Medical Biochemistry Commons^™

Hepatocyte Peroxisome Biogenesis And Phytol-Induced Metabolic Stress In Liver Disease, William Galloway

Theses, Dissertations and Capstones

Hepatocyte peroxisomes are required for metabolism of phytol-derived branched-chain fatty acids through the ACOX2-SCPx beta-oxidation pathway. This study tests whether hepatocyte-specific deletion of PEX16 (Pex16^Alb-Cre), which eliminates peroxisome biogenesis, sensitizes the liver to phytol-induced injury. The Pex16^Alb-Cre mice and their normal control Pex16^fl/fl mice were fed the Lieber-DeCarli liquid with or without 0.1 percent phytol for eight weeks. Serum alanine aminotransferase (ALT) and liver index were measured. Liver sections were stained with hematoxylin and eosin and Masson’s trichrome. Immunoblot analysis of peroxisomal enzyme expression was also performed. Phytol had no effect in Pex16^fl/fl mice as …

Disruption Of The Placenta–Brain Axis In Transgenic Mice Lacking Serotonin Transporter (Sert) In Trophoblast Cells, David T. Ellenberger, Zhen Lyu, Rosalind T. B. Herrington, Jessica A. Kinkade, Gustavo W. Leone, Ji Ying Sze, Nathan J. Bivens, R. Frank Baker, R. Michael Roberts, Trupti Joshi, Cheryl S. Rosenfeld

Biomedical Sciences

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental–brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked …

Abnormal Morphology And Synaptogenic Signaling In Astrocytes Following Prenatal Opioid Exposure, Ethan B. Niebergall, Daron Weekley, Anna Mazur, Nathan A. Olszewski, Kayla M. Deschepper, N. Radant, Aishwarya S. Vijay

Biomedical Sciences

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and …

Alterations In Excitatory And Inhibitory Synaptic Development Within The Mesolimbic Dopamine Pathway In A Mouse Model Of Prenatal Drug Exposure, Taylor Boggess, James C. Williamson, Ethan B. Niebergall, Hannah Sexton, Richard D. Egleton, Larry Grover, Chris Risher

Biomedical Sciences

The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of information regarding the long-term effects of prenatal exposure to drugs of abuse on neurological development. The primary goal of this study was to investigate the effects of prenatal drug exposure on synaptic connectivity within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway associated with drug abuse and addiction, in a mouse model. Our secondary …

Astrocyte-Derived Thrombospondin Induces Cortical Synaptogenesis In A Sex-Specific Manner, Anna Mazur, Ean H. Bills, Kayla M. Deschepper, James C. Williams, Brandon J. Henderson, W. Christopher Risher

Biomedical Sciences

The regulation of synaptic connectivity in the brain is vital to proper functioning and development of the CNS. Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared with female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response …

Role Of Thymidine Phosphorylase In Type 2 Diabetes-Associated High-Risk Of Thrombosis, Adam Belcher

Theses, Dissertations and Capstones

Cardiovascular diseases (CVDs), such as ischemic heart disease and stroke, are the leading causes of death globally that disproportionally affects patients with type 2 diabetes mellitus (T2DM) at a 2-4-fold rate compared to non-diabetic patients. These CVDs result from a blood clot, also known as a thrombus, formed in arteries that can block blood flow resulting in tissue damage and death. Antiplatelet drugs, such as aspirin and clopidogrel, used to prevent thrombosis have been found to be less effective in diabetics and increase the risk of hemorrhagic events. The T2DM epidemic has made it imperative to find therapies that decrease …

Dysfunctional Mitochondrial Biogenesis: A Potential Underlying Cause For Metabolic Diseases, Caroline Ann Hunter

Theses, Dissertations and Capstones

Mitochondria are essential organelles that play crucial roles in many aspects of cellular homeostasis. More importantly, the mitochondria are home to the majority of the metabolic pathways within the cell and are responsible for producing most of the cell’s useable energy in the form of adenine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). In mammals, the majority of OXPHOS complex subunits are encoded by nuclear deoxyribonucleic acid (DNA); however, 13 core subunits essential for the function of OXPHOS complexes I, III, IV, and V are encoded in the mitochondrial (mt) DNA (mtDNA) and are synthesized within the mitochondria by its own …

Thrombospondin Receptor Α2Δ-1 Promotes Synaptogenesis And Spinogenesis Via Postsynaptic Rac1, W. Chris Risher, Namsoo Kim, Sehwon Koh, Ji‑Eun Cho, Petar Mitev, Erin F. Spence, Louis‑Jan Pilaz, Dongqing Wang, Guoping Feng, Debra L. Silver, Scott H. Soderling, Henry H. Yin, Cagla Eroglu

Biomedical Sciences

Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit α2δ-1. α2δ-1 is a drug target for epilepsy and neuropathic pain; thus the TSP–α2δ-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for α2δ-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of α2δ-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic α2δ-1 …

Optimizing Heart Failure Outcomes Through Diet: A Review, Farley B. Neasman Iii

Marshall Journal of Medicine

Heart failure is a growing epidemic that will add significant monetary and human costs to an already overtaxed health-care system. Though promising new medications have recently been approved, this complex condition is largely preventable through aggressive risk factor modification, with diet being shown to have a greater effect than exercise. An underrated component of a healthy diet is the simple addition of nuts – the anti-inflammatory fatty acids, healthy proteins, and general availability have been shown to improve survival and reduce the primary risk factors contributing to heart failure, making the addition of nuts and legumes to the diet an …

Na/K-Atpase Signaling And Salt Sensitivity: The Role Of Oxidative Stress, Jiang Liu, Yanling Yan, Ying Nie

Biochemistry and Microbiology

Other than genetic regulation of salt sensitivity of blood pressure, many factors have been shown to regulate renal sodium handling which contributes to long-term blood pressure regulation and have been extensively reviewed. Here we present our progress on the Na/K-ATPase signaling mediated sodium reabsorption in renal proximal tubules, from cardiotonic steroids-mediated to reactive oxygen species (ROS)-mediated Na/K-ATPase signaling that contributes to experimental salt sensitivity.

Epoxyeicosatrienoic Acids Regulate Adipocyte Differentiation Of Mouse 3t3 Cells, Via Pgc-1Α Activation, Which Is Required For Ho-1 Expression And Increased Mitochondrial Function, Maayan Waldman, Lars Bellner, Luca Vanella, Joseph Schragenheim, Komal Sodhi, Shailendra P. Singh, Daohong Lin, Anand Lakhkar, Jiangwei Li, Edith Hochhauser, Michael Arad, Zbigniew Darzynkiewicz, Attallah Kappas, Nader G. Abraham

Biochemistry and Microbiology

Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) expression, and increased mitochondrial function in the 3T3-L1 preadipocyte subjected to adipogenesis. Cells treated with EET resulted in an increase, P < 0.05, in PGC-1α and a decrease in mitochondria-derived ROS (MitoSox), P < 0.05. The EET increase in heme oxygenase-1 (HO-1) levels is dependent on activation of PGC-1α as cells deficient in PGC-1α (PGC-1α knockout adipocyte cell) have an impaired ability to express HO-1, P < 0.02. Additionally, adipocytes treated with EET exhibited an increase in mitochondrial superoxide dismutase (SOD) in a PGC-1α-dependent manner, P < 0.05. The increase in PGC-1α was associated with an increase in β-catenin, P < 0.05, adiponectin expression, P < 0.05, and lipid accumulation, P < 0.02. EET decreased heme levels and mitochondria-derived ROS (MitoSox), P < 0.05, compared to adipocytes that were untreated. EET also decreased mesoderm-specific transcript (MEST) mRNA and protein levels (P < 0.05). Adipocyte secretion of EET act in an autocrine/paracrine manner to increase PGC-1α is required for activation of HO-1 expression. This is the first study to dissect the mechanism by which the antiadipogenic and anti-inflammatory lipid, EET, induces the PGC-1α signaling cascade and reprograms the adipocyte phenotype by regulating mitochondrial function and HO-1 expression, leading to an increase in healthy, that is, small, adipocytes and a decrease in adipocyte enlargement and terminal differentiation. This is manifested by an increase in mitochondrial function and an increase in the canonical Wnt signaling cascade during adipocyte proliferation and terminal differentiation.

Incidence Of Hypomagnesemia On Proton Pump Inhibitors At The Huntington Veterans Affairs Medical Center – Ihop, Ebrahim Sabbagh, Do, Chelsey R. Houchins, James Allman, Ii, Pharmd, Samson Teka, Md

Marshall Journal of Medicine

Abstract

Title: Incidence of hypomagnesemia on proton pump inhibitors at the Huntington Veterans Affairs Medical Center – IHOP

Purpose:

Proton pump inhibitors (PPIs), both prescription and over-the-counter, are widely used for the treatment of acid-related disease states such as dyspepsia, gastroesophageal reflex disease, esophagitis, and peptic ulcers. These medications are generally considered safe in most patient populations; however, there are several adverse effects that may occur with long-term use. Hypomagnesemia is a newer complication arising in the literature following multiple case reports over the past several years, although the true incidence of hypomagnesemia associated with PPI use remains unclear at …

Role Of Serum Biomarkers In Early Detection Of Non-Alcoholic Steatohepatitis And Fibrosis In West Virginian Children, Komal Sodhi, Lucas Bracero, Andrew S. Feyh, Alexandra Nichols, Krithika Srikanthan, Tariq M. Latif, Deborah L. Preston, Joseph I. Shapiro, Yoram Elitsur

Biochemistry and Microbiology

Background: Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is wellestablished contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH.

Methods: Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR …

Dashing Away Hypertension: Evaluating The Efficacy Of The Dietary Approaches To Stop Hypertension Diet In Controlling High Blood Pressure, Preeya Shah Phd, Kyle D. Maxwell, Joseph I. Shapiro Md

Biochemistry and Microbiology

The dietary approaches to stop hypertension (DASH) diet has been developed and popularized as a non-pharmaceutical intervention for high blood pressure reduction since 1995. However, to date, a comprehensive description of the biochemical rationale behind the diet’s principal guidelines has yet to be compiled. With rising interest for healthy and reliable life-style modifications to combat cardiovascular disease, this review aims to compile the most recent and relevant studies on this topic and make an informed assessment as to the efficacy of and underlying mechanisms operant in the DASH diet. Specifically, the merits of lowering dietary intake of sodium and saturated …

Adolescent Intermittent Alcohol Exposure: Deficits In Object Recognition Memory And Forebrain Cholinergic Markers, H. Scott Swartzwelder, Shawn K. Acheson, Kelsey M. Miller, Hannah G. Sexton, Wen Liu, Fulton T. Crews, Mary-Louise Risher

Biomedical Sciences

The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational …

Pnaktide Inhibits Na/K-Atpase Reactive Oxygen Species Amplification And Attenuates Adipogenesis, Komal Sodhi, Kyle Maxwell, Yanling Yan, Jiang Liu, Muhammad Chaudhry, Morgan Getty, Zijian Xie, Nader G. Abraham, Joseph I. Shapiro Md

Biochemistry and Microbiology

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed …

Platelet-Activating Factor Receptor Affects Food Intake And Body Weight, Wei Li, Thomas M. Mcintyre

Biomedical Sciences

“Let’s Move!” is a comprehensive initiative, launched by the First Lady, Michelle Obama, dedicates to solving problems of obesity, which is growing in child. The life behaviors do affect obesity; however, the mechanistic insight in molecular level is still not clear. In this study, by continually monitoring mouse body weight under chow and high fat western diets as well as metabolic, physical activity and food intake behaviors assessed in a CLAMS Comprehensive Lab Animal Monitoring System, we demonstrated that the platelet-activating factor receptor (PTAFR) contributes to modification of life behaviors. PTAFR does not affect metabolism of ingested dietary fat and …

The Sox9 Upstream Region Prone To Chromosomal Aberrations Causing Campomelic Dysplasia Contains Multiple Cartilage Enhancers, Baojin Yao, Qiuqing Wang, Chia-Feng Liu, Pallavi Bhattaram, Wei Li, Timothy J. Mead, James F. Crish, Véronique Lefebvre

Biomedical Sciences

Two decades after the discovery that heterozygous mutations within and around SOX9 cause campomelic dysplasia, a generalized skeleton malformation syndrome, it is well established that SOX9 is a master transcription factor in chondrocytes. In contrast, the mechanisms whereby translocations in the –350/–50-kb region 5 of SOX9 cause severe disease and whereby SOX9 expression is specified in chondrocytes remain scarcely known. We here screen this upstream region and uncover multiple enhancers that activate Sox9-promoter transgenes in the SOX9 expression domain. Three of them are primarily active in chondrocytes. E250 (located at – 250 kb) confines its activity to condensed prechondrocytes, …

Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel

Pharmaceutical Science and Research

The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation …

Epigenetics As An Answer To Darwin’S “Special Difficulty,” Part 2: Natural Selection Of Metastable Epialleles In Honey Bee Castes, Douglas M. Ruden, Pablo E. Cingolani, Arko Sen, Wen Qu, Luan Wang, Marie-Claude Senut, Mark D. Garfinkel, Vincent E. Sollars, Xiangyi Lu

Biochemistry and Microbiology

In a recent perspective in this journal, Herb (2014) discussed how epigenetics is a possible mechanism to circumvent Charles Darwin’s “special difficulty” in using natural selection to explain the existence of the sterile-fertile dimorphism in eusocial insects. Darwin’s classic book “On the Origin of Species by Means of Natural Selection” explains how natural selection of the fittest individuals in a population can allow a species to adapt to a novel or changing environment. However, in bees and other eusocial insects, such as ants and termites, there exist two or more castes of genetically similar females, from fertile queens to multiple …

Rgs16, A Novel P53 And Prb Cross-Talk Candidate Inhibits Migration And Invasion Of Pancreatic Cancer Cells, Miranda B. Carper, James Denvir, Goran Boskovic, Donald A. Primerano, Pier Paolo Claudio

Biochemistry and Microbiology

Data collected since the discovery of p53 and pRb/RB1 suggests these tumor suppressors cooperate to inhibit tumor progression. Patients who have mutations in both p53 and RB1 genes have increased tumor reoccurrence and decreased survival compared to patients with only one tumor suppressor gene inactivated. It remains unclear how p53 and pRb cooperate toward inhibiting tumorigenesis. Using RNA expression profiling we identified 179 p53 and pRb cross-talk candidates in normal lung fibroblasts (WI38) cells exogenously coexpressing p53 and pRb. Regulator of G protein signaling 16 (RGS16) was among the p53 and pRb cross-talk candidates and has been implicated in inhibiting …

Helicobacter-Pylori Negative Gastritis In Children—A New Clinical Enigma, Yoram Elitsur, Deborah L. Preston

Biochemistry and Microbiology

The decrease in the prevalence of Helicobacter pylori (Hp) infection in children in the world gave rise to a new pathological finding termed as Hp-negative gastritis. Unfortunately, the term “Hp-negative gastritis” has not been identified as a pathological process and has the status of a “second cousin”; in most publications it was never mentioned as a subject to be dealt with, but was “left over” data that was never the topic of the manuscripts’ discussions. Only recently has the topic captured the attention of the pathologists who described this phenomenon in adults, yet the pathological and/or clinical spectrum or significance …

Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf

Theses, Dissertations and Capstones

Isothiocyanates (ITCs) are natural phytochemicals produced by cruciferous vegetables. Recent evidence supports that, in addition to cancer prevention, ITCs can use various mechanisms to target malignant cells. Current therapies for cancer often provoke detrimental side effects, however clinical evidence supports that ITCs have little to no side effects in patients. Consequently, ITCs may be a promising treatment option for cancer patients, especially patients suffering from head and neck squamous cell carcinoma (HNSCC).

Despite recent improvements in cancer treatment, overall survival of advanced HNSCC has not improved in the past three decades. Metastasis and chemoresistance represent two detrimental events that greatly …

Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti

Biochemistry and Microbiology

Aims: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants.

Results: Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was obliterated in arteries pretreated with antioxidants, including tempol, pegylated superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting radicals downstream of H(2)O(2), also uncovered vasodilation.

Innovations: Redox-dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 μM), thromboxane (TP) synthase (CGS13080-10 μM), and TP receptor antagonist (SQ29548-1 μM). However, H(2)O(2) …

Effects Of Acute Or Chronic Ethanol Exposure During Adolescence On Behavioral Inhibition And Efficiency In A Modified Water Maze Task, Shawn K. Acheson, Craig Bearison, Mary-Louise Risher, Sabri H. Abdelwahab, Wilkie A. Wilson, H. Scott Swartzwelder

Biomedical Sciences

Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape) and a new hidden platform was added …

Pparδ Binding To Heme Oxygenase 1 Promoter Prevents Angiotensin Ii-Induced Adipocyte Dysfunction In Goldblatt Hypertensive Rats, Komal Sodhi, Nitin Puri, Dong Hyun Kim, Terry D. Hinds Jr., Lance A. Stechschulte, Gaia Favero, Luigi Rodella, Joseph I. Shapiro M.D., David C. Jude, Nader X. Abraham

Biochemistry and Microbiology

Abstract:

OBJECTIVE: Renin–angiotensin system (RAS) regulates adipogenic response with adipocyte hypertrophy by increasing oxidative stress. Recent studies have shown the role of peroxisome proliferator-activated receptor-d (PPARδ) agonist in attenuation of angiotensin II-induced oxidative stress. The aim of this study was to explore a potential mechanistic link between PPARδ and the cytoprotective enzyme heme oxygenase-1 (HO-1) and to elucidate the contribution of HO-1 to the adipocyte regulatory effects of PPARδ agonism in an animal model of enhanced RAS, the Goldblatt 2 kidney 1 clip (2K1C) model.

METHOD: We first established a direct stimulatory effect of the PPARδ agonist (GW 501516) on …

Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ²²). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …

Long-Term Effects Of Chronic Intermittent Ethanol Exposure In Adolescent And Adult Rats: Radial-Arm Maze Performance And Operant Food Reinforced Responding, Mary-Louise Risher, Rebekah L. Fleming, Nathalie Boutros, Svetlana Semenova, Wilkie A. Wilson, Edward D. Levin, Athina Markou, H. Scott Swartzwelder, Shawn K. Acheson

Biomedical Sciences

Background: Adolescence is not only a critical period of late-stage neurological development in humans, but is also a period in which ethanol consumption is often at its highest. Given the prevalence of ethanol use during this vulnerable developmental period we assessed the long-term effects of chronic intermittent ethanol (CIE) exposure during adolescence, compared to adulthood, on performance in the radial-arm maze (RAM) and operant food-reinforced responding in male rats.

Methodology/Principal Findings: Male Sprague Dawley rats were exposed to CIE (or saline) and then allowed to recover. Animals were then trained in either the RAM task or an operant task using …

Principles Of Quantitative Fluid And Cation Replacement In Extreme Hyperglycemia, Antonios H. Tzamaloukas, Yijuan Sun, Nikifor K. Konstantinov, Richard I. Dorin, Todd S. Ing, Deepak Malhorta, Glenn H. Murata, Joseph I. Shapiro M.D.

Biochemistry and Microbiology

Hyperglycemia may cause profound deficits of water, sodium and potassium through osmotic diuresis, which continues during treatment as long as there is glucosuria. Replacement fluids should cover both the deficits at presentation and the ongoing losses during treatment. At presentation with hyperglycemia, quantitative estimates of the deficits in water, sodium and potassium are based on rapid body weight changes, which indicate changes in body water, and on the serum sodium concentration corrected to a normal serum glucose level. The corrected serum sodium concentration provides a measure of the water deficit relative to the cation deficit (sodium, plus potassium) that is …

Increased Heme-Oxygenase 1 Expression In Mesenchymal Stem Cell-Derived Adipocytes Decreases Differentiation And Lipid Accumulation Via Upregulation Of The Canonical Wnt Signaling Cascade, Luca Vanella, Komal Sodhi, Dong Hyun Kim, Nitin Puri, Mani Maheshwari, Terry D . Hinds, Lars Bellner, Dov Goldstein, Stephen J . Peterson, Joseph I. Shapiro M.D., Nader G. Abraham

Biochemistry and Microbiology

Introduction:

Heme oxygenase (HO), a major cytoprotective enzyme, attenuates oxidative stress and obesity. The canonical Wnt signaling cascade plays a pivotal role in the regulation of adipogenesis. The present study examined the interplay between HO-1and the Wnt canonical pathway in the modulation of adipogenesis in mesenchymal stem cell (MSC)-derived adipocytes.

Methods:

To verify the role of HO-1 in generating small healthy adipocytes, cobalt protoporphyrin (CoPP), inducer of HO-1, was used during adipocyte differentiation. Lipid accumulation was measured by Oil red O staining and lipid droplet size was measured by BODIPY staining.

Results:

During adipogenesis in vitro, differentiating pre-adipocytes display transient …