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Full-Text Articles in Biology

Expression Of Human Amyloid Precursor Protein In The Skeletal Muscles Of Drosophila Results In Age- And Activity-Dependent Muscle Weakness, Lawrence M. Schwartz, Chul Kim, Sapeckshita Srivastava, Marian Rice, Tanja A. Godenschwege, Brooke Bentley, Saranya Ravi, Shuang Shao, Ig T. Woodard Apr 2011

Expression Of Human Amyloid Precursor Protein In The Skeletal Muscles Of Drosophila Results In Age- And Activity-Dependent Muscle Weakness, Lawrence M. Schwartz, Chul Kim, Sapeckshita Srivastava, Marian Rice, Tanja A. Godenschwege, Brooke Bentley, Saranya Ravi, Shuang Shao, Ig T. Woodard

Lawrence M. Schwartz

Background One of the hallmarks of Alzheimer's disease, and several other degenerative disorders such as Inclusion Body Myositis, is the abnormal accumulation of amyloid precursor protein (APP) and its proteolytic amyloid peptides. To better understand the pathological consequences of inappropriate APP expression on developing tissues, we generated transgenic flies that express wild-type human APP in the skeletal muscles, and then performed anatomical, electrophysiological, and behavioral analysis of the adults. Results We observed that neither muscle development nor animal longevity was compromised in these transgenic animals. However, human APP expressing adults developed age-dependent defects in both climbing and flying. We could …


Investigation Of Gene Expression In C2c12 Myotubes Following Simvastatin Application And Mechanical Strain, Ji-Gu Yu, Kimberly Sewright, Monica J. Hubal, Jing-Xia Liu, Lawrence M. Schwartz, Eric P. Hoffman, Priscilla M. Clarkson Jan 2009

Investigation Of Gene Expression In C2c12 Myotubes Following Simvastatin Application And Mechanical Strain, Ji-Gu Yu, Kimberly Sewright, Monica J. Hubal, Jing-Xia Liu, Lawrence M. Schwartz, Eric P. Hoffman, Priscilla M. Clarkson

Lawrence M. Schwartz

Aim: The 3-hydroxy-3methylgutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are the most effective prescribed drugs for lowering serum cholesterol; however, although statins are extremely safe medications and have brought significant benefits to patients with hypercholesterolemia, they have been shown to produce myalgia, cramps, exercise intolerance and fatigue. The aim of the study was to investigate the molecular mechanisms that may mediate statin myopathy. Methods: We used DNA microarray analysis to examine the changes in gene expression profiles induced by 1 hour and 6 hours of statin treatment on differentiated C2C12 myotubes. Four genes were selected for analysis at the protein …


Lepidopteran Dalp, And Its Mammalian Ortholog Hic-5, Function As Negative Regulators Of Muscle Differentiation, Lawrence M. Schwartz, Y. Hu, P. Cascone, L. Cheng, D. Sun, J. R. Nambu Jan 1999

Lepidopteran Dalp, And Its Mammalian Ortholog Hic-5, Function As Negative Regulators Of Muscle Differentiation, Lawrence M. Schwartz, Y. Hu, P. Cascone, L. Cheng, D. Sun, J. R. Nambu

Lawrence M. Schwartz

During myogenesis, reductions in trophic factor availability signal most myoblasts to fuse, up-regulate the expression of muscle-specific genes, and form myotubes. Those cells failing to differentiate into myotubes initiate apoptosis and rapidly die. At present, the signal-transduction molecules that determine whether myoblasts should differentiate or die are largely unknown. In this report, we describe the cloning and characterization of DALP, a small LIM-only type zinc-finger protein that is induced when the intersegmental muscles (ISMs) of the moth Manduca sexta become committed to die at the end of metamorphosis. Forced expression of death-associated LIM-only protein (DALP) in Drosophila results in skeletal …


Cooperative Functions Of The Reaper And Head Involution Defective Genes In The Programmed Cell Death Of Drosophila Central Nervous System Midline Cells, Lawrence M. Schwartz, L. Zhou, A. Schnitzler, J. Agapite, H. Steller, J. R. Nambu Jan 1997

Cooperative Functions Of The Reaper And Head Involution Defective Genes In The Programmed Cell Death Of Drosophila Central Nervous System Midline Cells, Lawrence M. Schwartz, L. Zhou, A. Schnitzler, J. Agapite, H. Steller, J. R. Nambu

Lawrence M. Schwartz

In Drosophila, the chromosomal region 75C1–2 contains at least three genes, reaper (rpr), head involution defective (hid), and grim, that have important functions in the activation of programmed cell death. To better understand how cells are killed by these genes, we have utilized a well defined set of embryonic central nervous system midline cells that normally exhibit a specific pattern of glial cell death. In this study we show that both rpr and hid are expressed in dying midline cells and that the normal pattern of midline cell death requires the function of multiple genes in the 75C1–2 interval. We …


Do All Programmed Cell Deaths Occur Via Apoptosis?, Lawrence M. Schwartz, S. Smith, M.E. E. Jones, B. A. Osborne Jan 1993

Do All Programmed Cell Deaths Occur Via Apoptosis?, Lawrence M. Schwartz, S. Smith, M.E. E. Jones, B. A. Osborne

Lawrence M. Schwartz

During development, large numbers of cells die by a nonpathological process referred to as programmed cell death. In many tissues, dying cells display similar changes in morphology and chromosomal DNA organization, which has been termed apoptosis. Apoptosis is such a widely documented phenomenon that many authors have assumed all programmed cell deaths occur by this process. Two well-characterized model systems for programmed cell death are (i) the death of T cells during negative selection in the mouse thymus and (ii) the loss of intersegmental muscles of the moth Manduca sexta at the end of metamorphosis. In this report we compare …


Gene Activation Is Required For Developmentally Programmed Cell Death, Lawrence M. Schwartz, L. Kosz, B. K. Kay Jan 1990

Gene Activation Is Required For Developmentally Programmed Cell Death, Lawrence M. Schwartz, L. Kosz, B. K. Kay

Lawrence M. Schwartz

The intersegmental muscles of the tobacco hawkmoth Manduca sexta die during the 36-hr period after metamorphosis. The trigger for cell death is a fall in the ecdysteroid titer. Commitment of the intersegmental muscles to degenerate involves selective repression and activation of ecdysteroid-responsive genes. When the pattern of gene expression is altered after injection of either 20-hydroxyecdysone or actinomycin D, the muscles persist. cDNA clones have been isolated for four genes that become abundantly expressed coincident with the commitment to degenerate. The data presented here indicate that programmed cell death is not due to the cessation of macromolecular synthesis in condemned …


Cyclic Gmp May Serve As A Second Messenger In Peptide-Induced Muscle Degeneration In An Insect, Lawrence M. Schwartz, J. W. Truman Jan 1984

Cyclic Gmp May Serve As A Second Messenger In Peptide-Induced Muscle Degeneration In An Insect, Lawrence M. Schwartz, J. W. Truman

Lawrence M. Schwartz

At the end of metamorphosis, the intersegmental muscles of the moth Antheraea polyphemus undergo rapid degeneration in response to the peptide eclosion hormone (EH). Muscle death was preceded by a 22-fold increase in muscle guanosine-3',5'-cyclic monophosphate (cGMP) titers, which peaked 60 min after peptide exposure; adenosine-3'5'-cyclic monophosphate (cAMP) titers remained unchanged. EH induced a dose-dependent increase in muscle cGMP content with a threshold dose similar to that needed to induce cell death. Exogenous cGMP, but not cAMP, mimicked the action of EH. Sodium nitroprusside, a potent stimulator of guanylate cyclase, and methylated xanthines, a class of 3',5'-cyclic-nucleotide phosphodiesterase inhibitors, also …