Allogeneic and xenogeneic lymphoid reconstitution in a severe combined immunodeficient pig: A preclinical model for intrauterine hematopoietic transplantation.

Mice with severe combined immunodeficiency are commonly used as hosts of human cells. Size, longevity, and physiology, however, limit the extent to which immunodeficient mice can model human systems. To address these limitations, we generated immunodeficient pigs and demonstrate successful engraftment of SLA mismatched allogeneic D42 fetal liver cells, tagged with pH2B-eGFP, and human CD34 hematopoietic stem cells after cell transplantation.

The use of autologous skeletal muscle progenitor cells for adjunctive treatment of presumptive urethral sphincter mechanism incompetence in female dogs.

Background: Urethral sphincter mechanism incompetence (USMI) is a common problem in female dogs, but some dogs fail to achieve continence with standard treatment. Urethral submucosal injection of autologous skeletal muscle progenitor cells (skMPCs) previously has been shown to restore urethral function in a canine model of USMI.

Hypothesis/objective: To determine if urethral submucosal injection of skMPC alters continence in dogs with USMI that had previously failed standard medical management.

LGR5 is a conserved marker of hair follicle stem cells in multiple species and is present early and throughout follicle morphogenesis.

Hair follicle stem cells are key for driving growth and homeostasis of the hair follicle niche, have remarkable regenerative capacity throughout hair cycling, and display fate plasticity during cutaneous wound healing. Due to the need for a transgenic reporter, essentially all observations related to LGR5-expressing hair follicle stem cells have been generated using transgenic mice, which have significant differences in anatomy and physiology from the human. Using a transgenic pig model, a widely accepted model for human skin and human skin repair, we demonstrate that LGR5 is a marker of hair follicle stem cells across species in homeostasis and development.

Validation of Transgene Expression in Gene-Edited Pigs Using CRISPR Transcriptional Activators.

The use of CRISPR-Cas and RNA-guided endonucleases has drastically changed research strategies for understanding and exploiting gene function, particularly for the generation of gene-edited animal models. This has resulted in an explosion in the number of gene-edited species, including highly biomedically relevant pig models. However, even with error-free DNA insertion or deletion, edited genes are occasionally not expressed and/or translated as expected.

Premenstrual dysphoric disorder in women with epilepsy: relationships to potential epileptic, antiepileptic drug, and reproductive endocrine factors.

The purpose of this prospective observational investigation was to determine whether the frequency of premenstrual dysphoric disorder (PMDD) and the severity of PMDD symptoms differ between women with epilepsy and controls without epilepsy and whether there exists a relationship between the severity of PMDD symptoms and some epileptic, antiepileptic drug, and reproductive endocrine features. The results suggest that epilepsy, antiepileptic drug levels, ovulatory status, and hormone levels and ratios may all influence PMDD in women with epilepsy. PMDD severity scores may be greater in people with right-sided than in those with left-sided epilepsy, and in people with temporal than in those with nontemporal epileptic foci.

Differential effects of Phe19 and Phe20 on fibril formation by amyloidogenic peptide A beta 16-22 (Ac-KLVFFAE-NH2).

The sequence KLVFFAE (A beta 16-22) in Alzheimer's beta-amyloid is thought to be a core beta-structure that could act as a template for folding other parts of the polypeptide or molecules into fibrillar assemblies rich in beta-sheet. To elucidate the mechanism of the initial folding process, we undertook combined X-ray fiber/powder diffraction and infrared (IR) spectroscopy to analyze lyophilized A beta 16-22 and solubilized/dried peptide containing nitrile probes at F19 and/or F20. Solubilized/dried wild-type (WT) A beta 16-22 and the peptide containing cyanophenylalanine at F19 (19CN) or at F20 (20CN) gave fiber patterns consistent with slab-like beta-crystallites that were cylindrically averaged around the axis parallel to the polypeptide chain direction.

Fiber diffraction as a screen for amyloid inhibitors.

Targeting the initial formation of amyloid assemblies is a preferred approach to therapeutic intervention in amyloidoses, which include such diseases as Alzheimer's, Parkinson's, Huntington's, etc., as the early-stage, oligomers that form before the development of beta-conformation-rich fibers are thought to be toxic. X-ray patterns from amyloid assemblies always show two common intensity maxima: one at 4.