Viatorr Stent Migration and Retrieval during Transjugular Intrahepatic Portosystemic Shunt Revision.

Transjugular intrahepatic portosystemic shunt (TIPS) is an important interventional option for the treatment of complications related to cirrhosis and portal hypertension. Emergent TIPS placement can be a life-saving measure in patients with uncontrolled variceal hemorrhage. After TIPS placement, patients may benefit from additional interventions for clinical optimization including stent dilation, stent extension, and embolization of varices.

Surveillance Imaging following Endovascular Aneurysm Repair: State of the Art.

Endovascular aneurysmal repair (EVAR) has become a prominent modality for the treatment of abdominal aortic aneurysm. Surveillance imaging is important for the detection of device-related complications, which include endoleak, structural abnormalities, and infection. Currently used modalities include ultrasound, X-ray, computed tomography, magnetic resonance imaging, and angiography.

SNARE protein SEC22B regulates early embryonic development.

The highly conserved SNARE protein SEC22B mediates diverse and critical functions, including phagocytosis, cell growth, autophagy, and protein secretion. However, these characterizations have thus far been limited to in vitro work. Here, we expand our understanding of the role Sec22b plays in vivo.

miR-142 controls metabolic reprogramming that regulates dendritic cell activation.

DCs undergo metabolic reprogramming from a predominantly oxidative phosphorylation (OXPHOS) to glycolysis to mount an immunogenic response. The mechanism underpinning the metabolic reprogramming remains elusive. We demonstrate that miRNA-142 (miR-142) is pivotal for this shift in metabolism, which regulates the tolerogenic and immunogenic responses of DCs.

Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance.

Maintenance of the regulatory T (Treg) cell pool is essential for peripheral tolerance and prevention of autoimmunity. Integrins, heterodimeric transmembrane proteins consisting of α and β subunits that mediate cell-to-cell and cell-to-extracellular matrix interactions, play an important role in facilitating Treg cell contact-mediated suppression. In this article, we show that integrin activation plays an essential, previously unappreciated role in maintaining murine Treg cell function.

Proteasome activity regulates CD8+ T lymphocyte metabolism and fate specification.

During an immune response, CD8+ T lymphocytes can undergo asymmetric division, giving rise to daughter cells that exhibit distinct tendencies to adopt terminal effector and memory cell fates. Here we show that "pre-effector" and "pre-memory" cells resulting from the first CD8+ T cell division in vivo exhibited low and high rates of endogenous proteasome activity, respectively. Pharmacologic reduction of proteasome activity in CD8+ T cells early during differentiation resulted in acquisition of terminal effector cell characteristics, whereas enhancement of proteasome activity conferred attributes of memory lymphocytes.

A Critical Analysis of the Role of SNARE Protein SEC22B in Antigen Cross-Presentation.

Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8 T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs) established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the in vivo contribution of SEC22B to cross-presentation has not been tested.

Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool.

Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery.

Early transcriptional and epigenetic regulation of CD8 T cell differentiation revealed by single-cell RNA sequencing.

During microbial infection, responding CD8 T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA-sequencing approach and analyzed individual CD8 T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants that controlled the fate specification of CD8 T lymphocytes.

Percutaneous Transhepatic Biliary Drainage Complicated by Bilothorax.

Percutaneous transhepatic biliary drainage (PTBD) is a well-established and safe technique for the management of biliary obstructions and leaks. While approach is variable based on operator preference, patient anatomy, and indications; PTBD is commonly performed via a right-sided intercostal route. With a right-sided approach, pleural complications may be encountered.

Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with phenotypic plasticity that can facilitate the formation of cancer stem cells (CSCs) and contribute to the metastatic cascade. While there is substantial support for the role of EMT in driving cancer cell dissemination, less is known about the intracellular molecular mechanisms that govern formation of CSCs via EMT. Here we show that β2 and β5 proteasome subunit activity is downregulated during EMT in immortalized human mammary epithelial cells.

Regulation of Asymmetric Division by Atypical Protein Kinase C Influences Early Specification of CD8(+) T Lymphocyte Fates.

Naïve CD8(+) T lymphocytes responding to microbial pathogens give rise to effector T cells that provide acute defense and memory T cells that provide long-lived immunity. Upon activation, CD8(+) T lymphocytes can undergo asymmetric division, unequally distributing factors to the nascent daughter cells that influence their eventual fate towards the effector or memory lineages. Individual loss of either atypical protein kinase C (aPKC) isoform, PKCζ or PKCλ/ι, partially impairs asymmetric divisions and increases CD8(+) T lymphocyte differentiation toward a long-lived effector fate at the expense of memory T cell formation.

Osteoprotegerin deficiency results in disruption of posterofrontal suture closure in mice: implications in nonsyndromic craniosynostosis.

Background: Little is known about the role of osteoclasts in cranial suture fusion. Osteoclasts are predominantly regulated by receptor activator of nuclear factor kappa B and receptor activator of nuclear factor kappa B ligand, both of which lead to osteoclast differentiation, activation, and survival; and osteoprotegerin, a soluble inhibitor of receptor activator of nuclear factor kappa B. The authors' work examines the role of osteoprotegerin in this process using knockout technology.

Immunodeficiency and autoimmune enterocolopathy linked to NFAT5 haploinsufficiency.

The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome.

Regulation of asymmetric division and CD8+ T lymphocyte fate specification by protein kinase Cζ and protein kinase Cλ/ι.

During an immune response against a microbial pathogen, activated naive T lymphocytes give rise to effector cells that provide acute host defense and memory cells that provide long-lived immunity. It has been shown that T lymphocytes can undergo asymmetric division, enabling the daughter cells to inherit unequal amounts of fate-determining proteins and thereby acquire distinct fates from their inception. In this study, we show that the absence of the atypical protein kinase C (PKC) isoforms, PKCζ and PKCλ/ι, disrupts asymmetric CD8(+) T lymphocyte division.

Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses.

T lymphocytes responding to microbial infection give rise to effector cells that mediate acute host defense and memory cells that provide long-lived immunity, but the fundamental question of when and how these cells arise remains unresolved. Here we combined single-cell gene-expression analyses with 'machine-learning' approaches to trace the transcriptional 'roadmap' of individual CD8(+) T lymphocytes throughout the course of an immune response in vivo. Gene-expression signatures predictive of eventual fates could be discerned as early as the first T lymphocyte division and may have been influenced by asymmetric partitioning of the receptor for interleukin 2 (IL-2Rα) during mitosis.

Endoplasmic reticulum (ER) stress inducible factor cysteine-rich with EGF-like domains 2 (Creld2) is an important mediator of BMP9-regulated osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors that can undergo osteogenic differentiation under proper stimuli. We demonstrated that BMP9 is one of the most osteogenic BMPs. However, the molecular mechanism underlying BMP9-initiated osteogenic signaling in MSCs remains unclear.

BMP signaling in mesenchymal stem cell differentiation and bone formation.

Bone morphogenetic proteins (BMPs) are members of the TGF- superfamily and have diverse functions during development and organogenesis. BMPs play a major role in skeletal development and bone formation, and disruptions in BMP signaling cause a variety of skeletal and extraskeletal anomalies. Several knockout models have provided insight into the mechanisms responsible for these phenotypes.

Cross-talk between EGF and BMP9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors, which give rise to several lineages, including bone, cartilage and fat. Epidermal growth factor (EGF) stimulates cell growth, proliferation and differentiation. EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface and stimulating the intrinsic protein tyrosine kinase activity of its receptor, which initiates a signal transduction cascade causing a variety of biochemical changes within the cell and regulating cell proliferation and differentiation.

BMP9 signaling in stem cell differentiation and osteogenesis.

Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily and play a critical role in skeletal development, bone formation and stem cell differentiation. Disruptions in BMP signaling result in a variety of skeletal and extraskeletal anomalies. BMP9 is a poorly characterized member of the BMP family and is among the most osteogenic BMPs, promoting osteoblastic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo.

IGFBP5 domains exert distinct inhibitory effects on the tumorigenicity and metastasis of human osteosarcoma.

Osteosarcoma (OS) is the most common primary malignancy of bone. We investigated the roles of insulin-like growth factor binding protein 5 (IGFBP5) domains in modulating OS tumorigenicity and metastasis. The N-terminal (to a lesser extent the C-terminal) domain inhibited cell proliferation and induced apoptosis while the C-terminal domain inhibited cell migration and invasion.

Wnt signaling in bone formation and its therapeutic potential for bone diseases.

The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states.

BMP9-regulated angiogenic signaling plays an important role in the osteogenic differentiation of mesenchymal progenitor cells.

Mesenchymal stromal progenitor cells (MSCs) are multipotent progenitors that can be isolated from numerous tissues. MSCs can undergo osteogenic differentiation under proper stimuli. We have recently demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most osteogenic BMPs.