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Humans

2014

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Articles 1 - 30 of 178

Full-Text Articles in Life Sciences

Mtorc2 Is Required For Rit-Mediated Oxidative Stress Resistance, Weikang Cai, Douglas A. Andres Dec 2014

Mtorc2 Is Required For Rit-Mediated Oxidative Stress Resistance, Weikang Cai, Douglas A. Andres

Molecular and Cellular Biochemistry Faculty Publications

Rit, a member of the Ras family of GTPases, has been shown to promote cell survival in response to oxidative stress, in part by directing an evolutionarily conserved p38 MAPK-Akt survival cascade. Aberrant Rit signaling has recently been implicated as a driver mutation in human cancer, adding importance to the characterization of critical Rit effector pathways. However, the mechanism by which Rit-p38 signaling regulated Akt activity was unknown. Here, we identify mTORC2 as a critical downstream mediator of Rit-dependent survival signaling in response to reactive oxygen species (ROS) stress. Rit interacts with Sin1 (MAPKAP1), and Rit loss compromises ROS-dependent mTORC2 …

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Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald Dec 2014

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …

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Color Updating On The Apparent Motion Path, Edmund Chong, Sang Wook Hong, Won Mok Shim Dec 2014

Color Updating On The Apparent Motion Path, Edmund Chong, Sang Wook Hong, Won Mok Shim

Dartmouth Scholarship

When a static stimulus appears successively at two distant locations, we perceive illusory motion of the stimulus across them–long-range apparent motion (AM). Previous studies have shown that when the apparent motion stimuli differ in shape, interpolation between the two shapes is perceived across the AM path. In contrast, the perceived color during AM has been shown to abruptly change from the color of the first stimulus into that of the second, suggesting interpolation does not occur for color during AM. Here, we report the first evidence to our knowledge, that an interpolated color, distinct from the colors of either apparent …

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A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu Dec 2014

A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu

NYMC Faculty Publications

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased …

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Cd151-Α3Β1 Integrin Complexes Suppress Ovarian Tumor Growth By Repressing Slug-Mediated Emt And Canonical Wnt Signaling, Lauren A. Baldwin, John T. Hoff, Jason Lefringhouse, Michael Zhang, Changhe Jia, Zeyi Liu, Sonia Erfani, Hongyan Jin, Mei Xu, Qing-Bai She, John R. Van Nagell Jr., Chi Wang, Li Chen, Rina Plattner, David M. Kaetzel, Jia Luo, Michael Lu, Dava West, Chunming Liu, Fred R. Ueland, Ronny Drapkin, Binhua P. Zhou, Xiuwei H. Yang Dec 2014

Cd151-Α3Β1 Integrin Complexes Suppress Ovarian Tumor Growth By Repressing Slug-Mediated Emt And Canonical Wnt Signaling, Lauren A. Baldwin, John T. Hoff, Jason Lefringhouse, Michael Zhang, Changhe Jia, Zeyi Liu, Sonia Erfani, Hongyan Jin, Mei Xu, Qing-Bai She, John R. Van Nagell Jr., Chi Wang, Li Chen, Rina Plattner, David M. Kaetzel, Jia Luo, Michael Lu, Dava West, Chunming Liu, Fred R. Ueland, Ronny Drapkin, Binhua P. Zhou, Xiuwei H. Yang

Pharmacology and Nutritional Sciences Faculty Publications

Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by …

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Coral Spawning In The Gulf Of Oman And Relationship To Latitudinal Variation In Spawning Season In The Northwest Indian Ocean, E. J. Howells, D. Abrego, G. O. Vaughan, J. A. Burt Dec 2014

Coral Spawning In The Gulf Of Oman And Relationship To Latitudinal Variation In Spawning Season In The Northwest Indian Ocean, E. J. Howells, D. Abrego, G. O. Vaughan, J. A. Burt

All Works

Despite a wealth of information on sexual reproduction in scleractinian corals, there are regional gaps in reproductive records. In the Gulf of the Oman in the Arabian Sea, reproductive timing was assessed in four common species of broadcast spawning corals using field surveys of gamete maturity and aquarium observations of spawning activity. The appearance of mature gametes within the same month for Acropora downingi, A. hemprichii, Cyphastrea microphthalma and Platygyra daedalea (≥ 75% of colonies, n = 848) indicated a synchronous and multi-specific spawning season. Based on gamete disappearance and direct observations, spawning predominantly occurred during April in 2013 (75- …

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Gaip Interacting Protein C-Terminus Regulates Autophagy And Exosome Biogenesis Of Pancreatic Cancer Through Metabolic Pathways, Santanu Bhattacharya, Krishnendu Pal, Anil K. Sharma, Shamit K. Dutta, Julie S. Lau, Irene K. Yan, Enfeng Wang, Ahmed Elkhanany, Khalid M. Alkharfy, Arunik Sanyal, Tushar C. Patel, Suresh T. Chari, Mark R. Spaller, Debabrata Mukhopadhyay Dec 2014

Gaip Interacting Protein C-Terminus Regulates Autophagy And Exosome Biogenesis Of Pancreatic Cancer Through Metabolic Pathways, Santanu Bhattacharya, Krishnendu Pal, Anil K. Sharma, Shamit K. Dutta, Julie S. Lau, Irene K. Yan, Enfeng Wang, Ahmed Elkhanany, Khalid M. Alkharfy, Arunik Sanyal, Tushar C. Patel, Suresh T. Chari, Mark R. Spaller, Debabrata Mukhopadhyay

Dartmouth Scholarship

GAIP interacting protein C terminus (GIPC) is known to play an important role in a variety of physiological and disease states. In the present study, we have identified a novel role for GIPC as a master regulator of autophagy and the exocytotic pathways in cancer. We show that depletion of GIPC-induced autophagy in pancreatic cancer cells, as evident from the upregulation of the autophagy marker LC3II. We further report that GIPC regulates cellular trafficking pathways by modulating the secretion, biogenesis, and molecular composition of exosomes. We also identified the involvement of GIPC on metabolic stress pathways regulating autophagy and microvesicular …

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Dprp: A Database Of Phenotype-Specific Regulatory Programs Derived From Transcription Factor Binding Data, David T. W. Tzeng, Yu-Ting Tseng, Matthew Ung, I-En Liao, Chun-Chi Liu, Chao Cheng Dec 2014

Dprp: A Database Of Phenotype-Specific Regulatory Programs Derived From Transcription Factor Binding Data, David T. W. Tzeng, Yu-Ting Tseng, Matthew Ung, I-En Liao, Chun-Chi Liu, Chao Cheng

Dartmouth Scholarship

Gene expression profiling has been extensively used in the past decades, resulting in an enormous amount of expression data available in public databases. These data sets are informative in elucidating transcriptional regulation of genes underlying various biological and clinical conditions. However, it is usually difficult to identify transcription factors (TFs) responsible for gene expression changes directly from their own expression, as TF activity is often regulated at the posttranscriptional level. In recent years, technical advances have made it possible to systematically determine the target genes of TFs by ChIP-seq experiments. To identify the regulatory programs underlying gene expression profiles, we …

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Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman Dec 2014

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

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Transcription Of The Streptococcus Pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated By Previously Unknown Upstream Elements, Marina Falaleeva, Oliwia W. Zurek, Robert L. Watkins, Robert W. Reed, Hadeel Ali, Paul Sumby, Jovanka M. Voyich, Natalia Korotkova Dec 2014

Transcription Of The Streptococcus Pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated By Previously Unknown Upstream Elements, Marina Falaleeva, Oliwia W. Zurek, Robert L. Watkins, Robert W. Reed, Hadeel Ali, Paul Sumby, Jovanka M. Voyich, Natalia Korotkova

Molecular and Cellular Biochemistry Faculty Publications

The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an …

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The Formin Fmnl3 Assembles Plasma Membrane Protrusions That Participate In Cell–Cell Adhesion, Timothy J. Gauvin, Lorna E. Young, Henry N. Higgs Nov 2014

The Formin Fmnl3 Assembles Plasma Membrane Protrusions That Participate In Cell–Cell Adhesion, Timothy J. Gauvin, Lorna E. Young, Henry N. Higgs

Dartmouth Scholarship

FMNL3 is a vertebrate-specific formin protein previously shown to play a role in angiogenesis and cell migration. Here we define the cellular localization of endogenous FMNL3, the dynamics of GFP-tagged FMNL3 during cell migration, and the effects of FMNL3 suppression in mammalian culture cells. The majority of FMNL3 localizes in a punctate pattern, with >95% of these puncta being indistinguishable from the plasma membrane by fluorescence microscopy. A small number of dynamic cytoplasmic FMNL3 patches also exist, which enrich near cell–cell contact sites and fuse with the plasma membrane at these sites. These cytoplasmic puncta appear to be part of …

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Nuclear Transport Of Single Molecules: Dwell Times At The Nuclear Pore Complex, Ulrich Kubitscheck, David Grunwald, Andreas Hoekstra, Daniel Rohleder, Thorsten Kues, Jan Peter Siebrasse, Reiner Peters Nov 2014

Nuclear Transport Of Single Molecules: Dwell Times At The Nuclear Pore Complex, Ulrich Kubitscheck, David Grunwald, Andreas Hoekstra, Daniel Rohleder, Thorsten Kues, Jan Peter Siebrasse, Reiner Peters

David Grünwald

The mechanism by which macromolecules are selectively translocated through the nuclear pore complex (NPC) is still essentially unresolved. Single molecule methods can provide unique information on topographic properties and kinetic processes of asynchronous supramolecular assemblies with excellent spatial and time resolution. Here, single-molecule far-field fluorescence microscopy was applied to the NPC of permeabilized cells. The nucleoporin Nup358 could be localized at a distance of 70 nm from POM121-GFP along the NPC axis. Binding sites of NTF2, the transport receptor of RanGDP, were observed in cytoplasmic filaments and central framework, but not nucleoplasmic filaments of the NPC. The dwell times of …

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Intranuclear Binding Kinetics And Mobility Of Single Native U1 Snrnp Particles In Living Cells, David Grunwald, Beatrice Spottke, Volker Buschmann, Ulrich Kubitscheck Nov 2014

Intranuclear Binding Kinetics And Mobility Of Single Native U1 Snrnp Particles In Living Cells, David Grunwald, Beatrice Spottke, Volker Buschmann, Ulrich Kubitscheck

David Grünwald

Uridine-rich small nuclear ribonucleoproteins (U snRNPs) are splicing factors, which are diffusely distributed in the nucleoplasm and also concentrated in nuclear speckles. Fluorescently labeled, native U1 snRNPs were microinjected into the cytoplasm of living HeLa cells. After nuclear import single U1 snRNPs could be visualized and tracked at a spatial precision of 30 nm at a frame rate of 200 Hz employing a custom-built microscope with single-molecule sensitivity. The single-particle tracks revealed that most U1 snRNPs were bound to specific intranuclear sites, many of those presumably representing pre-mRNA splicing sites. The dissociation kinetics from these sites showed a multiexponential decay …

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Conversion Of Red Fluorescent Protein Into A Bright Blue Probe, Oksana M. Subach, Illia S. Gundorov, Masami Yoshimura, Fedor V. Subach, Jinghang Zhang, David Grunwald, Ekaterina A. Souslova, Dmitriy M. Chudakov, Vladislav V. Verkhusha Nov 2014

Conversion Of Red Fluorescent Protein Into A Bright Blue Probe, Oksana M. Subach, Illia S. Gundorov, Masami Yoshimura, Fedor V. Subach, Jinghang Zhang, David Grunwald, Ekaterina A. Souslova, Dmitriy M. Chudakov, Vladislav V. Verkhusha

David Grünwald

We used a red chromophore formation pathway, in which the anionic red chromophore is formed from the neutral blue intermediate, to suggest a rational design strategy to develop blue fluorescent proteins with a tyrosine-based chromophore. The strategy was applied to red fluorescent proteins of the different genetic backgrounds, such as TagRFP, mCherry, HcRed1, M355NA, and mKeima, which all were converted into blue probes. Further improvement of the blue variant of TagRFP by random mutagenesis resulted in an enhanced monomeric protein, mTagBFP, characterized by the substantially higher brightness, the faster chromophore maturation, and the higher pH stability than blue fluorescent proteins …

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Autonomy And Robustness Of Translocation Through The Nuclear Pore Complex: A Single-Molecule Study, Thomas Dange, David Grunwald, Antje Grunwald, Reiner Peters, Ulrich Kubitscheck Nov 2014

Autonomy And Robustness Of Translocation Through The Nuclear Pore Complex: A Single-Molecule Study, Thomas Dange, David Grunwald, Antje Grunwald, Reiner Peters, Ulrich Kubitscheck

David Grünwald

All molecular traffic between nucleus and cytoplasm occurs via the nuclear pore complex (NPC) within the nuclear envelope. In this study we analyzed the interactions of the nuclear transport receptors kapalpha2, kapbeta1, kapbeta1DeltaN44, and kapbeta2, and the model transport substrate, BSA-NLS, with NPCs to determine binding sites and kinetics using single-molecule microscopy in living cells. Recombinant transport receptors and BSA-NLS were fluorescently labeled by AlexaFluor 488, and microinjected into the cytoplasm of living HeLa cells expressing POM121-GFP as a nuclear pore marker. After bleaching the dominant GFP fluorescence the interactions of the microinjected molecules could be studied using video microscopy …

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Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives Nov 2014

Nuclear Pore Component Nup98 Is A Potential Tumor Suppressor And Regulates Posttranscriptional Expression Of Select P53 Target Genes, Stephan Singer, Ruiying Zhao, Anthony M. Barsotti, Anette Ouwehand, Mina Fazollahi, Elias Coutavas, Kai Breuhahn, Olaf Neumann, Thomas Longerich, Tobias Pusterla, Maureen A. Powers, Keith M. Giles, Peter J. Leedman, Jochen Hess, David Grunwald, Harmen J. Bussemaker, Robert H. Singer, Peter Schirmacher, Carol Prives

David Grünwald

The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The expression …

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Xk Aprosencephaly And Anencephaly In Sibs, Phillip Townes, Karen Reuter, E. Rosquete, B. Magee Nov 2014

Xk Aprosencephaly And Anencephaly In Sibs, Phillip Townes, Karen Reuter, E. Rosquete, B. Magee

B. Dale Magee

Recent studies have suggested a causal and pathogenetic relationship between holoprosencephaly and anencephaly. In support of the proposed relationship we report a sibship that includes anencephalic male twins and a female infant with a severe form of alobar holoprosencephaly, radial aplasia, and oligodactyly. The upper limb and brain malformations are considered to represent aprosencephaly syndrome. The coexistence of anencephaly and aprosencephaly within a sibship suggests that XK aprosencephaly syndrome may be an autosomal recessive disorder.

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Kynurenine Aminotransferase Iii And Glutamine Transaminase L Are Identical Enzymes That Have Cysteine S-Conjugate Beta-Lyase Activity And Can Transaminate L-Selenomethionine, John T. Pinto, Boris F. Krasnikov, Steven Alcutt, Melanie E. Jones, Thambi Dorai, Arthur J L Cooper Nov 2014

Kynurenine Aminotransferase Iii And Glutamine Transaminase L Are Identical Enzymes That Have Cysteine S-Conjugate Beta-Lyase Activity And Can Transaminate L-Selenomethionine, John T. Pinto, Boris F. Krasnikov, Steven Alcutt, Melanie E. Jones, Thambi Dorai, Arthur J L Cooper

NYMC Faculty Publications

Three of the four kynurenine aminotransferases (KAT I, II, and IV) that synthesize kynurenic acid, a neuromodulator, are identical to glutamine transaminase K (GTK), α-aminoadipate aminotransferase, and mitochondrial aspartate aminotransferase, respectively. GTK/KAT I and aspartate aminotransferase/KAT IV possess cysteine S-conjugate β-lyase activity. The gene for the former enzyme, GTK/KAT I, is listed in mammalian genome data banks as CCBL1 (cysteine conjugate beta-lyase 1). Also listed, despite the fact that no β-lyase activity has been assigned to the encoded protein in the genome data bank, is a CCBL2 (synonym KAT III). We show that human KAT III/CCBL2 possesses cysteine S-conjugate β-lyase …

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Exercise Maintains Sexual Activity In Men Undergoing Androgen Suppression For Prostate Cancer: A Randomized Controlled Trial, Prue Cormie, Robert Newton, Dennis Taaffe, Nigel Spry, David Joseph, M Akhlil Hamid, Daniel Galvao Nov 2014

Exercise Maintains Sexual Activity In Men Undergoing Androgen Suppression For Prostate Cancer: A Randomized Controlled Trial, Prue Cormie, Robert Newton, Dennis Taaffe, Nigel Spry, David Joseph, M Akhlil Hamid, Daniel Galvao

Prue Cormie

Background:Previous research has shown exercise to be an effective method to mitigate many adverse treatment-related effects of androgen suppression therapy (AST) but the potential impact of exercise on sexual activity remains unknown. The purpose of this investigation was to report the effect of a 12-week exercise program on sexual activity in prostate cancer patients undergoing AST.Methods:Fifty-seven prostate cancer patients undergoing AST were randomly assigned to an exercise program (resistance and aerobic modes; n=29) or usual care control (n=28). Sexual activity was assessed by the European Organization for Research and Treatment of Cancer prostate cancer-specific quality of life questionnaire (QLQ-PR25).Results:QLQ-PR25 data …

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Knee Angle-Specific Emg Normalization: The Use Of Polynomial Based Emg-Angle Relationships, J Earp, R Newton, Prue Cormie, A Blazevich Nov 2014

Knee Angle-Specific Emg Normalization: The Use Of Polynomial Based Emg-Angle Relationships, J Earp, R Newton, Prue Cormie, A Blazevich

Prue Cormie

The normalization of EMG signals to those recorded during a maximal voluntary contraction provides a valid construct for comparisons of relative muscle activity. However, the length dependence of muscle activation and purported, substantial, muscle translocation and changes in muscle architecture during dynamic movements presents a need for joint angle-dependent normalization processes. The purposes of the present study were to: (1) quantify variations in muscle activity across a large ROM, (2) determine the accuracy with which fitted EMG-joint angle curves accurately characterized these variations, and (3) compare peak (EMG-P) and average (EMG-A) EMG amplitudes obtained during a countermovement leg extension when …

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Imp3 Expression Is Associated With Poor Outcome And Epigenetic Deregulation In Intrahepatic Cholangiocarcinoma, Yuanyuan Gao, Michelle Yang, Zhong Jiang, Bruce A. Woda, Arthur M. Mercurio, Jianjie Qin, Xinli Huang, Feng Zhang Nov 2014

Imp3 Expression Is Associated With Poor Outcome And Epigenetic Deregulation In Intrahepatic Cholangiocarcinoma, Yuanyuan Gao, Michelle Yang, Zhong Jiang, Bruce A. Woda, Arthur M. Mercurio, Jianjie Qin, Xinli Huang, Feng Zhang

Arthur M. Mercurio

IMP3 is a fetal protein not expressed in normal adult tissues. IMP3 is an oncoprotein and a useful biomarker for a variety of malignancies and is associated with reduced overall survival of a number of them. IMP3 expression and its prognostic value for patients with intrahepatic cholangiocarcinoma (ICC) have not been well investigated. The molecular mechanism underlying IMP3 expression in human cancer cells remains to be elucidated. Here we investigated IMP3 expression in ICC and adjacent nonneoplastic liver in 72 unifocal primary ICCs from a single institute by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction. IMP3 was specifically expressed in …

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Novel Ubiquitin Neuropathology In Frontotemporal Dementia With Valosin-Containing Protein Gene Mutations, Mark Forman, Ian Mackenzie, Nigel Cairns, Eric Swanson, Philip Boyer, David Drachman, Bharati Jhaveri, Jason Karlawish, Alan Pestronk, Thomas Smith, Pang-Hsien Tu, Giles Watts, William Markesbery, Charles Smith, Virginia Kimonis Nov 2014

Novel Ubiquitin Neuropathology In Frontotemporal Dementia With Valosin-Containing Protein Gene Mutations, Mark Forman, Ian Mackenzie, Nigel Cairns, Eric Swanson, Philip Boyer, David Drachman, Bharati Jhaveri, Jason Karlawish, Alan Pestronk, Thomas Smith, Pang-Hsien Tu, Giles Watts, William Markesbery, Charles Smith, Virginia Kimonis

Jason Karlawish

Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). However, there is limited information on the neuropathology in IBMPFD. We performed a detailed, systematic analysis of the neuropathologic changes in 8 patients with VCP mutations. A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene …

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The Capacity To Vote Of Persons With Alzheimer's Disease, Paul Appelbaum, Richard Bonnie, Jason Karlawish Nov 2014

The Capacity To Vote Of Persons With Alzheimer's Disease, Paul Appelbaum, Richard Bonnie, Jason Karlawish

Jason Karlawish

OBJECTIVE: The right to vote can be abrogated when persons become incompetent to cast a ballot. This applies particularly to people with Alzheimer's disease, who at some point will lose capacity. A 2001 federal court decision offered the first clear criteria ("Doe voting capacity standard") for determining voting competence, focused on understanding the nature and effect of voting and on the ability to choose. This article explores how persons with Alzheimer's disease perform on these criteria. METHOD: The Doe standard was operationalized in a brief questionnaire, along with measures of appreciation and reasoning about voting choices. Performance was assessed in …

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Beneath The Surface: Discovering The Unvoiced Concerns Of Older Adults With Type 2 Diabetes Mellitus, Jennifer Tjia, Jane Givens, Jason Karlawish, A. Okoli-Umeweni, Frances Barg Nov 2014

Beneath The Surface: Discovering The Unvoiced Concerns Of Older Adults With Type 2 Diabetes Mellitus, Jennifer Tjia, Jane Givens, Jason Karlawish, A. Okoli-Umeweni, Frances Barg

Jason Karlawish

Emerging clinical guidelines recommend shared decision making to individualize drug regimens for older adults with Type 2 diabetes mellitus. While the current health education campaign for diabetes in the United States recommends physician-initiated medication-related discussions about adherence and side effects, little emphasis is placed on soliciting patient concerns. This study's aim was to explore the concerns of older adults with diabetes about the complexity of their drug regimens and to determine whether they discussed medication-related concerns with their physician. Twenty-two patients with Type 2 diabetes age 65 years and older who used five or more medications were selected from an …

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Candida Albicans Ethanol Stimulates Pseudomonas Aeruginosa Wspr-Controlled Biofilm Formation As Part Of A Cyclic Relationship Involving Phenazines, Annie I. Chen, Emily F. Dolben, Chinweike Okegbe, Colleen E. Harty, Yuriy Golub, Sandy Thao, Dae Gon Ha, Sven D. Willger, George A. O'Toole, Caroline S. Harwood, Lars E. P Dietrich, Deborah A. Hogan Oct 2014

Candida Albicans Ethanol Stimulates Pseudomonas Aeruginosa Wspr-Controlled Biofilm Formation As Part Of A Cyclic Relationship Involving Phenazines, Annie I. Chen, Emily F. Dolben, Chinweike Okegbe, Colleen E. Harty, Yuriy Golub, Sandy Thao, Dae Gon Ha, Sven D. Willger, George A. O'Toole, Caroline S. Harwood, Lars E. P Dietrich, Deborah A. Hogan

Dartmouth Scholarship

In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF) and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic- di-GMP (c-di-GMP), and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol …

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Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood Oct 2014

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …

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The Role Of Correctional Officers In Multidisciplinary Mental Health Care In Prisons, Kenneth Appelbaum, James Hickey, Ira Packer Oct 2014

The Role Of Correctional Officers In Multidisciplinary Mental Health Care In Prisons, Kenneth Appelbaum, James Hickey, Ira Packer

Ira K Packer

Prisons have become the homes of thousands of inmates who have mental disorders. The stress of incarceration can cause morbidity among these individuals, resulting in more severe symptoms and more disruptive behavior. Effective treatment for such inmates often involves services provided by a multidisciplinary treatment team that includes correctional officers. Correctional officers can assist in observations and interventions, and they play a unique role on specialized housing units. Successful collaboration between correctional officers and treatment teams requires a foundation of mutual respect, shared training, and ongoing communication and cooperation. With these elements in place, correctional officers can assist the treatment …

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Relationship Between Race And Ethnicity And Forensic Clinical Triage Dispositions, Debra Pinals, Ira Packer, William Fisher, Kristen Roy-Bujnowski Oct 2014

Relationship Between Race And Ethnicity And Forensic Clinical Triage Dispositions, Debra Pinals, Ira Packer, William Fisher, Kristen Roy-Bujnowski

Ira K Packer

OBJECTIVE: Racial and ethnic disparities in the criminal justice system have been widely reported, as have racial and ethnic disparities in diagnoses and certain aspects of clinical management. This study examined the association between race and ethnicity and dispositions for pretrial defendants who were referred for forensic mental health evaluations. METHODS: Available data were reviewed for all defendants in Massachusetts who were referred to a Massachusetts court clinic from 1994 to 2001 for a screening evaluation of their competence to stand trial, their criminal responsibility, or both. Logistic regression models were developed to assess the relationship between defendants' race and …

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Use Of A State Inpatient Forensic System Under Managed Mental Health Care, William Fisher, Barbara Dickey, Sharon-Lise Normand, Ira Packer, Albert Grudzinskas, Hocine Azeni Oct 2014

Use Of A State Inpatient Forensic System Under Managed Mental Health Care, William Fisher, Barbara Dickey, Sharon-Lise Normand, Ira Packer, Albert Grudzinskas, Hocine Azeni

Ira K Packer

OBJECTIVES: One of the goals of managed mental health care has been to lower the use of inpatient psychiatric treatment. In the past, interventions that have limited hospitalization for persons with severe mental illness have led to greater involvement of these individuals with the criminal justice and forensic mental health systems. The authors examined associations between Medicaid managed mental health care in Massachusetts and rates of admission to the inpatient forensic mental health service maintained by the state's mental health department. METHODS: A total of 7,996 persons who were receiving services from the department before and after the introduction of …

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Dissociation Between Face Perception And Face Memory In Adults, But Not Children, With Developmental Prosopagnosia, Kirsten A. Dalrymple, Lúcia Garrido, Brad Duchaine Oct 2014

Dissociation Between Face Perception And Face Memory In Adults, But Not Children, With Developmental Prosopagnosia, Kirsten A. Dalrymple, Lúcia Garrido, Brad Duchaine

Dartmouth Scholarship

Cognitive models propose that face recognition is accomplished through a series of discrete stages, including perceptual representation of facial structure, and encoding and retrieval of facial information. This implies that impaired face recognition can result from failures of face perception, face memory, or both. Studies of acquired prosopagnosia, autism spectrum disorders, and the development of normal face recognition support the idea that face perception and face memory are distinct processes, yet this distinction has received little attention in developmental prosopagnosia (DP). To address this issue, we tested the face perception and face memory of children and adults with DP. By …

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