Life Sciences Commons^™

Requirement For Golgi-Localized Pi(4)P In Fusion Of Copii Vesicles With Golgi Compartments, Andres Lorente-Rodriguez, Charles Barlowe

Dartmouth Scholarship

The role of specific membrane lipids in transport between endoplasmic reticulum (ER) and Golgi compartments is poorly understood. Using cell-free assays that measure stages in ER-to-Golgi transport, we screened a variety of enzyme inhibitors, lipid-modifying enzymes, and lipid ligands to investigate requirements in yeast. The pleckstrin homology (PH) domain of human Fapp1, which binds phosphatidylinositol-4-phosphate (PI(4)P) specifically, was a strong and specific inhibitor of anterograde transport. Analysis of wild type and mutant PH domain proteins in addition to recombinant versions of the Sac1p phosphoinositide-phosphatase indicated that PI(4)P was required on Golgi membranes for fusion with coat protein complex II (COPII) …

Integrin (Alpha 6 Beta 4) Regulation Of Eif-4e Activity And Vegf Translation: A Survival Mechanism For Carcinoma Cells, Jun Chung, Robin E. Bachelder, Elizabeth A. Lipscomb, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

We define a novel mechanism by which integrins regulate growth factor expression and the survival of carcinoma cells. Specifically, we demonstrate that the alpha 6 beta 4 integrin enhances vascular endothelial growth factor (VEGF) translation in breast carcinoma cells. The mechanism involves the ability of this integrin to stimulate the phosphorylation and inactivation of 4E-binding protein (4E-BP1), a translational repressor that inhibits the function of eukaryotic translation initiation factor 4E (eIF-4E). The regulation of 4E-BP1 phosphorylation by alpha 6 beta 4 derives from the ability of this integrin to activate the PI-3K-Akt pathway and, consequently, the rapamycin-sensitive kinase mTOR that …

The Integrin Alpha6beta4 Functions In Carcinoma Cell Migration On Laminin-1 By Mediating The Formation And Stabilization Of Actin-Containing Motility Structures, Isaac Rabinovitz, Arthur M. Mercurio

Arthur M. Mercurio

Functional studies on the alpha6beta4 integrin have focused primarily on its role in the organization of hemidesmosomes, stable adhesive structures that associate with the intermediate filament cytoskeleton. In this study, we examined the function of the alpha6beta4 integrin in clone A cells, a colon carcinoma cell line that expresses alpha6beta4 but no alpha6beta1 integrin and exhibits dynamic adhesion and motility on laminin-1. Time-lapse videomicroscopy of clone A cells on laminin-1 revealed that their migration is characterized by filopodial extension and stabilization followed by lamellae that extend in the direction of stabilized filopodia. A function-blocking mAb specific for the alpha6beta4 integrin …

Integrin Alpha 6 Beta 4 Mediates Dynamic Interactions With Laminin, Aydin Tozeren, Hynda K. Kleinman, Stephen Wu, Arthur M. Mercurio, Stephen W. Byers

Arthur M. Mercurio

We present here a novel form of dynamic adhesion in which both the integrin receptor and the ligand supporting dynamic adhesion have been identified. Laminar flow assays showed that laminin supported attachment of alpha 6 beta 4-positive cells in the presence of fluid shear stress (tau < or = 2 dyn/cm2), indicating that these cells adhered to laminin within a fraction of a second. Further increases in flow rate (3.5 dyn/cm2 < or = tau < or = 100 dyn/cm2) initiated rolling of attached cells in the direction of flow, suggesting that rapidly formed adhesion is reversible and repeatable. Laminin fragment E8, which …

Role Of E-Cadherin In The Response Of Tumor Cell Aggregates To Lymphatic, Venous And Arterial Flow: Measurement Of Cell-Cell Adhesion Strength, Stephen W. Byers, Connie L. Sommers, Becky Hoxter, Arthur M. Mercurio, Aydin Tozeren

Arthur M. Mercurio

Defects in the expression or function of the calcium dependent cell-cell adhesion molecule E-cadherin are common in invasive, metastatic carcinomas. In the present study the response of aggregates of breast epithelial cells and breast and colon carcinoma cells to forces imposed by laminar flow in a parallel plate flow channel was examined. Although E-cadherin negative tumor cells formed cell aggregates in the presence of calcium, these were significantly more likely than E-cadherin positive cell aggregates to disaggregate in response to low shear forces, such as those found in a lymphatic vessel or venule (< 3.5 dyn/cm2). E-cadherin positive normal breast epithelial cells and E-cadherin positive breast tumor cell aggregates could not be disaggregated when exposed to shear forces in excess of those found in arteries (> 100 dyn/cm2). E-cadherin negative cancer cells …

Human Colon Carcinoma Cells Use Multiple Receptors To Adhere To Laminin: Involvement Of Alpha 6 Beta 4 And Alpha 2 Beta 1 Integrins, Margaret M. Lotz, Cynthia A. Korzelius, Arthur M. Mercurio

Arthur M. Mercurio

In this study, we used clone A, a human colon carcinoma cell line, to characterize those integrins that mediate colon carcinoma adhesion to laminin. Monoclonal antibodies specific for the human beta 1 subunit inhibited clone A adhesion to laminin. They also precipitated a complex of surface proteins that exhibited an electrophoretic behavior characteristic of alpha 2 beta 1 and alpha 3 beta 1. A monoclonal antibody specific for alpha 2 (PIH5) blocked clone A adhesion to laminin, as well as to collagen I. An alpha 3-specific antibody (P1B5) had no effect on clone A adhesion to laminin, even though it …

Adam12 Induces Actin Cytoskeleton And Extracellular Matrix Reorganization During Early Adipocyte Differentiation By Regulating Beta1 Integrin Function, Nobuko Kawaguchi, Christina Sundberg, Marie Kveiborg, Behzad Moghadaszadeh, Meena Asmar, Nikolaj Dietrich, Charles Kumar Thodeti, Finn C. Nielsen, Peter Moller, Arthur M. Mercurio, Reidar Albrechtsen, Ulla M. Wewer

Arthur M. Mercurio

Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression …

Endothelial Cells Assemble Two Distinct Alpha6beta4-Containing Vimentin-Associated Structures: Roles For Ligand Binding And The Beta4 Cytoplasmic Tail, Suzanne M. Homan, Arthur M. Mercurio, Susan E. Laflamme

Arthur M. Mercurio

The alpha6beta4 laminin binding integrin functions in the assembly of type I hemidesmosomes, which are specialized cell-matrix adhesion sites found in stratified epithelial cells. Although endothelial cells do not express all the components of type I hemidesmosomes, endothelial cells can express the alpha6beta4 integrin. Because endothelial cells lose expression of alpha6beta4 in culture, we expressed recombinant alpha6beta4 in the dermal microvascular endothelial cell line, HMEC-1, to test whether endothelial cells can assemble adhesion structures containing alpha6beta4. Using immunofluorescence microscopy, we found that recombinant alpha6beta4 concentrates specifically in a novel fibrillar structure on the basal surface of endothelial cells in the …

Regulation Of Alpha 6 Beta 1 Integrin Laminin Receptor Function By The Cytoplasmic Domain Of The Alpha 6 Subunit, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

The alpha 6 beta 1 integrin is expressed on the macrophage surface in an inactive state and requires cellular activation with PMA or cytokines to function as a laminin receptor (Shaw, L. M., J. M. Messier, and A. M. Mercurio. 1990. J. Cell Biol. 110:2167-2174). In the present study, the role of the alpha 6 subunit cytoplasmic domain in alpha 6 beta 1 integrin activation was examined. The use of P388D1 cells, an alpha 6-integrin deficient macrophage cell line, facilitated this analysis because expression of either the alpha 6A or alpha 6B subunit cDNAs restores their activation responsive laminin adhesion …

Transcriptional Activation Of Integrin Beta6 During The Epithelial-Mesenchymal Transition Defines A Novel Prognostic Indicator Of Aggressive Colon Carcinoma, Richard C. Bates, David I. Bellovin, Courtney Brown, Elizabeth Maynard, Bingyan Wu, Hisaaki Kawakatsu, Dean Sheppard, Peter Oettgen, Arthur M. Mercurio

Arthur M. Mercurio

We used a spheroid model of colon carcinoma to analyze integrin dynamics as a function of the epithelial-mesenchymal transition (EMT), a process that provides a paradigm for understanding how carcinoma cells acquire a more aggressive phenotype. This EMT involves transcriptional activation of the beta6 integrin subunit and a consequent induction of alphavbeta6 expression. This integrin enhances the tumorigenic properties of colon carcinoma, including activation of autocrine TGF-beta and migration on interstitial fibronectin. Importantly, this study validates the clinical relevance of the EMT. Kaplan-Meier analysis of beta6 expression in 488 colorectal carcinomas revealed a striking reduction in median survival time of …

P53 Inhibits Alpha 6 Beta 4 Integrin Survival Signaling By Promoting The Caspase 3-Dependent Cleavage Of Akt/Pkb, Robin E. Bachelder, Mark J. Ribick, Alessandra Marchetti, Rita Falcioni, Silvia Soddu, Kathryn R. Davis, Arthur M. Mercurio

Arthur M. Mercurio

Although the interaction of matrix proteins with integrins is known to initiate signaling pathways that are essential for cell survival, a role for tumor suppressors in the regulation of these pathways has not been established. We demonstrate here that p53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase AKT/PKB. Specifically, we show that the alpha6beta4 integrin promotes the survival of p53-deficient carcinoma cells by activating AKT/PKB. In contrast, this integrin does not activate AKT/PKB in carcinoma cells that express wild-type p53 and it actually stimulates their apoptosis, in agreement with …

The Integrin Alpha 6 Beta 4 Is A Laminin Receptor, Edward C. Lee, Margaret M. Lotz, Glenn D. Steele Jr., Arthur M. Mercurio

Arthur M. Mercurio

In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as …

Glycogen Synthase Kinase-3 Is An Endogenous Inhibitor Of Snail Transcription: Implications For The Epithelial-Mesenchymal Transition, Robin E. Bachelder, Sang-Oh Yoon, Clara Franci, Antonio Garcia De Herreros, Arthur M. Mercurio

Arthur M. Mercurio

We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial-mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFkappaB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. …

Release Of Camp Gating By The Alpha6beta4 Integrin Stimulates Lamellae Formation And The Chemotactic Migration Of Invasive Carcinoma Cells, Kathleen L. O'Connor, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

The alpha6beta4 integrin promotes carcinoma in-vasion by its activation of a phosphoinositide 3-OH (PI3-K) signaling pathway (Shaw, L.M., I. Rabinovitz, H.H.-F. Wang, A. Toker, and A.M. Mercurio. Cell. 91: 949-960). We demonstrate here using MDA-MB-435 breast carcinoma cells that alpha6beta4 stimulates chemotactic migration, a key component of invasion, but that it has no influence on haptotaxis. Stimulation of chemotaxis by alpha6beta4 expression was observed in response to either lysophosphatidic acid (LPA) or fibroblast conditioned medium. Moreover, the LPA-dependent formation of lamellae in these cells is dependent upon alpha6beta4 expression. Both lamellae formation and chemotactic migration are inhibited or "gated" by …

Protein Kinase C-Dependent Mobilization Of The Alpha6beta4 Integrin From Hemidesmosomes And Its Association With Actin-Rich Cell Protrusions Drive The Chemotactic Migration Of Carcinoma Cells, Isaac Rabinovitz, Alex Toker, Arthur M. Mercurio

Arthur M. Mercurio

We explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the alpha6beta4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express alpha6beta4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the alpha6beta4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis ( approximately 1 ng/ml), the alpha6beta4 integrin is …

Cyanidin-3-Glucoside Inhibits Ethanol-Induced Invasion Of Breast Cancer Cells Overexpressing Erbb2, Mei Xu, Kimberly A. Bower, Siying Wang, Jacqueline A. Frank, Gang Chen, Min Ding, Shiow Wang, Xianglin Shi, Zunji Ke, Jia Luo

Internal Medicine Faculty Publications

BACKGROUND: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This …

Plant Phenolics: Extraction, Analysis And Their Antioxidant And Anticancer Properties, Jin Dai, Russell J. Mumper

Pharmaceutical Sciences Faculty Publications

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro …

Alterations In Multiple Measures Of White Matter Integrity In Normal Women At High Risk For Alzheimer's Disease, Brian T. Gold, David K. Powell, Anders H. Andersen, Charles D. Smith

Neuroscience Faculty Publications

There is evidence that disruption of white matter (WM) microstructure is an early event in the course of Alzheimer's disease (AD). However, the neurobiological bases of WM microstructural declines in presymptomatic AD are unknown. In the present study we address this issue using a multimodal imaging approach to the study of presymptomatic AD. Participants were 37 high-risk (both family history of dementia and one or more APOE4 alleles) women and 20 low-risk (neither family history nor APOE4) women. Groups were matched for age, education, neuropsychological performance, and vascular factors that could affect white matter. Whole-brain analyses of diffusion tensor imaging …

The Mir-15/107 Group Of Microrna Genes: Evolutionary Biology, Cellular Functions, And Roles In Human Diseases, John R. Finnerty, Wang-Xia Wang, Sébastien S. Hébert, Bernard R. Wilfred, Guogen Mao, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

The miR-15/107 group of microRNA (miRNA) gene is increasingly appreciated to serve key functions in humans. These miRNAs regulate gene expression involved in cell division, metabolism, stress response, and angiogenesis in vertebrate species. The miR-15/107 group has also been implicated in human cancers, cardiovascular disease and neurodegenerative disease, including Alzheimer's disease. Here we provide an overview of the following: (1) the evolution of miR-15/107 group member genes; (2) the expression levels of miRNAs in mammalian tissues; (3) evidence for overlapping gene-regulatory functions by different miRNAs; (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs; and (5) the roles played …

The Armadillo Repeat Protein Pf16 Is Essential For Flagellar Structure And Function In Plasmodium Male Gametes, Ursula Straschil, Arthur M. Talman, David J. P. Ferguson, Karen A. Bunting, Zhengyao Xu, Elizabeth Bailes, Robert E. Sinden, Anthony A. Holder, Elizabeth F. Smith

Dartmouth Scholarship

Malaria, caused by the apicomplexan parasite Plasmodium, threatens 40% of the world's population. Transmission between vertebrate and insect hosts depends on the sexual stages of the life-cycle. The male gamete of Plasmodium parasite is the only developmental stage that possesses a flagellum. Very little is known about the identity or function of proteins in the parasite's flagellar biology. Here, we characterise a Plasmodium PF16 homologue using reverse genetics in the mouse malaria parasite Plasmodium berghei. PF16 is a conserved Armadillo-repeat protein that regulates flagellar structure and motility in organisms as diverse as green algae and mice. We show that …

Hepatitis C Virus Core-Derived Peptides Inhibit Genotype 1b Viral Genome Replication Via Interaction With Ddx3x, Chaomin Sun, Cara T. Pager, Guangxiang Luo, Peter Sarnow, Jamie H. D. Cate

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The protein DDX3X is a DEAD-box RNA helicase that is essential for the hepatitis C virus (HCV) life cycle. The HCV core protein has been shown to bind to DDX3X both in vitro and in vivo. However, the specific interactions between these two proteins and the functional importance of these interactions for the HCV viral life cycle remain unclear. We show that amino acids 16-36 near the N-terminus of the HCV core protein interact specifically with DDX3X both in vitro and in vivo. Replication of HCV replicon NNeo/C-5B RNA (genotype 1b) is significantly suppressed in HuH-7-derived cells expressing green fluorescent …

Mip/Mtmr14 And Muscle Aging, Scott K. Powers, Michael B. Reid

Physiology Faculty Publications

No abstract.

Nona-Arginine Facilitates Delivery Of Quantum Dots Into Cells Via Multiple Pathways, Yi Xu, Betty Revon Liu, Han Jung Lee, Katie Shannon, Jeffrey G. Winiarz, Tien-Chun Wang, Huey-Jenn Chiang, Yue-Wern Huang

Biological Sciences Faculty Research & Creative Works

Semiconductor quantum dots (QDs) have recently been used to deliver and monitor biomolecules, such as drugs and proteins. However, QDs alone have a low efficiency of transport across the plasma membrane. In order to increase the efficiency, we used synthetic nona-arginine (SR9), a cell-penetrating peptide, to facilitate uptake. We found that SR9 increased the cellular uptake of QDs in a noncovalent binding manner between QDs and SR9. Further, we investigated mechanisms of QD/SR9 cellular internalization. Low temperature and metabolic inhibitors markedly inhibited the uptake of QD/SR9, indicating that internalization is an energy-dependent process. Results from both the pathway inhibitors and …

Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano

NYMC Faculty Publications

The enzyme catalase converts solar radiation into reactive oxidant species (ROS). In this study, we report that several bacterial catalases (hydroperoxidases, HP), including Escherichia coli HP-I and HP-II also generate reactive oxidants in response to ultraviolet B light (UVB). HP-I and HP-II are identical except for the presence of NADPH. We found that only one of the catalases, HPI, produces oxidants in response to UVB light, indicating a potential role for the nucleotide in ROS production. This prompts us to speculate that NADPH may act as a cofactor regulating ROS generation by mammalian catalases. Structural analysis of the NADPH domains …

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou

Natural Sciences and Mathematics | Faculty Scholarship

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …

Distribution Of Health Care Expenditures For Hiv-Infected Patients, Ray Y. Chen, Neil A. Accortt, Andrew O. Westfall, Michael J. Mugavero, James L. Raper, Gretchen A. Cloud, Beth K. Stone, Jerome Carter, Stephanie Call, Maria Pisu, Jeroan J. Allison, Michael S. Saag

Jeroan J. Allison

BACKGROUND: Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy.

METHODS: Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on …

Trends In Aids-Defining And Non-Aids-Defining Malignancies Among Hiv-Infected Patients: 1989-2002, Roger Bedimo, Ray Y. Chen, Neil A. Accortt, James L. Raper, Carol Linn, Jeroan J. Allison, John Dubay, Michael S. Saag, Craig J. Hoesley

Jeroan J. Allison

In a comparison of rates of acquired immunodeficiency syndrome (AIDS)-defining malignancies (ADMs) for 1989-1996 versus 1997-2002, we found a decrease in ADMs (rate ratio, 0.31; P<.0001) and a significant increase in non-AIDS-defining malignancies (non-ADMs; rate ratio, 10.87; P<.0002). The mean CD4 cell count was lower among patients with ADMs than among those with non-ADMs. A longer duration of survival during highly active antiretroviral therapy might explain the increasing incidence of non-ADMs.

Cross-Reactivity Of Antibodies Against Leptospiral Recurrent Uveitis-Associated Proteins A And B (Lrua And Lrub) With Eye Proteins, Ashutosh Verma, Pawan Kumar, Kelly Babb, John F. Timoney, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Infection by Leptospira interrogans has been causally associated with human and equine uveitis. Studies in our laboratories have demonstrated that leptospiral lipoprotein LruA and LruB are expressed in the eyes of uveitic horses, and that antibodies directed against LruA and LruB react with equine lenticular and retinal extracts, respectively. These reactivities were investigated further by performing immunofluorescent assays on lenticular and retinal tissue sections. Incubation of lens tissue sections with LruA-antiserum and retinal sections with LruB-antiserum resulted in positive fluorescence. By employing two-dimensional gel analyses followed by immunoblotting and mass spectrometry, lens proteins cross-reacting with LruA antiserum were identified to …

Reverse Engineering Of Oxygen Transport In The Lung: Adaptation To Changing Demands And Resources Through Space-Filling Networks, Chen Hou, Stefan Gheorghiu, Virginia H. Huxley, Peter Pfeifer

Biological Sciences Faculty Research & Creative Works

The space-filling fractal network in the human lung creates a remarkable distribution system for gas exchange. Landmark studies have illuminated how the fractal network guarantees minimum energy dissipation, slows air down with minimum hardware, maximizes the gas- exchange surface area, and creates respiratory flexibility between rest and exercise. In this paper, we investigate how the fractal architecture affects oxygen transport and exchange under varying physiological conditions, with respect to performance metrics not previously studied. We present a renormalization treatment of the diffusion-reaction equation which describes how oxygen concentrations drop in the airways as oxygen crosses the alveolar membrane system. The …

Meditation Acutely Improves Psychomotor Vigilance, And May Decrease Sleep Need, Prashant Kaul, Jason Passafiume, Craig R. Sargent, Bruce F. O'Hara

Biology Faculty Publications

BACKGROUND: A number of benefits from meditation have been claimed by those who practice various traditions, but few have been well tested in scientifically controlled studies. Among these claims are improved performance and decreased sleep need. Therefore, in these studies we assess whether meditation leads to an immediate performance improvement on a well validated psychomotor vigilance task (PVT), and second, whether longer bouts of meditation may alter sleep need.

METHODS: The primary study assessed PVT reaction times before and after 40 minute periods of mediation, nap, or a control activity using a within subject cross-over design. This study utilized novice …