Mark A. Smith

IZO: Applications of Large-Window Compression to Virtual Machine Management (2009)

Mark A. Smith, Jan Pieper, Daniel Gruhl, Lucas Villa, Real Ibm

The increased use of virtual machines in the enterprise environment presents an interesting new set of challenges for the administrators of today’s information systems. In addition to the...

Evidence for the Novel Expression of Human Kallikrein-related Peptidase 3, Prostate-Specific Antigen, in the Brain. (2009)

Stone, Jeremy G., Rolston, Raj K., Ueda, Masumi, Lee, Hyoung-Gon, Richardson, Sandy L., Castellani, Rudy J., ...

Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases. With...

Molecular Pathogenesis of Alzheimer’s Disease: Reductionist versus Expansionist Approaches (2009)

Rudy J. Castellani, Xiongwei Zhu, Hyoung-Gon Lee, Mark A. Smith, George Perry

Alzheimer’s disease (AD) is characterized clinically by dementia and pathologically by two hallmark lesions, senile plaques and neurofibrillary tangles. About a quarter century ago these hallmark...

Molecular Pathogenesis of Alzheimer's Disease: Reductionist versus Expansionist Approaches. (2009)

Castellani, Rudy J., Zhu, Xiongwei, Lee, Hyoung-Gon, Smith, Mark A., Perry, George

Alzheimer's disease (AD) is characterized clinically by dementia and pathologically by two hallmark lesions, senile plaques and neurofibrillary tangles. About a quarter century ago these hallmark...

Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease. (2009)

Su, Bo, Liu, Haihua, Wang, Xinglong, Chen, Shu G, Siedlak, Sandra L, Kondo, Eisaku, ...

ABSTRACT: Lewy bodies and Lewy neurites constitute the cardinal neuropathological features of both Parkinson's disease (PD) and Lewy body dementia (LBD). Whereas alpha-synuclein has been found to be...

Mitochondrial Drugs for Alzheimer Disease (2009)

David J. Bonda, Xinglong Wang, Katarzyna A. Gustaw-Rothenberg, George Perry, Mark A. Smith, Xiongwei Zhu

Therapeutic strategies for Alzheimer disease (AD) have yet to offer a diseasemodifying effect to stop the debilitating progression of neurodegeneration and cognitive decline. Rather, treatments thus...

Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets (2009)

Susana Cardoso, Renato Santos, Sonia Correia, Cristina Carvalho, Xiongwei Zhu, Hyoung-Gon Lee, ...

Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic...

GaAs Photovoltaics on Polycrystalline Ge Substrates (2008)

David M. Wilt, Annamaria T. Pal, Jeremiah S. Mcnatt, David S. Wolford, A. Landis, Mark A. Smith, ...

High efficiency III-V multijunction solar cells deposited on metal foil or even polymer substrates can provide tremendous advantages in mass and stowage, particularly for planetary missions. As a...

Associate Editors (2008)

Mark A. Smith, George Perry, Xiongwei Zhu, Abdelali Haoudi, Neurodegenerative Diseases, Mark A. Smith, ...

distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease (2008)

Bryan, Kathryn J, Zhu, Xiongwei, Harris, Peggy L, Perry, George, Castellani, Rudy J, Smith, Mark A, ...

Abstract Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of...

The role of metabotropic glutamate receptors in Alzheimer’s disease (2008)

Neu Obiologi E, Addressed To M. A. Smith, Hyoung-gon Lee, Xiongwei Zhu, Michael J. O’neill, Gemma Casadesus, ...

Abstract. While glutamatergic transmission is severely altered by early degeneration of cortico-cortical connections and hippocampal projections in Alzheimer’s disease (AD), the role of glutamate...

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes (2008)

Spanel-Borowski, Katharina, Smith, Mark A., Simone, Cristiano, Simonsen, Anne, Simon, Hans-Uwe, Silva-Zacarin, Elaine C.M., ...

Research in autophagy continues to accelerate, and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring...

Retinoblastoma Protein Phosphorylation at Multiple Sites is Associated with Neurofibrillary Pathology in Alzheimer Disease. (2008)

Thakur, Akanksha, Siedlak, Sandra L, James, Sheronica L, Bonda, David J, Rao, Akanksha, Webber, Kate M, ...

The re-expression of multiple cell cycle markers representing various cell cycle phases in postmitotic pyramidal neurons suggests that neurons in Alzheimer disease (AD) attempt to re-enter the cell...

Sublethal RNA Oxidation as a Mechanism for Neurodegenerative Disease (2008)

Rudy J. Castellani, Akihiko Nunomura, Raj K. Rolston, Paula I. Moreira, Atsushi Takeda, George Perry, ...

Although cellular RNA is subjected to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigations of the biological...

Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease. (2008)

Bryan, Kathryn J, Zhu, Xiongwei, Harris, Peggy L, Perry, George, Castellani, Rudy J, Smith, Mark A, ...

ABSTRACT: Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of...

The Autistic Phenotype Exhibits a Remarkably Localized Modification of Brain Protein by Products of Free Radical-Induced Lipid Oxidation (2008)

Teresa A. Evans, Sandra L. Siedlak, Liang Lu, Xiaoming Fu, Zeneng Wang, Woody R. McGinnis, ...

Oxidative damage has been documented in the peripheral tissues of autism patients. In this study, we sought evidence of oxidative injury in autistic brain. Carboxyethyl pyrrole (CEP) and...

Dimension-Splitting for Simplifying Diffusion in Lattice-Gas Models (2007)

Raissa M. D’souza, Norman H. Margolus, Mark A. Smith

We introduce a simplified technique for incorporating diffusive phenomena into lattice-gas molecular dynamics models. In this method, spatial interactions take place one dimension at a time, with a...

Quantitative Languages for Complex Systems (2007)

Applied To Biological, Mark A. Smith, Yaneer Bar-yam, William Gelbart

We believe that many fields of scientific study are hampered by the lack of precise language to describe the structure and dynamics of complex systems. New quantitative languages are needed. The...

The contribution of luteinizing hormone to Alzheimer disease pathogenesis. (2007)

Webber, Kate M., Perry, George, Smith, Mark A., Casadesus, Gemma

Several hypotheses have been proposed that attempt to explain the pathogenesis of Alzheimer Disease (AD) including theories involving senile plaque and neurofibrillary tangle formation, increased...

Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease. (2007)

Casadesus, Gemma, Smith, Mark A, Basu, Samar, Hua, Jing, Capobianco, Dae E, Siedlak, Sandra L, ...

BACKGROUND: Inflammation and oxidative stress are both involved in the pathogenesis of Alzheimer disease and have been shown to be reciprocally linked. One group of molecules that have been directly...

BRCA1 may modulate neuronal cell cycle re-entry in Alzheimer disease. (2007)

Evans, Teresa A., Raina, Arun K., Delacourte, Andr, Aprelikova, Olga, Lee, Hyoung-gon, Zhu, Xiongwei, ...

In Alzheimer disease, neuronal degeneration and the presence of neurofibrillary tangles correlate with the severity of cognitive decline. Neurofibrillary tangles contain the antigenic profile of many...

The contribution of luteinizing hormone to Alzheimer disease pathogenesis. (2007)

Webber, Kate M., Perry, George, Smith, Mark A., Casadesus, Gemma

Several hypotheses have been proposed that attempt to explain the pathogenesis of Alzheimer Disease (AD) including theories involving senile plaque and neurofibrillary tangle formation, increased...

The Pathology of Alzheimer Disease Elicits an In Vivo Immunological Response (2007)

David J. Bonda, Kate M. Webber, Sandra L. Siedlak, George Perry, Robert P. Friedland, Mark A. Smith

The mechanism(s) responsible for the loss of neurons that characterizes Alzheimer disease is incompletely understood. Nonetheless, there is considerable evidence suggestive of immuneabnormalities...

Targeting gonadotropins: an alternative option for Alzheimer disease treatment. (2006)

Casadesus, Gemma, Puig, Emma Ramiro, Webber, Kate M., Atwood, Craig S., Escuer, Margarida Castell, Bowen, Richard L., ...

Recent evidence indicates that, alongside oxidative stress, dysregulation of the cell cycle in neurons susceptible to degeneration in Alzheimer disease may play a crucial role in the initiation of...

Oxidative damage to RNA in neurodegenerative diseases. (2006)

Nunomura, Akihiko, Honda, Kazuhiro, Takeda, Atsushi, Hirai, Keisuke, Zhu, Xiongwei, Smith, Mark A., ...

Since 1999, oxidative damage to RNA molecules has been described in several neurological diseases including Alzheimer's disease, Parkinson's disease, Down syndrome, dementia with Lewy bodies, prion...

LRRK2 in Parkinson's disease and dementia with Lewy bodies. (2006)

Zhu, Xiongwei, Babar, Asim, Siedlak, Sandra L, Yang, Qiwei, Ito, Genta, Iwatsubo, Takeshi, ...

BACKGROUND: Mutations in LRRK2 encoding leucine-rich repeat kinase 2 are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson's disease (PD). To...

Steroidogenic acute regulatory protein (StAR): evidence of gonadotropin-induced steroidogenesis in Alzheimer disease. (2006)

Webber, Kate M, Stocco, Douglas M, Casadesus, Gemma, Bowen, Richard L, Atwood, Craig S, Previll, Laura A, ...

BACKGROUND: Alzheimer disease (AD) is clinically characterized by progressive memory loss, impairments in behavior, language and visual-spatial skills and ultimately, death. Epidemiological data...

Heme deficiency in Alzheimer's disease: a possible connection to porphyria. (2006)

Dwyer, Barney E., Stone, Meghan L., Zhu, Xiongwei, Perry, George, Smith, Mark A.

Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD...

Heme Deficiency in Alzheimer's Disease: A Possible Connection to Porphyria (2006)

Barney E. Dwyer, Meghan L. Stone, Xiongwei Zhu, George Perry, Mark A. Smith

Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD...

Targeting Gonadotropins: An Alternative Option for Alzheimer Disease Treatment (2006)

Gemma Casadesus, Emma Ramiro Puig, Kate M. Webber, Craig S. Atwood, Margarida Castell Escuer, Richard L. Bowen, ...

Recent evidence indicates that, alongside oxidative stress, dysregulation of the cell cycle in neurons susceptible to degeneration in Alzheimer disease may play a crucial role in the initiation of...

Oxidative Damage to RNA in Neurodegenerative Diseases (2006)

Akihiko Nunomura, Kazuhiro Honda, Atsushi Takeda, Keisuke Hirai, Xiongwei Zhu, Mark A. Smith, ...

Since 1999, oxidative damage to RNA molecules has been described in several neurological diseases including Alzheimer's disease, Parkinson's disease, Down syndrome, dementia with Lewy bodies, prion...

Vicksburg: The Campaign That Opened the Mississippi (review) (2005)

Smith, Mark A.

The Journal of Military History - Volume 69, Number 3, July 2005

Involvement of complex carbohydrate chemistry in Alzheimer’s disease (2005)

Dewitt, David A., Castellani, Rudy J., Perry, George, Smith, Mark A.

The cardinal feature of Alzheimer disease is the extracellular deposition of proteinaceous amyloid-β fibrils as senile plaques. Amyloid-β plays an essential role in disease diagnosis and is...

Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution (2005)

Richards, Stephen, Liu, Yue, Bettencourt, Brian R., Hradecky, Pavel, Letovsky, Stan, Nielsen, Rasmus, ...

We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout...

Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction (2005)

Hagemann, Tracy L., Gaeta, Stephen A., Smith, Mark A., Johnson, Delinda A., Johnson, Jeffrey A., Messing, Albee

Alexander disease is a fatal neurodegenerative disorder resulting from missense mutations of the intermediate filament protein, GFAP. The pathological hallmark of this disease is the formation of...

Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction (2005)

Hagemann, Tracy L., Gaeta, Stephen A., Smith, Mark A., Johnson, Delinda A., Johnson, Jeffrey A., Messing, Albee

Alexander disease is a fatal neurodegenerative disorder resulting from missense mutations of the intermediate filament protein, GFAP. The pathological hallmark of this disease is the formation of...

Comparative genome sequencing of drosophila pseudoobscura: Chromosomal, gene and cis-element evolution (2004)

Richards, Stephen, Liu, Yue, Bettencourt, Brian R., Hradecky, Pavel, Letovsky, Stan, Nielsen, Rasmus, ...

The genome sequence of a second fruit fly, D. pseudoobscura, presents an opportunity for comparative analysis of a primary model organism D. melanogaster. The vast majority of Drosophila genes have...

Alzheimer model for drug screening (2003)

Smith, Mark A., McShea, Andrew

Field of the invention: The present invention relates to reagents and methods for drug screening and, more particularly, neuronal cells and tissue for screening potential Alzheimer therapeutics....

Alzheimer model for drug screening (2003)

Smith, Mark A., McShea, Andrew

Field of the invention: The present invention relates to reagents and methods for drug screening and, more particularly, neuronal cells and tissue for screening potential Alzheimer therapeutics....

Impaired regulation of synaptic strength in hippocampal neurons from GluR1-deficient mice (2003)

Andrásfalvy, Bertalan K., Smith, Mark A., Borchardt, Thilo, Sprengel, Rolf, Magee, Jeffrey C.

Neurons of the central nervous system (CNS) exhibit a variety of forms of synaptic plasticity, including associative long-term potentiation and depression (LTP/D), homeostatic activity-dependent...

Microtubule reduction in Alzheimer's disease and aging is independent of tau filament formation. (2003)

Cash, Adam D., Aliev, Gjumrakch, Siedlak, Sandra L., Nunomura, Akihiko, Fujioka, Hisashi, Zhu, Xiongwei, ...

Biochemical studies show that phosphorylated tau, like that found in paired helical filaments (PHFs), does not promote microtubule assembly leading to the view that PHF formation leads to microtubule...

Alzheimer Disease and Oxidative Stress. (2002)

Perry, George, Cash, Adam D., Smith, Mark A.

Research in Alzheimer disease has recently demonstrated compelling evidence on the importance of oxidative processes in its pathogenesis. Cellular changes show that oxidative stress is an event that...

Alzheimer Disease and Oxidative Stress (2002)

George Perry, Adam D. Cash, Mark A. Smith

Research in Alzheimer disease has recently demonstrated compelling evidence on the importance of oxidative processes in its pathogenesis. Cellular changes show that oxidative stress is an event that...

Dimension-splitting for simplifying diffusion in lattice-gas models (2001)

D'Souza, Raissa M., Margolus, Norman H., Smith, Mark A.

We introduce a simplified technique for incorporating diffusive phenomena into lattice-gas molecular dynamics models. In this method, spatial interactions take place one dimension at a time, with a...

Hibernation, a model of neuroprotection. (2001)

Zhou, Fang, Zhu, Xiongwei, Castellani, Rudy J., Stimmelmayr, Raphaela, Perry, George, Smith, Mark A., ...

Hibernation, a natural model of tolerance to cerebral ischemia, represents a state of pronounced fluctuation in cerebral blood flow where no brain damage occurs. Numerous neuroprotective aspects may...

The early word catches the weights (2001)

Mark A. Smith, Garrison W. Cottrell, Karen L. Anderson

The strong correlation between the frequency of words and their naming latency has been well documented. However, as early as 1973, the Age of Acquisition (AoA) of a word was alleged to be the actual...

The early word catches the weights (2001)

Mark A. Smith, Garrison W. Cottrell, Karen L. Anderson

The strong correlation between the frequency of words and their naming latency has been well documented. However, as early as 1973, the Age of Acquisition (AoA) of a word was alleged to be the actual...

The early word catches the weights (2001)

Mark A. Smith, Garrison W. Cottrell

The strong correlation between the frequency of words and their naming latency has been well documented. However, as early as 1973, the Age of Acquisition (AoA) of a word was alleged to be the actual...

Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation. (2000)

Mah, Alex L., Perry, George, Smith, Mark A., Monteiro, Mervyn J.

Mutations in the highly homologous presenilin genes encoding presenilin-1 and presenilin-2 (PS1 and PS2) are linked to early-onset Alzheimer's disease (AD). However, apart from a role in early...

Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. (1999)

Barlow, Carrolee, Dennery, Phyllis A., Shigenaga, Mark K., Smith, Mark A., Morrow, Jason D., Roberts, L. Jackson, ...

Ataxia-telangiectasia (A-T) is characterized by a markedly increased sensitivity to ionizing radiation, increased incidence of cancer, and neurodegeneration, especially of the cerebellar Purkinje...

Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. (1999)

Zhang, Jing, Perry, George, Smith, Mark A., Robertson, David, Olson, Sandra J., Graham, Doyle G., ...

Oxidative damage, including modification of nucleic acids, may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson's disease (PD). To investigate the...

Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. (1997)

Smith, Mark A., Harris, Peggy L. R., Sayre, Lawrence M., Perry, George

Damage from free radicals has been demonstrated in susceptible neuronal populations in cases of Alzheimer disease. In this study, we investigated whether iron, a potent source of the highly reactive...

Minimal sets of connectives : senior honors thesis / (1996)

Smith, Mark A.

Thesis (B.S. )--Appalachian State University, 1996.

Asthma Presentations to Emergency Departments in Western Sydney during the January 1994 Bushfires (1996)

SMITH, MARK A, JALALUDIN, BIN, BYLES, JULIE E, LIM, LYNETTE, LEEDER, STEPHEN R

Smith M A (Western Sector Public Health Unit, 13 New St, Parramatta Nth, 2151, Sydney, Australia), Jalaludin B, Byles J E, Lim L and Leader S R. Asthma presentations to emergency departments in...

Redox potential and oxygen concentration as factors in the susceptibility of Helicobacter pylori to nitroheterocyclic drugs (1995)

Smith, Mark A., Edwards, David I.

Metronidazole sensitive (Mtzs) and resistant (MtzR) strains of Helicobacter pylori were tested for their sensitivities to eleven nitroheterocyclic drugs of known reduction potential under a wide...

The influence of microaerophilia and anaerobiosis on metronidazole uptake in Helicobacter pylori (1995)

Smith, Mark A., Edwards, David I.

Resistance of Helicobacter pylori to metronidazole during therapy for gastroduodenal ulcers is claimed to be responsible for failure to eradicate the pathogen and thus the disease. Resistance to...

Reducing alcohol consumption among university students: recruitment and program design strategies based on Social Marketing Theory (1994)

Black, David R., Smith, Mark A.

Recruitment of program participants and development of appealing comprehensive alcohol abuse prevention programs is an exigent priority for university campuses due to the serious physical and...

Expression of a borage desaturase cDNA containing an N-terminal cytochrome b5 domain results in the accumulation of high levels of Δ6-desaturated fatty acids in transgenic tobacco

Sayanova, Olga, Smith, Mark A., Lapinskas, Peter, Stobart, A. Keith, Dobson, Gary, Christie, William W., ...

γ-Linolenic acid (GLA; C18:3 Δ6,9,12) is a component of the seed oils of evening primrose (Oenothera spp.), borage (Borago officinalis L.), and some other plants. It is widely used as a dietary...

Loss of the ataxia–telangiectasia gene product causes oxidative damage in target organs

Barlow, Carrolee, Dennery, Phyllis A., Shigenaga, Mark K., Smith, Mark A., Morrow, Jason D., Roberts, L. Jackson, ...

Ataxia–telangiectasia (A-T) is characterized by a markedly increased sensitivity to ionizing radiation, increased incidence of cancer, and neurodegeneration, especially of the cerebellar Purkinje...

Iron accumulation in Alzheimer disease is a source of redox-generated free radicals

Smith, Mark A., Harris, Peggy L. R., Sayre, Lawrence M., Perry, George

Damage from free radicals has been demonstrated in susceptible neuronal populations in cases of Alzheimer disease. In this study, we investigated whether iron, a potent source of the highly reactive...

A Condensing Enzyme from the Seeds of Lesquerella fendleri That Specifically Elongates Hydroxy Fatty Acids1

Moon, Hangsik, Smith, Mark A., Kunst, Ljerka

Lesquerella fendleri seed oil contains up to 60% hydroxy fatty acids, nearly all of which is the 20-carbon hydroxy fatty acid lesquerolic acid (d-14-hydroxyeicos-cis-11-enoic acid). Previous work...

Alzheimer Disease and Oxidative Stress

Perry, George, Cash, Adam D., Smith, Mark A.

Research in Alzheimer disease has recently demonstrated compelling evidence on the importance of oxidative processes in its pathogenesis. Cellular changes show that oxidative stress is an event that...

Selective thyroid hormone receptor-β activation: A strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability

Grover, Gary J., Mellström, Karin, Ye, Liu, Malm, Johan, Li, Yi-Lin, Bladh, Lars-Göran, ...

Few treatments for obesity exist and, whereas efficacious therapeutics for hyperlipidemia are available, further improvements are desirable. Thyroid hormone receptors (TRs) regulate both body weight...

Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

Richards, Stephen, Liu, Yue, Bettencourt, Brian R., Hradecky, Pavel, Letovsky, Stan, Nielsen, Rasmus, ...

We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout...

The role of insulin receptor substrate 2 in hypothalamic and β cell function

Choudhury, Agharul I., Heffron, Helen, Smith, Mark A., Al-Qassab, Hind, Xu, Allison W., Selman, Colin, ...

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons...

Heme Deficiency in Alzheimer's Disease: A Possible Connection to Porphyria

Dwyer, Barney E., Stone, Meghan L., Zhu, Xiongwei, Perry, George, Smith, Mark A.

Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD...

Targeting Gonadotropins: An Alternative Option for Alzheimer Disease Treatment

Casadesus, Gemma, Puig, Emma Ramiro, Webber, Kate M., Atwood, Craig S., Escuer, Margarida Castell, Bowen, Richard L., ...

Recent evidence indicates that, alongside oxidative stress, dysregulation of the cell cycle in neurons susceptible to degeneration in Alzheimer disease may play a crucial role in the initiation of...

Oxidative Damage to RNA in Neurodegenerative Diseases

Nunomura, Akihiko, Honda, Kazuhiro, Takeda, Atsushi, Hirai, Keisuke, Zhu, Xiongwei, Smith, Mark A., ...

Since 1999, oxidative damage to RNA molecules has been described in several neurological diseases including Alzheimer's disease, Parkinson's disease, Down syndrome, dementia with Lewy bodies, prion...

Melanocortins and agouti-related protein modulate the excitability of two arcuate nucleus neuron populations by alteration of resting potassium conductances

Smith, Mark A, Hisadome, Kazunari, Al-Qassab, Hind, Heffron, Helen, Withers, Dominic J, Ashford, Michael L J

The hypothalamic melanocortin system is crucial for the control of appetite and body weight. Two of the five melanocortin receptors, MC3R and MC4R are involved in hypothalamic control of energy...

BRCA1 May Modulate Neuronal Cell Cycle Re-Entry in Alzheimer Disease

Evans, Teresa A., Raina, Arun K., Delacourte, André, Aprelikova, Olga, Lee, Hyoung-gon, Zhu, Xiongwei, ...

In Alzheimer disease, neuronal degeneration and the presence of neurofibrillary tangles correlate with the severity of cognitive decline. Neurofibrillary tangles contain the antigenic profile of many...

Parkinson’s Disease Is Associated with Oxidative Damage to Cytoplasmic DNA and RNA in Substantia Nigra Neurons

Zhang, Jing, Perry, George, Smith, Mark A., Robertson, David, Olson, Sandra J., Graham, Doyle G., ...

Oxidative damage, including modification of nucleic acids, may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson’s disease (PD). To investigate...

Microtubule Reduction in Alzheimer’s Disease and Aging Is Independent of τ Filament Formation

Cash, Adam D., Aliev, Gjumrakch, Siedlak, Sandra L., Nunomura, Akihiko, Fujioka, Hisashi, Zhu, Xiongwei, ...

Biochemical studies show that phosphorylated τ, like that found in paired helical filaments (PHFs), does not promote microtubule assembly leading to the view that PHF formation leads to microtubule...

Hibernation, a Model of Neuroprotection

Zhou, Fang, Zhu, Xiongwei, Castellani, Rudy J., Stimmelmayr, Raphaela, Perry, George, Smith, Mark A., ...

Hibernation, a natural model of tolerance to cerebral ischemia, represents a state of pronounced fluctuation in cerebral blood flow where no brain damage occurs. Numerous neuroprotective aspects may...

AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Claret, Marc, Smith, Mark A., Batterham, Rachel L., Selman, Colin, Choudhury, Agharul I., Fryer, Lee G.D., ...

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the...

The Contribution of Luteinizing Hormone to Alzheimer Disease Pathogenesis

Webber, Kate M., Perry, George, Smith, Mark A., Casadesus, Gemma

Several hypotheses have been proposed that attempt to explain the pathogenesis of Alzheimer Disease (AD) including theories involving senile plaque and neurofibrillary tangle formation, increased...

The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1

Kadrmas, Julie L., Smith, Mark A., Clark, Kathleen A., Pronovost, Stephen M., Muster, Nemone, Yates, John R., ...

Cell adhesion and migration are dynamic processes requiring the coordinated action of multiple signaling pathways, but the mechanisms underlying signal integration have remained elusive. Drosophila...

Identification of Ubiquilin, a Novel Presenilin Interactor That Increases Presenilin Protein Accumulation

Mah, Alex L., Perry, George, Smith, Mark A., Monteiro, Mervyn J.

Mutations in the highly homologous presenilin genes encoding presenilin-1 and presenilin-2 (PS1 and PS2) are linked to early-onset Alzheimer's disease (AD). However, apart from a role in early...

Mechanism of the distance-dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons

Smith, Mark A, Ellis-Davies, Graham C R, Magee, Jeffrey C

Schaffer collateral axons form excitatory synapses that are distributed across much of the dendritic arborization of hippocampal CA1 pyramidal neurons. Remarkably, AMPA-receptor-mediated miniature...

Impaired Regulation of Synaptic Strength in Hippocampal Neurons from GluR1-Deficient Mice

Andrásfalvy, Bertalan K, Smith, Mark A, Borchardt, Thilo, Sprengel, Rolf, Magee, Jeffrey C

Neurons of the central nervous system (CNS) exhibit a variety of forms of synaptic plasticity, including associative long-term potentiation and depression (LTP/D), homeostatic activity-dependent...

Sequestration of p27 within the cytoplasm of cardiac myocytes in chronic ischemic heart disease: pathogenic implications for ischemic cardiomyopathy

Smith, Mark A., Zhu, Xiongwei, Lee, Hyoung-gon, Harris, Peggy L.R., Fortino, Anne E., Perry, George, ...

A number of recent studies have suggested that cardiac myocytes, previously considered post-mitotic, re-enter the cell cycle and possess the ability to proliferate with certain pathogenic stimuli. To...

Retinoblastoma Protein Phosphorylation at Multiple Sites is Associated with Neurofibrillary Pathology in Alzheimer Disease

Thakur, Akanksha, Siedlak, Sandra L, James, Sheronica L, Bonda, David J, Rao, Akanksha, Webber, Kate M, ...

The re-expression of multiple cell cycle markers representing various cell cycle phases in postmitotic pyramidal neurons suggests that neurons in Alzheimer disease (AD) attempt to re-enter the cell...

Expression of CD74 is increased in neurofibrillary tangles in Alzheimer's disease

Bryan, Kathryn J, Zhu, Xiongwei, Harris, Peggy L, Perry, George, Castellani, Rudy J, Smith, Mark A, ...

Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss. Pathological markers of AD include neurofibrillary tangles, accumulation of amyloid-β...

Atherosclerotic lesions and mitochondria DNA deletions in brain microvessels: Implication in the pathogenesis of Alzheimer’s disease

Aliev, Gjumrakch, Gasimov, Eldar, Obrenovich, Mark E, Fischbach, Kathryn, Shenk, Justin C, Smith, Mark A, ...

The pathogenesis that is primarily responsible for Alzheimer’s disease (AD) and cerebrovascular accidents (CVA) appears to involve chronic hypoperfusion. We studied the ultrastructural features of...

Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates

Geisbert, Thomas W., Daddario-DiCaprio, Kathleen M., Lewis, Mark G., Geisbert, Joan B., Grolla, Allen, Leung, Anders, ...

Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over...

Copper Induces Apoptosis of Neuroblastoma Cells Via Post-translational Regulation of the Expression of Bcl-2-family Proteins and the txJ Mouse is a Better Model of Hepatic than Brain Cu Toxicity

Chan, Hsien W., Liu, Tianbing, Verdile, Giuseppe, Bishop, Glenda, Haasl, Ryan J., Smith, Mark A., ...

The basic mechanism(s) by which altered Cu homeostasis is toxic to hepatocytes and neurons, the two major cell types affected in copper storage diseases such as Wilson's disease (WD), remain unclear....

Evidence for the Novel Expression of Human Kallikrein-related Peptidase 3, Prostate-Specific Antigen, in the Brain

Stone, Jeremy G., Rolston, Raj K., Ueda, Masumi, Lee, Hyoung-Gon, Richardson, Sandy L., Castellani, Rudy J., ...

Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein family of serine proteases. With...

Sublethal RNA Oxidation as a Mechanism for Neurodegenerative Disease

Castellani, Rudy J., Nunomura, Akihiko, Rolston, Raj K., Moreira, Paula I., Takeda, Atsushi, Perry, George, ...

Although cellular RNA is subjected to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigations of the biological...

Molecular Pathogenesis of Alzheimer’s Disease: Reductionist versus Expansionist Approaches

Castellani, Rudy J., Zhu, Xiongwei, Lee, Hyoung-Gon, Smith, Mark A., Perry, George

Alzheimer’s disease (AD) is characterized clinically by dementia and pathologically by two hallmark lesions, senile plaques and neurofibrillary tangles. About a quarter century ago these hallmark...

Structure of a xenon derivative of Escherichia coli copper amine oxidase: confirmation of the proposed oxygen-entry pathway

Pirrat, Pascale, Smith, Mark A., Pearson, Arwen R., McPherson, Michael J., Phillips, Simon E. V.

The structure of a xenon derivative of E. coli copper amine oxidase confirms the pathway of oxygen entry to the buried active site proposed for this class of enzymes.

Ectopic localization of FOXO3a protein in Lewy bodies in Lewy body dementia and Parkinson's disease

Su, Bo, Liu, Haihua, Wang, Xinglong, Chen, Shu G, Siedlak, Sandra L, Kondo, Eisaku, ...

Lewy bodies and Lewy neurites constitute the cardinal neuropathological features of both Parkinson's disease (PD) and Lewy body dementia (LBD). Whereas α-synuclein has been found to be the major...

Antibodies to Potato Virus Y Bind the Amyloid β Peptide: IMMUNOHISTOCHEMICAL AND NMR STUDIES*

Friedland, Robert P., Tedesco, Johnathan M., Wilson, Andrea C., Atwood, Craig S., Smith, Mark A., Perry, George, ...

Studies in transgenic mice bearing mutated human Alzheimer disease (AD) genes show that active vaccination with the amyloid β (Aβ) protein or passive immunization with anti-Aβ antibodies has...

A detector to measure 9Li production rate in liquid scintillator at the earth’s surface by cosmic ray muons

Smith, Mark A.

The next generation of nuclear fission reactor based neutrino experiments seeking to measure the Theta-13 mixing angle rely upon measurements made by detectors placed close to the reactor, and...

A detector to measure 9Li production rate in liquid scintillator at the earth’s surface by cosmic ray muons

Smith, Mark A.

The next generation of nuclear fission reactor based neutrino experiments seeking to measure the Theta-13 mixing angle rely upon measurements made by detectors placed close to the reactor, and...

The Neuronal Expression of MYC Causes a Neurodegenerative Phenotype in a Novel Transgenic Mouse

Lee, Hyoung-gon, Casadesus, Gemma, Nunomura, Akihiko, Zhu, Xiongwei, Castellani, Rudy J., Richardson, Sandy L., ...

Many different proteins associated with the cell cycle, including cyclins, cyclin-dependent kinases, and proto-oncogenes such as c-MYC (MYC), are increased in degenerating neurons. Consequently, an...

Cell Cycle Re-Entry and Mitochondrial Defects in Myc-Mediated Hypertrophic Cardiomyopathy and Heart Failure

Lee, Hyoung-gon, Chen, Qun, Wolfram, Julie A., Richardson, Sandy L., Liner, Anna, Siedlak, Sandra L., ...

While considerable evidence supports the causal relationship between increases in c-Myc (Myc) and cardiomyopathy as a part of a “fetal re-expression” pattern, the functional role of Myc in...

Large-Scale Functional Annotation and Expanded Implementations of the P{wHy} Hybrid Transposon in the Drosophila melanogaster Genome

Myrick, Kyl V., Huet, François, Mohr, Stephanie E., Álvarez-García, Inés, Lu, Jeffrey T., Smith, Mark A., ...

Whole genome sequencing of the model organisms has created increased demand for efficient tools to facilitate the genome annotation efforts. Accordingly, we report the further implementations and...

A detector to measure 9Li production rate in liquid scintillator at the earth’s surface by cosmic ray muons

Smith, Mark A.

The next generation of nuclear fission reactor based neutrino experiments seeking to measure the Theta-13 mixing angle rely upon measurements made by detectors placed close to the reactor, and...

Evidence of DNA damage in Alzheimer disease: phosphorylation of histone H2AX in astrocytes

Myung, Na-Hye, Zhu, Xiongwei, Kruman, Inna I., Castellani, Rudy J., Petersen, Robert B., Siedlak, Sandra L., ...

Phosphorylation of the histone family is not only a response to cell signaling stimuli, but also an important indicator of DNA damage preceding apoptotic changes. While astrocytic degeneration,...

A detector to measure 9Li production rate in liquid scintillator at the earth’s surface by cosmic ray muons

Smith, Mark A.

The next generation of nuclear fission reactor based neutrino experiments seeking to measure the Theta-13 mixing angle rely upon measurements made by detectors placed close to the reactor, and...

Direct and Indirect Roles of Cyclin-dependent Kinase 5 as an Upstream Regulator in the c-Jun NH2-Terminal Kinase Cascade: Relevance to Neurotoxic Insults in Alzheimer's Disease

Sun, Kai-Hui, Lee, Hyoung-gon, Smith, Mark A., Shah, Kavita

Significant increase in JNK, c-Jun, and Cdk5 activities are reported in Alzheimer's disease (AD). Inhibition of c-Jun prevents neuronal cell death in in vivo AD models, highlighting it as a major JNK...

The Effects of Repeated Opioid Administration on Locomotor Activity: I. Opposing Actions of μ and κ Receptors

Smith, Mark A., Greene-Naples, Jennifer L., Lyle, Megan A., Iordanou, Jordan C., Felder, Jennifer N.

Repeated administration of many addictive drugs leads to a progressive increase in their locomotor effects. This increase in locomotor activity often develops concomitantly with increases in their...

The Effects of Repeated Opioid Administration on Locomotor Activity: II. Unidirectional Cross-Sensitization to Cocaine

Smith, Mark A., Greene-Naples, Jennifer L., Felder, Jennifer N., Iordanou, Jordan C., Lyle, Megan A., Walker, Katherine L.

Sensitization refers to an increase in sensitivity to the effects of a drug and is believed to play a role in the etiology of substance use disorders. Cross-sensitization has been observed between...

Dominant Role of the p110β Isoform of PI3K over p110α in Energy Homeostasis Regulation by POMC and AgRP Neurons

Al-Qassab, Hind, Smith, Mark A., Irvine, Elaine E., Guillermet-Guibert, Julie, Claret, Marc, Choudhury, Agharul I., ...

PI3K signaling is thought to mediate leptin and insulin action in hypothalamic pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, through...