--can influence reproductive success. This insight provides a foundation for translational studies that explore whether intercourse timed to the circadian rhythms of the couple might help to increase fertility chances.

physiology↗

bioRxiv2022

Syndecan-4 Proteoliposomes Enhance Revascularization in a Rabbit Hind Limb Ischemia Model of Peripheral Ischemia

Regenerative therapeutics for treating peripheral arterial disease are an appealing strategy for creating more durable solutions for limb ischemia. In this work, we performed preclinical testing of an injectable formulation of syndecan-4 proteoliposomes combined with growth factors as treatment for peripheral ischemia delivered in an alginate hydrogel. We tested this therapy in an advanced model of hindlimb ischemia in rabbits with diabetes and hyperlipidemia. Our studies demonstrate enhancement in vascularity and new blood vessel growth with treatment with syndecan-4 proteoliposomes in combination with FGF-2 or FGF-2/PDGF-BB. The effects of the treatments were particularly effective in enhancing vascularity in the lower limb with a 2-4 increase in blood vessels in the treatment group in comparison to the control group. In addition, we demonstrate that the syndecan-4 proteoliposomes have stability for at least 28 days when stored at 4{degrees}C to allow transport and use in the hospital environment. In addition, we performed toxicity studies in the mice and found no toxic effects even when injected at high concentration. Overall, our studies support that syndecan-4 proteoliposomes markedly enhance the therapeutic potential of growth factors in the context of disease and may be promising therapeutics for inducing vascular regeneration in peripheral ischemia.

bioengineering↗

bioRxiv2020

A Non-Destructive Method for Quantifying Tissue Vascularity Using Quantitative Deep Learning Image Processing

The quantitative analysis of blood vessel networks is an important component in the understanding and analysis of vascular disease, ischemia, cancer and many other disease states. However, many imaging techniques used for imaging vascular networks are time consuming, prevent further analyses or are technically challenging. Here, we describe a nondestructive technique for imaging the vessels in harvested tissue samples that relatively rapid and effective visualization of in situ vasculature. Furthermore, this technique allows for further analysis of the sample using histochemical staining, immunostaining and other techniques that can be performed on fixed tissue. The method uses ex vivo permeation of the tissue with an iodine solution and micro CT imaging to visualize the vascular network. Using a deep learning algorithm, we trained a convolutional neural network to automatically segment blood vessels from the surrounding tissue for analysis and create a map of the vasculature. While this method cannot achieve the resolution obtainable through destructive techniques, it is a simple and quick method for visualizing and quantifying vascular networks in three dimensions prior to analysis with conventional histological techniques. The global visualization of the three-dimensional vascular network provided by this method gives additional insights into complex changes in the vascular structure and can guide further histological analyses to specific regions of the vascular network. Overall, this method is a simple technique that can be added to most conventional tissue analyses to enhance the quantification and information derived from animal models with vascular network remodeling.

bioengineering↗

bioRxiv2020

Biomechanical Regulation of Breast Cancer Metastasis and Progression

Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysis of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3K{gamma} inhibitor.

cancer biology↗

bioRxiv2018

Mechanobiological Conditioning of Mesenchymal Stem Cells Enhances Therapeutic Angiogenesis by Inducing a Hybrid Pericyte-Endothelial Phenotype

Stem cell therapies have great promise for revolutionizing treatments for cardiovascular disease and other disorders but have not yet achieved their potential due to poor efficacy and heterogeneity in patient response. Here, we used a novel high throughput screening system to optimize the conditioning of mesenchymal stem cells using a combinatorial set of biochemical factors, pharmacological inhibitors and biomechanical forces. Our studies revealed that a combination of specific kinase inhibitors and a complex mechanical strain waveform dramatically increased the population of mesenchymal stem cells that express markers for both pericytes and endothelial cells. These mechanically and pharmacologically conditioned mesenchymal stem cells had superior properties in enhancing endothelial tube formation, production of angiogenic growth factors and induction of angiogenesis following implantation. Overall, our work supports that combinatorial optimization of mechanical conditioning and pharmacological treatments can significantly enhance the regenerative properties of mesenchymal stem cells.

bioengineering↗