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Articles 91 - 120 of 129
Full-Text Articles in Other Medical Specialties
Using Accreditation Standards As A Framework To Evaluate And Improve A Community-Based Diabetes Self-Management Education Program., Neva White, Mary Lou Manning, Rickie Brawer, James Plumb
Using Accreditation Standards As A Framework To Evaluate And Improve A Community-Based Diabetes Self-Management Education Program., Neva White, Mary Lou Manning, Rickie Brawer, James Plumb
Department of Nursing papers and presentations
Diabetes self-management education is an essential component of diabetes clinical management, and community-based programs are an effective intervention for improving glycemic control among adults living with diabetes. The National Standards for Diabetes Self-Management Education and Support are designed to define quality diabetes self-management education and support, and to assist diabetes educators to provide evidence-based education and self-management support. These standards are used in the field for recognition and accreditation. This article presents the results of a program evaluation conducted by the Center for Urban Health at the Thomas Jefferson University and Hospital, examines the outcomes of the community-based diabetes self-management …
Isprm Discussion Paper: Proposing A Conceptual Description Of Health-Related Rehabilitation Services., Thorsten Meyer, Christoph Gutenbrunner, Carlotte Kiekens, Dimitrios Skempes, John L Melvin, Kuno Schedler, Marta Imamura, Gerold Stucki
Isprm Discussion Paper: Proposing A Conceptual Description Of Health-Related Rehabilitation Services., Thorsten Meyer, Christoph Gutenbrunner, Carlotte Kiekens, Dimitrios Skempes, John L Melvin, Kuno Schedler, Marta Imamura, Gerold Stucki
Department of Rehabilitation Medicine Faculty Papers
There is a need for a comprehensive classification system of health-related rehabilitation services. For conceptual clarity our aim is to provide a health-related conceptual description of the term "rehabilitation service". First, we introduce a common understanding of the term "rehabilitation", based on the current definition in the World Health Organization's World Report on Disability, and a conceptual description of rehabilitation agreed upon by international Physical and Rehabilitation Medicine organizations. From a health perspective, rehabilitation can be regarded as a general health strategy with the aim of enabling persons with health conditions experiencing or likely to experience disability to achieve and …
Microrna-138 Regulates Hypoxia-Induced Endothelial Cell Dysfunction By Targeting S100a1., Anagha Sen, Shumei Ren, Carolin Lerchenmüller, Jianxin Sun, Norbert Weiss, Patrick Most, Karsten Peppel
Microrna-138 Regulates Hypoxia-Induced Endothelial Cell Dysfunction By Targeting S100a1., Anagha Sen, Shumei Ren, Carolin Lerchenmüller, Jianxin Sun, Norbert Weiss, Patrick Most, Karsten Peppel
Center for Translational Medicine Faculty Papers
The Ca(2+) sensor S100A1 is essential for proper endothelial cell (EC) nitric oxide (NO) synthase (eNOS) activation. S100A1 levels are greatly reduced in primary human microvascular ECs subjected to hypoxia, rendering them dysfunctional. However mechanisms that regulate S100A1 levels in ECs are unknown. Here we show that ECs transfected with a S100A1-3' untranslated region (UTR) luciferase reporter construct display significantly reduced gene expression when subjected to low oxygen levels or chemical hypoxia. Bioinformatic analysis suggested that microRNA -138 (MiR-138) could target the 3'UTR of S100A1. Patients with critical limb ischemia (CLI) or mice subjected to femoral artery resection (FAR) displayed …
Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini
Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini
Department of Biochemistry and Molecular Biology Faculty Papers
Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of many developmental pathways is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is critical for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase. …
Collagen Content In Skin And Internal Organs Of The Tight Skin Mouse: An Animal Model Of Scleroderma., Jayanthi Manne, Marina Markova, Linda D Siracusa, Sergio A Jimenez
Collagen Content In Skin And Internal Organs Of The Tight Skin Mouse: An Animal Model Of Scleroderma., Jayanthi Manne, Marina Markova, Linda D Siracusa, Sergio A Jimenez
Department of Microbiology and Immunology Faculty Papers
The Tight Skin mouse is a genetically induced animal model of tissue fibrosis caused by a large in-frame mutation in the gene encoding fibrillin-1 (Fbn-1). We examined the influence of gender on the collagen content of tissues in C57BL/6J wild type (+/+) and mutant Tight Skin (Tsk/+) mice employing hydroxyproline assays. Tissue sections were stained with Masson's trichrome to identify collagen in situ. Adult Tsk/+ mice skin contains ~15% more collagen, on average, than skin from +/+ mice of the same gender. The heart of Tsk/+ males had significantly more collagen than that of +/+ males. No significant gender differences …
Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth., Alexandra Aronin, Shira Amsili, Tatyana B Prigozhina, Kobi Tzdaka, Jacob Rachmilewitz, Noam Shani, Mark L Tykocinski, Michal Dranitzki Elhalel
Fn14•Trail Effectively Inhibits Hepatocellular Carcinoma Growth., Alexandra Aronin, Shira Amsili, Tatyana B Prigozhina, Kobi Tzdaka, Jacob Rachmilewitz, Noam Shani, Mark L Tykocinski, Michal Dranitzki Elhalel
Department of Medical Genetics Faculty Papers
BACKGROUND: New strategies for the treatment of hepatocellular carcinoma (HCC) are needed, given that currently available chemotherapeutics are inefficient. Since tumor growth reflects the net balance between pro-proliferative and death signaling, agents shifting the equilibrium toward the latter are of considerable interest. The TWEAK:Fn14 signaling axis promotes tumor cell proliferation and tumor angiogenesis, while TRAIL:TRAIL-receptor (TRAIL-R) interactions selectively induce apoptosis in malignant cells. Fn14•TRAIL, a fusion protein bridging these two pathways, has the potential to inhibit tumor growth, by interfering with TWEAK:Fn14 signaling, while at the same time enforcing TRAIL:TRAIL-R-mediated apoptosis. Consequently, Fn14•TRAIL's capacity to inhibit HCC growth was tested. …
The Drosophila Eve Insulator Homie Promotes Eve Expression And Protects The Adjacent Gene From Repression By Polycomb Spreading., Miki Fujioka, Guizhi Sun, James B Jaynes
The Drosophila Eve Insulator Homie Promotes Eve Expression And Protects The Adjacent Gene From Repression By Polycomb Spreading., Miki Fujioka, Guizhi Sun, James B Jaynes
Department of Biochemistry and Molecular Biology Faculty Papers
Insulators can block the action of enhancers on promoters and the spreading of repressive chromatin, as well as facilitating specific enhancer-promoter interactions. However, recent studies have called into question whether the activities ascribed to insulators in model transgene assays actually reflect their functions in the genome. The Drosophila even skipped (eve) gene is a Polycomb (Pc) domain with a Pc-group response element (PRE) at one end, flanked by an insulator, an arrangement also seen in other genes. Here, we show that this insulator has three major functions. It blocks the spreading of the eve Pc domain, preventing repression of the …
Perspectives Of Older Adults On Co-Management Of Low Back Pain By Doctors Of Chiropractic And Family Medicine Physicians: A Focus Group Study., Kevin J Lyons, Stacie A Salsbury, Maria A Hondras, Mark E Jones, Andrew A Andresen, Christine M Goertz
Perspectives Of Older Adults On Co-Management Of Low Back Pain By Doctors Of Chiropractic And Family Medicine Physicians: A Focus Group Study., Kevin J Lyons, Stacie A Salsbury, Maria A Hondras, Mark E Jones, Andrew A Andresen, Christine M Goertz
Department of Medical Genetics Faculty Papers
BACKGROUND: While older adults may seek care for low back pain (LBP) from both medical doctors (MDs) and doctors of chiropractic (DCs), co-management between these providers is uncommon. The purposes of this study were to describe the preferences of older adults for LBP co-management by MDs and DCs and to identify their concerns for receiving care under such a treatment model.
METHODS: We conducted 10 focus groups with 48 older adults who received LBP care in the past year. Interviews explored participants' care seeking experiences, co-management preferences, and perceived challenges to successful implementation of a MD-DC co-management model. We analyzed …
G Protein-Coupled Receptor Kinase 2 (Grk2) Is Localized To Centrosomes And Mediates Epidermal Growth Factor-Promoted Centrosomal Separation., Christopher H So, Allison Michal, Konstantin E Komolov, Jiansong Luo, Jeffrey L Benovic
G Protein-Coupled Receptor Kinase 2 (Grk2) Is Localized To Centrosomes And Mediates Epidermal Growth Factor-Promoted Centrosomal Separation., Christopher H So, Allison Michal, Konstantin E Komolov, Jiansong Luo, Jeffrey L Benovic
Department of Biochemistry and Molecular Biology Faculty Papers
G protein-coupled receptor kinases (GRKs) play a central role in regulating receptor signaling, but recent studies suggest a broader role in modulating normal cellular functions. For example, GRK5 has been shown to localize to centrosomes and regulate microtubule nucleation and cell cycle progression. Here we demonstrate that GRK2 is also localized to centrosomes, although it has no role in centrosome duplication or microtubule nucleation. Of interest, knockdown of GRK2 inhibits epidermal growth factor receptor (EGFR)-mediated separation of duplicated centrosomes. This EGFR/GRK2-mediated process depends on the protein kinases mammalian STE20-like kinase 2 (Mst2) and Nek2A but does not involve polo-like kinase …
Leukemia-Associated Rhogef (Larg) Is A Novel Rhogef In Cytokinesis And Required For The Proper Completion Of Abscission., Matthew K Martz, Elda Grabocka, Neil Beeharry, Timothy J Yen, Philip B Wedegaertner
Leukemia-Associated Rhogef (Larg) Is A Novel Rhogef In Cytokinesis And Required For The Proper Completion Of Abscission., Matthew K Martz, Elda Grabocka, Neil Beeharry, Timothy J Yen, Philip B Wedegaertner
Department of Biochemistry and Molecular Biology Faculty Papers
Proper completion of mitosis requires the concerted effort of multiple RhoGEFs. Here we show that leukemia-associated RhoGEF (LARG), a RhoA-specific RGS-RhoGEF, is required for abscission, the final stage of cytokinesis, in which the intercellular membrane is cleaved between daughter cells. LARG colocalizes with α-tubulin at the spindle poles before localizing to the central spindle. During cytokinesis, LARG is condensed in the midbody, where it colocalizes with RhoA. HeLa cells depleted of LARG display apoptosis during cytokinesis with unresolved intercellular bridges, and rescue experiments show that expression of small interfering RNA-resistant LARG prevents this apoptosis. Moreover, live cell imaging of LARG-depleted …
Presence Of Virus Neutralizing Antibodies In Cerebral Spinal Fluid Correlates With Non-Lethal Rabies In Dogs., Clement W Gnanadurai, Ming Zhou, Wenqi He, Christina M Leyson, Chien-Tsun Huang, Gregory Salyards, Stephen B Harvey, Zhenhai Chen, Biao He, Yang Yang, D C Hooper, Berhnard Dietzchold, Zhen F Fu
Presence Of Virus Neutralizing Antibodies In Cerebral Spinal Fluid Correlates With Non-Lethal Rabies In Dogs., Clement W Gnanadurai, Ming Zhou, Wenqi He, Christina M Leyson, Chien-Tsun Huang, Gregory Salyards, Stephen B Harvey, Zhenhai Chen, Biao He, Yang Yang, D C Hooper, Berhnard Dietzchold, Zhen F Fu
Department of Cancer Biology Faculty Papers
BACKGROUND: Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans.
METHODOLOGY/PRINCIPAL FINDINGS: Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico) correlates with the presence of high level of virus neutralizing antibodies (VNA) in the cerebral spinal fluid (CSF) and mild immune cell accumulation in the central nervous system (CNS). By contrast, dogs that succumbed to rabies showed only little or no VNA in the …
Spinal Anesthesia: Should Everyone Receive A Urinary Catheter?: A Randomized, Prospective Study Of Patients Undergoing Total Hip Arthroplasty., Adam G Miller, James Mckenzie, Max Greenky, Erica Shaw, Kishor Gandhi, William J Hozack, Javad Parvizi
Spinal Anesthesia: Should Everyone Receive A Urinary Catheter?: A Randomized, Prospective Study Of Patients Undergoing Total Hip Arthroplasty., Adam G Miller, James Mckenzie, Max Greenky, Erica Shaw, Kishor Gandhi, William J Hozack, Javad Parvizi
Rothman Institute Papers
BACKGROUND: The objective of this randomized prospective study was to determine whether a urinary catheter is necessary for all patients undergoing total hip arthroplasty under spinal anesthesia.
METHODS: Consecutive patients undergoing total hip arthroplasty under spinal anesthesia were randomized to treatment with or without insertion of an indwelling urinary catheter. All patients received spinal anesthesia with 15 to 30 mg of 0.5% bupivacaine. The catheter group was subjected to a standard postoperative protocol, with removal of the indwelling catheter within forty-eight hours postoperatively. The experimental group was monitored for urinary retention and, if necessary, had straight catheterization up to two …
Intracellular Reprogramming Of Expression, Glycosylation, And Function Of A Plant-Derived Antiviral Therapeutic Monoclonal Antibody., Jeong-Hwan Lee, Da-Young Park, Kyung-Jin Lee, Young-Kwan Kim, Yang-Kang So, Jae-Sung Ryu, Seung-Han Oh, Yeon-Soo Han, Kinarm Ko, Young-Kug Choo, Sung-Joo Park, Robert Brodzik, Kyoung-Ki Lee, Doo-Byoung Oh, Kyung-A Hwang, Hilary Koprowski, Yong Seong Lee, Kisung Ko
Intracellular Reprogramming Of Expression, Glycosylation, And Function Of A Plant-Derived Antiviral Therapeutic Monoclonal Antibody., Jeong-Hwan Lee, Da-Young Park, Kyung-Jin Lee, Young-Kwan Kim, Yang-Kang So, Jae-Sung Ryu, Seung-Han Oh, Yeon-Soo Han, Kinarm Ko, Young-Kug Choo, Sung-Joo Park, Robert Brodzik, Kyoung-Ki Lee, Doo-Byoung Oh, Kyung-A Hwang, Hilary Koprowski, Yong Seong Lee, Kisung Ko
Department of Cancer Biology Faculty Papers
Plant genetic engineering, which has led to the production of plant-derived monoclonal antibodies (mAb(P)s), provides a safe and economically effective alternative to conventional antibody expression methods. In this study, the expression levels and biological properties of the anti-rabies virus mAb(P) SO57 with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp-Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed. The expression levels of mAb(P) SO57 with KDEL (mAb(P)K) were significantly higher than those of mAb(P) SO57 without KDEL (mAb(P)) regardless of the transcription level. The Fc domains of both purified mAb(P) and mAb(P)K and hybridoma-derived mAb (mAb(H)) had similar …
Insulin Promotes Glucose Consumption Via Regulation Of Mir-99a/Mtor/Pkm2 Pathway., Wei Li, Jing Wang, Qiu-Dan Chen, Xu Qian, Qi Li, Yu Yin, Zhu-Mei Shi, Lin Wang, Jie Lin, Ling-Zhi Liu, Bing-Hua Jiang
Insulin Promotes Glucose Consumption Via Regulation Of Mir-99a/Mtor/Pkm2 Pathway., Wei Li, Jing Wang, Qiu-Dan Chen, Xu Qian, Qi Li, Yu Yin, Zhu-Mei Shi, Lin Wang, Jie Lin, Ling-Zhi Liu, Bing-Hua Jiang
Kimmel Cancer Center Faculty Papers
Insulin is known to regulate multiple cellular functions and is used for the treatment of diabetes. MicroRNAs have been demonstrated to be involved in many human diseases, including Type 2 diabetes. In this study, we showed that insulin decreased miR-99a expression levels, but induced glucose consumption and lactate production, and increased the expression of mTOR, HIF-1α and PKM2 in HepG2 and HL7702 cells. Forced expression of miR-99a or rapamycin treatment blocked insulin-induced PKM2 and HIF-1α expression, and glucose consumption and lactate production. Meanwhile, knockdown of HIF-1α inhibited PKM2 expression and insulin-induced glucose consumption. Taken together, these findings will reveal the …
A Public Health Response Against Strongyloides Stercoralis: Time To Look At Soil-Transmitted Helminthiasis In Full., Alejandro J Krolewiecki, Patrick Lammie, Julie Jacobson, Albis-Francesco Gabrielli, Bruno Levecke, Eugenia Socias, Luis M Arias, Nicanor Sosa, David Abraham, Ruben Cimino, Adriana Echazú, Favio Crudo, Jozef Vercruysse, Marco Albonico
A Public Health Response Against Strongyloides Stercoralis: Time To Look At Soil-Transmitted Helminthiasis In Full., Alejandro J Krolewiecki, Patrick Lammie, Julie Jacobson, Albis-Francesco Gabrielli, Bruno Levecke, Eugenia Socias, Luis M Arias, Nicanor Sosa, David Abraham, Ruben Cimino, Adriana Echazú, Favio Crudo, Jozef Vercruysse, Marco Albonico
Department of Microbiology and Immunology Faculty Papers
Strongyloides stercoralis infections have a worldwide distribution with a global burden in terms of prevalence and morbidity that is largely ignored. A public health response against soil-transmitted helminth (STH) infections should broaden the strategy to include S. stercoralis and overcome the epidemiological, diagnostic, and therapeutic challenges that this parasite poses in comparison to Ascaris lumbricoides, Trichuris trichiura, and hookworms. The relatively poor sensitivity of single stool evaluations, which is further lowered when quantitative techniques aimed at detecting eggs are used, also complicates morbidity evaluations and adequate drug efficacy measurements, since S. stercoralis is eliminated in stools in a larval stage. …
The Nordinet® International Outcome Study And Novonet® Answer Program®: Rationale, Design, And Methodology Of Two International Pharmacoepidemiological Registry-Based Studies Monitoring Long-Term Clinical And Safety Outcomes Of Growth Hormone Therapy (Norditropin®)., Charlotte Höybye, Lars Sävendahl, Henrik Thybo Christesen, Peter Lee, Birgitte Tønnes Pedersen, Michael Schlumpf, John Germak, Judith Ross
The Nordinet® International Outcome Study And Novonet® Answer Program®: Rationale, Design, And Methodology Of Two International Pharmacoepidemiological Registry-Based Studies Monitoring Long-Term Clinical And Safety Outcomes Of Growth Hormone Therapy (Norditropin®)., Charlotte Höybye, Lars Sävendahl, Henrik Thybo Christesen, Peter Lee, Birgitte Tønnes Pedersen, Michael Schlumpf, John Germak, Judith Ross
Department of Pediatrics Faculty Papers
OBJECTIVE: Randomized controlled trials have shown that growth hormone (GH) therapy has effects on growth, metabolism, and body composition. GH therapy is prescribed for children with growth failure and adults with GH deficiency. Carefully conducted observational study of GH treatment affords the opportunity to assess long-term treatment outcomes and the clinical factors and variables affecting those outcomes, in patients receiving GH therapy in routine clinical practice.
DESIGN: The NordiNet® International Outcome Study (IOS) and the American Norditropin® Studies: Web Enabled Research (ANSWER Program®) are two complementary, non-interventional, observational studies that adhere to current guidelines for pharmacoepidemiological data.
PATIENTS: The studies …
Pharmacology And Clinical Potential Of Guanylyl Cyclase C Agonists In The Treatment Of Ulcerative Colitis., Giovanni M Pitari
Pharmacology And Clinical Potential Of Guanylyl Cyclase C Agonists In The Treatment Of Ulcerative Colitis., Giovanni M Pitari
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Agonists of the transmembrane intestinal receptor guanylyl cyclase C (GCC) have recently attracted interest as promising human therapeutics. Peptide ligands that can specifically induce GCC signaling in the intestine include endogenous hormones guanylin and uroguanylin, diarrheagenic bacterial enterotoxins (ST), and synthetic drugs linaclotide, plecanatide, and SP-333. These agonists bind to GCC at intestinal epithelial surfaces and activate the receptor's intracellular catalytic domain, an event initiating discrete biological responses upon conversion of guanosine-5'-triphosphate to cyclic guanosine monophosphate. A principal action of GCC agonists in the colon is the promotion of mucosal homeostasis and its dependent barrier function. Herein, GCC agonists are …
Comparison Study Of Airway Reactivity Outcomes Due To A Pharmacologic Challenge Test: Impulse Oscillometry Versus Least Mean Squared Analysis Techniques., Elena Rodriguez, Charrell M Bullard, Milena H Armani, Thomas L Miller, Thomas H Shaffer
Comparison Study Of Airway Reactivity Outcomes Due To A Pharmacologic Challenge Test: Impulse Oscillometry Versus Least Mean Squared Analysis Techniques., Elena Rodriguez, Charrell M Bullard, Milena H Armani, Thomas L Miller, Thomas H Shaffer
Department of Medicine Faculty Papers
The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS) has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS) involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways). …
Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon
Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon
Center for Translational Medicine Faculty Papers
Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change …
Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon
Glucose Stimulation Induces Dynamic Change Of Mitochondrial Morphology To Promote Insulin Secretion In The Insulinoma Cell Line Ins-1e., Bong Sook Jhun, Hakjoo Lee, Zheng-Gen Jin, Yisang Yoon
Center for Translational Medicine Faculty Papers
Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change …
Global Analysis Of Sumo Chain Function Reveals Multiple Roles In Chromatin Regulation., Tharan Srikumar, Megan C Lewicki, Michael Costanzo, Johnny M Tkach, Harm Van Bakel, Kyle Tsui, Erica S Johnson, Grant W Brown, Brenda J Andrews, Charles Boone, Guri Giaever, Corey Nislow, Brian Raught
Global Analysis Of Sumo Chain Function Reveals Multiple Roles In Chromatin Regulation., Tharan Srikumar, Megan C Lewicki, Michael Costanzo, Johnny M Tkach, Harm Van Bakel, Kyle Tsui, Erica S Johnson, Grant W Brown, Brenda J Andrews, Charles Boone, Guri Giaever, Corey Nislow, Brian Raught
Department of Biochemistry and Molecular Biology Faculty Papers
Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric "chains," but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3(allR)) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chain function. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich …
Diet And Nutrition In Cancer Survivorship And Palliative Care., Anthony J Bazzan, Andrew B Newberg, William C Cho, Daniel A Monti
Diet And Nutrition In Cancer Survivorship And Palliative Care., Anthony J Bazzan, Andrew B Newberg, William C Cho, Daniel A Monti
Marcus Institute of Integrative Health Faculty Papers
The primary goal of palliative cancer care is typically to relieve suffering and improve quality of life. Most approaches to diet in this setting have focused only on eating as many calories as possible to avoid cachexia. However, as the concept of palliative care has evolved to include all aspects of cancer survivorship and not just end of life care, there is an increasing need to thoughtfully consider diet and nutrition approaches that can impact not only quality of life but overall health outcomes and perhaps even positively affect cancer recurrence and progression. In this regard, there has been a …
Necrostatin-1 Analogues: Critical Issues On The Specificity, Activity And In Vivo Use In Experimental Disease Models., N Takahashi, L Duprez, S Grootjans, A Cauwels, W Nerinckx, J B Duhadaway, V Goossens, R Roelandt, F Van Hauwermeiren, C Libert, W Declercq, N Callewaert, G C Prendergast, A Degterev, J Yuan, P Vandenabeele
Necrostatin-1 Analogues: Critical Issues On The Specificity, Activity And In Vivo Use In Experimental Disease Models., N Takahashi, L Duprez, S Grootjans, A Cauwels, W Nerinckx, J B Duhadaway, V Goossens, R Roelandt, F Van Hauwermeiren, C Libert, W Declercq, N Callewaert, G C Prendergast, A Degterev, J Yuan, P Vandenabeele
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × …
Quantifying The Cdk Inhibitor Vmy-1-103'S Activity And Tissue Levels In An In Vivo Tumor Model By Lc-Ms/Ms And By Mri., Paul Sirajuddin, Sudeep Das, Lymor Ringer, Olga C Rodriguez, Angiela Sivakumar, Yi-Chien Lee, Aykut Üren, Stanley T Fricke, Brian Rood, Alpay Ozcan, Sean S Wang, Sana Karam, Venkata Yenugonda, Patricia Salinas, Emanuel Petricoin, Michael Pishvaian, Michael P Lisanti, Yue Wang, Richard Schlegel, Bahram Moasser, Chris Albanese
Quantifying The Cdk Inhibitor Vmy-1-103'S Activity And Tissue Levels In An In Vivo Tumor Model By Lc-Ms/Ms And By Mri., Paul Sirajuddin, Sudeep Das, Lymor Ringer, Olga C Rodriguez, Angiela Sivakumar, Yi-Chien Lee, Aykut Üren, Stanley T Fricke, Brian Rood, Alpay Ozcan, Sean S Wang, Sana Karam, Venkata Yenugonda, Patricia Salinas, Emanuel Petricoin, Michael Pishvaian, Michael P Lisanti, Yue Wang, Richard Schlegel, Bahram Moasser, Chris Albanese
Kimmel Cancer Center Faculty Papers
The development of new small molecule-based therapeutic drugs requires accurate quantification of drug bioavailability, biological activity and treatment efficacy. Rapidly measuring these endpoints is often hampered by the lack of efficient assay platforms with high sensitivity and specificity. Using an in vivo model system, we report a simple and sensitive liquid chromatography-tandem mass spectrometry assay to quantify the bioavailability of a recently developed novel cyclin-dependent kinase inhibitor VMY-1-103, a purvalanol B-based analog whose biological activity is enhanced via dansylation. We developed a rapid organic phase extraction technique and validated wide and functional VMY-1-103 distribution in various mouse tissues, consistent with …
Life History Theory And Social Psychology., Donald F Sacco, Karol Osipowicz
Life History Theory And Social Psychology., Donald F Sacco, Karol Osipowicz
Department of Neurology Faculty Papers
No abstract provided.
Biosynthetic Pathways And The Role Of The Mas Receptor In The Effects Of Angiotensin-(1-7) In Smooth Muscles., Marcio Augusto Fressatto De Godoy, Larissa Pernomian, Ana Maria De Oliveira, Satish Rattan
Biosynthetic Pathways And The Role Of The Mas Receptor In The Effects Of Angiotensin-(1-7) In Smooth Muscles., Marcio Augusto Fressatto De Godoy, Larissa Pernomian, Ana Maria De Oliveira, Satish Rattan
Department of Medicine Faculty Papers
Ang-(1-7) is produced via degradation of Ang II by the human angiotensin converting enzyme, also known as ACE2. In the cardiovascular system, Ang-(1-7) has been shown to produce effects that are opposite to those of Ang II. These include smooth muscle relaxation and cardioprotection. While the roles of Ang-(1-7) in other systems are currently topic of intense research, functional data suggest a relaxation action in gastrointestinal smooth muscles in a way that corroborates the results obtained from vascular tissues. However, more studies are necessary to determine a relevant role for Ang-(1-7) in the gastrointestinal system. The Ang-(1-7) actions are mediated …
Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh
Perspectives On: Sgp Symposium On Mitochondrial Physiology And Medicine: Mitochondria Take Center Stage., Shey-Shing Sheu, Robert T Dirksen, Edward N Pugh
Center for Translational Medicine Faculty Papers
No abstract provided.
Management Of Hyperglycemia In Type 2 Diabetes: A Patient-Centered Approach: Position Statement Of The American Diabetes Association (Ada) And The European Association For The Study Of Diabetes (Easd)., Silvio E Inzucchi, Richard M Bergenstal, John B Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L Peters, Apostolos Tsapas, Richard Wender, David R. Matthews
Management Of Hyperglycemia In Type 2 Diabetes: A Patient-Centered Approach: Position Statement Of The American Diabetes Association (Ada) And The European Association For The Study Of Diabetes (Easd)., Silvio E Inzucchi, Richard M Bergenstal, John B Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L Peters, Apostolos Tsapas, Richard Wender, David R. Matthews
Department of Family & Community Medicine Faculty Papers
No abstract provided.
Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King
Mitochondrial Lysyl-Trna Synthetase Independent Import Of Trna Lysine Into Yeast Mitochondria., Naresh Babu V Sepuri, Madhavi Gorla, Michael P King
Department of Biochemistry and Molecular Biology Faculty Papers
Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present …
Dyschronic, A Drosophila Homolog Of A Deaf-Blindness Gene, Regulates Circadian Output And Slowpoke Channels., James E C Jepson, Mohammad Shahidullah, Angelique Lamaze, Drew Peterson, Huihui Pan, Kyunghee Koh
Dyschronic, A Drosophila Homolog Of A Deaf-Blindness Gene, Regulates Circadian Output And Slowpoke Channels., James E C Jepson, Mohammad Shahidullah, Angelique Lamaze, Drew Peterson, Huihui Pan, Kyunghee Koh
Farber Institute for Neuroscience Faculty Papers
Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc). dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause …