Vagal Nerve Paralysis in a Cow

The case described illustrates a possible syndrome due to paralysis of vagal nerve branches in cattle

The Carboxyl-Terminal Amino Acids Render Pro-Human LC3B Migration Similar to Lipidated LC3B in SDS-PAGE

LC3 is widely used marker for macroautophagy assays. After translation pro-LC3 is processed by Atg4 to expose C-terminal glycine residue for downstream conjugation reactions to accomplish the conversion of LC3-I to LC3-II. SDS-PAGE based Western blot (Wb) is generally utilized to quantify LC3-II levels where the LC3-I band migrates slower than LC3-II. We found that pro-human LC3B migrated at similar rate as LC3B-II in SDS-PAGE. The carboxyl-terminal five amino acids, particularly Lysine122 and Leucine123 of human LC3B play a major role in the faster migration of unprocessed LC3B, rendering it indistinguishable from LC3B-II in Wb assays. The unique faster migration of unprocessed LC3B than LC3B-I is also revealed in mouse LC3B, rat LC3B and rat LC3 but not in human LC3C. Our findings for the first time define pro-LC3 migration patterns for LC3 family member from human, mouse and rat species in SDS-PAGE. These findings provide a reference for pro-LC3 band patterns when Atg4 function is inhibited. © 2013 Wang et al

Toll-Like Receptors in Hepatic Ischemia/Reperfusion and Transplantation

The family of Toll-like receptors (TLRs) function as pattern-recognition receptors (PRRs) that respond to a myriad of highly conserved ligands. These substrates include pathogen-associated molecular patterns (PAMPs) for the recognition of invading pathogens, as well as damage-associated molecular patterns (DAMPs) for the recognition of endogenous tissue injury. While the functions of TLRs are diverse, they have received much attention for their roles in ischemia/reperfusion (I/R) injury of the liver and other organs. The TLRs play central roles in sensing tissue damage and activating the innate immune system following I/R. Engagement of TLRs by endogenous DAMPs activates proinflammatory signaling pathways leading to the production of cytokines, chemokines and further release of endogenous danger signals. This paper focuses on the most recent findings regarding TLR family members in hepatic I/R injury and transplantation

Geometric Control of YAP-dependent Mechanotransduction: A Proposed Model

The Billiar lab is interested in the interplay between mechanical tension and programmed cell death (namely, apoptosis) in cells growing on micro-contact printed aggregates. The Billiar lab uses a bioinspired hydrogel to develop an in vitro model for mechanosensitive signaling in mammalian cells. The micro-contact printed cell aggregates experience a loss of tensional homeostasis at the center of the aggregates, which results in selective cell death at the center, but not periphery of the aggregates, followed by calcification, similar to excised diseased aortic valves. However, the subcellular mechanisms responsible for transducing the mechanical cues from the loss of tensional homeostasis to pro-apoptotic signaling have yet to be elucidated; the Billiar lab is interested in finding this link. Mechanotransduction is the functional link between mechanical cues and the consequent subcellular biochemical response.1 Cells sense and respond to their physical surroundings via cell-cell junctions, cell-matrix adhesions, and intracellular actin networks.1 For example, in epithelial cells, restriction of cell growth to spatially patterned circular arrays leads to (1) increased proliferation and (2) higher tractional stresses at the periphery than at the center.2-3 Proliferation at the periphery of these circular cell aggregates is YAP-dependent, with nuclear localization of YAP at the periphery.4 Transcriptional co-activator YAP is (1) a nuclear relay of mechanical signals,5 (2) the main transcriptional effector of the Hippo pathway,6 and (3) involved in both proliferation (via TEAD promoter) and apoptosis (via p73 promoter).7 Cell competition is an apoptosis-dependent cell communication phenomenon based on cell fitness comparisons, and which creates “loser” cells that die via apoptosis and “winner” cells that survive.8-9 For example, co-culture of TEAD-activity-manipulated fibroblasts with WT induces cell competition, in which cells with higher TEAD activity “won,” and cells with lower TEAD activity “lost” (underwent apoptosis).10 Hypothesis: Culture of fibroblasts in geometrically constrained, circular cell aggregates induces cell competition via the formation of “winner” and “loser” cell populations due to differences in tensional homeostasis experienced at the periphery vs. center of the aggregates

Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4

The bone and immune systems are closely interconnected. The immediate inflammatory response after fracture is known to trigger a healing cascade which plays an important role in bone repair. Toll-like receptor 4 (TLR4) is a member of a highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate the systemic inflammatory response induced by exposed bone components during long-bone fracture. Here we tested the hypothesis that TLR4 activation affects the healing of calvarial defects. A 1.8 mm diameter calvarial defect was created in wild-type (WT) and TLR4 knockout (TLR4-/-) mice. Bone healing was tested using radiographic, histologic and gene expression analyses. Radiographic and histomorphometric analyses revealed that calvarial healing was accelerated in TLR4-/- mice. More bone was observed in TLR4-/- mice compared to WT mice at postoperative days 7 and 14, although comparable healing was achieved in both groups by day 21. Bone remodeling was detected in both groups on postoperative day 28. In TLR4-/- mice compared to WT mice, gene expression analysis revealed that higher expression levels of IL-1β, IL-6, TNF-α,TGF-β1, TGF-β3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (≤ postoperative 4 days); while higher expression levels of IL-1β and lower expression levels of VEGF, RANK, RANKL and OPG were detected at late time points (> postoperative 4 days). This study provides evidence of accelerated bone healing in TLR4-/- mice with earlier and higher expression of inflammatory cytokines and with increased osteoclastic activity. Further work is required to determine if this is due to inflammation driven by TLR4 activation. © 2012 Wang et al

Therapeutic Antioxidant Medical Gas

Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties