Radiology Posters - 2019

Radiology Posters - 2019https://scholarlycommons.libraryinfo.bhs.org/research_education/1015/thumbnail.jp

MMP-9, uPAR and Cathepsin B Silencing Downregulate Integrins in Human Glioma Xenograft Cells In Vitro and In Vivo in Nude Mice

Involvement of MMP-9, uPAR and cathepsin B in adhesion, migration, invasion, proliferation, metastasis and tumor growth has been well established. In the present study, MMP-9, uPAR and cathepsin B genes were downregulated in glioma xenograft cells using shRNA plasmid constructs and we evaluated the involvement of integrins and changes in their adhesion, migration and invasive potential.MMP-9, uPAR and cathepsin B single shRNA plasmid constructs were used to downregulate these molecules in xenograft cells. We also used MMP-9/uPAR and MMP-9/cathepsin B bicistronic constructs to evaluate the cumulative effects. MMP-9, uPAR and cathepsin B downregulation significantly inhibits xenograft cell adhesion to several extracellular matrix proteins. Treatment with MMP-9, uPAR and cathepsin B shRNA of xenografts led to the downregulation of several alpha and beta integrins. In all the assays, we noticed more prominent effects with the bicistronic plasmid constructs when compared to the single plasmid shRNA constructs. FACS analysis demonstrated the expression of alphaVbeta3, alpha6beta1 and alpha9beta1 integrins in xenograft cells. Treatment with bicistronic constructs reduced alphaVbeta3, alpha6beta1 and alpha9beta1 integrin expressions in xenograft injected nude mice. Migration and invasion were also inhibited by MMP-9, uPAR and cathepsin B shRNA treatments as assessed by spheroid migration, wound healing, and Matrigel invasion assays. As expected, bicistronic constructs further inhibited the adhesion, migration and invasive potential of the xenograft cells as compared to individual treatments.Downregulation of MMP-9, uPAR and cathespin B alone and in combination inhibits adhesion, migration and invasive potential of glioma xenografts by downregulating integrins and associated signaling molecules. Considering the existence of integrin inhibitor-resistant cancer cells, our study provides a novel and effective approach to inhibiting integrins by downregulating MMP-9, uPAR and cathepsin B in the treatment of glioma

Integrin Clustering Is Driven by Mechanical Resistance from the Glycocalyx and the Substrate

Integrins have emerged as key sensory molecules that translate chemical and physical cues from the extracellular matrix (ECM) into biochemical signals that regulate cell behavior. Integrins function by clustering into adhesion plaques, but the molecular mechanisms that drive integrin clustering in response to interaction with the ECM remain unclear. To explore how deformations in the cell-ECM interface influence integrin clustering, we developed a spatial-temporal simulation that integrates the micro-mechanics of the cell, glycocalyx, and ECM with a simple chemical model of integrin activation and ligand interaction. Due to mechanical coupling, we find that integrin-ligand interactions are highly cooperative, and this cooperativity is sufficient to drive integrin clustering even in the absence of cytoskeletal crosslinking or homotypic integrin-integrin interactions. The glycocalyx largely mediates this cooperativity and hence may be a key regulator of integrin function. Remarkably, integrin clustering in the model is naturally responsive to the chemical and physical properties of the ECM, including ligand density, matrix rigidity, and the chemical affinity of ligand for receptor. Consistent with experimental observations, we find that integrin clustering is robust on rigid substrates with high ligand density, but is impaired on substrates that are highly compliant or have low ligand density. We thus demonstrate how integrins themselves could function as sensory molecules that begin sensing matrix properties even before large multi-molecular adhesion complexes are assembled

Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly

Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is currently lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this dataset reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome likely represents a core cell adhesion machinery, centred around four axes comprising ILK-PINCH-kindlin, FAK-paxillin, talin-vinculin and α-actinin-zyxin-VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community

Galectin-3 alters the lateral mobility and clustering of beta 1-integrin receptors

Glycoprotein receptors are influenced by myriad intermolecular interactions at the cell surface. Specific glycan structures may interact with endogenous lectins that enforce or disrupt receptor-receptor interactions. Glycoproteins bound by multivalent lectins may form extended oligomers or lattices, altering the lateral mobility of the receptor and influencing its function through endocytosis or changes in activation. In this study, we have examined the interaction of Galectin-3 (Gal-3), a human lectin, with adhesion receptors. We measured the effect of recombinant Gal-3 added exogenously on the lateral mobility of the alpha 5 beta 1 integrin on HeLa cells. Using single-particle tracking (SPT) we detected increased lateral mobility of the integrin in the presence of Gal-3, while its truncated C-terminal domain (Gal-3C) showed only minor reductions in lateral mobility. Treatment of cells with Gal-3 increased beta 1-integrin mediated migration with no apparent changes in viability. In contrast, Gal-3C decreased both cell migration and viability. Fluorescence microscopy allowed us to confirm that exogenous Gal-3 resulted in reorganization of the integrin into larger clusters. We used a proteomics analysis to confirm that cells expressed endogenous Gal-3, and found that addition of competitive oligosaccharide ligands for the lectin altered the lateral mobility of the integrin. Together, our results are consistent with a Gal-3-integrin lattice model of binding and confirm that the lateral mobility of integrins is natively regulated, in part, by galectins

Nonhemorrhagic Adrenal Infarction in Pregnancy: Magnetic Resonance Imaging and Computed Tomography Evaluation

We present the case of unilateral nonhemorrhagic adrenal infarct in a 29-week pregnant 21-year-old woman. The patient presented with right upper quadrant pain, nausea, and vomiting. Ultrasonography of the right upper quadrant and appendix was negative for pathology. Magnetic resonance imaging of the abdomen demonstrated a right nonhemorrhagic adrenal infarct, subsequently confirmed with limited computed tomography of the upper abdomen. This case discusses the clinical presentation and pertinent imaging findings of adrenal infarction in pregnancy

Infections of the Hepatobiliary System

Hepatobiliary infections account for a small but clinically important proportion of emergency department presentations. They present a clinical challenge due to the broad range of imaging characteristics on presentation. Recognition of complications is imperative to drive appropriate patient care and resource utilization to avoid diagnostic pitfalls and avert adverse patient outcomes. A thorough understanding of anatomy infectious pathology of hepatobiliary system is essential in the emergency setting to confidently diagnose and guide medical intervention. Many presentations of hepatobiliary infection have characteristic imaging features on individual imaging modalities with others requiring the assimilation of findings of multiple imaging modalities along with incorporating the clinical context and multispecialist consultation. Familiarity with the strengths of individual imaging modalities in the radiologists\u27 arsenal is imperative to guide the appropriate utilization of resources, particularly in the emergent time sensitive setting. Accurate identification and diagnosis of hepatobiliary infections is vital for appropriate patient care and management stratification

Role of Interventional Radiology in the Management of Infection

Interventional radiology (IR) is plays a crucial role in the management of localized infections, utilizing percutaneous access to loculated fluid collections for drainage and source control. Interventions have been developed in multiple organs and systems and used over decades, allowing the IR physician to provide patient care in many cases where surgical options are not optimal. In this review, we will examine the emergent, urgent, and routine nature of various IR procedures in the infectious context and timelines for each in regards to the decision making process. An algorithmic approach should guide the clinician\u27s decision making for IR procedures in both large academic centers and smaller community hospitals. This approach and the pertinent procedural technique are described for multiple systems and organs including the biliary tree, gallbladder, genitourinary tract, and thoracic, abdominal, and pelvic abscesses. Increased awareness of the abilities and limitations of IR physicians in clinical scenarios needs to be implemented, to allow multispecialty input in efforts to decrease morbidity and mortality

Surveillance Benefit Components for Chronic Wasting Disease in White-Tailed Deer

Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government. The findings and conclusions in this material are those of the authors and do not necessarily represent the views of the U.S. Fish and Wildlife Service.Access to files is currently restricted due to recently discovered errors in dataset. Awaiting corrected dataset and detailed error log. At that point, the dataset will be updated and made open again. 20240222 emj.The Surveillance Benefit Components for Chronic Wasting Disease in White-Tailed Deer is multivariable data representing epidemiological, population, ecological, and anthropogenic attributes of chronic wasting disease (CWD) in wild, white-tailed deer (Odocoileus virginianus) in the region of the United States (US) containing the states of Arkansas, Florida, Georgia, Indiana, Iowa, Kentucky, Maryland, Michigan, Minnesota, Mississippi, New York, North Carolina, Ohio, Tennessee, and Wisconsin, and in the region of Canada containing the province of Ontario. The data was made available through state and provincial wildlife agencies in partnership with the Surveillance Optimization Project for Chronic Wasting Disease (SOP4CWD), administered by the Cornell Wildlife Health Lab (CWHL) at Cornell University and Boone and Crockett Quantitative Wildlife Center at Michigan State University. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Data collection was funded in part by Arkansas’s Wildlife Restoration funds, “State Wildlife Health”; State of Florida State Game Trust Fund Deer Management Program; Georgia’s Wildlife and Sport Fish Restoration Program; Indiana Department of Natural Resources and Fish and Wildlife # F18AF00484, W38R05 White-tailed Deer Management, F20AF10029-00, Monitoring Wildlife Populations and Health W-51-R-01, F21AF02467-01, Monitoring Wildlife Populations and Health W-51-R-02; Iowa’s Fish and Wildlife Trust Fund and Iowa’s award of the U. S. Fish and Wildlife Service Wildlife and Sport Fish Restoration Program; Maryland’s award of the U. S. Fish and Wildlife Service Wildlife and Sport Fish Restoration Program, #W-61-R-29; Minnesota Department of Natural Resources; New York’s Wildlife Health Unit and New York’s award for Federal Aid Wildlife Restoration Grant #W-178-R; North Carolina’s award for Federal Aid in Wildlife Restoration; Ohio’s award for the Wildlife Restoration Grant # F20AF12094; Tennessee’s award for the Wildlife Restoration Program; Wisconsin’s award for the Federal Aid in Wildlife Restoration; Multistate Conservation Grant Program # F21AP00722-01. The Michigan Disease Initiative # RC109358, Alabama Department of Conservation and Natural Resources, Florida Fish and Wildlife Conservation Commission, Tennessee Wildlife Resources Agency, and New York State Department of Environmental Conservation contributed funding to the overall project