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Sample records for blood protein disorders

  1. Symptoms of Blood Disorders

    Science.gov (United States)

    ... 2 Diabetes, Heart Disease a Dangerous Combo Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... Blood Disorders Bone Marrow Examination Blood disorders can cause various symptoms in almost any area of the ...

  2. Are Blood-Based Protein Biomarkers for Alzheimer's Disease also Involved in Other Brain Disorders?:A Systematic Review

    OpenAIRE

    Chiam, Justin Tao Wen; Dobson, Richard James Butler; Kiddle, Steven John; Sattlecker, Martina

    2015-01-01

    Background: Alzheimer's disease (AD) biomarkers are urgently needed for both early and accurate diagnosis and prediction of disease progression. Past research has studied blood-based proteins as potential AD biomarkers, revealing many candidate proteins. To date only limited effort has been made to investigate the disease specificity of AD candidate proteins and whether these proteins are also involved in other neurodegenerative or psychiatric conditions.Objective: This review seeks to determ...

  3. White Blood Cell Disorders

    Science.gov (United States)

    ... where they are needed, and then kill and digest the harmful organism or substance (see White blood ... Patel Hello Everyone! Hello to all of you readers! I know you will be seeing my biography, ...

  4. Blood disorders typically associated with renal transplantation.

    Science.gov (United States)

    Yang, Yu; Yu, Bo; Chen, Yun

    2015-01-01

    Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival. PMID:25853131

  5. Blood Disorders - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Blood Disorders URL of this page: https://medlineplus.gov/languages/blooddisorders.html Other topics A-Z A B ...

  6. Disordered regions in transmembrane proteins.

    Science.gov (United States)

    Tusnády, Gábor E; Dobson, László; Tompa, Peter

    2015-11-01

    The functions of transmembrane proteins in living cells are widespread; they range from various transport processes to energy production, from cell-cell adhesion to communication. Structurally, they are highly ordered in their membrane-spanning regions, but may contain disordered regions in the cytosolic and extra-cytosolic parts. In this study, we have investigated the disordered regions in transmembrane proteins by a stringent definition of disordered residues on the currently available largest experimental dataset, and show a significant correlation between the spatial distributions of positively charged residues and disordered regions. This finding suggests a new role of disordered regions in transmembrane proteins by providing structural flexibility for stabilizing interactions with negatively charged head groups of the lipid molecules. We also find a preference of structural disorder in the terminal--as opposed to loop--regions in transmembrane proteins, and survey the respective functions involved in recruiting other proteins or mediating allosteric signaling effects. Finally, we critically compare disorder prediction methods on our transmembrane protein set. While there are no major differences between these methods using the usual statistics, such as per residue accuracies, Matthew's correlation coefficients, etc.; substantial differences can be found regarding the spatial distribution of the predicted disordered regions. We conclude that a predictor optimized for transmembrane proteins would be of high value to the field of structural disorder. PMID:26275590

  7. Intrinsically disordered proteins and biomineralization.

    Science.gov (United States)

    Boskey, Adele L; Villarreal-Ramirez, Eduardo

    2016-01-01

    In vertebrates and invertebrates, biomineralization is controlled by the cell and the proteins they produce. A large number of these proteins are intrinsically disordered, gaining some secondary structure when they interact with their binding partners. These partners include the component ions of the mineral being deposited, the crystals themselves, the template on which the initial crystals form, and other intrinsically disordered proteins and peptides. This review speculates why intrinsically disordered proteins are so important for biomineralization, providing illustrations from the SIBLING (small integrin binding N-glycosylated) proteins and their peptides. It is concluded that the flexible structure, and the ability of the intrinsically disordered proteins to bind to a multitude of surfaces is crucial, but details on the precise-interactions, energetics and kinetics of binding remain to be determined. PMID:26807759

  8. Protein intrinsic disorder in plants

    Directory of Open Access Journals (Sweden)

    Florencio ePazos

    2013-09-01

    Full Text Available To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously with different partners. Similarly, they also serve as signal integrators in signalling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms can not escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  9. Transmission of Neurodegenerative Disorders Through Blood Transfusion

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Hjalgrim, Henrik; Rostgaard, Klaus;

    2016-01-01

    Background: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health...... implications. Objective: To investigate possible transfusion transmission of neurodegenerative disorders. Design: Retrospective cohort study. Setting: Nationwide registers of transfusions in Sweden and Denmark. Participants: 1 465 845 patients who received transfusions between 1968 and 2012. Measurements......: Observational study design, underascertainment of the outcome, and possible insufficient statistical power. Conclusion: The data provide no evidence for the transmission of neurodegenerative diseases and suggest that if transmission does occur, it is rare. Primary Funding Source: Swedish Research Council...

  10. What Should You Know about Blood Disorders in Women?

    Science.gov (United States)

    ... Although there are no cures for bleeding disorders, treatment is available to control symptoms and help women avoid complications and invasive procedures. Related Links Deep Vein Thrombosis Hemophilia Von Willebrand Disease Blood Disorders Home A- ...

  11. Evolution of Structurally Disordered Proteins Promotes Neostructuralization

    OpenAIRE

    Siltberg-Liberles, Jessica

    2010-01-01

    Protein structure is generally more conserved than sequence, but for regions that can adopt different structures in different environments, does this hold true? Understanding how structurally disordered regions evolve altered secondary structure element propensities as well as conformational flexibility among paralogs are fundamental questions for our understanding of protein structural evolution. We have investigated the evolutionary dynamics of structural disorder in protein families contai...

  12. CEREBRAL BLOOD FLOW AND METABOLISM IN ANXIETY AND ANXIETY DISORDERS

    OpenAIRE

    Mathew, Roy J.

    1994-01-01

    Anxiety disorders are some of the commonest psychiatric disorders and anxiety commonly co-exists with other psychiatric conditions. Anxiety can also be a normal emotion. Thus, study of the neurobiological effects of anxiety is of considerable significance. In the normal brain, cerebral blood flow (CBF) and metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected to provide new insight into alterations in brain function in anxiety disorders and other psychiatric disord...

  13. Bioinformatics analysis of disordered proteins in prokaryotes

    Directory of Open Access Journals (Sweden)

    Malkov Saša N

    2011-03-01

    Full Text Available Abstract Background A significant number of proteins have been shown to be intrinsically disordered, meaning that they lack a fixed 3 D structure or contain regions that do not posses a well defined 3 D structure. It has also been proven that a protein's disorder content is related to its function. We have performed an exhaustive analysis and comparison of the disorder content of proteins from prokaryotic organisms (i.e., superkingdoms Archaea and Bacteria with respect to functional categories they belong to, i.e., Clusters of Orthologous Groups of proteins (COGs and groups of COGs-Cellular processes (Cp, Information storage and processing (Isp, Metabolism (Me and Poorly characterized (Pc. We also analyzed the disorder content of proteins with respect to various genomic, metabolic and ecological characteristics of the organism they belong to. We used correlations and association rule mining in order to identify the most confident associations between specific modalities of the characteristics considered and disorder content. Results Bacteria are shown to have a somewhat higher level of protein disorder than archaea, except for proteins in the Me functional group. It is demonstrated that the Isp and Cp functional groups in particular (L-repair function and N-cell motility and secretion COGs of proteins in specific possess the highest disorder content, while Me proteins, in general, posses the lowest. Disorder fractions have been confirmed to have the lowest level for the so-called order-promoting amino acids and the highest level for the so-called disorder promoters. For each pair of organism characteristics, specific modalities are identified with the maximum disorder proteins in the corresponding organisms, e.g., high genome size-high GC content organisms, facultative anaerobic-low GC content organisms, aerobic-high genome size organisms, etc. Maximum disorder in archaea is observed for high GC content-low genome size organisms, high GC content

  14. CYPRINIDS TOTAL BLOOD PROTEINS DETERMINATION

    Directory of Open Access Journals (Sweden)

    TANŢI PATRICHE

    2013-07-01

    Full Text Available In aquaculture to get a high production is conditioned by awareness and keeping of an unaltered health condition of the biological material. To be aware of the health condition of the biological material in a fish farm allows us to establish the preventive measures required to prevent spreading of a disease and the treatment to be applied in case that a mass disease occurs. The level of the total protein in serum is, first of all, a synthetically indicator of the nutritional condition of the organism, presenting, at the same time, ample qualitative and quantitative variations depending on species, age, sex, stage of sexual maturity, water temperature and especially in correlation with the health condition of fish. Modification in value of the total protein point out some metabolic perturbations in fish body.

  15. Blood protein adsorption onto chitosan

    OpenAIRE

    Benesch, Johan; Tengvall, P.

    2002-01-01

    Chitosan was recently indicated to enhance osteogenesis, improve wound healing but to activate the coagulation and the complement systems. In the present study approximately 10nm thick chitosan film were prepared on aminopropyltriethoxysilane (APTES) coated silicon. The surfaces were incubated in serum or plasma and subsequently in antibodies towards key complement and contact activation of coagulation proteins. The deposited amounts were compared with those on hydrophilic and hydrop...

  16. Functional Human Blood Protein Obtained from Rice

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Under a research project funded by NSFC,Dr.Yang He of College of Life Sciences,Wuhan University obtained functional human blood protein from rice,and published their research findings in an article "Large-scale production of functional human serum albumin from transgenic rice seeds" on PNAS in November 2011.

  17. Predicting intrinsic disorder in proteins: an overview

    Institute of Scientific and Technical Information of China (English)

    Bo He; Kejun Wang; Yunlong Liu; Bin Xue; Vladimir N Uversky; A Keith Dunker

    2009-01-01

    The discovery of intrinsically disordered proteins IDP I.e., biologically active proteins that do not possess stable secondary and/or tertiary structures came as an unexpected surprise, as the existence of such proteins is in contradiction to the traditional "sequence---,structure--,function" paradigm. Accurate prediction of a protein's predisposition to be intrinsically disordered is a necessary prerequisite for the further understanding of principles and mechanisms of protein folding and function, and is a key for the elaboration of a new structural and functional hierarchy of proteins. Therefore, prediction of IDPs has attracted the attention of many researchers, and a number of prediction tools have been developed. Predictions of disorder, in turn, are playing major roles in directing labora-tory experiments that are leading to the discovery of ever more disordered proteins, and thereby leading to a positive feedback loop in the investigation of these proteins, in this review of algorithms for intrinsic disorder prediction, the basic concepts of various prediction methods for IDPs are summarized, the strengths and shortcomings of many of the methods are analyzed, and the difficulties and directions of future development of IDP prediction techniques are discussed.

  18. Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.

  19. Protein intrinsic disorder in plants

    OpenAIRE

    Florencio ePazos; Natalia ePietrosemoli; García-Martín, Juan A.; Roberto eSolano

    2013-01-01

    To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disor...

  20. Healthy pregnancy and prenatal disorders followed by blood plasma metabolomics

    OpenAIRE

    Pinto, Joana Isabel Monteiro

    2015-01-01

    The work presented in this thesis aimed to investigate the impact of healthy pregnancy and selected prenatal disorders on the metabolome and lipidome of maternal blood plasma, in order to define new potential biomarkers for non-invasive prediction and diagnosis. Chapter 1 describes the present status and challenges of the clinically relevant prenatal disorders, along with a presentation of the metabolomics strategy applied and the state of the art of metabolomics in prenatal research. All ...

  1. Disorder in milk proteins: caseins, intrinsically disordered colloids.

    Science.gov (United States)

    Redwan, Elrashdy M; Xue, Bin; Almehdar, Hussein A; Uversky, Vladimir N

    2015-01-01

    This article opens a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. The focus of this introductory article on caseins is symbolic, since caseins were among the first recognized functional unfolded proteins and since they are definitely the most disordered, the most abundant, and the most studied of all milk proteins. In eutherian milks, the casein family includes at least three and usually four major members (αs1-, αs2-, β-, and κ-caseins) that are unrelated in sequence. However, in some species, two different αS2-casein genes are active, and therefore the total number of caseins can be as high as five. These proteins have found a number of uses in food industry. The functional repertoire of caseins ranges from nutritional function to involvement in the improving and/or maintaining cardiovascular health, to crucial contribution to the milk capacity to transport calcium phosphate, to serve as molecular chaperones, and to protect the mother's mammary gland against amyloidoses and ectopic calcification. An intricate feature of caseins is their ability to assemble to colloidal protein particles, casein micelles, serving to sequester and transport amorphous calcium phosphate. These and many other functions of caseins are obviously dependent on their intrinsically disordered nature and are controlled by various posttranslational modifications. Since various aspects of casein structure and function are rather well studied and since several recent reviews emphasized the functional roles of caseins' intrinsic disorder, the major goal of this article is to show how intrinsic disorder is encoded in the amino acid sequences of these proteins. PMID:25714333

  2. Blood and Brain Glutamate Levels in Children with Autistic Disorder

    Science.gov (United States)

    Hassan, Tamer H.; Abdelrahman, Hadeel M.; Fattah, Nelly R. Abdel; El-Masry, Nagda M.; Hashim, Haitham M.; El-Gerby, Khaled M.; Fattah, Nermin R. Abdel

    2013-01-01

    Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children…

  3. Peripheral blood brain-derived neurotrophic factor in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, K; Vinberg, M; Kessing, L V

    2016-01-01

    Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent...... investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control...... subjects and between affective states in bipolar disorder patients, including assessment of the effect of treatment of acute episodes on BDNF levels. A systematic review of English language studies without considering publication status was conducted in PubMed (January 1950-November 2014), Embase (1974...

  4. RELATIONS BETWEEN SELECTED INDICATORS OF BLOOD AND MILK OF DAIRY COWS WITH METABOLIC DISORDERS

    Directory of Open Access Journals (Sweden)

    Jaroslav Kováčik

    2013-02-01

    Full Text Available The aim of this work was to monitor the relations between selected indicators of technological properties of milk and blood biochemical parameters of dairy cows with metabolic disorders. Thirty-two cows were chosen, which were divided into 3 groups: first group - cows with metabolic problems of acidosis, second group - cows with metabolic problems of alkalosis, third group - healthy cows. Blood, urine and milk samples were collected. Urea, total lipids, total proteins, glucose and calcium was determined in the blood serum. Pure acidobasic forms, pH and density of urine were determined. Proteins, lactose, non-fat-solids, somatic cells count, calcium, urea, titratable acidity, fermentability, rennetability and thermostability were determined in samples of milk. Significant negative dependences were observed in the group of cows with metabolic problems of acidosis between urea in blood and in milk (r = -0.694, P <0.05, between calcium in blood and in milk (r = -0.653, P <0, 05, and between calcium in milk and glucose in blood (r = -0.648, P <0.05. In the group of cows with alkalosis, statistically significant correlation between total lipids in blood and fat in milk was found (r = -0.879, P <0.05.

  5. Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer.

    Science.gov (United States)

    Da Costa, Lydie; Suner, Ludovic; Galimand, Julie; Bonnel, Amandine; Pascreau, Tiffany; Couque, Nathalie; Fenneteau, Odile; Mohandas, Narla

    2016-01-01

    Inherited red blood cell (RBC) membrane disorders, such as hereditary spherocytosis, elliptocytosis and hereditary ovalocytosis, result from mutations in genes encoding various RBC membrane and skeletal proteins. The RBC membrane, a composite structure composed of a lipid bilayer linked to a spectrin/actin-based membrane skeleton, confers upon the RBC unique features of deformability and mechanical stability. The disease severity is primarily dependent on the extent of membrane surface area loss. RBC membrane disorders can be readily diagnosed by various laboratory approaches that include RBC cytology, flow cytometry, ektacytometry, electrophoresis of RBC membrane proteins and genetics. The reference technique for diagnosis of RBC membrane disorders is the osmotic gradient ektacytometry. However, in spite of its recognition as the reference technique, this technique is rarely used as a routine diagnosis tool for RBC membrane disorders due to its limited availability. This may soon change as a new generation of ektacytometer has been recently engineered. In this review, we describe the workflow of the samples shipped to our Hematology laboratory for RBC membrane disorder analysis and the data obtained for a large cohort of French patients presenting with RBC membrane disorders using a newly available version of the ektacytomer. PMID:26603718

  6. Roles of Intrinsic Disorder in Protein-Nucleic Acid Interactions

    OpenAIRE

    Dyson, H. Jane

    2011-01-01

    Interactions between proteins and nucleic acids typify the role of disordered segments, linkers, tails and other entities in the function of complexes that must form with high affinity and specificity but which must be capable of dissociating when no longer needed. While much of the emphasis in the literature has been on the interactions of disordered proteins with other proteins, disorder is also frequently observed in nucleic acids (particularly RNA) and in the proteins that interact with t...

  7. 妊娠期高血压疾病患者24 h尿蛋白含量与动态血压的关系%Relationship between 24-hour urine protein content and ambulatory blood pressure in patients with hypertensive disorder complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    程琪辉; 林晓峰

    2011-01-01

    Objective: To study the relationship between 24 - hour urine protein content and ambulatory blood pressure in order to guide clinical practice. Methods: 16 patients with hypertensive disorder complicating pregnancy (HDCP) and 16 normotensive women received 24 -hour urine protein test, ambulatory blood pressure determination in day and night, the correlation between urine protein and ambulatory blood pressure was analyzed. Results: The urine protein content in cases with HDCP was significantly higher than that in normotensive women ( P < 0.01 ) . The contractive pressure, diastolic pressure and mean arterial pressure in day and night in cases with HDCP were significantly higher than those in normotensive women ( P < 0.05 ) . The contractive pressure and mean arterial pressure in day in cases with HDCP and normotensive women were significantly higher than those in night (P < 0.05 ) . There was no correlation between blood pressure and 24 - hour urine protein in cases with HDCP and normotensive women ( P > 0. 05 ) . Conclusion: The 24 - hour urine protein content in cases with HDCP increases, but circadian rhythm of blood pressure exists.%目的:研究妊娠期高血压疾病患者24 h尿蛋白含量与动态血压的关系,以指导临床.方法:对16例妊娠期高血压疾病患者和16例正常女性分别进行24 h尿蛋白测定,白天和晚上的动态血压检测,分析尿蛋白与动态血压的相关性.结果:妊娠期高血压疾病患者的尿蛋白含量明显大于正常人(P0.05).结论:妊娠期高血压疾病患者24 h尿蛋白含量升高,但是血压昼夜节律还是存在的.

  8. Treatment of cardiovascular disorders using the cell differentiation signaling protein Nell1

    Science.gov (United States)

    Culiat, Cymbeline T

    2014-05-13

    It has been identified in accordance with the present invention that Nell1 is essential for normal cardiovascular development by promoting proper formation of the heart and blood vessels. The present invention therefore provides therapeutic methods for treating cardiovascular disorders by employing a Nell1 protein or nucleic acid molecule.

  9. Blood-feeding and immunogenic aedes aegypti saliva proteins

    OpenAIRE

    Surasombatpattana, Pornapat; Wasinpiyamongkol, L.; Patramool, Sirilaksana; Luplertlop, N.; Doucouré, Souleymane; Mouchet, François; Seveno, M.; Remoué, Franck; Demettre, E.; Brizard, Jean-Paul; Jouin, P.; Biron, D.G; F. Thomas; Missé, Dorothée

    2010-01-01

    Mosquito-transmitted pathogens pass through the insect's midgut (MG) and salivary gland (SG). What occurs in these organs in response to a blood meal is poorly understood, but identifying the physiological differences between sugar-fed and blood-fed (BF) mosquitoes could shed light on factors important in pathogens transmission. We compared differential protein expression in the MGs and SGs of female Aedes aegypti mosquitoes after a sugar- or blood-based diet. No difference was observed in th...

  10. Interaction of blood plasma with protein resistant surfaces

    Czech Academy of Sciences Publication Activity Database

    Brynda, Eduard; Riedel, Tomáš; Rodriguez-Emmenegger, Cesar; Reicheltová, Z.; Májek, P.

    Strasbourg: European Materials Research Society, 2013. RP.1-13. [E- MRS 2013 Spring Meeting. 27.05.2013-31.05.2013, Strasbourg] Institutional support: RVO:61389013 Keywords : blood plasma * protein adsorption Subject RIV: CD - Macromolecular Chemistry

  11. Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Kurt A. Jellinger

    2011-01-01

    Full Text Available Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious.

  12. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    Science.gov (United States)

    ... 1999 Spotlight on Research 2014 February 2014 (historical) Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder Replacing a protein that is crucial to ensuring that the skin’s ...

  13. Intrinsic Structural Disorder Confers Cellular Viability on Oncogenic Fusion Proteins

    OpenAIRE

    Hedi Hegyi; László Buday; Peter Tompa

    2009-01-01

    Chromosomal translocations, which often generate chimeric proteins by fusing segments of two distinct genes, represent the single major genetic aberration leading to cancer. We suggest that the unifying theme of these events is a high level of intrinsic structural disorder, enabling fusion proteins to evade cellular surveillance mechanisms that eliminate misfolded proteins. Predictions in 406 translocation-related human proteins show that they are significantly enriched in disorder (43.3% vs....

  14. Path to facilitate the prediction of functional amino acid substitutions in red blood cell disorders--a computational approach.

    Directory of Open Access Journals (Sweden)

    Rajith B

    Full Text Available BACKGROUND: A major area of effort in current genomics is to distinguish mutations that are functionally neutral from those that contribute to disease. Single Nucleotide Polymorphisms (SNPs are amino acid substitutions that currently account for approximately half of the known gene lesions responsible for human inherited diseases. As a result, the prediction of non-synonymous SNPs (nsSNPs that affect protein functions and relate to disease is an important task. PRINCIPAL FINDINGS: In this study, we performed a comprehensive analysis of deleterious SNPs at both functional and structural level in the respective genes associated with red blood cell metabolism disorders using bioinformatics tools. We analyzed the variants in Glucose-6-phosphate dehydrogenase (G6PD and isoforms of Pyruvate Kinase (PKLR & PKM2 genes responsible for major red blood cell disorders. Deleterious nsSNPs were categorized based on empirical rule and support vector machine based methods to predict the impact on protein functions. Furthermore, we modeled mutant proteins and compared them with the native protein for evaluation of protein structure stability. SIGNIFICANCE: We argue here that bioinformatics tools can play an important role in addressing the complexity of the underlying genetic basis of Red Blood Cell disorders. Based on our investigation, we report here the potential candidate SNPs, for future studies in human Red Blood Cell disorders. Current study also demonstrates the presence of other deleterious mutations and also endorses with in vivo experimental studies. Our approach will present the application of computational tools in understanding functional variation from the perspective of structure, expression, evolution and phenotype.

  15. Comparison of Proteins in Whole Blood and Dried Blood Spot Samples by LC/MS/MS

    Science.gov (United States)

    Chambers, Andrew G.; Percy, Andrew J.; Hardie, Darryl B.; Borchers, Christoph H.

    2013-09-01

    Dried blood spot (DBS) sampling methods are desirable for population-wide biomarker screening programs because of their ease of collection, transportation, and storage. Immunoassays are traditionally used to quantify endogenous proteins in these samples but require a separate assay for each protein. Recently, targeted mass spectrometry (MS) has been proposed for generating highly-multiplexed assays for biomarker proteins in DBS samples. In this work, we report the first comparison of proteins in whole blood and DBS samples using an untargeted MS approach. The average number of proteins identified in undepleted whole blood and DBS samples by liquid chromatography (LC)/MS/MS was 223 and 253, respectively. Protein identification repeatability was between 77 %-92 % within replicates and the majority of these repeated proteins (70 %) were observed in both sample formats. Proteins exclusively identified in the liquid or dried fluid spot format were unbiased based on their molecular weight, isoelectric point, aliphatic index, and grand average hydrophobicity. In addition, we extended this comparison to include proteins in matching plasma and serum samples with their dried fluid spot equivalents, dried plasma spot (DPS), and dried serum spot (DSS). This work begins to define the accessibility of endogenous proteins in dried fluid spot samples for analysis by MS and is useful in evaluating the scope of this new approach.

  16. Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

    OpenAIRE

    González-Maeso, Javier; Meana, J. Javier

    2006-01-01

    Mood disorders such as major depression and bipolar disorder are common, severe, chronic and often life-threatening illnesses. Suicide is estimated to be the cause of death in up to approximately 10-15% of individuals with mood disorders. Alterations in the signal transduction through G protein-coupled receptor (GPCR) pathways have been reported in the etiopathology of mood disorders and the suicidal behavior. In this regard, the implication of certain GPCR subtypes such as α2A-adrenoceptor h...

  17. Globular and disordered-the non-identical twins in protein-protein interactions

    DEFF Research Database (Denmark)

    Teilum, Kaare; Olsen, Johan G; Kragelund, Birthe B

    2015-01-01

    In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a str...... of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1)....

  18. Supramolecular Structures with Blood Plasma Proteins, Sugars and Nanosilica

    Science.gov (United States)

    Turov, V. V.; Gun'ko, V. M.; Galagan, N. P.; Rugal, A. A.; Barvinchenko, V. M.; Gorbyk, P. P.

    Supramolecular structures with blood plasma proteins (albumin, immunoglobulin and fibrinogen (HPF)), protein/water/silica and protein/water/ silica/sugar (glucose, fructose and saccharose) were studied by NMR, adsorption, IR and UV spectroscopy methods. Hydration parameters, amounts of weakly and strongly bound waters and interfacial energy (γ S) were determined over a wide range of component concentrations. The γ S(C protein,C silica) graphs were used to estimate the energy of protein-protein, protein-surface and particle-particle interactions. It was shown that interfacial energy of self-association (γ as) of protein molecules depends on a type of proteins. A large fraction of water bound to proteins can be displaced by sugars, and the effect of disaccharide (saccharose) was greater than that of monosugars. Changes in the structural parameters of cavities in HPF molecules and complexes with HPF/silica nanoparticles filled by bound water were analysed using NMR-cryoporometry showing that interaction of proteins with silica leads to a significant decrease in the amounts of water bound to both protein and silica surfaces. Bionanocomposites with BSA/nanosilica/sugar can be used to influence states of living cells and tissues after cryopreservation or other treatments. It was shown that interaction of proteins with silica leads to strong decrease in the volume of all types of internal cavities filled by water.

  19. Molecular interactions of graphene oxide with human blood plasma proteins

    Science.gov (United States)

    Kenry, Affa Affb Affc; Loh, Kian Ping; Lim, Chwee Teck

    2016-04-01

    We investigate the molecular interactions between graphene oxide (GO) and human blood plasma proteins. To gain an insight into the bio-physico-chemical activity of GO in biological and biomedical applications, we performed a series of biophysical assays to quantify the molecular interactions between GO with different lateral size distributions and the three essential human blood plasma proteins. We elucidate the various aspects of the GO-protein interactions, particularly, the adsorption, binding kinetics and equilibrium, and conformational stability, through determination of quantitative parameters, such as GO-protein association constants, binding cooperativity, and the binding-driven protein structural changes. We demonstrate that the molecular interactions between GO and plasma proteins are significantly dependent on the lateral size distribution and mean lateral sizes of the GO nanosheets and their subtle variations may markedly influence the GO-protein interactions. Consequently, we propose the existence of size-dependent molecular interactions between GO nanosheets and plasma proteins, and importantly, the presence of specific critical mean lateral sizes of GO nanosheets in achieving very high association and fluorescence quenching efficiency of the plasma proteins. We anticipate that this work will provide a basis for the design of graphene-based and other related nanomaterials for a plethora of biological and biomedical applications.

  20. Environmental Pressure May Change the Composition Protein Disorder in Prokaryotes.

    Directory of Open Access Journals (Sweden)

    Esmeralda Vicedo

    Full Text Available Many prokaryotic organisms have adapted to incredibly extreme habitats. The genomes of such extremophiles differ from their non-extremophile relatives. For example, some proteins in thermophiles sustain high temperatures by being more compact than homologs in non-extremophiles. Conversely, some proteins have increased volumes to compensate for freezing effects in psychrophiles that survive in the cold. Here, we revealed that some differences in organisms surviving in extreme habitats correlate with a simple single feature, namely the fraction of proteins predicted to have long disordered regions. We predicted disorder with different methods for 46 completely sequenced organisms from diverse habitats and found a correlation between protein disorder and the extremity of the environment. More specifically, the overall percentage of proteins with long disordered regions tended to be more similar between organisms of similar habitats than between organisms of similar taxonomy. For example, predictions tended to detect substantially more proteins with long disordered regions in prokaryotic halophiles (survive high salt than in their taxonomic neighbors. Another peculiar environment is that of high radiation survived, e.g. by Deinococcus radiodurans. The relatively high fraction of disorder predicted in this extremophile might provide a shield against mutations. Although our analysis fails to establish causation, the observed correlation between such a simplistic, coarse-grained, microscopic molecular feature (disorder content and a macroscopic variable (habitat remains stunning.

  1. Peripheral whole blood microRNA alterations in major depression and bipolar disorder.

    Science.gov (United States)

    Maffioletti, Elisabetta; Cattaneo, Annamaria; Rosso, Gianluca; Maina, Giuseppe; Maj, Carlo; Gennarelli, Massimo; Tardito, Daniela; Bocchio-Chiavetto, Luisella

    2016-08-01

    Major depression (MD) and bipolar disorder (BD) are severe and potentially life-threating mood disorders whose etiology is to date not completely understood. MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein synthesis post-transcriptionally by base-pairing to target gene mRNAs. Growing evidence indicated that miRNAs might play a key role in the pathogenesis of neuropsychiatric disorders and in the action of psychotropic drugs. On these bases, in this study we evaluated the expression levels of 1733 mature miRNAs annotated in miRBase v.17, through a microarray technique, in the blood of 20 MD and 20 BD patients and 20 healthy controls, in order to identify putative miRNA signatures associated with mood disorders. We found that 5 miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-let-7f-5p, hsa-miR-24-3p and hsa-miR-425-3p) were specifically altered in MD patients and 5 (hsa-miR-140-3p, hsa-miR-30d-5p, hsa-miR-330-5p, hsa-miR-378a-5p and hsa-miR-21-3p) in BD patients, whereas 2 miRNAs (hsa-miR-330-3p and hsa-miR-345-5p) were dysregulated in both the diseases. The bioinformatic prediction of the genes targeted by the altered miRNAs revealed the possible involvement of neural pathways relevant for psychiatric disorders. In conclusion, the observed results indicate a dysregulation of miRNA blood expression in mood disorders and could indicate new avenues for a better understanding of their pathogenetic mechanisms. The identified alterations may represent potential peripheral biomarkers to be complemented with other clinical and biological features for the improvement of diagnostic accuracy. PMID:27152760

  2. Stiffening of Red Blood Cells Induced by Disordered Cytoskeleton Structures: A Joint Theory-experiment Study

    CERN Document Server

    Lai, Lipeng; Lim, Chwee Teck; Cao, Jianshu

    2015-01-01

    The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bi-layer. Among various cell types, the Red Blood Cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins. Recent experiments focusing on the malaria infected RBCs (iRBCs) showed that there is a correlation between the elongation of spectrins in the cytoskeletal network and the stiffening of the iRBCs. Here we rationalize the correlation between these two observations by combining the worm-like chain (WLC) model for single spectrins and the Effective Medium Theory (EMT) for the network elasticity. We specifically focus on how the disorders in the cytoskeletal network affect its macroscopic elasticity. Analytical and numerical solutions from our model reveal that the stiffness of the membrane increases with ...

  3. The unfoldomics decade: an update on intrinsically disordered proteins

    OpenAIRE

    Vacic Vladimir; Chen Jessica; Yang Jack Y; Romero Pedro; Meng Jingwei; Oldfield Christopher J; Dunker A Keith; Obradovic Zoran; Uversky Vladimir N

    2008-01-01

    Abstract Background Our first predictor of protein disorder was published just over a decade ago in the Proceedings of the IEEE International Conference on Neural Networks (Romero P, Obradovic Z, Kissinger C, Villafranca JE, Dunker AK (1997) Identifying disordered regions in proteins from amino acid sequence. Proceedings of the IEEE International Conference on Neural Networks, 1: 90–95). By now more than twenty other laboratory groups have joined the efforts to improve the prediction of prote...

  4. Core modular blood and brain biomarkers in social defeat mouse model for post traumatic stress disorder

    OpenAIRE

    Yang, Ruoting; Daigle Jr, Bernie J; Muhie, Seid Y; Hammamieh, Rasha; Jett, Marti; Petzold, Linda; Francis J Doyle

    2013-01-01

    Abstract Background Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Consequently, the identification of diagnostic and prognostic blood biomarkers for PTSD is of great interest. Previously, we assessed genome-wide gene expression of seven brain regions and whole blood in a social defeat mouse model subjected to various stress co...

  5. Fuzzy regions in an intrinsically disordered protein impair protein-protein interactions.

    Science.gov (United States)

    Gruet, Antoine; Dosnon, Marion; Blocquel, David; Brunel, Joanna; Gerlier, Denis; Das, Rahul K; Bonetti, Daniela; Gianni, Stefano; Fuxreiter, Monika; Longhi, Sonia; Bignon, Christophe

    2016-02-01

    Despite the partial disorder-to-order transition that intrinsically disordered proteins often undergo upon binding to their partners, a considerable amount of residual disorder may be retained in the bound form, resulting in a fuzzy complex. Fuzzy regions flanking molecular recognition elements may enable partner fishing through non-specific, transient contacts, thereby facilitating binding, but may also disfavor binding through various mechanisms. So far, few computational or experimental studies have addressed the effect of fuzzy appendages on partner recognition by intrinsically disordered proteins. In order to shed light onto this issue, we used the interaction between the intrinsically disordered C-terminal domain of the measles virus (MeV) nucleoprotein (NTAIL ) and the X domain (XD) of the viral phosphoprotein as model system. After binding to XD, the N-terminal region of NTAIL remains conspicuously disordered, with α-helical folding taking place only within a short molecular recognition element. To study the effect of the N-terminal fuzzy region on NTAIL /XD binding, we generated N-terminal truncation variants of NTAIL , and assessed their binding abilities towards XD. The results revealed that binding increases with shortening of the N-terminal fuzzy region, with this also being observed with hsp70 (another MeV NTAIL binding partner), and for the homologous NTAIL /XD pairs from the Nipah and Hendra viruses. Finally, similar results were obtained when the MeV NTAIL fuzzy region was replaced with a highly dissimilar artificial disordered sequence, supporting a sequence-independent inhibitory effect of the fuzzy region. PMID:26684000

  6. Genome-Wide Prediction of Intrinsic Disorder; Sequence Alignment of Intrinsically Disordered Proteins

    Science.gov (United States)

    Midic, Uros

    2012-01-01

    Intrinsic disorder (ID) is defined as a lack of stable tertiary and/or secondary structure under physiological conditions in vitro. Intrinsically disordered proteins (IDPs) are highly abundant in nature. IDPs possess a number of crucial biological functions, being involved in regulation, recognition, signaling and control, e.g. their functional…

  7. The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows

    Science.gov (United States)

    Brust, M.; Aouane, O.; Thiébaud, M.; Flormann, D.; Verdier, C.; Kaestner, L.; Laschke, M. W.; Selmi, H.; Benyoussef, A.; Podgorski, T.; Coupier, G.; Misbah, C.; Wagner, C.

    2014-03-01

    The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.

  8. Globular and disordered-the non-identical twins in protein-protein interactions.

    Science.gov (United States)

    Teilum, Kaare; Olsen, Johan G; Kragelund, Birthe B

    2015-01-01

    In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1). PMID:26217672

  9. Globular and disordered-the non-identical twins in protein-protein interactions

    DEFF Research Database (Denmark)

    Teilum, Kaare; Olsen, Johan Gotthardt; Kragelund, Birthe Brandt

    2015-01-01

    In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a...... strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those...... of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non-identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol(-1)....

  10. Globular and disordered – the non-identical twins in protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Kaare eTeilum

    2015-07-01

    Full Text Available In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP’s bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein interactions to put to the test if the thermodynamic profiles of IDP interactions differ from those of other protein-protein interactions. We find that ordered proteins and the disordered ones act as non identical twins operating by similar principles but where the disordered proteins complexes are on average less stable by 2.5 kcal mol-1.

  11. DSS1/Sem1, a Multifunctional and Intrinsically Disordered Protein

    DEFF Research Database (Denmark)

    Kragelund, Birthe B; Schenstrøm, Signe M; Rebula, Caio A;

    2016-01-01

    DSS1/Sem1 is a versatile intrinsically disordered protein. Besides being a bona fide subunit of the 26S proteasome, DSS1 associates with other protein complexes, including BRCA2-RPA, involved in homologous recombination; the Csn12-Thp3 complex, involved in RNA splicing; the integrator, involved in...

  12. Seafood Consumption and Blood Mercury Concentrations in Jamaican Children With and Without Autism Spectrum Disorders

    OpenAIRE

    Rahbar, Mohammad H.; Samms-Vaughan, Maureen; Loveland, Katherine A.; Ardjomand-Hessabi, Manouchehr; Chen, Zhongxue; Bressler, Jan; Shakespeare-Pellington, Sydonnie; Grove, Megan L.; Bloom, Kari; Pearson, Deborah A.; Lalor, Gerald C.; Boerwinkle, Eric

    2012-01-01

    Mercury is a toxic metal shown to have harmful effects on human health. Several studies have reported high blood mercury concentrations as a risk factor for autism spectrum disorders (ASDs), while other studies have reported no such association. The goal of this study was to investigate the association between blood mercury concentrations in children and ASDs. Moreover, we investigated the role of seafood consumption in relation to blood mercury concentrations in Jamaican children. Based on d...

  13. Intrinsic structural disorder confers cellular viability on oncogenic fusion proteins.

    Directory of Open Access Journals (Sweden)

    Hedi Hegyi

    2009-10-01

    Full Text Available Chromosomal translocations, which often generate chimeric proteins by fusing segments of two distinct genes, represent the single major genetic aberration leading to cancer. We suggest that the unifying theme of these events is a high level of intrinsic structural disorder, enabling fusion proteins to evade cellular surveillance mechanisms that eliminate misfolded proteins. Predictions in 406 translocation-related human proteins show that they are significantly enriched in disorder (43.3% vs. 20.7% in all human proteins, they have fewer Pfam domains, and their translocation breakpoints tend to avoid domain splitting. The vicinity of the breakpoint is significantly more disordered than the rest of these already highly disordered fusion proteins. In the unlikely event of domain splitting in fusion it usually spares much of the domain or splits at locations where the newly exposed hydrophobic surface area approximates that of an intact domain. The mechanisms of action of fusion proteins suggest that in most cases their structural disorder is also essential to the acquired oncogenic function, enabling the long-range structural communication of remote binding and/or catalytic elements. In this respect, there are three major mechanisms that contribute to generating an oncogenic signal: (i a phosphorylation site and a tyrosine-kinase domain are fused, and structural disorder of the intervening region enables intramolecular phosphorylation (e.g., BCR-ABL; (ii a dimerisation domain fuses with a tyrosine kinase domain and disorder enables the two subunits within the homodimer to engage in permanent intermolecular phosphorylations (e.g., TFG-ALK; (iii the fusion of a DNA-binding element to a transactivator domain results in an aberrant transcription factor that causes severe misregulation of transcription (e.g. EWS-ATF. Our findings also suggest novel strategies of intervention against the ensuing neoplastic transformations.

  14. Cord blood lymphocyte responses to food antigens for the prediction of allergic disorders.

    OpenAIRE

    Kondo, N.; Kobayashi, Y.; Shinoda, S; Kasahara, K.; Kameyama, T; Iwasa, S; Orii, T.

    1992-01-01

    Proliferative responses of cord blood lymphocytes (CBLs) to food antigens and cord blood IgE concentrations were measured in 37 full term newborn infants for the prediction of allergic disorders. In these 37 infants who were followed up for two years, allergic history of the family was found in four (sensitivity 57.1%) and cord blood IgE concentrations were greater than 0.5 IU/ml in three (sensitivity 42.9%) of seven infants who developed allergic disorders. When CBLs were stimulated twice by...

  15. Quantifying Protein Disorder through Measures of Excess Conformational Entropy.

    Science.gov (United States)

    Rajasekaran, Nandakumar; Gopi, Soundhararajan; Narayan, Abhishek; Naganathan, Athi N

    2016-05-19

    Intrinsically disordered proteins (IDPs) and proteins with a large degree of disorder are abundant in the proteomes of eukaryotes and viruses, and play a vital role in cellular homeostasis and disease. One fundamental question that has been raised on IDPs is the process by which they offset the entropic penalty involved in transitioning from a heterogeneous ensemble of conformations to a much smaller collection of binding-competent states. However, this has been a difficult problem to address, as the effective entropic cost of fixing residues in a folded-like conformation from disordered amino acid neighborhoods is itself not known. Moreover, there are several examples where the sequence complexity of disordered regions is as high as well-folded regions. Disorder in such cases therefore arises from excess conformational entropy determined entirely by correlated sequence effects, an entropic code that is yet to be identified. Here, we explore these issues by exploiting the order-disorder transitions of a helix in Pbx-Homeodomain together with a dual entropy statistical mechanical model to estimate the magnitude and sign of the excess conformational entropy of residues in disordered regions. We find that a mere 2.1-fold increase in the number of allowed conformations per residue (∼0.7kBT favoring the unfolded state) relative to a well-folded sequence, or ∼2(N) additional conformations for a N-residue sequence, is sufficient to promote disorder under physiological conditions. We show that this estimate is quite robust and helps in rationalizing the thermodynamic signatures of disordered regions in important regulatory proteins, modeling the conformational folding-binding landscapes of IDPs, quantifying the stability effects characteristic of disordered protein loops and their subtle roles in determining the partitioning of folding flux in ordered domains. In effect, the dual entropy model we propose provides a statistical thermodynamic basis for the relative

  16. Blood coagulation and its alterations in hemorrhagic and thrombotic disorders.

    OpenAIRE

    Rapaport, S I

    1993-01-01

    Clinical observations have added to the understanding of basic mechanisms of blood coagulation and its alterations in certain hemorrhagic and thrombotic states. Much clinical evidence exists for concluding that the exposure of blood to tissue factor (thromboplastin) on tissue cells represents the key event initiating fibrin clot formation after tissue injury. This then results in the formation of activated factor VII (VIIa)-tissue factor complexes, which must activate both factor X and factor...

  17. Understanding disordered and membrane protein recognition by molecular dynamics

    OpenAIRE

    Stanley, Nathaniel H., 1983-

    2015-01-01

    This thesis has been about the use of a simulation technique, known as molecular dynamics simulations, to study biophysics in proteins that have historically been difficult to study with other methods. We have studied numerous systems, namely binding to the membrane proteins Fatty acid amide hydrolase (FAAH) and the sphingosine-1-phosphate receptor 1 (S1P1R), and folding in the disordered protein kinase inducible domain (KID). In each case we have been able to analyze processes and uncover be...

  18. Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects.

    Science.gov (United States)

    Gubert, Carolina; Stertz, Laura; Pfaffenseller, Bianca; Panizzutti, Bruna Schilling; Rezin, Gislaine Tezza; Massuda, Raffael; Streck, Emilio Luiz; Gama, Clarissa Severino; Kapczinski, Flávio; Kunz, Maurício

    2013-10-01

    Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression. PMID:23870796

  19. Functional correlations of respiratory syncytial virus proteins to intrinsic disorder.

    Science.gov (United States)

    Whelan, Jillian N; Reddy, Krishna D; Uversky, Vladimir N; Teng, Michael N

    2016-04-26

    Protein intrinsic disorder is an important characteristic demonstrated by the absence of higher order structure, and is commonly detected in multifunctional proteins encoded by RNA viruses. Intrinsically disordered regions (IDRs) of proteins exhibit high flexibility and solvent accessibility, which permit several distinct protein functions, including but not limited to binding of multiple partners and accessibility for post-translational modifications. IDR-containing viral proteins can therefore execute various functional roles to enable productive viral replication. Respiratory syncytial virus (RSV) is a globally circulating, non-segmented, negative sense (NNS) RNA virus that causes severe lower respiratory infections. In this study, we performed a comprehensive evaluation of predicted intrinsic disorder of the RSV proteome to better understand the functional role of RSV protein IDRs. We included 27 RSV strains to sample major RSV subtypes and genotypes, as well as geographic and temporal isolate differences. Several types of disorder predictions were applied to the RSV proteome, including per-residue (PONDR®-FIT and PONDR® VL-XT), binary (CH, CDF, CH-CDF), and disorder-based interactions (ANCHOR and MoRFpred). We classified RSV IDRs by size, frequency and function. Finally, we determined the functional implications of RSV IDRs by mapping predicted IDRs to known functional domains of each protein. Identification of RSV IDRs within functional domains improves our understanding of RSV pathogenesis in addition to providing potential therapeutic targets. Furthermore, this approach can be applied to other NNS viruses that encode essential multifunctional proteins for the elucidation of viral protein regions that can be manipulated for attenuation of viral replication. PMID:27062995

  20. Protein misfolding disorders: pathogenesis and intervention

    DEFF Research Database (Denmark)

    Gregersen, Niels

    2006-01-01

    be accompanied by a gain-of-function pathogenesis, which in many cases determines the pathological and clinical features. Examples are Parkinson and Huntington diseases. Although a number of strategies have been tried to decrease the amounts of accumulated and aggregated proteins, a likely future......Newly synthesized proteins in the living cell must go through a folding process to attain their functional structure. To achieve this in an efficient fashion, all organisms, including humans, have evolved a large set of molecular chaperones that assist the folding as well as the maintenance of the...... functional structure of cellular proteins. Aberrant proteins, the result of production errors, inherited or acquired amino acid substitutions or damage, especially oxidative modifications, can in many cases not fold correctly and will be trapped in misfolded conformations. To rid the cell of misfolded...

  1. Globular and disordered-the non-identical twins in protein-protein interactions

    OpenAIRE

    Teilum, Kaare; Olsen, Johan G.; Kragelund, Birthe B.

    2015-01-01

    In biology proteins from different structural classes interact across and within classes in ways that are optimized to achieve balanced functional outputs. The interactions between intrinsically disordered proteins (IDPs) and other proteins rely on changes in flexibility and this is seen as a strong determinant for their function. This has fostered the notion that IDP's bind with low affinity but high specificity. Here we have analyzed available detailed thermodynamic data for protein-protein...

  2. Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

    Science.gov (United States)

    Toto, Angelo; Camilloni, Carlo; Giri, Rajanish; Brunori, Maurizio; Vendruscolo, Michele; Gianni, Stefano

    2016-02-01

    Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding upon binding’ process, however, has not been fully characterised yet. Here we present a study of the folding of the intrinsically disordered transactivation domain of c-Myb (c-Myb) upon binding its partner KIX. By determining the structure of the folding transition state for the binding of wild-type and three mutational variants of KIX, we found a remarkable plasticity of the folding pathway of c-Myb. To explain this phenomenon, we show that the folding of c-Myb is templated by the structure of KIX. This adaptive folding behaviour, which occurs by heterogeneous nucleation, differs from the robust homogeneous nucleation typically observed for globular proteins. We suggest that this templated folding mechanism may enable intrinsically disordered proteins to achieve specific and reliable binding with multiple partners while avoiding aberrant interactions.

  3. Bleeding Disorders

    Science.gov (United States)

    ... times I'd miss work and skip the gym because I felt so lousy. So I decided ... cell called platelets. Your body also needs blood proteins called clotting factors. In people with bleeding disorders, ...

  4. Altered Regional Cerebral Blood Flow in Chronic Whiplash Associated Disorders

    NARCIS (Netherlands)

    Vállez García, David; Doorduin, Janine; Willemsen, Antoon T.M.; Dierckx, Rudi A.j.o.; Otte, Andreas

    2016-01-01

    There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD). However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1) to validate previous results showing a

  5. Disorder and function: a review of the dehydrin protein family.

    Science.gov (United States)

    Graether, Steffen P; Boddington, Kelly F

    2014-01-01

    Dehydration proteins (dehydrins) are group 2 members of the late embryogenesis abundant (LEA) protein family. The protein architecture of dehydrins can be described by the presence of three types of conserved sequence motifs that have been named the K-, Y-, and S-segments. By definition, a dehydrin must contain at least one copy of the lysine-rich K-segment. Abiotic stresses such as drought, cold, and salinity cause the upregulation of dehydrin mRNA and protein levels. Despite the large body of genetic and protein evidence of the importance of these proteins in stress response, the in vivo protective mechanism is not fully known. In vitro experimental evidence from biochemical assays and localization experiments suggests multiple roles for dehydrins, including membrane protection, cryoprotection of enzymes, and protection from reactive oxygen species. Membrane binding by dehydrins is likely to be as a peripheral membrane protein, since the protein sequences are highly hydrophilic and contain many charged amino acids. Because of this, dehydrins in solution are intrinsically disordered proteins, that is, they have no well-defined secondary or tertiary structure. Despite their disorder, dehydrins have been shown to gain structure when bound to ligands such as membranes, and to possibly change their oligomeric state when bound to ions. We review what is currently known about dehydrin sequences and their structures, and examine the various ligands that have been shown to bind to this family of proteins. PMID:25400646

  6. Disorder and function: a review of the dehydrin protein family

    Directory of Open Access Journals (Sweden)

    Steffen P Graether

    2014-10-01

    Full Text Available Dehydration proteins (dehydrins are group 2 members of the late embryogenesis abundant (LEA protein family. The protein architecture of dehydrins can be described by the presence of three types of conserved sequence motifs that have been named the K-, Y- and S-segments. By definition, a dehydrin must contain at least one copy of the lysine-rich K-segment. Abiotic stresses such as drought, cold, and salinity cause the upregulation of dehydrin mRNA and protein levels. Despite the large body of genetic and protein evidence of the importance of these proteins in stress response, the in vivo protective mechanism is not fully known. In vitro experimental evidence from biochemical assays and localization experiments suggest multiple roles for dehydrins, including membrane protection, cryoprotection of enzymes, and protection from reactive oxygen species. Membrane binding by dehydrins is likely to be as a peripheral membrane protein, since the protein sequences are highly hydrophilic and contain many charged amino acids. Because of this, dehydrins in solution are intrinsically disordered proteins, that is, they have no well-defined secondary or tertiary structure. Despite their disorder, dehydrins have been shown to gain structure when bound to ligands such as membranes, and to possibly change their oligomeric state when bound to ions. We review what is currently known about dehydrin sequences and their structures, and examine the various ligands that have been shown to bind to this family of proteins.

  7. Conformational disorder in folded and intrinsically disordered proteins from nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Biological macromolecules are, by essence, dynamical systems. While the importance of this flexibility is nowadays well established, the accurate characterization of the conformational disorder of these systems remains an important challenge. Nuclear magnetic resonance spectroscopy is a unique tool to probe these motions at atomic level, through the analysis of spin relaxation or residual dipolar couplings. The latter allows all motions occurring at timescales faster than the millisecond to be investigated, including physiologically important timescales. The information presents in those couplings is interpreted here using mainly analytical approaches in order to quantify the amounts of dynamics present in folded protein, to determine the direction of those motions and to obtain structural information within this conformational disorder. These analytical approaches are complemented by numerical methods, that allowed the observation of phenomena from a different point of view or the investigation of other systems such as intrinsically disordered proteins. All of these studies demonstrate an important complementarity between structural order and conformational disorder. (author)

  8. The importance of intrinsic disorder for protein phosphorylation

    OpenAIRE

    Lilia M Iakoucheva; Radivojac, Predrag; Celeste J Brown; O'Connor, Timothy R.; Sikes, Jason G.; Obradovic, Zoran; Dunker, A. Keith

    2004-01-01

    Reversible protein phosphorylation provides a major regulatory mechanism in eukaryotic cells. Due to the high variability of amino acid residues flanking a relatively limited number of experimentally identified phosphorylation sites, reliable prediction of such sites still remains an important issue. Here we report the development of a new web-based tool for the prediction of protein phosphorylation sites, DISPHOS (DISorder-enhanced PHOSphorylation predictor, http://www.ist.temple.edu/DISPHOS...

  9. Blood plasma proteins and protein fractions in roe deer Capreolus capreolus L.

    Directory of Open Access Journals (Sweden)

    Dorota CYGAN-SZCZEGIELNIAK

    2015-09-01

    Full Text Available The aim of the research was to investigate some selected biochemical blood parameters in roe deer (Capreolus capreolus L.. The experiment covered 15 from 2 to 3-year-old bucks from Kuyavian-Pomeranian Voivodeship. The animals were shot by individual hunters on the shooting grounds during the hunting season of 2008/2009 (in the accordance with the Journal of Laws No 48. The material for the research was blood plasma obtained after centrifuging full, nonhemolyzed blood. The blood was collected from the zygomatic vein directly to the test tubes with EDTA and transported in cooling conditions to the laboratory. After transporting the samples of blood to a certified analytical laboratory, the following elements of the obtained blood plasma were examined: ceruloplasmin . using turbidimetric method; transferrin . using immunoturbimetric method; troponin- using a third generation assay on an Elecsys; total protein, albumin, globulin . using spectrophotometric method and total iron . using colorimetric method. The results were statistically analyzed, i.e. the correlation between the parameters was measured by means of Pearsonfs correlation coefficient. The analysis of the results revealed a number of statistically significant relations between the parameters under the investigation, especially among the compounds directly responsible for metabolism of iron and copper. A statistically important positive correlation was observed between ceruloplasmin and ferritin (r = 0.563; P.0.05 and a negative one between transferrin and troponin (r = -0.609; P.0.05. Moreover, the content of transferrin . an iron-binding protein . was 0.17 g/l, while the concentration of iron was 58 ƒĘmol/l. The content of ceruloplasmin . a protein responsible for metabolism of copper . was very low (0.036 g/l. The level of proteins in the blood plasma of the animals under the research was approximately 72 g/l, with the share of albumins about 46%. The albumin-globulin ratio was 0.86.

  10. Subclinical Posttraumatic Stress Disorder Symptoms: Relationships with Blood Pressure, Hostility, and Sleep

    Science.gov (United States)

    Zinzow, Heidi M.; Hibdon, Melissa A.; Nathan, Aaron W.; Morrison, Anastasia V.; Hayden, Gregg W.; Lindberg, Caitlyn; Switzer, Fred S.

    2016-01-01

    The purpose of this study was to examine the relationships among subclinical PTSD symptoms, blood pressure, and several variables linked to both frank PTSD and the basic psychobiological adaptation to stress. The authors recruited a sample of 91 healthy, young men and women between 18 and 35 years. We examined links among subclinical posttraumatic stress disorder symptoms, blood pressure, sleep quality, and hostility. Posttraumatic stress disorder symptoms were associated with poorer sleep quality and higher hostility scores in both women and men. In men, PTSD symptoms were also associated with elevated resting diastolic blood pressure, and sex was an important moderator of that relationship. Moreover, sleep quality and hostility are substantive mediators of the relationship between diastolic blood pressure and PTSD. Behavioral interventions designed to increase sleep quality and restructure hostile attitudes could potentially serve as preventive interventions for PTSD and the underlying cardiovascular comorbidities in young adults. PMID:27403340

  11. Laboratory tests for disorders of complement and complement regulatory proteins.

    Science.gov (United States)

    Shih, Angela R; Murali, Mandakolathur R

    2015-12-01

    The complement pathway is a cascade of proteases that is involved in immune surveillance and innate immunity, as well as adaptive immunity. Dysfunction of the complement cascade may be mediated by aberrations in the pathways of activation, complement regulatory proteins, or complement deficiencies, and has been linked to a number of hematologic disorders, including paroxysmal noctural hemoglobinuria (PNH), hereditary angioedema (HAE), and atypical hemolytic-uremic syndrome (aHUS). Here, current laboratory tests for disorders of the complement pathway are reviewed, and their utility and limitations in hematologic disorders and systemic diseases are discussed. Current therapeutic advances targeting the complement pathway in treatment of complement-mediated hematologic disorders are also reviewed. PMID:26437749

  12. Alterations of Regional Cerebral Blood Flow in Major Depressive Disorder

    International Nuclear Information System (INIS)

    The authors analyzed how the regional cerebral blood flow (rCBF) findings of patients with major depression differ from the normal control, and our results were compared to previous reports. Twelve patients fulfilling DSM-IV criteria for major depression who were off all psychotropic medications for > 4 weeks (male: 7, female: 5, age range: 19∼52 years, average age: 29.3±9.9 years) and 14 normal volunteers (male: 8, female: 6, age range: 19∼53 years, average age: 31.4±9.2 years) were recruited. Images of brain perfusion SPECT were obtained using Tc-99m ECD and patterns of the rCBF were compared between patients with major depression and the healthy control subjects. The patients with major depression showed increase of the r-CBF in right lingual gyrus, right fusiform gyrus, left lingual gyrus, left precuneus, and left superior temporal gyrus, and showed decrease of r-CBF in right pons, left medial frontal gyrus, cingulate gyrus of left limbic lobe, cingulate gyrus of right frontal lobe, and cingulate gyrus of right limbic lobe compared to the normal control. The Tc-99m ECD brain perfusion SPECT findings in our study did not differ from the previously reported regional cerebral blood flow pattern of patients with major depression. Especially, decreased rCBF pattern typical to major depression patients in the right pons, left medial frontal gyrus, and cingulate regions was clearly demonstrated

  13. Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

    Directory of Open Access Journals (Sweden)

    Daniela Marasco

    2015-04-01

    Full Text Available Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs.

  14. Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins.

    Science.gov (United States)

    Uversky, Vladimir N

    2016-03-25

    Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. PMID:26851286

  15. Intrinsic disorder of human Yin Yang 1 protein.

    Science.gov (United States)

    Górecki, Andrzej; Bonarek, Piotr; Górka, Adam Kazimierz; Figiel, Małgorzata; Wilamowski, Mateusz; Dziedzicka-Wasylewska, Marta

    2015-07-01

    YY1 (Yin Yang 1) is a zinc finger protein with an essential role in various biological functions via DNA- and protein-protein interactions with numerous partners. YY1 is involved in the regulation of a broad spectrum of cellular processes such as embryogenesis, proliferation, tumorigenesis, and snRNA transcription. The more than 100 reported targets of the YY1 protein suggest that it contains intrinsically disordered regions that are involved in such diverse interactions. Here, we present a study of the structural properties of human YY1 using several biochemical and biophysical techniques (fluorescence, circular dichroism, gel filtration chromatography, proteolytic susceptibility) together with various bioinformatics approaches. To facilitate our exploration of the YY1 structure, the full-length protein as well as an N-terminal fragment (residues 1-295) and the C-terminal DNA binding domain were used. We found the N-terminus to be a non-compact fragment of YY1 with little residual secondary structure and lacking a well-defined tertiary structure. The results of our study indicate that YY1 belongs to the family of intrinsically disordered proteins (IDPs), which exist natively in a partially unfolded conformation. Proteins 2015; 83:1284-1296. © 2015 Wiley Periodicals, Inc. PMID:25963536

  16. Pharmaceutical protein production by yeast: towards production of human blood proteins by microbial fermentation

    DEFF Research Database (Denmark)

    Martínez, José L; Liu, Lifang; Petranovic, Dina;

    2012-01-01

    Since the approval of recombinant insulin from Escherichia coli for its clinical use in the early 1980s, the amount of recombinant pharmaceutical proteins obtained by microbial fermentations has significantly increased. The recent advances in genomics together with high throughput analysis...... techniques (the so-called—omics approaches) and integrative approaches (systems biology) allow the development of novel microbial cell factories as valuable platforms for large scale production of therapeutic proteins. This review summarizes the main achievements and the current situation in the field of...... recombinant therapeutics using yeast Saccharomyces cerevisiae as a model platform, and discusses the future potential of this platform for production of blood proteins and substitutes....

  17. Stiffening of Red Blood Cells Induced by Cytoskeleton Disorders: A Joint Theory-Experiment Study.

    Science.gov (United States)

    Lai, Lipeng; Xu, Xiaofeng; Lim, Chwee Teck; Cao, Jianshu

    2015-12-01

    The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bilayer. Among various cell types, the red blood cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two-dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins. Recent experiments focusing on the malaria-infected RBCs (iRBCs) show that there is a correlation between the elongation of spectrins in the cytoskeletal network and the stiffening of the iRBCs. Here we rationalize the correlation between these two observations by combining the wormlike chain model for single spectrins and the effective medium theory for the network elasticity. We specifically focus on how the disorders in the cytoskeletal network affect its macroscopic elasticity. Analytical and numerical solutions from our model reveal that the stiffness of the membrane increases with increasing end-to-end distances of spectrins, but has a nonmonotonic dependence on the variance of the end-to-end distance distributions. These predictions are verified quantitatively by our atomic force microscopy and micropipette aspiration measurements of iRBCs. The model may, from a molecular level, provide guidelines for future identification of new treatment methods for RBC-related diseases, such as malaria infection. PMID:26636940

  18. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    Science.gov (United States)

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25% of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD,…

  19. Cerebral blood flow and metabolism analysis in parkinsonian disorders

    International Nuclear Information System (INIS)

    Main metabolic and hemodynamic abnormalities detected by single photon emission computerized tomography and positron emission tomography in extra-pyramidal disorders are reported. In the first stage of Parkinson's disease, cortical metabolism and perfusion can be in normal range or moderately and uniformly reduced. A significant decrease may appear with the disease evolution. Marked abnormalities are observed in parkinsonian patients with dementia (subcortical dementia), involving especially the frontal cortex. A marked diffuse cortical hypo-metabolism (temporal, parietal, occipital and frontal cortex) may suggest the diagnosis of dementia with Lewy bodies, especially in case of fluctuating cognitive decline with recurrent visual hallucinations. In progressive supra-nuclear palsy, a frontal cortex hypo-metabolism is reported precociously, preceding sometimes the cognitive impairment. Metabolic pattern find in multiple system atrophy reflects dysfunction of both nigrostriatal pathways and striatum, with a decrease glucose uptake in putamen and caudate nucleus which also involves cerebellum for the patients with cerebellar syndrome. In cortico-basal degeneration, asymmetric fronto-parietal and striatal hypo-metabolism observed in the controlateral hemisphere to the clinically most affected side, constitute the main characteristic well correlated with apraxia. (author)

  20. Diagnosis and epidemiology of red blood cell enzyme disorders

    Directory of Open Access Journals (Sweden)

    Richard Van Wijk

    2013-03-01

    Full Text Available The red blood cell possess an active metabolic machinery that provides the cell with energy to pump ions against electrochemical gradients, to maintain its shape, to keep hemoglobin iron in the reduced (ferrous form, and to maintain enzyme and hemoglobin sulfhydryl groups. The main source of metabolic energy comes from glucose. Glucose is metabolized through the glycolytic pathway and through the hexose monophosphate shunt. Glycolysis catabolizes glucose to pyruvate and lactate, which represent the end products of glucose metabolism in the erythrocyte. Adenosine diphosphate (ADP is phosphorylated to adenosine triphosphate (ATP, and nicotinamide adenine dinucleotide (NAD+ is reduced to NADH in glycolysis. 2,3- Bisphosphoglycerate, an important regulator of the oxygen affinity of hemoglobin, is generated during glycolysis by the Rapoport-Luebering shunt. The hexose monophosphate shunt oxidizes glucose-6-phosphate, reducing NADP+ to reduced nicotinamide adenine dinucleotide phosphate (NADPH. The red cell lacks the capacity for de novo purine synthesis but has a salvage pathway that permits synthesis of purine nucleotides from purine bases...

  1. A Novel Approach for Predicting Disordered Regions in A Protein Sequence

    OpenAIRE

    Li, Meijing; Cho, Seong Beom; Ryu, Keun Ho

    2014-01-01

    Objectives A number of published predictors are based on various algorithms and disordered protein sequence properties. Although many predictors have been published, the study of protein disordered region prediction is ongoing because different prediction methods can find different disordered regions in a protein sequence. Methods Therefore we have used a new approach to find the more varying disordered regions for more efficient and accurate prediction of protein structures. In this study, w...

  2. Rotational order–disorder structure of fluorescent protein FP480

    International Nuclear Information System (INIS)

    An analysis of the rotational order–disorder structure of fluorescent protein FP480 is presented. In the last decade, advances in instrumentation and software development have made crystallography a powerful tool in structural biology. Using this method, structural information can now be acquired from pathological crystals that would have been abandoned in earlier times. In this paper, the order–disorder (OD) structure of fluorescent protein FP480 is discussed. The structure is composed of tetramers with 222 symmetry incorporated into the lattice in two different ways, namely rotated 90° with respect to each other around the crystal c axis, with tetramer axes coincident with crystallographic twofold axes. The random distribution of alternatively oriented tetramers in the crystal creates a rotational OD structure with statistically averaged I422 symmetry, although the presence of very weak and diffuse additional reflections suggests that the randomness is only approximate

  3. Conformational propensities of intrinsically disordered proteins from NMR chemical shifts

    International Nuclear Information System (INIS)

    The realization that a protein can be fully functional even in the absence of a stable three-dimensional structure has motivated a large number of studies describing the conformational behaviour of these proteins at atomic resolution. Here, we review recent advances in the determination of local structural propensities of intrinsically disordered proteins (IDPs) from experimental NMR chemical shifts. A mapping of the local structure in IDPs is of paramount importance in order to understand the molecular details of complex formation, in particular, for IDPs that fold upon binding or undergo structural transitions to pathological forms of the same protein. We discuss experimental strategies for the spectral assignment of IDPs, chemical shift prediction algorithms and the generation of representative structural ensembles of IDPs on the basis of chemical shifts. Additionally, we highlight the inherent degeneracies associated with the determination of IDP sub-state populations from NMR chemical shifts alone. (authors)

  4. PHYSICAL MODELING OF GEOMETRICALLY CONFINED DISORDERED PROTEIN ASSEMBLIES

    OpenAIRE

    Ando, David

    2015-01-01

    The transport of cargo across the nuclear membrane is highly selective and accomplished by a poorly understood mechanism involving hundreds of nucleoporins lining the inside of the nuclear pore complex (NPC). Currently, there is no clear picture of the overall structure formed by this collection of proteins within the pore, primarily due to their disordered nature and uncertainty regarding the properties of individual nucleoporins. We first study the defining characteristics of the amino acid...

  5. Transactivating-transduction protein-polyethylene glycol modified liposomes traverse the blood-spinal cord and blood-brain barriers

    Institute of Scientific and Technical Information of China (English)

    Xianhu Zhou; Chunyuan Wang; Shiqing Feng; Jin Chang; Xiaohong Kong; Yang Liu; Shijie Gao

    2012-01-01

    Naive liposomes can cross the blood-brain barrier and blood-spinal cord barrier in small amounts. Liposomes modified by a transactivating-transduction protein can deliver antibiotics for the treatment of acute bacterial infection-induced brain inflammation. Liposomes conjugated with polyethylene glycol have the capability of long-term circulation. In this study we prepared transactivating-transduction protein-polyethylene glycol-modified liposomes labeled with fluorescein isothiocyanate. Thus, liposomes were characterized by transmembrane, long-term circulation and fluorescence tracing. Uptake, cytotoxicity, and the ability of traversing blood-spinal cord and blood-brain barriers were observed following coculture with human breast adenocarcinoma cells (MCF-7). Results demonstrated that the liposomes had good biocompatibility, and low cytotoxicity when cocultured with human breast adenocarcinoma cells. Liposomes could traverse cell membranes and entered the central nervous system and neurocytes through the blood-spinal cord and blood-brain barriers of rats via the systemic circulation. These results verified that fluorescein isothiocyanate-modified transactivating-transduction protein-polyethylene glycol liposomes have the ability to traverse the blood-spinal cord and blood-brain barriers.

  6. Modeling of band-3 protein diffusion in the normal and defective red blood cell membrane.

    Science.gov (United States)

    Li, He; Zhang, Yihao; Ha, Vi; Lykotrafitis, George

    2016-04-13

    We employ a two-component red blood cell (RBC) membrane model to simulate lateral diffusion of band-3 proteins in the normal RBC and in the RBC with defective membrane proteins. The defects reduce the connectivity between the lipid bilayer and the membrane skeleton (vertical connectivity), or the connectivity of the membrane skeleton itself (horizontal connectivity), and are associated with the blood disorders of hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) respectively. Initially, we demonstrate that the cytoskeleton limits band-3 lateral mobility by measuring the band-3 macroscopic diffusion coefficients in the normal RBC membrane and in a lipid bilayer without the cytoskeleton. Then, we study band-3 diffusion in the defective RBC membrane and quantify the relation between band-3 diffusion coefficients and percentage of protein defects in HE RBCs. In addition, we illustrate that at low spectrin network connectivity (horizontal connectivity) band-3 subdiffusion can be approximated as anomalous diffusion, while at high horizontal connectivity band-3 diffusion is characterized as confined diffusion. Our simulations show that the band-3 anomalous diffusion exponent depends on the percentage of protein defects in the membrane cytoskeleton. We also confirm that the introduction of attraction between the lipid bilayer and the spectrin network reduces band-3 diffusion, but we show that this reduction is lower than predicted by the percolation theory. Furthermore, we predict that the attractive force between the spectrin filament and the lipid bilayer is at least 20 times smaller than the binding forces at band-3 and glycophorin C, the two major membrane binding sites. Finally, we explore diffusion of band-3 particles in the RBC membrane with defects related to vertical connectivity. We demonstrate that in this case band-3 diffusion can be approximated as confined diffusion for all attraction levels between the spectrin network and the lipid bilayer

  7. Protein-associated water and secondary structure effect removal of blood proteins from metallic substrates.

    Science.gov (United States)

    Anand, Gaurav; Zhang, Fuming; Linhardt, Robert J; Belfort, Georges

    2011-03-01

    Removing adsorbed protein from metals has significant health and industrial consequences. There are numerous protein-adsorption studies using model self-assembled monolayers or polymeric substrates but hardly any high-resolution measurements of adsorption and removal of proteins on industrially relevant transition metals. Surgeons and ship owners desire clean metal surfaces to reduce transmission of disease via surgical instruments and minimize surface fouling (to reduce friction and corrosion), respectively. A major finding of this work is that, besides hydrophobic interaction adhesion energy, water content in an adsorbed protein layer and secondary structure of proteins determined the access and hence ability to remove adsorbed proteins from metal surfaces with a strong alkaline-surfactant solution (NaOH and 5 mg/mL SDS in PBS at pH 11). This is demonstrated with three blood proteins (bovine serum albumin, immunoglobulin, and fibrinogen) and four transition metal substrates and stainless steel (platinum (Pt), gold (Au), tungsten (W), titanium (Ti), and 316 grade stainless steel (SS)). All the metallic substrates were checked for chemical contaminations like carbon and sulfur and were characterized using X-ray photoelectron spectroscopy (XPS). While Pt and Au surfaces were oxide-free (fairly inert elements), W, Ti, and SS substrates were associated with native oxide. Difference measurements between a quartz crystal microbalance with dissipation (QCM-D) and surface plasmon resonance spectroscopy (SPR) provided a measure of the water content in the protein-adsorbed layers. Hydrophobic adhesion forces, obtained with atomic force microscopy, between the proteins and the metals correlated with the amount of the adsorbed protein-water complex. Thus, the amount of protein adsorbed decreased with Pt, Au, W, Ti and SS, in this order. Neither sessile contact angle nor surface roughness of the metal substrates was useful as predictors here. All three globular proteins

  8. Intrinsically Disordered Proteins in a Physics-Based World

    Directory of Open Access Journals (Sweden)

    Jianhan Chen

    2010-12-01

    Full Text Available Intrinsically disordered proteins (IDPs are a newly recognized class of functional proteins that rely on a lack of stable structure for function. They are highly prevalent in biology, play fundamental roles, and are extensively involved in human diseases. For signaling and regulation, IDPs often fold into stable structures upon binding to specific targets. The mechanisms of these coupled binding and folding processes are of significant importance because they underlie the organization of regulatory networks that dictate various aspects of cellular decision-making. This review first discusses the challenge in detailed experimental characterization of these heterogeneous and dynamics proteins and the unique and exciting opportunity for physics-based modeling to make crucial contributions, and then summarizes key lessons from recent de novo simulations of the structure and interactions of several regulatory IDPs.

  9. Detection of protein biomarker using a blood glucose meter.

    Science.gov (United States)

    Lan, Tian; Xiang, Yu; Lu, Yi

    2015-01-01

    mHeath technologies are recognized to play important roles in the future of personal care and medicine. However, their full potentials have not been reached, as most of current technologies are restricted to monitoring physical and behavioral parameters, such as body temperature, heart rate, blood pressure, and physical movement, while direct monitoring of biomarkers in body fluids can provide much more accurate and useful information for medical diagnostics. A major barrier to realizing the full potential of mHealth is the high costs and long cycles of developing mHealth devices capable of monitoring biomarkers in body fluids. To lower the costs and shorten the developmental cycle, we have demonstrated the leveraging of the most successful portable medical monitoring device on the market, the blood glucose meter (BGM), with FDA-approved smartphone technologies that allow for wireless transmission and remote monitoring of a wide range of non-glucose targets. In this protocol, an aptamer-based assay for quantification of interferon-γ (IFN-γ) using an off-the-shelf BGM is described. In this assay, an aptamer-based target recognition system is employed. When IFN-γ binds to the aptamer, it triggers the release of a reporter enzyme, invertase, which can catalyze the conversion of sucrose (not detected by BGM) to glucose. The glucose being produced is then detected using a BGM. The system mimics a competitive enzyme-linked immunosorbent assay (ELISA), where the traditional immunoassay is replaced by an aptamer binding assay; the reporter protein is replaced by invertase, and finally the optical or fluorescence detector is replaced with widely available BGMs. PMID:25626534

  10. BMC Blood Disorders becomes BMC Hematology: evolving along with the hematology field

    OpenAIRE

    Chap, Christna

    2013-01-01

    This Editorial marks the launch of BMC Hematology, formerly known as BMC Blood Disorders, within the BMC series of journals published by BioMed Central. The scope of BMC Hematology encompasses basic, experimental and clinical research related to hematology. In this Editorial we will discuss the rationale behind this relaunch and how, as an open access journal providing unrestricted and free access to scientific and scholarly work, BMC Hematology will help disseminate research in the hematolog...

  11. Structural disproportions in regional medical standards in treatment of blood circulatory disorders

    OpenAIRE

    Sazanova G.Yu.

    2012-01-01

    The research goal is to consider the opinion of physicians about the financial medical assistance standards to patients with blood circulatory disorders. Materials and methods: 530 doctors of different specialties were interviewed. Some sociological and statistical methods were used in the study. Results: The majority of respondents (83%) considered that it was necessary to coordinate financial support of diagnostic and treatment expenditures with the standards of the regional program of rend...

  12. Blood levels of glial fibrillary acidic protein (GFAP in patients with neurological diseases.

    Directory of Open Access Journals (Sweden)

    Christoph A Mayer

    Full Text Available BACKGROUND AND PURPOSE: The brain-specific astroglial protein GFAP is a blood biomarker candidate indicative of intracerebral hemorrhage in patients with symptoms suspicious of acute stroke. Comparably little, however, is known about GFAP release in other neurological disorders. In order to identify potential "specificity gaps" of a future GFAP test used to diagnose intracerebral hemorrhage, we measured GFAP in the blood of a large and rather unselected collective of patients with neurological diseases. METHODS: Within a one-year period, we randomly selected in-patients of our university hospital for study inclusion. Patients with ischemic stroke, transient ischemic attack and intracerebral hemorrhage were excluded. Primary endpoint was the ICD-10 coded diagnosis reached at discharge. During hospital stay, blood was collected, and GFAP plasma levels were determined using an advanced prototype immunoassay at Roche Diagnostics. RESULTS: A total of 331 patients were included, covering a broad spectrum of neurological diseases. GFAP levels were low in the vast majority of patients, with 98.5% of cases lying below the cut-off that was previously defined for the differentiation of intracerebral hemorrhage and ischemic stroke. No diagnosis or group of diagnoses was identified that showed consistently increased GFAP values. No association with age and sex was found. CONCLUSION: Most acute and chronic neurological diseases, including typical stroke mimics, are not associated with detectable GFAP levels in the bloodstream. Our findings underline the hypothesis that rapid astroglial destruction as in acute intracerebral hemorrhage is mandatory for GFAP increase. A future GFAP blood test applied to identify patients with intracerebral hemorrhage is likely to have a high specificity.

  13. ROLE OF SERUM EOSINOPHILIC CATIONIC PROTEIN AND TRYPTASE IN MYELOPROLIFERATIVE AND LYMPHOPROLIFERATIVE DISORDERS

    Directory of Open Access Journals (Sweden)

    L. S. Komarova

    2008-01-01

    Full Text Available Abstract. A role of intracellular proteins of eosinophils and mast cells remains unclear in the patients with hematological neoplasia. There is a substantial evidence that eosinophils possess some common mechanisms of cooperation with mast cells. Therapeutic interventions into key events controlling eosinophil migration may be a leading factor in treatment of hypereosinophylic states in onco-hematological disorders. Due to unknown functions of eosinophils in majority of eosinophilia-associated diseases, it would be useful to establish an algorithm of accurate diagnostics in the patients with eosinophilia, in order to choose more effective treatment in future.We studied serum levels of secretable eosinophil and mast cells proteins in oncohematological patients with increased eosinophil counts. The aim of our study was to test a significance of quantitative assay for tryptase and ECP in the patients with myelo- and lymphoproliferative diseases. The study group included thirty-eight patients with oncohematological diseases, accompanied by a marked eosinophilia (> 0.4 x 109/L. Eighteen patients with bronchial asthma (BA, and eight cases of solid tumors comprised a reference group for polyclonal eosinophilia. The levels of ECP and tryptase were measured in blood serum using a commercial fluoroimmunoenzyme assay («Pharmacia», Uppsala, Sweden. Total ECP levels were markedly increased in general group with hematological malignancies (p < 0.03, , and in cases of chronic GvHD (p < 0.03, and in a sub-group with lymphoproliferative disorders (р = 0.007 as compared to the group of non-hematological diseases.Serum levels of tryptase were significantly increased in the patients with chronic GvHD after allo-HSCT and lymphoproliferative diseases, as compared to the group of patients with solid tumors (р = 0.03, as well in GvHD compared with lymphoproliferative disorders (р < 0.05.A direct correlation was found between serum ECP levels and absolute

  14. An Overview of Practical Applications of Protein Disorder Prediction and Drive for Faster, More Accurate Predictions

    Directory of Open Access Journals (Sweden)

    Xin Deng

    2015-07-01

    Full Text Available Protein disordered regions are segments of a protein chain that do not adopt a stable structure. Thus far, a variety of protein disorder prediction methods have been developed and have been widely used, not only in traditional bioinformatics domains, including protein structure prediction, protein structure determination and function annotation, but also in many other biomedical fields. The relationship between intrinsically-disordered proteins and some human diseases has played a significant role in disorder prediction in disease identification and epidemiological investigations. Disordered proteins can also serve as potential targets for drug discovery with an emphasis on the disordered-to-ordered transition in the disordered binding regions, and this has led to substantial research in drug discovery or design based on protein disordered region prediction. Furthermore, protein disorder prediction has also been applied to healthcare by predicting the disease risk of mutations in patients and studying the mechanistic basis of diseases. As the applications of disorder prediction increase, so too does the need to make quick and accurate predictions. To fill this need, we also present a new approach to predict protein residue disorder using wide sequence windows that is applicable on the genomic scale.

  15. Evaluation of whole blood zinc and copper levels in children with autism spectrum disorder.

    Science.gov (United States)

    Crăciun, Elena Cristina; Bjørklund, Geir; Tinkov, Alexey A; Urbina, Mauricio A; Skalny, Anatoly V; Rad, Florina; Dronca, Eleonora

    2016-08-01

    Zinc (Zn) and copper (Cu) are important trace elements for cognitive development and normal neurological functioning. Autism spectrum disorder (ASD) is a common neurological disorder, which has previously been associated with the levels of some trace elements in the blood. However, clinical data regarding the potential implication of Zn and Cu in patients with ASD are still insufficient. Therefore, the aim of the present study was to investigate the whole blood levels of Zn and Cu in a cohort of 28 children with ASD and 28 age- and gender-matched healthy controls. Whole blood Zn and Cu levels were assessed using inductively-coupled plasma-sector field mass spectrometry. Both in the control and in the ASD group, the values of whole blood Cu and Zn were characterized by a Gaussian distribution. The results indicate that the ASD children were characterized by ~10 % (p = 0.005) and ~12 % (p = 0.015) lower levels of whole blood Zn and Zn/Cu ratio, respectively, in comparison to controls. No significant difference in whole blood Cu was observed. However, Cu/Zn ratio was ~15 % (p = 0.008) higher in ASD children than that in the control ones. The results of the present study may be indicative of Zn deficiency in ASD children. Taking into account Zn-mediated up-regulation of metallothionein (MT) gene expression, these findings suggest a possible alteration in the functioning of the neuroprotective MT system. However, further investigations are required to test this hypothesis. PMID:27059237

  16. Regulation of blood-testis barrier by actin binding proteins and protein kinases.

    Science.gov (United States)

    Li, Nan; Tang, Elizabeth I; Cheng, C Yan

    2016-03-01

    The blood-testis barrier (BTB) is an important ultrastructure in the testis, since the onset of meiosis and spermiogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular, at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin-binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases. PMID:26628556

  17. Random coil chemical shift for intrinsically disordered proteins

    DEFF Research Database (Denmark)

    Kjærgaard, Magnus; Brander, Søren; Poulsen, Flemming Martin

    2011-01-01

    Secondary chemical shift analysis is the main NMR method for detection of transiently formed secondary structure in intrinsically disordered proteins. The quality of the secondary chemical shifts is dependent on an appropriate choice of random coil chemical shifts. We report random coil chemical....... Temperature has a non-negligible effect on the (13)C random coil chemical shifts, so temperature coefficients are reported for the random coil chemical shifts to allow extrapolation to other temperatures. The pH dependence of the histidine random coil chemical shifts is investigated in a titration series...

  18. Understanding Viral Transmission Behavior via Protein Intrinsic Disorder Prediction: Coronaviruses

    OpenAIRE

    Gerard Kian-Meng Goh; A. Keith Dunker; Vladimir N Uversky

    2012-01-01

    Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model a...

  19. Direct observation of interaction between proteins and blood-compatible polymer surfaces.

    Science.gov (United States)

    Hayashi, Tomohiro; Tanaka, Masaru; Yamamoto, Sadaaki; Shimomura, Masatsugu; Hara, Masahiko

    2007-12-01

    The adhesion force between blood-compatible polymer (poly(2-methoxyethyl acrylate: PMEA) and proteins (fibrinogen and bovine serum albumin (BSA)) were measured by atomic force microscopy. The PMEA surface showed almost no adhesion to native protein molecules, whereas non-blood-compatible poly(n-butyl acrylate): PBA strongly adhered to proteins. Interestingly, adhesion did appear between PMEA and proteins when the proteins were denatured. In all cases, these trends were not affected by the conditions of the solution. Combining the results with previous reports, the authors conclude that interfacial water molecules play a critical role in the protein resistance of PMEA. PMID:20408647

  20. Surfactant protein D levels in umbilical cord blood and capillary blood of premature infants. The influence of perinatal factors

    DEFF Research Database (Denmark)

    Dahl, Marianne; Holmskov, Uffe; Husby, Steffen;

    2006-01-01

    Surfactant protein D (SP-D) is a collectin that plays an important role in the innate immune system and takes part in the surfactant homeostasis by regulating the surfactant pool size. The aims of this study were to investigate the values of SP-D in umbilical cord blood and capillary blood of...... premature infants and to relate the levels to perinatal conditions. A total of 254 premature infants were enrolled in the present study. Umbilical cord blood was drawn at the time of birth and capillary blood at regular intervals throughout the admission. The concentration of SP-D in umbilical cord blood...... concentration of SP-D in capillary blood day 1 was 1,466 ng/mL (range 410-5,051 ng/mL), with lowest values in infants born with ROM and delivered vaginally. High SP-D levels in umbilical cord blood and capillary blood on day 1 were found to be more likely in infants in need for respiratory support or surfactant...

  1. Structural biology of intrinsically disordered proteins: Revisiting unsolved mysteries.

    Science.gov (United States)

    Sigalov, Alexander B

    2016-06-01

    The emergence of intrinsically disordered proteins (IDPs) has challenged the classical protein structure-function paradigm by introducing a new paradigm of "coupled binding and folding". This paradigm suggests that IDPs fold upon binding to their partners. Further studies, however, revealed a novel and previously unrecognized phenomenon of "uncoupled binding and folding" suggesting that IDPs do not necessarily fold upon interaction with their lipid and protein partners. The complex and often unusual biophysics of IDPs makes structural characterization of these proteins and their complexes not only challenging but often resulting in opposite conclusions. For this reason, some crucial questions in this field remain unsolved for well over a decade. Considering an important role of IDPs in cellular regulation, signaling and control in health and disease, more efforts are needed to solve these mysteries. Here, I focus on two long-standing contradictions in the literature concerning dimerization and membrane-binding activities of IDPs. Molecular explanation of these discrepancies is provided. I also demonstrate how resolution of these critical issues in the field of IDPs results in our expanded understanding of cell function and has multiple applications in biology and medicine. PMID:27004461

  2. Regulation of homeostasis in the process of protein absorption from small intestine to blood

    OpenAIRE

    Akmal Yuldashev; Ravshan Rahmanov; Mukaddas Rahmatova; Margarita Tarinova; Aziza Nishanova; Gulnara Islamova

    2010-01-01

    Electron microscopic and immunоfluorescent study in rats aged 1 and 3 days after birth allowed to establish a process of absorption of protein from the small intestine into the lymph and blood. Blood homeostasis was provided by the proteins filtrated from glomerular capillaries of nephrons and reabsorbed by the epithelial cells in canaliculi of nephrons. The absorbed natural heterologous protein was depleted by lysosomes of epithelial cells of intestine and kidneys and macrophages. It support...

  3. Evaluation of Peripheral Blood Circulation Disorder in Scleroderma Patients Using an Optical Sensor with a Pressurization Mechanism

    Science.gov (United States)

    Yamakoshi, Yoshiki

    2016-01-01

    Blood circulation function of peripheral blood vessels in skin dermis was evaluated employing an optical sensor with a pressurization mechanism using the blood outflow and reflow characteristics. The device contains a light source and an optical sensor. When applied to the skin surface, it first exerts the primary pressure (higher than the systolic blood pressure), causing an outflow of blood from the dermal peripheral blood vessels. After two heartbeats, the pressure is lowered (secondary pressure) and blood reflows into the peripheral blood vessels. Hemoglobin concentration, which changes during blood outflow and reflow, is derived from the received light intensity using the Beer–Lambert law. This method was evaluated in 26 healthy female volunteers and 26 female scleroderma patients. In order to evaluate the blood circulation function of the peripheral blood vessels of scleroderma patients, pressurization sequence which consists of primary pressure followed by secondary pressure was adopted. Blood reflow during the first heartbeat period after applying the secondary pressure of 40mmHg was (mean±SD) 0.059±0.05%mm for scleroderma patients and 0.173±0.104%mm for healthy volunteers. Blood reflow was significantly lower in scleroderma patients than in healthy volunteers (p<0.05). This result indicates that the information necessary for assessing blood circulation disorder of peripheral blood vessels in scleroderma patients is objectively obtained by the proposed method. PMID:27479094

  4. Content of intrinsic disorder influences the outcome of cell-free protein synthesis

    OpenAIRE

    Tokmakov, Alexander A.; Kurotani, Atsushi; Ikeda, Mariko; Terazawa, Yumiko; Shirouzu, Mikako; Stefanov, Vasily; SAKURAI, Tetsuya; Yokoyama, Shigeyuki

    2015-01-01

    Cell-free protein synthesis is used to produce proteins with various structural traits. Recent bioinformatics analyses indicate that more than half of eukaryotic proteins possess long intrinsically disordered regions. However, no systematic study concerning the connection between intrinsic disorder and expression success of cell-free protein synthesis has been presented until now. To address this issue, we examined correlations of the experimentally observed cell-free protein expression yield...

  5. [Prediction of short loops in the proteins with internal disorder].

    Science.gov (United States)

    Deriusheva, E I; Galzitskaia, O V; Serdiuk, I N

    2008-01-01

    New possibility of the FoldUnfold program for prediction of short disordered regions (loops), which appears by using the short window width (3 amino acid residues), was described. For three representatives of the proteins G family the FoldUnfold program predicted almost all short loops and yield results are well compatible with the X-ray structure data. We have classified the loops predicted in the protein Ras-p21 structure in two types. In the first type, loops have high values of the Debye-Waller factor typical of the so-called functional loops (flexible loops). In the other type, loops have lower values of the Debye-Waller factor and can be considered as loops connecting secondary structure elements (rigid loops). When the results of prediction with the use of our program are compared with the results of other programs (PONDR, RONN, DisEMBL, PreLINK, IUPred, GlobPlot 2, FoldIndex), it is seen that the first enables far better prediction of short loop positions. Use of FoldUnfold for ubiquitin-like domain h-PLIC-2 allows to resolve such task as definition of boundary between the structured and unstructured regions in proteins with a big portion of disordered regions. The FoldUnfold program defines a clear boundary between the structured and unstructured regions at amino acid residues 30-31,whereas each of the other programs outlines the boundary from the 28-th amino acid residues through the 70th. PMID:19140328

  6. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood Clots Blood Clotting and Pregnancy Clots and ... Increased maternal age Other medical illness (e.g., cancer, infection) back to top How are Blood Clots ...

  7. The in vitro antioxidant properties of alcalase hydrolysate prepared from silkie fowl (Gallus gallus) blood protein.

    Science.gov (United States)

    Cheng, Fu-Yuan; Lai, I-Chun; Lin, Liang-Chuan; Sakata, Ryoichi

    2016-07-01

    Two types of proteins including blood plasma protein and blood cell protein were isolated from silkie fowl (Gallus gallus) blood and hydrolyzed using alcalase for 0, 2, 4 and 6 h. The blood plasma protein hydrolysate (BPH) and blood cell protein hydrolysate (BCH) were analyzed for pH value, peptide content and antioxidative properties. The significantly higher peptide contents were observed in BPH than that of BCH, which showed that blood plasma protein was more suitable to hydrolysis by alcalase than blood cell protein. Both BPH and BCH showed strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and Fe(2+) chelating ability. BPH at 4 h of hydrolysis (BPH4) demonstrated significantly higher antioxidant capacity than those treated by alcalase in most of the assays. The BPH4 was separated using ultra-filtration and assessment of the fractions and indicated that low molecular weight of peptides (< 3 kDa) possessed greater DPPH scavenging activity, Fe(2+) chelating ability and inhibitory activity of lipid peroxidation. These results show that BPH has the potential to be ingredients in the food industry as a replacement of synthetic antioxidants. PMID:26556592

  8. Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder

    Science.gov (United States)

    Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Gillespie, Catherine Hagan; Anderson, George M.; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy

    2016-01-01

    Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD. PMID:26527110

  9. A study on regional cerebral blood flow at rest and stress state in anxiety disorder patients

    International Nuclear Information System (INIS)

    Objective: To investigate he characteristics of rest and stress regional cerebral blood flow (rCBF) in naive anxiety disorder patients. Methods: Twenty naive anxiety disorder patients were enrolled in the study with twenty healthy volunteers as controls. The rest and stress 99Tcm-ethylene cystein dimer (ECD) SPECT were performed separately at 2 consecutive days, Raven reasoning test was used as a stressor. Results: 1) Compared to the healthy controls, the patients' rest rCBF of the frontal lobe, temporal lobe, thalamus and basal ganglia were significantly lower (P<0.05 and 0.01). 2)The patients' stress rCBF of the frontal lobe, temporal lobe, part occipital lobe, part parietal lobe, thalamus and basal ganglia were significantly lower compared to the healthy controls' (P<0.05 and 0.01). 3) Opposite to the healthy controls, the rCBF of patients increased significantly after stressor simulating. Conclusions: The hypofunction of frontal lobe, temporal lobe, thalamus and basal ganglia may exist in naive anxiety disorder patients. The abnormal rCBF of patients after simulating may be one of the characteristics of anxiety disorder

  10. Role of fluid shear stress in regulating VWF structure, function and related blood disorders.

    Science.gov (United States)

    Gogia, Shobhit; Neelamegham, Sriram

    2015-01-01

    Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα-VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure-function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries. PMID:26600266

  11. Blood profiling of proteins and steroids during weight maintenance with manipulation of dietary protein level and glycaemic index

    DEFF Research Database (Denmark)

    Wang, Ping; Holst, Claus; Astrup, Arne;

    2012-01-01

    ), evenly selected from four dietary groups that varied in protein and GI levels. The blood concentrations of twenty-nine proteins and three steroid hormones were measured. The changes in analytes during weight maintenance largely correlated negatively with the changes during weight loss, with some...

  12. The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows

    OpenAIRE

    Brust, Matthias,; Aouane, Othmane; Thiébaud, Marine; Flormann, Daniel; Verdier, Claude; Kaestner, Lars; Laschke, Matthias; Selmi, Hassib; Benyoussef, Abdellilah; Podgorski, Thomas; Coupier, Gwennou; Misbah, Chaouqi; Wagner, Christian

    2014-01-01

    The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule netw...

  13. INFLUENCE OF NATURAL IMMUNOMODULATORS ON PROTEIN FRACTIONS AND CORTISOL CONTENT IN RABBIT BLOOD UNDER STRESS

    OpenAIRE

    Grabovskyi S.; Grabovska O.

    2015-01-01

    The results of determination of protein fractions, cortisol content in blood of rabbits, which further added to the feed of natural origin biologically active substances are presented in the article. As an antistressors and immunomodulators in pre-slaughter period are using of spleen extract biologically active substances were obtained with ultrasound application. The purpose of research — determination of changes of protein fractions, cortisol content in rabbits blood before slaughter and th...

  14. Multiscale enhanced sampling of intrinsically disordered protein conformations.

    Science.gov (United States)

    Lee, Kuo Hao; Chen, Jianhan

    2016-03-01

    In a recently developed multiscale enhanced sampling (MSES) technique, topology-based coarse-grained (CG) models are coupled to atomistic force fields to enhance the sampling of atomistic protein conformations. Here, the MSES protocol is refined by designing more sophisticated Hamiltonian/temperature replica exchange schemes that involve additional parameters in the MSES coupling restraint potential, to more carefully control how conformations are coupled between the atomistic and CG models. A specific focus is to derive an optimal MSES protocol for simulating conformational ensembles of intrinsically disordered proteins (IDPs). The efficacy of the refined protocols, referred to as MSES-soft asymptote (SA), was evaluated using two model peptides with various levels of residual helicities. The results show that MSES-SA generates more reversible helix-coil transitions and leads to improved convergence on various ensemble conformational properties. This study further suggests that more detailed CG models are likely necessary for more effective sampling of local conformational transition of IDPs. © 2015 Wiley Periodicals, Inc. PMID:26052838

  15. Marked variability in the extent of protein disorder within and between viral families.

    Directory of Open Access Journals (Sweden)

    Ravindra Pushker

    Full Text Available Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues, and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively. Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses, except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel

  16. Silica Nanoparticles Effects on Blood Coagulation Proteins and Platelets

    OpenAIRE

    Volodymyr Gryshchuk; Natalya Galagan

    2016-01-01

    Interaction of nanoparticles with the blood coagulation is important prior to their using as the drug carriers or therapeutic agents. The aim of present work was studying of the primary effects of silica nanoparticles (SiNPs) on haemostasis in vitro. We studied the effect of SiNPs on blood coagulation directly estimating the activation of prothrombin and factor X and to verify any possible effect of SiNPs on human platelets. It was shown that SiNPs shortened coagulation time in APTT and PT te...

  17. Changes in Regional Cerebral Blood Flow with Cognitive Behavioral Therapy in the Treatment of Panic Disorder

    Energy Technology Data Exchange (ETDEWEB)

    Won, K. S.; Jun, S. K.; Kim, J. B.; Jang, E. J. [College of Medicine, Univ. of Kyemyoung, Taegu (Korea, Republic of)

    2003-07-01

    This study attempted to prospectively investigate changes in regional cerebral blood flow (rCBF) on SPECT and clinical response to cognitive behavioral therapy (CBT) in patients with panic disorder with (PDA) and without (PD) agoraphobia. Using 99mTc-ECD brain SPECT, we assessed brain perfusion in 5 out patients at rest before and after CBT. The subjects received 12 weekly sessions of CBT. Subjects were assessed by Agoraphobic Cognitions Questionnaire, Body Sensations Questionnaire, Beck Anxiety Inventory, Anxiety Sensitivity Index, Beck Depression Inventory-II, Panic Disorder Severity Scale (PDSS) and clinical global improvement (CGI) scale measurement were used as outcome measures. Patients were considered responders to CBT if they are much or very much improved on CGI scale and have a PDSS score at least 30% below their baseline. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The baseline scans were compared to the post-CBT scans by using the statistics option multi subject, different conditions. Of 5 subjects 4 were male, 3 diagnosed PDA, and 4 on anti-anxiety medication. All of the subjects were classified as CBT responders. Their mean pretreatment and posttreatment PDSS were 17.4 (SD=8.2) and 4.2 (SD=3.1), respectively. The results of SPM analysis showed a significant decrease in blood flow after CBT in the thalamus bilaterally and right middle frontal gyrus (Brodmann's area 6). All results were thresholded at an uncorrected p<0.001 (for voxel height) and a corrected p<0.04 (for spatial extent). These preliminary data suggest that SPM analysis of 99mTc-ECD brain SPECT can reveal the change of rCBF in patient with panic disorder before and after CBT and the CBT effect may be associated with limbic and thalamic networks. However this study was a short trial with small number of subjects. Further studies with larger patient cohorts are needed.

  18. Changes in Regional Cerebral Blood Flow with Cognitive Behavioral Therapy in the Treatment of Panic Disorder

    International Nuclear Information System (INIS)

    This study attempted to prospectively investigate changes in regional cerebral blood flow (rCBF) on SPECT and clinical response to cognitive behavioral therapy (CBT) in patients with panic disorder with (PDA) and without (PD) agoraphobia. Using 99mTc-ECD brain SPECT, we assessed brain perfusion in 5 out patients at rest before and after CBT. The subjects received 12 weekly sessions of CBT. Subjects were assessed by Agoraphobic Cognitions Questionnaire, Body Sensations Questionnaire, Beck Anxiety Inventory, Anxiety Sensitivity Index, Beck Depression Inventory-II, Panic Disorder Severity Scale (PDSS) and clinical global improvement (CGI) scale measurement were used as outcome measures. Patients were considered responders to CBT if they are much or very much improved on CGI scale and have a PDSS score at least 30% below their baseline. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The baseline scans were compared to the post-CBT scans by using the statistics option multi subject, different conditions. Of 5 subjects 4 were male, 3 diagnosed PDA, and 4 on anti-anxiety medication. All of the subjects were classified as CBT responders. Their mean pretreatment and posttreatment PDSS were 17.4 (SD=8.2) and 4.2 (SD=3.1), respectively. The results of SPM analysis showed a significant decrease in blood flow after CBT in the thalamus bilaterally and right middle frontal gyrus (Brodmann's area 6). All results were thresholded at an uncorrected p<0.001 (for voxel height) and a corrected p<0.04 (for spatial extent). These preliminary data suggest that SPM analysis of 99mTc-ECD brain SPECT can reveal the change of rCBF in patient with panic disorder before and after CBT and the CBT effect may be associated with limbic and thalamic networks. However this study was a short trial with small number of subjects. Further studies with larger patient cohorts are needed

  19. Intake of total protein, plant protein and animal protein in relation to blood pressure : a meta-analysis of observational and intervention studies

    NARCIS (Netherlands)

    Tielemans, S. M. A. J.; Altorf-van der Kuil, W.; Engberink, M. F.; Brink, E. J.; van Baak, M. A.; Bakker, S. J. L.; Geleijnse, J. M.

    2013-01-01

    There is growing evidence from epidemiological studies that dietary protein may beneficially influence blood pressure (BP), but findings are inconclusive. We performed a meta-analysis of 29 observational studies and randomized controlled trials (RCTs) of dietary protein and types of protein in relat

  20. Protein secondary structure appears to be robust under in silico evolution while protein disorder appears not to be.

    KAUST Repository

    Schaefer, Christian

    2010-01-16

    MOTIVATION: The mutation of amino acids often impacts protein function and structure. Mutations without negative effect sustain evolutionary pressure. We study a particular aspect of structural robustness with respect to mutations: regular protein secondary structure and natively unstructured (intrinsically disordered) regions. Is the formation of regular secondary structure an intrinsic feature of amino acid sequences, or is it a feature that is lost upon mutation and is maintained by evolution against the odds? Similarly, is disorder an intrinsic sequence feature or is it difficult to maintain? To tackle these questions, we in silico mutated native protein sequences into random sequence-like ensembles and monitored the change in predicted secondary structure and disorder. RESULTS: We established that by our coarse-grained measures for change, predictions and observations were similar, suggesting that our results were not biased by prediction mistakes. Changes in secondary structure and disorder predictions were linearly proportional to the change in sequence. Surprisingly, neither the content nor the length distribution for the predicted secondary structure changed substantially. Regions with long disorder behaved differently in that significantly fewer such regions were predicted after a few mutation steps. Our findings suggest that the formation of regular secondary structure is an intrinsic feature of random amino acid sequences, while the formation of long-disordered regions is not an intrinsic feature of proteins with disordered regions. Put differently, helices and strands appear to be maintained easily by evolution, whereas maintaining disordered regions appears difficult. Neutral mutations with respect to disorder are therefore very unlikely.

  1. Near infrared light induces post-translational modifications of human red blood cell proteins.

    Science.gov (United States)

    Walski, Tomasz; Dyrda, Agnieszka; Dzik, Małgorzata; Chludzińska, Ludmiła; Tomków, Tomasz; Mehl, Joanna; Detyna, Jerzy; Gałecka, Katarzyna; Witkiewicz, Wojciech; Komorowska, Małgorzata

    2015-11-01

    There is a growing body of evidence that near infrared (NIR) light exerts beneficial effects on cells. Its usefulness in the treatment of cancer, acute brain injuries, strokes and neurodegenerative disorders has been proposed. The mechanism of the NIR action is probably of photochemical nature, however it is not fully understood. Here, using a relatively simple biological model, human red blood cells (RBCs), and a polychromatic non-polarized light source, we investigate the impact of NIR radiation on the oxygen carrier, hemoglobin (Hb), and anion exchanger (AE1, Band 3). The exposure of intact RBCs to NIR light causes quaternary transitions in Hb, dehydration of proteins and decreases the amount of physiologically inactive methemoglobin, as detected by Raman spectroscopy. These effects are accompanied by a lowering of the intracellular pH (pHi) and changes in the cell membrane topography, as documented by atomic force microscopy (AFM). All those changes are in line with our previous studies where alterations of the membrane fluidity and membrane potential were attributed to NIR action on RBCs. The rate of the above listed changes depends strictly on the dose of NIR light that the cells receive, nonetheless it should not be considered as a thermal effect. PMID:26329012

  2. The role of metals in protein conformational disorders - The case of prion protein and Aβ -peptide

    Science.gov (United States)

    De Santis, E.; Minicozzi, V.; Morante, S.; Rossi, G. C.; Stellato, F.

    2016-02-01

    Protein conformational disorders are members of a vast class of pathologies in which endogenous proteins or peptides undergo a misfolding process by switching from the physiological soluble configuration to a pathological fibrillar insoluble state. An important, but not yet fully elucidated, role in the process appears to be played by transition metal ions, mainly copper and zinc. X-ray absorption spectroscopy is one of the most suitable techniques for the structural characterization of biological molecules in complex with metal. Owing to its chemical selectivity and sensitivity to the local atomic geometry around the absorber, it can be successfully used to study the environment of metal ions in complex with proteins and peptides in physiological conditions. In this paper we present X-ray absorption spectroscopy studies of the metal ions coordination modes in systems where metals are complexed with specific amyloidogenic proteins and peptides. In particular, we show results concerning the Amyloid β peptide, that is involved in Alzheimer's disease, and the Prion protein, that is responsible for the Transmissible Spongiform Encephalopathy. Our findings suggest that the copper and zinc ions may play a crucial role in the aggregation and fibril formation process of these two biomolecules. Elucidating this kind of interaction could be a key preliminary step before any viable therapy can be conceived or designed.

  3. Disorder Prediction Methods, Their Applicability to Different Protein Targets and Their Usefulness for Guiding Experimental Studies

    Directory of Open Access Journals (Sweden)

    Jennifer D. Atkins

    2015-08-01

    Full Text Available The role and function of a given protein is dependent on its structure. In recent years, however, numerous studies have highlighted the importance of unstructured, or disordered regions in governing a protein’s function. Disordered proteins have been found to play important roles in pivotal cellular functions, such as DNA binding and signalling cascades. Studying proteins with extended disordered regions is often problematic as they can be challenging to express, purify and crystallise. This means that interpretable experimental data on protein disorder is hard to generate. As a result, predictive computational tools have been developed with the aim of predicting the level and location of disorder within a protein. Currently, over 60 prediction servers exist, utilizing different methods for classifying disorder and different training sets. Here we review several good performing, publicly available prediction methods, comparing their application and discussing how disorder prediction servers can be used to aid the experimental solution of protein structure. The use of disorder prediction methods allows us to adopt a more targeted approach to experimental studies by accurately identifying the boundaries of ordered protein domains so that they may be investigated separately, thereby increasing the likelihood of their successful experimental solution.

  4. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... About Awards Membership ASH Foundation Global Programs Newsroom facebook twitter youtube linkedin Research In This Section Agenda ... View all publications For Patients Blood Basics Blood Disorders Anemia Bleeding Disorders Blood Cancers Blood Clots Blood ...

  5. The Effects of Different Levels of Dietary Protein and L-Carnitine on Blood Sugar and Lipids of the New GIFT Strain of Juvenile Nile Tilapia (Oreochromis niloticus

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2009-01-01

    Full Text Available The new GIFT (Genetically Improved Farmed Tilapia strain of Nile tilapia is a popular cultivated fish in Asia, but intensive aquaculture using nutritionally imbalanced feed has led to disorder of lipid metabolisms. An 8-week feeding experiment was conducted in order to assess the effects of different levels of L-carnitine (0, 200, 400, 600, and 800 mg/kg and dietary protein (22, 25, and 28% on blood sugar and blood lipid contents of the new juvenile GIFT strain of Nile tilapia. Results showed that dietary protein and L-carnitine had significant influences on glucose (GLU, high-density lipoprotein–cholesterol (HDL-C, total cholesterol (TC, triglyceride (TG, and low-density lipoprotein–cholesterol (LDL-C in the blood serum. The contents of GLU and HDL-C increased with the increases in dietary protein and L-carnitine levels, while the contents of TC, LDL-C, and TG decreased with the increases in dietary protein and L-carnitine levels. The interactive effect of both dietary protein and L-carnitine was most significant on GLU (p = 0.0001, followed by TG (p = 0.001, TC (p = 0.005, HDL-C (p = 0.056, and LDL-C (p = 0.109. These results suggested that high levels of dietary protein and L-carnitine supplementation reduce blood lipids and the burden of the fish liver.

  6. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kun ZENG; Daniel G REMICK; Xian WANG

    2004-01-01

    AIM: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood. METHODS: Human whole blood or different type of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP- 1 and IL-8 level were measured by ELISA assay. RESULTS: Hcy 10-1000 μmol/L induced production of MCP-1 and IL-8 in cultured human whole blood (P<0.05). The major cellular source of these chemokines comed from monocytes.Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/L in the cultured whole blood.secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism.

  7. A high confidence, manually validated human blood plasma protein reference set

    DEFF Research Database (Denmark)

    Schenk, Susann; Schoenhals, Gary J; de Souza, Gustavo;

    2008-01-01

    BACKGROUND: The immense diagnostic potential of human plasma has prompted great interest and effort in cataloging its contents, exemplified by the Human Proteome Organization (HUPO) Plasma Proteome Project (PPP) pilot project. Due to challenges in obtaining a reliable blood plasma protein list......, HUPO later re-analysed their own original dataset with a more stringent statistical treatment that resulted in a much reduced list of high confidence (at least 95%) proteins compared with their original findings. In order to facilitate the discovery of novel biomarkers in the future and to realize the...... full diagnostic potential of blood plasma, we feel that there is still a need for an ultra-high confidence reference list (at least 99% confidence) of blood plasma proteins. METHODS: To address the complexity and dynamic protein concentration range of the plasma proteome, we employed a linear ion...

  8. The Effects of Different Levels of Dietary Protein and L-Carnitine on Blood Sugar and Lipids of the New GIFT Strain of Juvenile Nile Tilapia (Oreochromis niloticus)

    OpenAIRE

    Gang Chen; Minghui Zhang; Jiandong Zhang; Hongbiao Dong; Hui Zhou; Baogui Tang; Jiansheng Huang; Gang Shi; Ling Jiang; Zhaohe Wu

    2009-01-01

    The new GIFT (Genetically Improved Farmed Tilapia) strain of Nile tilapia is a popular cultivated fish in Asia, but intensive aquaculture using nutritionally imbalanced feed has led to disorder of lipid metabolisms. An 8-week feeding experiment was conducted in order to assess the effects of different levels of L-carnitine (0, 200, 400, 600, and 800 mg/kg) and dietary protein (22, 25, and 28%) on blood sugar and blood lipid contents of the new juvenile GIFT strain of Nile tilapia. Results sho...

  9. Studies of protein metabolism with labelled proteins and protein-like substances in nutritional disorders

    International Nuclear Information System (INIS)

    Adult human volunteers were studied using I131-labelled albumin and I131-labelled gamma-globulin under standardized metabolic conditions; while on a normal diet; after 3-6 weeks of isocaloric low-protein intake; and after a similar period of high-protein intake. The results were analysed by the 'equilibrium time' method, which was developed in 1957. Synthesis and transfer rates were derived according to methods developed in 1961 by C.M.E. Matthews. 2 figs, 6 tabs

  10. Regional cerebral blood flow and cognitive function in patients with obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Huirong Guo

    2014-01-01

    Full Text Available Objective: To explore the relationship between regional cerebral blood flow (CBF and cognitive function in obsessive-compulsive disorder (OCD. Method: Single-photon emission computed tomography (SPECT was performed for 139 OCD patients and 139 controls, and the radioactivity rate (RAR was calculated. Cognitive function was assessed by the Wisconsin Card Sorting Test (WCST. Results: The RARs of the prefrontal, anterior temporal, and right occipital lobes were higher in patients than controls. For the WCST, correct and classification numbers were significantly lower, and errors and persistent errors were significantly higher in OCD patients. Right prefrontal lobe RAR was negatively correlated with correct numbers, right anterior temporal lobe RAR was positively correlated with errors, and the RARs of the right prefrontal lobe and left thalamus were positively correlated with persistent errors. Conclusion: OCD patients showed higher CBF in the prefrontal and anterior temporal lobes, suggesting that these areas may be related with cognitive impairment.

  11. Mixed matrix membrane adsorbers for protein and blood purification

    OpenAIRE

    Saiful

    2007-01-01

    Biotechnology and bio-manufacturing markets are continuously growing, generating new sources of many valuable healthcare and life science products including therapeutic proteins and polysaccharides, monoclonals, vaccines, diagnostics, pharmaceutical chemicals and enzymes. These bioproducts have to be isolated and purified from complex mixtures before they can be used to ensure safety and efficacy. Nowadays, there are different techniques available for biomolecules isolation and purification. ...

  12. The relative nutritive value of irradiated spray-dried blood powder and heat-sterilized blood meal as measured in combination with whey protein

    International Nuclear Information System (INIS)

    A method of processing blood meal in which nutritive value of the protein is preserved is described, since appreciable losses occur in the nutritive value of the protein when prepared by heat sterilization with drying at atmospheric pressure in steam jacketed vessels. Blood was spray dried and irradiated at an intensity of 10 kGy. Collectively the heat of spray drying and irradiation was effective in killing both the virus plaque-forming units and the bacteria, thus producing a commercially acceptable sterile product of higher nutritive value. The relative nutritive values (RNV) of 50:50 protein were 0,56 for whey protein concentrate plus heat-sterilized blood meal and 0.90 for whey protein concentrate plus irradiated spray-dried blood powder. Whey protein concentrate used as a control has a RNV of 1,0

  13. A comparative study of the relationship between protein structure and beta-aggregation in globular and intrinsically disordered proteins

    DEFF Research Database (Denmark)

    Linding, Rune; Schymkowitz, Joost; Rousseau, Frederic;

    2004-01-01

    solubility problems. Further, some IDPs such as the human prion protein, synuclein and Tau protein are related to major protein conformational diseases. However, this scenario contrasts with the large number of unstructured proteins identified, especially in higher eukaryotes, and the fact that the......A growing number of proteins are being identified that are biologically active though intrinsically disordered, in sharp contrast with the classic notion that proteins require a well-defined globular structure in order to be functional. At the same time recent work showed that aggregation and...... amyloidosis are initiated in amino acid sequences that have specific physico-chemical properties in terms of secondary structure propensities, hydrophobicity and charge. In intrinsically disordered proteins (IDPs) such sequences would be almost exclusively solvent-exposed and therefore cause serious...

  14. Detection of Intracellular Factor VIII Protein in Peripheral Blood Mononuclear Cells by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Gouri Shankar Pandey

    2013-01-01

    Full Text Available Flow cytometry is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. Detection of specific host proteins for diagnosis predominantly uses quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based detection assay for Factor VIII protein in peripheral blood mononuclear cells (PBMCs. An indirect intracellular staining (ICS method was standardized using monoclonal antibodies to different domains of human Factor VIII protein. The FVIII protein expression level was estimated by calculating the mean and median fluorescence intensities (MFI values for each monoclonal antibody. ICS staining of transiently transfected cell lines supported the method's specificity. Intracellular FVIII protein expression was also detected by the monoclonal antibodies used in the study in PBMCs of five blood donors. In summary, our data suggest that intracellular FVIII detection in PBMCs of hemophilia A patients can be a rapid and reliable method to detect intracellular FVIII levels.

  15. Probing Bio-Nano Interactions between Blood Proteins and Monolayer-Stabilized Graphene Sheets.

    Science.gov (United States)

    Gan, Shiyu; Zhong, Lijie; Han, Dongxue; Niu, Li; Chi, Qijin

    2015-11-18

    Meeting proteins is regarded as the starting event for nanostructures to enter biological systems. Understanding their interactions is thus essential for a newly emerging field, nanomedicine. Chemically converted graphene (CCG) is a wonderful two-dimensional (2D) material for nanomedicine, but its stability in biological environments is limited. Systematic probing on the binding of proteins to CCG is currently lacking. Herein, we report a comprehensive study on the interactions between blood proteins and stabilized CCG (sCCG). CCG nanosheets are functionalized by monolayers of perylene leading to significant improvement in their resistance to electrolyte salts and long-term stability, but retain their core structural characteristics. Five types of model human blood proteins including human fibrinogen, γ-globulin, bovine serum albumin (BSA), insulin, and histone are tested. The main driving forces for blood protein binding involve the π-π interacations between the π-plane of sCCG and surface aromatic amonic acid (sAA) residues of proteins. Several key binding parameters including the binding amount, Hill coefficient, and binding constant are determined. Through a detailed analysis of key controlling factors, we conclude that the protein binding to sCCG is determined mainly by the protein size, the number, and the density of the sAA. PMID:26413807

  16. Aptamer-based surface plasmon resonance sensing of glycated human blood proteins

    Science.gov (United States)

    Reaver, Nathan G. F.; Zheng, Rui; Kim, Dong-Shik; Cameron, Brent D.

    2013-02-01

    The concentration ratio of glycated to non-glycated forms of various blood proteins can be used as a diagnostic measure in diabetes to determine a history of glycemic compliance. Depending on a protein's half-life in blood, compliance can be assessed from a few days to several months in the past, which can then be used to provide additional therapeutic guidance. Current glycated protein detection methods are limited in their ability to measure multiple proteins, and are susceptible to interference from other blood pathologies. In this study, we developed and characterized DNA aptamers for use in Surface Plasmon Resonance (SPR) sensors to assess the blood protein hemoglobin. The aptamers were developed by way of a modified Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process which selects DNA sequences that have a high binding affinity to a specific protein. DNA products resulting from this process are sequenced and identified aptamers are then synthesized. The SELEX process was performed to produce aptamers for a glycated form of hemoglobin. Equilibrium dissociation constants for the binding of the identified aptamer to glycated hemoglobin, hemoglobin, and fibrinogen were calculated from fitted Langmuir isotherms obtained through SPR. These constants were determined to be 94 nM, 147 nM, and 244 nM respectively. This aptamer can potentially be used to create a SPR aptamer based biosensor for detection of glycated hemoglobin, a technology that has the potential to deliver low-cost and immediate glycemic compliance assessment in either a clinical or home setting.

  17. Adsorbed plasma proteins modulate the effects of single-walled carbon nanotubes on neutrophils in blood.

    Science.gov (United States)

    Vlasova, Irina I; Mikhalchik, Elena V; Barinov, Nikolay A; Kostevich, Valeria A; Smolina, Natalia V; Klinov, Dmitry V; Sokolov, Alexey V

    2016-08-01

    Proteins adsorbed on a surface may affect the interaction of this surface with cells. Here, we studied the binding of human serum albumin (HSA), fibrinogen (FBG) and immunoglobulin G (IgG) to PEGylated single-walled carbon nanotubes (PEG-SWCNTs) and evaluated the impact of PEG-SWCNT treated by these proteins on neutrophils in whole blood samples. Measurements of adsorption parameters revealed tight binding of proteins to PEG-SWCNTs. AFM was employed to directly observe protein binding to sidewalls of PEG-SWCNTs. Fluorescein-labeled IgG was used to ascertain the stability of PEG-SWCNT-IgG complexes in plasma. In blood samples, all plasma proteins mitigated damage of neutrophils observed just after blood exposure to PEG-SWCNTs, while only treatment of PEG-SWCNTs with IgG resulted in dose- and time-dependent enhancement of CNT-induced neutrophil activation and in potentiation of oxidative stress. Our study demonstrates the ability of adsorbed plasma proteins to influence neutrophil response caused by PEG-SWCNTs in whole blood. PMID:27015767

  18. Oxidation of Lipids and Proteins in Lens and Blood Plasma of Rats in Ageing

    Directory of Open Access Journals (Sweden)

    Ivanova I.P.

    2011-09-01

    Full Text Available The aim of the study is to assess the intensity of oxidation of lipids and proteins in lens and blood plasma of Wistar rats in ageing. Materials and Methods. The experiments were carried out on 25 Wistar male rats of four age groups: 5, 12, 24 and 36 months. Materials for study were lens and blood plasma. Lipids were extracted using Folch partition. The content of diene and triene conjugates was assessed by means of spectrophotometry. The level of Schiff’s bases was studied according to fluorescence intensity, malon dialdehyde concentration — according to the intensity of interaction with thiobarbituric acid. Potentiality of substrate oxidation in specimen was assessed using the method of induced chemoluminescence, and the degree of protein oxidative modification was assessed according to the level of carbonyl derivatives with 2.4-dinitrophenylhydrasine. The investigation of the content of total lipids and total proteins were carried out using “Bio-Test Total Lipids” and “Total Protein-Vital”. Results. The processes of lipid peroxidation of lens membranes are increasing in animals aged 5—12 months and decreasing in the period of 12—24 months. The level of lipid peroxidation in blood plasma has an expressed tendency for increasing in ageing. Over the years, there is the level decrease of carbonyl derivatives of aminoacids of lens proteins and the tendency for the increase of oxidative modification of proteins in blood plasma.

  19. Diminished Expression of Complement Regulatory Proteins on Peripheral Blood Cells from Systemic Lupus Erythematosus Patients

    OpenAIRE

    Ricardo Machado Xavier; João Carlos Tavares Brenol; Priscila Schmidt Lora; Odirlei Andre Monticielo; Amanda Kirchner Piccoli; Laiana Schneider; Ana Paula Alegretti

    2012-01-01

    CD55, CD59, CD46, and CD35 are proteins with complement regulatory (Creg) properties that ensure cell and tissue integrity when this system is activated. The aim of this study was to evaluate the Creg expression on peripheral blood cells from SLE patients and its association with cytopenia and disease activity. Flow cytometric analyses were performed on blood cells from 100 SLE patients and 61 healthy controls. Compared with healthy controls, we observed in SLE patients with lymphopenia and n...

  20. Translational diffusion of hydration water correlates with functional motions in folded and intrinsically disordered proteins

    Science.gov (United States)

    Schirò, Giorgio; Fichou, Yann; Gallat, Francois-Xavier; Wood, Kathleen; Gabel, Frank; Moulin, Martine; Härtlein, Michael; Heyden, Matthias; Colletier, Jacques-Philippe; Orecchini, Andrea; Paciaroni, Alessandro; Wuttke, Joachim; Tobias, Douglas J.; Weik, Martin

    2015-03-01

    Hydration water is the natural matrix of biological macromolecules and is essential for their activity in cells. The coupling between water and protein dynamics has been intensively studied, yet it remains controversial. Here we combine protein perdeuteration, neutron scattering and molecular dynamics simulations to explore the nature of hydration water motions at temperatures between 200 and 300 K, across the so-called protein dynamical transition, in the intrinsically disordered human protein tau and the globular maltose binding protein. Quasi-elastic broadening is fitted with a model of translating, rotating and immobile water molecules. In both experiment and simulation, the translational component markedly increases at the protein dynamical transition (around 240 K), regardless of whether the protein is intrinsically disordered or folded. Thus, we generalize the notion that the translational diffusion of water molecules on a protein surface promotes the large-amplitude motions of proteins that are required for their biological activity.

  1. Disordered nucleiome: Abundance of intrinsic disorder in the DNA- and RNA-binding proteins in 1121 species from Eukaryota, Bacteria and Archaea.

    Science.gov (United States)

    Wang, Chen; Uversky, Vladimir N; Kurgan, Lukasz

    2016-05-01

    Intrinsically disordered proteins (IDPs) are abundant in various proteomes, where they play numerous important roles and complement biological activities of ordered proteins. Among functions assigned to IDPs are interactions with nucleic acids. However, often, such assignments are made based on the guilty-by-association principle. The validity of the extension of these correlations to all nucleic acid binding proteins has never been analyzed on a large scale across all domains of life. To fill this gap, we perform a comprehensive computational analysis of the abundance of intrinsic disorder and intrinsically disordered domains in nucleiomes (∼548 000 nucleic acid binding proteins) of 1121 species from Archaea, Bacteria and Eukaryota. Nucleiome is a whole complement of proteins involved in interactions with nucleic acids. We show that relative to other proteins in the corresponding proteomes, the DNA-binding proteins have significantly increased disorder content and are significantly enriched in disordered domains in Eukaryotes but not in Archaea and Bacteria. The RNA-binding proteins are significantly enriched in the disordered domains in Bacteria, Archaea and Eukaryota, while the overall abundance of disorder in these proteins is significantly increased in Bacteria, Archaea, animals and fungi. The high abundance of disorder in nucleiomes supports the notion that the nucleic acid binding proteins often require intrinsic disorder for their functions and regulation. PMID:27037624

  2. Electrophoretic pattern of blood serum proteins of some of the vertebrates of Pakistan

    International Nuclear Information System (INIS)

    The electrophoretic pattern of blood serum proteins of some of the common fishes e.g. Catla catla, Cirrhina mrigala, Channa punctatus, Channa marulius, Wallago attu, Heterop-neustes fossilis; amphibia e.g., Rana tigrina, Rana cyanophlyctis, Bufo melanostictus; reptiles e.g. Varanus bengalensis, Uromastix hardwickii; birds e.g. Columba livia, Gallus domesticus, Passer domestica, Anas platyrhynchos; and mammals e.g. Homo sapiens, Mus musculus, Lepus cuniculus have been described. The mobility of proteins of blood sera has been studied over cellulose acetate paper and then a comparative pattern analysed

  3. Effects of Electron Beam and Microwave Irradiation on Human Blood Proteins

    International Nuclear Information System (INIS)

    The effects of separated and combined accelerated electron beam (EB) of 6.23 MeV and microwave (MW) of 2.45GHz irradiation on proteins in samples of human serum, human plasma and human integral blood are presented. Also, it was studied the effect of separate and combined EB and MW irradiation on proteins irradiated in samples of human integral blood, without and in the presence of a synthetic compound solution (S.C.S.) which is expected to exhibit various biological actions, such as to diminish or to increase the irradiation effects

  4. On the abundance of intrinsically disordered proteins in the human proteome and its relation to diseases: there is no enrichment

    OpenAIRE

    Deiana, Antonio; Giansanti, Andrea

    2014-01-01

    Intrinsically disordered proteins are fascinating the community of protein science since the last decade, at least. There is a well-established line of research that intends to reveal the crucial role played by intrinsically disordered proteins (IDPs) in the development of human diseases. The main argument is that IDPs are differentially more present in groups of disease-related proteins. In this note we compare the frequency of disorder in human proteins, both disease-related and not. The fr...

  5. Gold nanoparticles: role of size and surface chemistry on blood protein adsorption

    International Nuclear Information System (INIS)

    Material interaction with blood proteins is a critical issue, since it could influence the biological processes taking place in the body following implantation/injection. This is particularly important in the case of nanoparticles, where innovative properties, such as size and high surface to volume ratio can lead to a behavioral change with respect to bulk macroscopic materials and could be responsible for a potential risk for human health. The aim of this work was to compare gold nanoparticles (AuNP) and planar surfaces to study the role of surface curvature moving from the macro- to the nano-size in the process of blood protein adsorption. In the course of the study, different protocols were tested to optimize the analysis of protein adsorption on gold nanoparticles. AuNP with different size (10, 60 and 200 nm diameter) and surface coatings (citrate and polyethylene glycol) were carefully characterized. The stabilizing action of blood proteins adsorbed on AuNP was studied measuring the variation of size and solubility of the nanoparticles following incubation with single protein solutions (human serum albumin and fibrinogen) and whole blood plasma. In addition, we developed a method to elute proteins from AuNP to study the propensity of gold materials to adsorb plasma proteins in function of dimensional characteristics and surface chemistry. We showed a different efficacy of the various eluting media tested, proving that even the most aggressive agent cannot provide a complete detachment of the protein corona. Enhanced protein adsorption was evidenced on AuNP if compared to gold laminae (bare and PEGylated) used as macroscopic control, probably due to the superior AuNP surface reactivity.

  6. DisCons: a novel tool to quantify and classify evolutionary conservation of intrinsic protein disorder

    OpenAIRE

    Varadi, Mihaly; Guharoy, Mainak; Zsolyomi, Fruzsina; Tompa, Peter

    2015-01-01

    Background Analyzing the amino acid sequence of an intrinsically disordered protein (IDP) in an evolutionary context can yield novel insights on the functional role of disordered regions and sequence element(s). However, in the case of many IDPs, the lack of evolutionary conservation of the primary sequence can hamper the study of functionality, because the conservation of their disorder profile and ensuing function(s) may not appear in a traditional analysis of the evolutionary history of th...

  7. Boymaw, overexpressed in brains with major psychiatric disorders, may encode a small protein to inhibit mitochondrial function and protein translation.

    Science.gov (United States)

    Ji, Baohu; Kim, Minjung; Higa, Kerin K; Zhou, Xianjin

    2015-06-01

    The t(1,11) chromosome translocation co-segregates with major psychiatric disorders in a large Scottish family. The translocation disrupts the DISC1and Boymaw (DISC1FP1) genes on chromosomes 1 and 11, respectively. After translocation, two fusion genes are generated. Our recent studies found that the DISC1-Boymaw fusion protein is localized in mitochondria and inhibits oxidoreductase activity, rRNA expression, and protein translation. Mice carrying the DISC1-Boymaw fusion genes display intermediate behavioral phenotypes related to major psychiatric disorders. Here, we report that the Boymaw gene may encode a small protein predominantly localized in mitochondria. The Boymaw protein inhibits oxidoreductase activity, rRNA expression, and protein translation in the same way as the DISC1-Boymaw fusion protein. Interestingly, Boymaw expression is up-regulated by different stressors at RNA and/or protein translational levels. In addition, we found that Boymaw RNA expression is significantly increased in the postmortem brains of patients with major psychiatric disorders. Our studies therefore suggest that the Boymaw gene could potentially be a susceptibility gene for major psychiatric disorders in both the Scottish t(1,11) family and the general population of patients. PMID:25943690

  8. C-reactive protein prolongs blood coagulation time in phospholipids-dependent coagulation tests

    Directory of Open Access Journals (Sweden)

    L D Kozmin

    2003-01-01

    Full Text Available C-refctive protein prolongs blood coagulation time in phospholipids-dependent coagulation tests. O.P. Bliznukov, L.D. Kostin, A.J. Martinov, T.A. Lisitsina, T.M. Reshetnyak, V.J. Lauga Objective. To study influence of different CRP forms on blood clotting time in standard phospholipid clotting tests. Material and methods. Purified native CRP. monomeric CRP (0-1.6 M, immune complexes of native CRP and rabbit polyclonal anti-CRP antibodies (1.6 M were added to blood plasma of healthy donors. Blood clotting time was registered using optical coagulometer. Phospholipid dependent prothrombin time (PT, activated partial tromboplastin time (APTT, kaolin clotting time (KCT with kaolin and ellagic acid, dilute Russel viper venom time (dRVVT were determined. Results. Native CRP was able to increase blood clotting time in all mentioned clotting tests, excluding prothrombin time. CRP influence on blood clotting time showed a concentration dependence. Polyclonal rabbit anti-CRP antibodies had no inhibitory effect on CRP prolonged blood clotting time. Monomeric CRP (0-1.6 M had no influence on blood clotting time in all phospholipid-dependent clotting tests.

  9. Adherence Issues in Inherited Metabolic Disorders Treated by Low Natural Protein Diets

    NARCIS (Netherlands)

    MacDonald, A.; van Rijn, M.; Feillet, F.; Lund, A. M.; Bernstein, L.; Bosch, A. M.; Gizewska, M.; van Spronsen, F. J.

    2012-01-01

    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor-free or essenti

  10. Assessment of protein disorder region predictions in CASP10

    KAUST Repository

    Monastyrskyy, Bohdan

    2013-11-22

    The article presents the assessment of disorder region predictions submitted to CASP10. The evaluation is based on the three measures tested in previous CASPs: (i) balanced accuracy, (ii) the Matthews correlation coefficient for the binary predictions, and (iii) the area under the curve in the receiver operating characteristic (ROC) analysis of predictions using probability annotation. We also performed new analyses such as comparison of the submitted predictions with those obtained with a Naïve disorder prediction method and with predictions from the disorder prediction databases D2P2 and MobiDB. On average, the methods participating in CASP10 demonstrated slightly better performance than those in CASP9.

  11. Inhibition of bacterial aggregation by serum- and blood-derived proteins.

    OpenAIRE

    Malamud, D; Brown, C; Goldman, R

    1984-01-01

    Human and animal sera contain potent inhibitors of saliva-mediated aggregation of oral streptococci. The inhibitors consist of a high-molecular-weight heat-labile factor and a lower-molecular-weight heat-activated factor. The latter appears to be serum albumin. Analyses of purified blood-derived proteins indicated that several high-molecular-weight proteins (fibrinogen, fibronectin, and ferritin) were able to inhibit aggregation at low concentrations. These data suggest that high-molecular-we...

  12. A decade and a half of protein intrinsic disorder: Biology still waits for physics

    OpenAIRE

    Vladimir N Uversky

    2013-01-01

    The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of o...

  13. Biology of Blood

    Science.gov (United States)

    ... Mail Facebook TwitterTitle Google+ LinkedIn Home Blood Disorders Biology of Blood Overview of Blood Medical Dictionary Also ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  14. Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study

    OpenAIRE

    Hayes, J. F.; Khandaker, G. M.; Anderson, J.; Mackay, D.; Zammit, S.; Lewis, G; Smith, D J; Osborn, D. P. J.

    2016-01-01

    Background: There are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood. Method: Participants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood s...

  15. Cognitive profiles and regional cerebral blood flow changes in individuals with Asperger's disorder and Schizophrenia

    International Nuclear Information System (INIS)

    Described are differences of the profiles and blood flow (CBF) changes in the title between individuals with Asperger's disorder (AD) and Schizophrenia (SZ). Children with AD syndrome have been suggested to have reasoning and fluid intelligence superior to normally developed ones, and to be of cognitive disability for the spatial composition which is thought to reflect the impairment in the right hemisphere. These characteristics are not suggested in SZ. Presented are examinations by authors of 99m ethyl cysteinate dimer (ECD)-single photon emission computed tomography (SPECT) images with Patlak method of 7 AD males (average age 24.4 y), 4 AD females (25.5 y), and 4 males and 2 females with SZ (25.8 y). Image analysis is done by SPM99 (Statistical Parametric Mapping) with standardized brain. Control with the matched age and sex is obtained from database of the normal healthy ones. In AD, clearly lowered CBF is observed in the right lateral and medial parietal lobe and right superior temporal convolution (particularly, in females), and in SZ, in the dorsolateral and dorsomedial regions of frontal lobe of both sides. The finding in the right superior temporal convolution in AD is considered to be important from the aspect of impairment of eye gaze processing. (R.T.)

  16. Blood parameters in growing pigs fed increasing levels of bacterial protein meal

    DEFF Research Database (Denmark)

    Hellwing, Anne Louise Frydendahl; Tauson, Anne-Helene; Skrede, Anders

    2007-01-01

    The experiment investigated the effects of increasing dietary levels of bacterial protein meal (BPM) on various blood parameters reflecting protein and fat metabolism, liver function, and purine base metabolism in growing pigs. Sixteen barrows were allocated to four different experimental diets....... The control diet was based on soybean meal. In the other three diets soybean meal was replaced with increasing levels of BPM, approximately 17%, 35%, and 50% of the nitrogen being derived from BPM. Blood samples from the jugular vein were taken when the body weights of the pigs were approximately 10 kg, 21 kg......, 45 kg, and 77 kg. The blood parameters reflecting fat metabolism and liver funtion were not affected by diet. Both the plasma albumin and uric acid concentrations tended to decrease (P = 0.07 and 0.01, respectively) with increasing dietary BPM content, whereas the plasma glucose concentration tended...

  17. Reduced Cytotoxicity of Graphene Nanosheets Mediated by Blood-Protein Coating.

    Science.gov (United States)

    Chong, Yu; Ge, Cuicui; Yang, Zaixing; Garate, Jose Antonio; Gu, Zonglin; Weber, Jeffrey K; Liu, Jiajia; Zhou, Ruhong

    2015-06-23

    The advent and pending wide use of nanoscale materials urges a biosafety assessment and safe design of nanomaterials that demonstrate applicability to human medicine. In biological microenvironment, biomolecules will bind onto nanoparticles forming corona and endow nanoparticles new biological identity. Since blood-circulatory system will most likely be the first interaction organ exposed to these nanomaterials, a deep understanding of the basic interaction mechanisms between serum proteins and foreign nanoparticles may help to better clarify the potential risks of nanomaterials and provide guidance on safe design of nanomaterials. In this study, the adsorption of four high-abundance blood proteins onto the carbon-based nanomaterial graphene oxide (GO) and reduced GO (rGO) were investigated via experimental (AFM, florescence spectroscopy, SPR) and simulation-based (molecular dynamics) approaches. Among the proteins in question, we observe competitive binding to the GO surface that features a mélange of distinct packing modes. Our MD simulations reveal that the protein adsorption is mainly enthalpically driven through strong π-π stacking interactions between GO and aromatic protein residues, in addition to hydrophobic interactions. Overall, these results were in line with previous findings related to adsorption of serum proteins onto single-walled carbon nanotubes (SWCNTs), but GO exhibits a dramatic enhancement of adsorption capacity compared to this one-dimensional carbon form. Encouragingly, protein-coated GO resulted in a markedly less cytotoxicity than pristine and protein-coated SWCNTs, suggesting a useful role for this planar nanomaterial in biomedical applications. PMID:26040772

  18. Identification of Residual Blood Proteins in Ticks by Mass Spectrometry Proteomics

    OpenAIRE

    Wickramasekara, Samanthi; Bunikis, Jonas; Wysocki, Vicki; Barbour, Alan G.

    2008-01-01

    Mass spectrometry–based proteomics of individual ticks demonstrated persistence of mammalian host blood components, including α- and β-globin chains, histones, and mitochondrial enzymes, in Ixodes scapularis and Amblyomma americanum ticks for months after molting. Residual host proteins may identify sources of infection for ticks.

  19. Proteolytic system of blood-feeding ticks: An update on protein structures

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Zuzana; Hobizalová, Radka; Žebrakovská, Iva; Brynda, Jiří; Řezáčová, Pavlína; Horn, Martin; Mareš, Michael

    2015-01-01

    Roč. 22, č. 1 (2015), s. 43-44. ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] Institutional support: RVO:61388963 ; RVO:68378050 Keywords : blood-feeding ticks * protein structure * proteolytic system Subject RIV: CE - Biochemistry

  20. Central Gi(2) proteins, sympathetic nervous system and blood pressure regulation

    Czech Academy of Sciences Publication Activity Database

    Zicha, Josef

    2016-01-01

    Roč. 216, č. 3 (2016), s. 258-259. ISSN 1748-1708 Institutional support: RVO:67985823 Keywords : inhibitory G proteins * sympathetic nervous system * central blood pressure control Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.382, year: 2014

  1. The plasma protein fibrinogen stabilizes clusters of red blood cells in microcapillary flows

    CERN Document Server

    Brust, M; Thiebaud, M; Flormann, D; Verdier, C; Kaestner, L; Laschke, M W; Selmi, H; Benyoussef, A; Podgorski, T; Coupier, G; Misbah, C; Wagner, C

    2014-01-01

    The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These pers...

  2. Probing Bio-Nano Interactions between Blood Proteins and Monolayer-Stabilized Graphene Sheets

    DEFF Research Database (Denmark)

    Gan, Shiyu; Zhong, Lijie; Han, Dongxue;

    2015-01-01

    Meeting proteins is regarded as the starting event for nanostructures to enter biological systems. Understanding their interactions is thus essential for a newly emerging field, nanomedicine. Chemically converted graphene (CCG) is a wonderful two-dimesional (2D) material for nanomedecine, but its...... stability in biological environments is limited. Systematic probing on the binding of proteins to CCG is currently lacking. Herein, we report a comprehensive study on the interactions between blood proteins and stabilized CCG (sCCG). CCG nanosheets are functionalized by monolayers of perylene leading to...

  3. Plasma protein thiols, ceruloplasmin, C-reactive protein and red blood cell acetylcholinesterase in patients undergoing intrauterine insemination

    OpenAIRE

    Krishnananda Prabhu; Pratap Kumar; Satish Kumar Adiga; Anjali Rao; Anupama Lanka; Jaipal Singh

    2009-01-01

    Objective: To estimate acetylcholinesterase (AChE), protein thiols (PT), ceruloplasmin (CP) and C-reactive proteins (CRPs) to assess any change in their levels following intrauterine insemination (IUI). Materials and Methods: Forty-two patients aged 31 ± 4.65 years (mean ± SD) with primary infertility selected for IUI. All of them had induced ovulation with clomiphene citrate 50 mg from day 2 to day 6. After taking the consent, 2 ml of blood was withdrawn before and after 24 h of IUI for bio...

  4. Identification of transferrin as the principal neptunium-binding protein in the blood serum of rats

    Energy Technology Data Exchange (ETDEWEB)

    Wirth, R.; Taylor, D.M.; Duffield, J.

    1985-01-01

    The binding of 239Np(V) to blood serum components of rats was examined in vivo and in vitro. After gel filtration of the serum using a Sephacryl S-300 column, 98% of the applied activity appeared with protein fractions representing coeluted albumins and transferrin. A separation of the albumin- and transferrin-proteins by ion-exchange chromatography using DEAE-cellulose showed the 239Np being entirely bound to the iron-carrier protein transferrin. The high elution yields from the ion-exchange columns, greater than 90%, suggest that the binding may be quite strong. The binding capacity of transferrin for neptunium in vivo was found to decline when the iron level in blood serum was increased. Precipitation experiments showed that 84 +/- 2% of the 239Np was precipitated with 10% (w/v) trichloracetic acid, 77 +/- 3% with 90% ethanol but only 6 +/- 1% with saturated ammonium sulphate at pH 7.4. The available data indicate that as for plutonium, thorium, americium and curium, the iron transport protein, transferrin, may be the main carrier protein for neptunium in mammalian blood serum.

  5. Effects of Different Exercise Intensities with Isoenergetic Expenditures on C-Reactive Protein and Blood Lipid Levels

    Science.gov (United States)

    Tsao, Te Hung; Yang, Chang Bin; Hsu, Chin Hsing

    2012-01-01

    We investigated the effects of different exercise intensities on C-reactive protein (CRP), and whether changes in CRP levels correlated with blood lipid levels. Ten men exercised at 25%, 65%, and 85% of their maximum oxygen consumption rates. Participants' blood was analyzed for CRP and blood lipid levels before and after the exercise sessions.…

  6. Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)

    DEFF Research Database (Denmark)

    Altmeyer, Matthias; Neelsen, Kai J; Teloni, Federico;

    2015-01-01

    Intrinsically disordered proteins can phase separate from the soluble intracellular space, and tend to aggregate under pathological conditions. The physiological functions and molecular triggers of liquid demixing by phase separation are not well understood. Here we show in vitro and in vivo...... disordered proteins at DNA break sites. Demixing, which relies on electrostatic interactions between positively charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR......-seeded liquid demixing is a general mechanism to dynamically reorganize the soluble nuclear space with implications for pathological protein aggregation caused by derailed phase separation....

  7. [The effect of blood serum proteins from the seal on the analgetic action of narcotic analgesics].

    Science.gov (United States)

    Aslaniants, Zh K; Melik-Eganov, G R; Evstratov, A V; Ivanov, M P; Batrakov, S G; Korobov, N V; Iasnetsov, V V

    1991-11-01

    The protein fraction isolated from blood of seal, Phoca groenlandica, has been found to produce hyperalgesic effect on rats exposed to thermic or electrocutaneous nociceptive stimulation, but fail to affect writhes provoked by intraperitoneal injection of acetic acid solution on mice. When combined with morphine, the fraction lowered completely its narcotic analgetic action in the above mentioned tests. On the contrary, these same proteins combined with promedol or fentanil enhanced and prolonged analgetic effect of the latter. Tested in vitro the protein showed neither opioid nor anti-opioid activity. Therefore it is reasonable to suppose that neurophysiological activity of the isolated fraction is due to the peptides formed on enzymatic hydrolysis of proteins in vivo rather than these proteins as such. PMID:1687360

  8. The therapeutic effect of monocyte chemoattractant protein-1 delivered by an electrospun scaffold for hyperglycemia and nephrotic disorders

    Directory of Open Access Journals (Sweden)

    Yong C

    2014-02-01

    Full Text Available Cai Yong,2,* Zhengxin Wang,1,* Xing Zhang,3 Xiaomin Shi,1 Zhijia Ni,1 Hong Fu,1 Guoshan Ding,1 Zhiren Fu,1 Hao Yin1,3 1Department of Surgery, Organ Transplant Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Transplantation, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, People's Republic of China; 3Department of Surgery, University of Chicago, Chicago, IL, USA *These authors contributed equally to this article Abstract: Here, we investigated in diabetic mice the therapeutic effect of monocyte chemoattractant protein-1 (MCP-1, locally delivered by an electrospun scaffold, on transplanted islets. This therapeutic scheme is expected to exert a synergistic effect to ameliorate hyperglycemia and its associated nephrotic disorders. The cumulative amount of MCP-1 released from the scaffold in vitro within a 3-week window was 267.77±32.18 ng, without a compromise in bioactivity. After 8 weeks following the transplantation, the islet population stimulated by MCP-1 was 35.14%±7.23% larger than the non-stimulated islet population. Moreover, MCP-1 increased concentrations of blood insulin and C-peptide 2 by 49.83%±5.29% and 43.49%±9.21%, respectively. Consequently, the blood glucose concentration in the MCP-1 group was significantly lower than that in the control group at week 2 post-surgery. MCP-1 also enhanced the tolerance of sudden oral glucose challenge. The rapid decrease of blood creatinine, urine creatinine, and blood urea nitrogen suggested that the recovery of renal functions compromised by hyperglycemia could also be attributed to MCP-1. Our study shed new light on a synergistic strategy to alleviate hyperglycemia and nephrotic disorders in diabetic patients. Keywords: MCP-1, electrospinning, islet transplantation, diabetes

  9. Metabolomics as a Tool for Discovery of Biomarkers of Autism Spectrum Disorder in the Blood Plasma of Children

    OpenAIRE

    West, Paul R.; Amaral, David G.; Bais, Preeti; Smith, Alan M.; Egnash, Laura A.; Ross, Mark E.; Palmer, Jessica A.; Fontaine, Burr R.; Conard, Kevin R.; Corbett, Blythe A.; Cezar, Gabriela G.; Donley, Elizabeth L. R.; Burrier, Robert E.

    2014-01-01

    Background The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age. Objectives To discover metabolic features present in plasma samples that can discriminate children with ASD from typical...

  10. Team-based learning on a third-year pediatric clerkship improves NBME subject exam blood disorder scores

    OpenAIRE

    Saudek, Kris; Treat, Robert

    2015-01-01

    Purpose: At our institution, speculation amongst medical students and faculty exists as to whether team-based learning (TBL) can improve scores on high-stakes examinations over traditional didactic lectures. Faculty with experience using TBL developed and piloted a required TBL blood disorders (BD) module for third-year medical students on their pediatric clerkship. The purpose of this study is to analyze the BD scores from the NBME subject exams before and after the introduction of the modul...

  11. Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes

    OpenAIRE

    Appari Mahesh; Cario Gunnar; Richter-Unruh Annette; Demeter Janos; Werner Ralf; Bebermeier Jan-Hendrik; Holterhus Paul-Martin; Siebert Reiner; Riepe Felix; Brooks James D; Hiort Olaf

    2009-01-01

    Abstract Background Gender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development. To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of peripheral blood mononuclear cells (PBMC) in patients with rare defined "disorders of sex development" (DSD, e.g., 46, XY-females due to defective androgen biosynthesis) compared to normal 46...

  12. Self-assembly of protein aggregates in ageing disorders: the lens and cataract model

    OpenAIRE

    Clark, John I.

    2013-01-01

    Cataract, neurodegenerative disease, macular degeneration and pathologies of ageing are often characterized by the slow progressive destabilization of proteins and their self-assembly to amyloid-like fibrils and aggregates. During normal cell differentiation, protein self-assembly is well established as a dynamic mechanism for cytoskeletal organization. With the increased emphasis on ageing disorders, there is renewed interest in small-molecule regulators of protein self-assembly. Synthetic p...

  13. Translational diffusion of hydration water correlates with functional motions in folded and intrinsically disordered proteins.

    OpenAIRE

    Schirò, Giorgio; Fichou, Yann; Paciaroni, Alessandro; Wuttke, Joachim; Tobias, Douglas J.; Weik, Martin; Gallat, Francois-Xavier,; Wood, Kathleen; Gabel, Frank; Moulin, Martine; Härtlein, Michael; Heyden, Matthias; Colletier, Jacques-Philippe; Orecchini, Andrea

    2015-01-01

    Hydration ​water is the natural matrix of biological macromolecules and is essential for their activity in cells. The coupling between ​water and protein dynamics has been intensively studied, yet it remains controversial. Here we combine protein perdeuteration, neutron scattering and molecular dynamics simulations to explore the nature of hydration ​water motions at temperatures between 200 and 300 K, across the so-called protein dynamical transition, in the intrinsically disordered human pr...

  14. Increased cortical expression of FK506 binding protein-51 in HIV-associated neurocognitive disorders

    OpenAIRE

    Soontornniyomkij, Virawudh; Everall, Ian P.; Moore, David J.; Gouaux, Ben; Tatro, Erick T.; Gospodarev, Vadim; Masliah, Eliezer; Yin, Nicole S.; Vinters, Harry V.; Achim, Cristian L.

    2012-01-01

    FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic stress, we hypothesized that altered cortical expression of these proteins was associated with HIV-associated neurocognitive disorders (HAND). We used quantitative immunohistochemistry to assess ex...

  15. Old diseases and contemporary crisis. Inherited blood disorders in the Sultanate of Oman.

    Science.gov (United States)

    Beaudevin, Claire

    2013-01-01

    This contribution draws on ethnographic research conducted in Oman on inherited blood disorders (IBD). By interpreting results from population genomics studies that trace mutation processes over centuries of human activities, lay-representations of IBD often consider them historical evidence. The perceived spread of IBD in Oman may thus provide unusual historical depth in a country where past conflicts have been erased from historiography and representations of time are politically prescribed. Through the notions of crisis and diversification, this contribution shows how IBD's chronicity challenges the healthcare system and became a national issue, politically labelled as urgent. The paper casts light on several aspects of contemporary Omani society: it first addresses the dynamics of disease taxonomies - although biomedically described in the early twentieth century, IBD were not individualized within local nosologies until the 1970s. Secondly, it shows how biomedical knowledge about IBD led to diversification within the healthcare system, through the introduction of clinical genetics, genomics, and community genetics. Thirdly, it attempts to broach modalities of the biopower exerted by the Omani regime over its citizens: IBD are targeted by various public health measures that jeopardize patients' autonomy by aiming to control their bodies through their matrimonial behaviour. In addition, two aspects of the intersections between Omani social hierarchy and IBD are noteworthy: the creation of a patients' association that constitutes a potential disturbance of the social order; and the way IBD mutations traced by genomics are considered direct historical documents that challenge representations of the recently crafted 'Omanity' in a context of regional concern regarding national identities' durability. PMID:23898837

  16. The Ising model for prediction of disordered residues from protein sequence alone

    Science.gov (United States)

    Lobanov, Michail Yu; Galzitskaya, Oxana V.

    2011-06-01

    Intrinsically disordered regions serve as molecular recognition elements, which play an important role in the control of many cellular processes and signaling pathways. It is useful to be able to predict positions of disordered residues and disordered regions in protein chains using protein sequence alone. A new method (IsUnstruct) based on the Ising model for prediction of disordered residues from protein sequence alone has been developed. According to this model, each residue can be in one of two states: ordered or disordered. The model is an approximation of the Ising model in which the interaction term between neighbors has been replaced by a penalty for changing between states (the energy of border). The IsUnstruct has been compared with other available methods and found to perform well. The method correctly finds 77% of disordered residues as well as 87% of ordered residues in the CASP8 database, and 72% of disordered residues as well as 85% of ordered residues in the DisProt database.

  17. The Ising model for prediction of disordered residues from protein sequence alone

    International Nuclear Information System (INIS)

    Intrinsically disordered regions serve as molecular recognition elements, which play an important role in the control of many cellular processes and signaling pathways. It is useful to be able to predict positions of disordered residues and disordered regions in protein chains using protein sequence alone. A new method (IsUnstruct) based on the Ising model for prediction of disordered residues from protein sequence alone has been developed. According to this model, each residue can be in one of two states: ordered or disordered. The model is an approximation of the Ising model in which the interaction term between neighbors has been replaced by a penalty for changing between states (the energy of border). The IsUnstruct has been compared with other available methods and found to perform well. The method correctly finds 77% of disordered residues as well as 87% of ordered residues in the CASP8 database, and 72% of disordered residues as well as 85% of ordered residues in the DisProt database

  18. Nifedipine effect on the labelling of blood cells and plasma proteins with Tc-99m

    International Nuclear Information System (INIS)

    The labeling of red blood cells (RBC) with Tc-99m depends on the presence of stannous ion (Sn) that helps this radionuclide's fixation on the hemoglobin molecule. Nifedipine is an agent capable to block a specific way where calcius (Ca) ion acrosses the cellular membrane and to bind itself on plasma proteins. The effect of nifedipine in the labeling of RBC and plasma proteins with Tc-99m was studied because of similarities between Ca and Sn ions. Blood with anticoagulant was treated with nifedipine concentration of 10-6M for 15 min at 370C. The labeling of RBC with Tc-99m was done incubating with Sn ion solution (3 uM) for different times. The % of radioactivity in RBC was determined. Samples of plasma were precipited with trichloroacetic acid and the % of radiocctivity in insoluble fraction was calculated. The same procedure was done using different nifedipine concentrations and the blood was incubated for 60 min with Sn ion. The determination of the % of Tc-99m labeled in RBC and plasma proteins showed that this drug does not have the capability to alter this incorporation because the results are similar to control. It is suggested that the Sn ions passage across RBC is not altered by nifedipine although this drug could bind to plasma protein, it does not modify the Tc-99m fixation on it. (author)

  19. Whole blood BDNF levels in healthy twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Vinberg, Maj; Aznar, Susana;

    2008-01-01

    BACKGROUND: Depression has been associated with decreased blood BDNF concentrations; but it is unclear if low blood BDNF levels are a state or a trait marker of depression. METHODS: We investigated blood BDNF concentrations in a twin population including both subjects highly predisposed and prote...

  20. Self-assembly of protein aggregates in ageing disorders: the lens and cataract model.

    Science.gov (United States)

    Clark, John I

    2013-05-01

    Cataract, neurodegenerative disease, macular degeneration and pathologies of ageing are often characterized by the slow progressive destabilization of proteins and their self-assembly to amyloid-like fibrils and aggregates. During normal cell differentiation, protein self-assembly is well established as a dynamic mechanism for cytoskeletal organization. With the increased emphasis on ageing disorders, there is renewed interest in small-molecule regulators of protein self-assembly. Synthetic peptides, mini-chaperones, aptamers, ATP and pantethine reportedly regulate self-assembly mechanisms involving small stress proteins, represented by human αB-crystallin, and their targets. Small molecules are being considered for direct application as molecular therapeutics to protect against amyloid and protein aggregation disorders in ageing cells and tissues in vivo. The identification of specific interactive peptide sites for effective regulation of protein self-assembly is underway using conventional and innovative technologies. The quantification of the functional interactions between small stress proteins and their targets in vivo remains a top research priority. The quantitative parameters controlling protein-protein interactions in vivo need characterization to understand the fundamental biology of self-assembling systems in normal cells and disorders of ageing. PMID:23530262

  1. Regional cerebral blood flow in mood disorders. I. Comparison of major depressives and normal controls at rest

    International Nuclear Information System (INIS)

    We measured regional cerebral blood flow with the xenon 133 inhalation technique in 41 patients with major depressive disorder and 40 matched, normal controls during an eyes-closed, resting condition. The depressed group had a marked reduction in global cortical blood flow. To examine topographic abnormalities, traditional multivariate analyses were applied, as well as a new scaled subprofile model developed to identify abnormal functional neural networks in clinical samples. Both approaches indicated that the depressed sample had an abnormality in topographic distribution of blood flow, in addition to the global deficit. The scaled subprofile model identified the topographic abnormality as being due to flow reduction in the depressed patients in selective frontal, central, superior temporal, and anterior parietal regions. This pattern may reflect dysfunction in the parallel distributed cortical network involving frontal and temporoparietal polymodal association areas. The extent of this topographic abnormality, as revealed by the scaled subprofile model, was associated with both patient age and severity of depressive symptoms

  2. Blood pressure lowering effect of a pea protein hydrolysate in hypertensive rats and humans.

    Science.gov (United States)

    Li, Huan; Prairie, Natalie; Udenigwe, Chibuike C; Adebiyi, Abayomi P; Tappia, Paramjit S; Aukema, Harold M; Jones, Peter J H; Aluko, Rotimi E

    2011-09-28

    The blood pressure lowering effect of a pea protein hydrolysate (PPH) that contained isolated by membrane ultrafiltration from the thermolysin digest of pea protein isolate (PPI), was examined using different rat models of hypertension as well as hypertensive human subjects. The PPH showed weak in vitro activities against renin and angiotensin converting enzyme (ACE) with inhibitory activities of 17 and 19%, respectively, at 1 mg/mL test concentration. Oral administration of the PPH to spontaneously hypertensive rats (SHR) at doses of 100 and 200 mg/kg body weight led to a lowering of hourly systolic blood pressure (SBP), with a maximum reduction of 19 mmHg at 4 h. In contrast, orally administered unhydrolyzed PPI had no blood pressure reducing effect in SHR, suggesting that thermolysin hydrolysis may have been responsible for releasing bioactive peptides from the native protein. Oral administration of the PPH to the Han:SPRD-cy rat (a model of chronic kidney disease) over an 8-week period led to 29 and 25 mmHg reductions in SBP and diastolic blood pressure, respectively. The PPH-fed rats had lower plasma levels of angiotensin II, the major vasopressor involved in development of hypertension, but there was no effect on plasma activity or renal mRNA levels of ACE. However, renal expression of renin mRNA levels was reduced by approximately 50% in the PPH-fed rats, suggesting that reduced renin may be responsible for the reduced levels of angiotensin II. In a 3-week randomized double blind placebo-controlled crossover human intervention trial (7 volunteers), significant (p<0.05) reductions (over placebo) in SBP of 5 and 6 mmHg were obtained in the second and third weeks, respectively, for the PPH group. Therefore, thermolysin derived bioactive peptides from PPH reduced blood pressure in hypertensive rats and human subjects, likely via effects on the renal angiotensin system. PMID:21854068

  3. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites.

    Science.gov (United States)

    Absalon, Sabrina; Robbins, Jonathan A; Dvorin, Jeffrey D

    2016-01-01

    Blood-stage replication of the human malaria parasite Plasmodium falciparum occurs via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. Here we identify a parasite protein, which we name P. falciparum Merozoite Organizing Protein (PfMOP), as essential for cytokinesis of blood-stage parasites. We show that, following PfMOP knockdown, parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While organelles develop normally, the structural scaffold of daughter parasites, the inner membrane complex (IMC), fails to form in this agglomerate causing flawed segmentation. In PfMOP-deficient gametocytes, the IMC formation defect causes maturation arrest with aberrant morphology and death. Our results provide insight into the mechanisms of replication and maturation of malaria parasites. PMID:27121004

  4. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites

    Science.gov (United States)

    Absalon, Sabrina; Robbins, Jonathan A.; Dvorin, Jeffrey D.

    2016-01-01

    Blood-stage replication of the human malaria parasite Plasmodium falciparum occurs via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. Here we identify a parasite protein, which we name P. falciparum Merozoite Organizing Protein (PfMOP), as essential for cytokinesis of blood-stage parasites. We show that, following PfMOP knockdown, parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While organelles develop normally, the structural scaffold of daughter parasites, the inner membrane complex (IMC), fails to form in this agglomerate causing flawed segmentation. In PfMOP-deficient gametocytes, the IMC formation defect causes maturation arrest with aberrant morphology and death. Our results provide insight into the mechanisms of replication and maturation of malaria parasites. PMID:27121004

  5. In Silico Analysis of Correlations between Protein Disorder and Post-Translational Modifications in Algae

    Directory of Open Access Journals (Sweden)

    Atsushi Kurotani

    2015-08-01

    Full Text Available Recent proteome analyses have reported that intrinsically disordered regions (IDRs of proteins play important roles in biological processes. In higher plants whose genomes have been sequenced, the correlation between IDRs and post-translational modifications (PTMs has been reported. The genomes of various eukaryotic algae as common ancestors of plants have also been sequenced. However, no analysis of the relationship to protein properties such as structure and PTMs in algae has been reported. Here, we describe correlations between IDR content and the number of PTM sites for phosphorylation, glycosylation, and ubiquitination, and between IDR content and regions rich in proline, glutamic acid, serine, and threonine (PEST and transmembrane helices in the sequences of 20 algae proteomes. Phosphorylation, O-glycosylation, ubiquitination, and PEST preferentially occurred in disordered regions. In contrast, transmembrane helices were favored in ordered regions. N-glycosylation tended to occur in ordered regions in most of the studied algae; however, it correlated positively with disordered protein content in diatoms. Additionally, we observed that disordered protein content and the number of PTM sites were significantly increased in the species-specific protein clusters compared to common protein clusters among the algae. Moreover, there were specific relationships between IDRs and PTMs among the algae from different groups.

  6. ProteinSplit: splitting of multi-domain proteins using prediction of ordered and disordered regions in protein sequences for virtual structural genomics

    International Nuclear Information System (INIS)

    The annotation of protein folds within newly sequenced genomes is the main target for semi-automated protein structure prediction (virtual structural genomics). A large number of automated methods have been developed recently with very good results in the case of single-domain proteins. Unfortunately, most of these automated methods often fail to properly predict the distant homology between a given multi-domain protein query and structural templates. Therefore a multi-domain protein should be split into domains in order to overcome this limitation. ProteinSplit is designed to identify protein domain boundaries using a novel algorithm that predicts disordered regions in protein sequences. The software utilizes various sequence characteristics to assess the local propensity of a protein to be disordered or ordered in terms of local structure stability. These disordered parts of a protein are likely to create interdomain spacers. Because of its speed and portability, the method was successfully applied to several genome-wide fold annotation experiments. The user can run an automated analysis of sets of proteins or perform semi-automated multiple user projects (saving the results on the server). Additionally the sequences of predicted domains can be sent to the Bioinfo.PL Protein Structure Prediction Meta-Server for further protein three-dimensional structure and function prediction. The program is freely accessible as a web service at http://lucjan.bioinfo.pl/proteinsplit together with detailed benchmark results on the critical assessment of a fully automated structure prediction (CAFASP) set of sequences. The source code of the local version of protein domain boundary prediction is available upon request from the authors

  7. Further insight into the roles of the glycans attached to human blood protein C inhibitor

    DEFF Research Database (Denmark)

    Sun, Wei; Parry, Simon; Ubhayasekera, Wimal;

    2010-01-01

    . Furthermore, we have provided experimental evidence that PCI in both individuals is O-glycosylated on Thr20 with a core type 1 O-glycan, which is mostly NeuAcGalGalNAc. Modeling suggested that the O-glycan attachment site is located in proximity to several ligand-binding sites of the inhibitor.......Protein C inhibitor (PCI) is a 57-kDa glycoprotein that exists in many tissues and secretions in human. As a member of the serpin superfamily of proteins it displays unusually broad protease specificity. PCI is implicated in the regulation of a wide range of processes, including blood coagulation...

  8. Optical tweezers study of red blood cell aggregation and disaggregation in plasma and protein solutions

    Science.gov (United States)

    Lee, Kisung; Kinnunen, Matti; Khokhlova, Maria D.; Lyubin, Evgeny V.; Priezzhev, Alexander V.; Meglinski, Igor; Fedyanin, Andrey A.

    2016-03-01

    Kinetics of optical tweezers (OT)-induced spontaneous aggregation and disaggregation of red blood cells (RBCs) were studied at the level of cell doublets to assess RBC interaction mechanics. Measurements were performed under in vitro conditions in plasma and fibrinogen and fibrinogen + albumin solutions. The RBC spontaneous aggregation kinetics was found to exhibit different behavior depending on the cell environment. In contrast, the RBC disaggregation kinetics was similar in all solutions qualitatively and quantitatively, demonstrating a significant contribution of the studied proteins to the process. The impact of the study on assessing RBC interaction mechanics and the protein contribution to the reversible RBC aggregation process is discussed.

  9. Blood parameters in growing pigs fed increasing levels of bacterial protein meal

    Directory of Open Access Journals (Sweden)

    Tauson Anne-Helene

    2007-11-01

    Full Text Available Abstract The experiment investigated the effects of increasing dietary levels of bacterial protein meal (BPM on various blood parameters reflecting protein and fat metabolism, liver function, and purine base metabolism in growing pigs. Sixteen barrows were allocated to four different experimental diets. The control diet was based on soybean meal. In the other three diets soybean meal was replaced with increasing levels of BPM, approximately 17%, 35%, and 50% of the nitrogen being derived from BPM. Blood samples from the jugular vein were taken when the body weights of the pigs were approximately 10 kg, 21 kg, 45 kg, and 77 kg. The blood parameters reflecting fat metabolism and liver function were not affected by diet. Both the plasma albumin and uric acid concentrations tended to decrease (P = 0.07 and 0.01, respectively with increasing dietary BPM content, whereas the plasma glucose concentration tended to increase (P = 0.07 with increasing dietary BPM content. It was concluded that up to 50% of the nitrogen could be derived from BPM without affecting metabolic function, as reflected in the measured blood parameters.

  10. SLiMPrints: conservation-based discovery of functional motif fingerprints in intrinsically disordered protein regions

    OpenAIRE

    Davey, Norman E.; Cowan, Joanne L; Shields, Denis C.; Gibson, Toby J.; Coldwell, Mark J; Edwards, Richard J

    2012-01-01

    Large portions of higher eukaryotic proteomes are intrinsically disordered, and abundant evidence suggests that these unstructured regions of proteins are rich in regulatory interaction interfaces. A major class of disordered interaction interfaces are the compact and degenerate modules known as short linear motifs (SLiMs). As a result of the difficulties associated with the experimental identification and validation of SLiMs, our understanding of these modules is limited, advocating the use ...

  11. Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins.

    OpenAIRE

    S Herrera; Herrera, M. A.; Perlaza, B L; Burki, Y; Caspers, P; Döbeli, H; Rotmann, D; Certa, U

    1990-01-01

    The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falciparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe the vaccination of Aotus monkeys with two recombinant blood-stage antigens (recombinant p41 and 190N) that were considered as vaccine candidates because parasite-derived antigen pr...

  12. Test and Evaluation of ff99IDPs Force Field for Intrinsically Disordered Proteins.

    Science.gov (United States)

    Ye, Wei; Ji, Dingjue; Wang, Wei; Luo, Ray; Chen, Hai-Feng

    2015-05-26

    Over 40% of eukaryotic proteomic sequences have been predicted to be intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) and confirmed to be associated with many diseases. However, widely used force fields cannot well reproduce the conformers of IDPs. Previously the ff99IDPs force field was released to simulate IDPs with CMAP energy corrections for the eight disorder-promoting residues. In order to further confirm the performance of ff99IDPs, three representative IDP systems (arginine-rich HIV-1 Rev, aspartic proteinase inhibitor IA3, and α-synuclein) were used to test and evaluate the simulation results. The results show that for free disordered proteins, the chemical shifts from the ff99IDPs simulations are in quantitative agreement with those from reported NMR measurements and better than those from ff99SBildn. Thus, ff99IDPs can sample more clusters of disordered conformers than ff99SBildn. For structural proteins, both ff99IDPs and ff99SBildn can well reproduce the conformations. In general, ff99IDPs can successfully be used to simulate the conformations of IDPs and IDRs in both bound and free states. However, relative errors could still be found at the boundaries of ordered residues scattered in long disorder-promoting sequences. Therefore, polarizable force fields might be one of the possible ways to further improve the performance on IDPs. PMID:25919886

  13. Evaluation of C-reactive protein and interleukin-6 in the peripheral blood of patients with chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Gani Dhruva

    2009-01-01

    Full Text Available Aims and Objectives: The aim of the present study was to investigate systemic levels of inflammatory markers of cardiovascular diseases like C-reactive protein and interleukin-6 in patients with chronic periodontitis, in comparison to periodontally healthy individuals. Materials and Methods: A total of 42 individuals, both males and females above the age of 30 years, were included in the study. Healthy controls (Group I, n = 14, chronic localized periodontitis (Group II, n = 14, and chronic generalized periodontitis (Group III, n = 14, all without any medical disorder, were recruited. Peripheral blood samples were taken and C-reactive protein (CRP levels were estimated in the serum samples by using the Particle-Enhanced Turbidimetric Immunoassay (PETIA technique. Serum samples of Interleukin-6 (IL-6 were assayed by using the Chemiluminescent Immunoassay (IMMULITE technique. Results: When mean CRP levels were compared between the groups, group III showed statistical significance when compared to group I (P = 0.04. Group III had a higher median IL-6 level (6.35 pg/mL than Group II (< 5.0 pg/ mL and group I (< 5.0 pg/mL. Differences in median values of IL-6 were not statistically significant in any group (P = 0.29. Conclusion: Periodontitis results in higher systemic levels of CRP and IL-6. These elevated inflammatory factors may increase inflammatory activity in atherosclerotic lesions and potentially increasing the risk for cardiovascular events.

  14. Blood protein turnover in parasitized ruminants. The influence of host nutrition

    International Nuclear Information System (INIS)

    Ruminants infected with helminth or protozoal parasites generally become anaemic and hypoalbuminaemic, as well as losing their appetite. Since feed intake plays an important part in determining blood protein levels, it is necessary, when attempting to determine the mechanisms by which parasites cause anaemia and hypoalbuminaemia, to differentiate between the effects of feed intake per se and the specific effects of the parasite on blood protein turnover. This can be done by a variety of radioisotope techniques using infected and pair-fed control animals. Additionally, animals on a poor plane of nutrition suffer more from parasitism than those which are well fed. To understand the reason for this, it is necessary to determine whether diet influences susceptibility to parasite establishment or survival, and/or susceptibility to the metabolic consequences of parasitism. Described here is the current state of knowledge on the interaction between host nutrition and susceptibility to parasitic infection and parasitic disease processes, with particular reference to anaemia and hypoalbuminaemia. It is concluded that there is little evidence that nutrition has a significant bearing on resistance or susceptibility to infection, but that it does not have a profound influence on the ability of animals to withstand the pathogenic effects of parasites. The reasons for this are discussed in detail, but the principal benefit of a good plane of nutrition is that it enables the synthetic machinery of the host to keep pace with the concurrent parasite-induced hypercatabolism of blood proteins. (author)

  15. Physical modeling of geometrically confined disordered protein assemblies

    Science.gov (United States)

    Ando, David

    The mental health of soldiers is a growing concern as rates of depression and suicide have increased in soldiers with recently more deaths attributed to suicide than deaths due to combat in Afghanistan in 2012. Previous research has demonstrated the potential for eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), vitamin D, physical activity, and physical fitness to improve and arachidonic acid (AA) to threaten depression/quality of life scores. This study examined whether blood fatty acid levels, vitamin D status and/or physical activity are associated with physical fitness scores, measures of mood, and measures of resiliency in active duty soldiers. 100 active duty males at Fort Hood, TX underwent a battery of psychometric tests, anthropometric, fitness tests, and donated fasting blood samples. Pearson bivariate correlation analysis revealed significant correlations among psychometric tests, anthropometric, physical performance, reported physical inactivity (sitting time), and fatty acid and vitamin D blood levels. Categorical analysis revealed significant difference in levels of fatty acids and vitamin D, anthropometric, physical performance, and psychometric measures. Based on these findings, a regression equation was developed to predict a depressed mood status as determined by the Patient Health Questionnaire-9. The equation accurately predicted 80% of our participants with a sensitivity of 76.9% and a specificity of 80.5%. Results indicate that lack of physical activity and fitness, high levels of AA and low levels of EPA, DHA, and vitamin D could increase the risk of depressed mood and that use of a regression equation may be helpful in identifying soldiers at higher risk for possible intervention. Future studies should evaluate the impact of exercise and diet interventions as a means of improving resiliency and reducing depressed mood in soldiers.

  16. Adherence issues in inherited metabolic disorders treated by low natural protein diets

    DEFF Research Database (Denmark)

    MaCdonald, A; van Rijn, M; Feillet, F;

    2012-01-01

    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor...... on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist L-AAs for non-PKU AA disorders has...

  17. Effects of a protein glycocalyx in the hemodynamics of small blood vessels

    Science.gov (United States)

    Dimakopoulos, Yiannis; Delidakis, George; Tsamopoulos, John

    2015-11-01

    Glycocalyx is a protein layer of approximate thickness 0.5 μm that lines vessel walls. We study the effects this layer has on the blood flow inside arterioles and venules, where the relative size of the glycocalyx is significant. To properly describe phenomena that naturally occur in blood flow, such as the inhomogeneous distribution of red blood cells and their aggregation, we use an improved viscoelastic constitutive model. The glycocalyx layer is modeled as fixed porous media. Cells cannot penetrate inside it, since its hydraulic permeability is very low, and the flow inside this layer is described by the equations for a viscous fluid with an extra Brinkman term to account for the effects the porous medium has on the flow. The closed set of equations is solved using the Finite Element method, assuming steady-state with dependence only in the r-direction. Our results are favorably compared with the in vivo velocity profiles in venules of mice produced by Damiano et al. (2004) and the formation of cell-free layer near glycocalyx. Flow inside the glycocalyx layer is found to be severely attenuated due to the low hydraulic permeability, which can have interesting implications in the transport of various substances form the blood to the tissues or in the use of shear stresses as signals for the endothelial surface cells. Finally, we simulate the transient blood flow under pulsatile conditions.

  18. [MORPHOFUNCTIONAL STATE OF BLOOD CELLS AFTER CHRONIC EXPOSURE OF THE PROTEIN KINASES INHIBITOR MALEIMIDE DERIVATIVE].

    Science.gov (United States)

    Byelinska, I V; Lynchak, O V; Tsyvinska, S M; Rybalchenko, V K

    2015-01-01

    The effect of the protein kinases inhibitor maleimide derivative (MI-1, 1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrole-2,5-dione), inhibitor of VEGF-R1,2,3, FGF-R1, EGF-R(h), PDK1, Src(h), Syk(h), YES, ZAP70 et al. with antineoplastic activity, on blood cells parameters of rats after chronic exposure has been studied. Administration of MI-1 at doses 0.027 and 2.7 mg/kg (suppress colon carcinogenesis) for 20 and 26 weeks does not affect the morphofunctional state of red blood cells in healthy rats. This is confirmed by the lack of differences in the concentration of hemoglobin in blood, red blood cells count, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration, hematocrit and mean corpuscular volume, and the number of reticulocytes in blood after 20 and 26 weeks of exposure compared with the control group. MI-1 at indicated doses does not influence total leukocytes count and content (eosinophilic and neutrophilic granulocytes, lymphocytes, monocytes) and does not inhibit thrombocytopoiesis (platelet count remains unchanged). No negative effect of MI-1 on hematopoiesis is not limited (by the hemopoietic system) use of this compound as a potential antitumor drug PMID:26552308

  19. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... For Patients Blood Disorders Blood Clots Blood Clotting & Pregnancy If you are pregnant, or you have just ... The risk of developing a blood clot during pregnancy is increased by the following: Previous blood clots ...

  20. Analysis of zinc oxide nanoparticles binding proteins in rat blood and brain homogenate

    Directory of Open Access Journals (Sweden)

    Shim KH

    2014-12-01

    Full Text Available Kyu Hwan Shim,1 John Hulme,1 Eun Ho Maeng,2 Meyoung-Kon Kim,3 Seong Soo A An1 1Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Sungnam-si, Gyeonggi-do, South Korea; 2Department of Analysis, KTR, Kimpo, Gyeonggi-do, South Korea; 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea Abstract: Nanoparticles (NPs are currently used in chemical, cosmetic, pharmaceutical, and electronic products. Nevertheless, limited safety information is available for many NPs, especially in terms of their interactions with various binding proteins, leading to potential toxic effects. Zinc oxide (ZnO NPs are included in the formulation of new products, such as adhesives, batteries, ceramics, cosmetics, cement, glass, ointments, paints, pigments, and supplementary foods, resulting in increased human exposures to ZnO. Hence, we investigated the potential ZnO nanotoxic pathways by analyzing the adsorbed proteins, called protein corona, from blood and brain from four ZnO NPs, ZnOSM20(-, ZnOSM20(+, ZnOAE100(-, and ZnOAE100(+, in order to understand their potential mechanisms in vivo. Through this study, liquid chromatography–mass spectroscopy/mass spectroscopy technology was employed to identify all bound proteins. Totals of 52 and 58 plasma proteins were identified as being bound to ZnOSM20(- and ZnOSM20(+, respectively. For ZnOAE100(- and ZnOAE100(+, 58 and 44 proteins were bound, respectively. Similar numbers of proteins were adsorbed onto ZnO irrespective of size or surface charge of the nanoparticle. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Interactions between diverse proteins and ZnO nanoparticles could result in an alteration of their functions, conformation, and clearance, eventually affecting many biological processes. Keywords: brain

  1. Clinical significance of determination of cord blood S100B protein contents in neonates with intrauterine asphyxia

    International Nuclear Information System (INIS)

    Objective: To study the clinical significance of determination of cord blood S100B protein (a specific neural glia protein reflecting CNS injury) in neonates with intrauterine asphyxia. Methods: Cord blood S100B protein contents were measured with ELISA in (1) 41 neonates from normal vaginal delivery (2) 48 neonates from caesarean section without asphyxia and (3) 36 caesarean section neonates with intrauterine asphyxia. Results: Cord blood S100B protein contents in neonates with intrauterine asphyxia were significantly higher than those in the other 2 groups (P0.05). Conclusion: Cord blood S100B protein is a uesful indicator for the diagnosis of neonatal asphyxia and identification of brain damage following neonatal asphyxia. (authors)

  2. Proteins involved in invasion of human red blood cells by malaria parasites

    Directory of Open Access Journals (Sweden)

    Ewa Jaśkiewicz

    2010-11-01

    Full Text Available Malaria is a disease caused by parasites of Plasmodium species. It is responsible for around 1-2 million deaths annually, mainly children under the age of 5. It occurs mainly in tropical and subtropical areas.Malaria is caused by five Plasmodium species:[i] P. falciparum, P. malariae, P. vivax, P. knowlesi[/i] and [i]P. ovale[/i]. Mosquitoes spread the disease by biting humans. The malaria parasite has two stages of development: the human stage and the mosquito stage. The first stage occurs in the human body and is divided into two phases: the liver phase and the blood phase.The invasion of erythrocytes by [i]Plasmodium[/i] merozoites is a multistep process of specific protein interactions between the parasite and red blood cell. The first step is the reversible merozoite attachment to the erythrocyte followed by its apical reorientation, then formation of an irreversible “tight” junction and finally entry into the red cell in a parasitophorous vacuole.The blood phase is supported by a number of proteins produced by the parasite. The merozoite surface GPI-anchored proteins (MSP-1, 2, 4, 5, 8 and 10 assist in the process of recognition of susceptible erythrocytes, apical membrane antigen (AMA-1 may be directly responsible for apical reorientation of the merozoite and apical proteins which function in tight junction formation. These ligands are members of two families: Duffy binding-like (DBL and reticulocyte binding-like (RBL proteins. In [i]Plasmodium[/i] [i]falciparum[/i] the DBL family includes: EBA-175, EBA-140 (BAEBL, EBA-181 (JESEBL, EBA-165 (PEBL and EBL-1 ligands.To date, no effective antimalarial vaccine has been developed, but there are several studies for this purpose. Therefore, it is crucial to understand the molecular basis of host cells invasion by parasites. Major efforts are focused on developing a multiantigenic and multiepitope vaccine preventing all steps of [i]Plasmodium[/i] invasion.

  3. Rap G protein signal in normal and disordered lymphohematopoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Minato, Nagahiro, E-mail: minato@imm.med.kyoto-u.ac.jp

    2013-09-10

    Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the development and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy.

  4. Rap G protein signal in normal and disordered lymphohematopoiesis

    International Nuclear Information System (INIS)

    Rap proteins (Rap1, Rap2a, b, c) are small molecular weight GTPases of the Ras family. Rap G proteins mediate diverse cellular events such as cell adhesion, proliferation, and gene activation through various signaling pathways. Activation of Rap signal is regulated tightly by several specific regulatory proteins including guanine nucleotide exchange factors and GTPase-activating proteins. Beyond cell biological studies, increasing attempts have been made in the past decade to define the roles of Rap signal in specific functions of normal tissue systems as well as in cancer. In the immune and hematopoietic systems, Rap signal plays crucial roles in the development and function of essentially all lineages of lymphocytes and hematopoietic cells, and importantly, deregulated Rap signal may lead to unique pathological conditions depending on the affected cell types, including various types of leukemia and autoimmunity. The phenotypical studies have unveiled novel, even unexpected functional aspects of Rap signal in cells from a variety of tissues, providing potentially important clues for controlling human diseases, including malignancy

  5. INFLUENCE OF NATURAL IMMUNOMODULATORS ON PROTEIN FRACTIONS AND CORTISOL CONTENT IN RABBIT BLOOD UNDER STRESS

    Directory of Open Access Journals (Sweden)

    Grabovskyi S.

    2015-08-01

    Full Text Available The results of determination of protein fractions, cortisol content in blood of rabbits, which further added to the feed of natural origin biologically active substances are presented in the article. As an antistressors and immunomodulators in pre-slaughter period are using of spleen extract biologically active substances were obtained with ultrasound application. The purpose of research — determination of changes of protein fractions, cortisol content in rabbits blood before slaughter and their correction of natural origin biologically active substances (spleen extract. Object and research methods. The experiment was conducted on 15 rabbits with standard diet. Three groups of rabbits five month of age (5 rabbits each was formed for research. The spleen extract were using as an biologically active substances to the feed rabbits in pre-slaughter period (five days before slaughter. The extracts were applied to feed by aerosol method (70 °alcohol solution of spleen extract volume of 1.4 ml per rabbit (group I. The rabbits (group II received to the feed in the same way of 70 °alcohol solution in the same volume. The control group rabbits received the standard feed in the same volume. The feed eating by rabbits was exercised daily. The rabbits ate food completely. The rabbits slaughter was carried out in the morning. The blood plasma protein fractions separation was carried out by horizontal electrophoresis in polyacrylamide gel (PAAG. Mathematical treatment of the research results worked statistically using the software package Statistica 6.0 and Microsoft Excel for Windows XP. Probability differences was assessed by Student t-test and results considered likely at P ≤ 0.05. Results and discussion. We measured the ratio of blood plasma protein fractions of rabbits, which in addition to the feed fed of natural origin biologically active substances. As a result of research was found that aerosol introduction of the spleen extract to the rabbits

  6. Disorder of blood-aqueous barrier following Ahmed Glaucoma Valve implantation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Min-wen; WANG Wei; CHEN Shi-da; HUANG Wen-bin; ZHANG Xiu-lan

    2013-01-01

    Background Ahmed Glaucoma Valve implantation (AGVI) is used to treat refractory glaucoma.Breakdown of the blood-aqueous barrier (BAB) has been noted after some surgical techniques.The current study was designed to assess BAB disruption after AGVI.Methods Anterior chamber protein content was measured by the laser flare cell photometry in 22 eyes of 22 patients with refractory glaucoma before AGVI and at each postoperative visit up to 1 month.Results Before AGVI the mean aqueous flare values in all eyes were (15.17±9.84) photon counts/ms.After AGVI,the values significantly increased at day 1,day 3,and week 1 compared to those before AGVI (all P <0.05) with a peak at day 3.They returned to pre-operative levels at week 2,and were lower than preoperative level at month 1.Eyes with previous intraocular surgery history had greater aqueous flare values than those without previous intraocular surgery history,but there were no significant differences at all time points postoperatively (all P >0.05).Furthermore,eyes with shallow anterior chambers had greater aqueous flare values at day 3 and week 1 (all P <0.05).When comparing eyes with other refractory glaucoma conditions,neovascular glaucoma combined with intravitreal bevacizumab injection resulted in lower aqueous flare values after AGVI,but no significant differences were observed at all time points,postoperatively (all P>0.05).Conclusions The BAB was impaired and inflammation was present in the anterior chamber in refractory glaucomatous eyes following AGVI.However,such conditions were resolved within 1 month postoperatively.Intravitreal bevacizumab treatment in neovascular glaucoma eyes before AGVI may prevent BAB breakdown.

  7. Investigation of Fasciculation and Elongation Protein ζ-1 (FEZ1 in Peripheral Blood Reveals Differences in Gene Expression in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Vachev T.I.

    2015-06-01

    Full Text Available Schizophrenia (SZ is a chronic neuropsychiatric disorder characterized by affective, neuromorphological and cognitive impairment, deteriorated social functioning and psychosis with underlying molecular abnormalities, including gene expression changes. Observations have suggested that fasciculation and elongation protein ζ-1 (FEZ1 may be implicated in the pathogenesis of schizophrenia. Nevertheless, our current knowledge of the expression of FEZ1 in peripheral blood of schizophrenia patients remains unclear. The purpose of this study was to identify the characteristic gene expression patterns of FEZ1 in peripheral blood samples from schizophrenia patients. We performed quantitative reverse-transcriptase (qRT-PCR analysis using peripheral blood from drug-free schizophrenia patients (n = 29 and age and gender-matched general population controls (n = 24. For the identification of FEZ1 gene expression patterns, we applied a comparative threshold cycle (CT method. A statistically significant difference of FEZ1 mRNA level was revealed in schizophrenia subjects compared to healthy controls (p = 0.0034. To the best of our knowledge, this study is the first describing a down-regulation of FEZ1 gene expression in peripheral blood of patients with schizophrenia. Our results suggested a possible functional role of FEZ1 in the pathogenesis of schizophrenia and confirmed the utility of peripheral blood samples for molecular profiling of psychiatric disorders including schizophrenia. The current study describes FEZ1 gene expression changes in peripheral blood of patients with schizophrenia with significantly down-regulation of FEZ1 mRNA. Thus, our results provide support for a model of SZ pathogenesis that includes the effects of FEZ1 expression.

  8. STUDIES ON BLOOD GLUTATHIONE PEROXIDASE PROTEIN LEVEL OF CHILDREN IN KESHAN DISEASE AND KASHIN-BECK DISEASE AREAS

    Institute of Scientific and Technical Information of China (English)

    谭武红; 种晓红; 杨占田; 翟连榜; 王立新; 徐光禄

    2002-01-01

    Objective To oberve the change in blood glutathione peroxidase (GSH-Px) protein levels of residents in the low-selenium (Se) area by contrasting the blood GSH-Px protein level of the children in the Keshan disease area with those in the Kashin-Beck disease and non-endemic areas. Methods GSH-Px protein levels were measured by enzyme-linked immunosorbent assays (ELISA). The Se content and GSH-Px activity were assayed by the 2,3-diaminonaphthalene spectrofluorimetric method and glutathione reductase-coupled method respectively. Results ①The blood Se content and GSH-Px protein level of children in Keshan disease area (Moding) were significantly lower than those in Xi'an non-endemic area, however, there was no significant difference when compared with the low-Se non-endemic area; ②The blood Se content, GSH-Px activity and GSH-Px protein level of children in the Kashin-Beck disease area (Yulin) were significantly lower than those of children in two non-endemic areas and in the Keshan disease area; ③The blood Se content and GSH-Px activity were positively correlated to the GSH-Px protein level respectively. Conclusion These results indicate that the blood GSH-Px protein level is decreased in the low-Se residents. The Se status not only affects the GSH-Px activity but also regulate the GSH-Px protein level.

  9. Molecular cloning and protein structure of a human blood group Rh polypeptide

    International Nuclear Information System (INIS)

    cDNA clones encoding a human blood group Rh polypeptide were isolated from a human bone marrow cDNA library by using a polymerase chain reaction-amplified DNA fragment encoding the known common N-terminal region of the Rh proteins. The entire primary structure of the Rh polypeptide has been deduced from the nucleotide sequence of a 1384-base-pair-long cDNA clone. Translation of the open reading frame indicates that the Rh protein is composed of 417 amino acids, including the initiator methionine, which is removed in the mature protein, lacks a cleavable N-terminal sequence, and has no consensus site for potential N-glycosylation. The predicted molecular mass of the protein is 45,500, while that estimated for the Rh protein analyzed in NaDodSO4/polyacrylamide gels is in the range of 30,000-32,000. These findings suggest either that the hydrophobic Rh protein behaves abnormally on NaDodSO4 gels or that the Rh mRNA may encode a precursor protein, which is further matured by a proteolytic cleavage of the C-terminal region of the polypeptide. Hydropathy analysis and secondary structure predictions suggest the presence of 13 membrane-spanning domains, indicating that the Rh polypeptide is highly hydrophobic and deeply buried within the phospholipid bilayer. These results suggest that the expression of the Rh gene(s) might be restricted to tissues or cell lines expressing erythroid characters

  10. Serotonin binding in vitro by releasable proteins from human blood platelets

    International Nuclear Information System (INIS)

    Among the substances released from human blood platelets are serotonin and various proteins. It was hypothesized that one of these proteins binds serotonin and that serotonin might be important to the protein's function or that the protein might be important to serotonin's function. Two platelet-specific proteins, platelet factor 4 (PF4) and β-thromboglobulin (βTG) were found to bind serotonin in vitro. Endogenous PF4 was isolated by serotonin-affinity chromatography and was identified by radioimmunoassay. Purified [125I] -PF4 and native PF4 bound to and eluted from a serotonin-affinity column similarly. Ultrafiltration of the homologous protein, βTG, with [14C]-serotonin demonstrated binding of about 8 moles serotonin per mole tetrameric βTG with a dissociation constant of about 4 X 10(sup-8) M. Equilibrium dialysis of PF4 with radiolabelled serotonin was attempted, but no binding constant values were obtained because serotonin apparently bound to the dialysis membrane. Since EDTA was one of the two agents that eluted PF4 from the serotonin-affinity gel, calcium binding by PF4 was investigated by equilibrium dialysis. Evidence was obtained for positively cooperative binding of calcium ions by PF4. It is concluded that PF4 and βTG bind serotonin in vitro, that they may also bind in vivo when platelets undergo release, and that the functions of serotonin, PF4 and βTG may be mediated in part by serotonin-protein associations

  11. Influence of heparin and thromboplastin in half-life of 125I-protein C in rat blood

    International Nuclear Information System (INIS)

    The influence of heparin and thromboplastin on the halflife of 125I-protein C in rat blood was under investigation. The intravenous administration of heparin resulted in the prolongation of t1/2 to 6.5 h, that could be explained by inhibition of thrombin generation. Upon the 40-min infusion of thromboplastin the rate of 125I-protein C decay in blood enhanced. That could be explained by the generation of the endogenous thrombin and participation of thrombomodulin in the protein C activation as well as in the removal of the endogenous thrombin from blood

  12. The Expression of Caspases Is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients

    Science.gov (United States)

    Siniscalco, Dario; Sapone, Anna; Giordano, Catia; Cirillo, Alessandra; de Novellis, Vito; de Magistris, Laura; Rossi, Francesco; Fasano, Alessio; Maione, Sabatino; Antonucci, Nicola

    2012-01-01

    Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and…

  13. Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders

    Directory of Open Access Journals (Sweden)

    Tachikawa Masanori

    2011-02-01

    Full Text Available Abstract Guanidino compounds (GCs, such as creatine, phosphocreatine, guanidinoacetic acid, creatinine, methylguanidine, guanidinosuccinic acid, γ-guanidinobutyric acid, β-guanidinopropionic acid, guanidinoethane sulfonic acid and α-guanidinoglutaric acid, are present in the mammalian brain. Although creatine and phosphocreatine play important roles in energy homeostasis in the brain, accumulation of GCs may induce epileptic discharges and convulsions. This review focuses on how physiologically important and/or neurotoxic GCs are distributed in the brain under physiological and pathological conditions. Transporters for GCs at the blood-brain barrier (BBB and the blood-cerebrospinal fluid (CSF barrier (BCSFB have emerged as substantial contributors to GCs distribution in the brain. Creatine transporter (CRT/solute carrier (SLC 6A8 expressed at the BBB regulates creatine concentration in the brain, and represents a major pathway for supply of creatine from the circulating blood to the brain. CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6 and organic cation transporter (OCT3/SLC22A3 expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters. Instead, the BCSFB functions as a major cerebral clearance system for GCs. In conclusion, transport of GCs at the BBB and BCSFB appears to be the key determinant of the cerebral levels of GCs, and changes in the transport characteristics may cause the abnormal distribution of GCs in the brain seen

  14. Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins

    Directory of Open Access Journals (Sweden)

    Li Junlin

    2013-02-01

    Full Text Available Abstract Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd, which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX, Williams syndrome (WS, Rett syndrome and Rubinstein-Taybi syndrome (RTS. A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders.

  15. Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins.

    Science.gov (United States)

    Li, Junlin; Zhao, Guifang; Gao, Xiaocai

    2013-01-01

    Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders. PMID:23425632

  16. Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.

    Directory of Open Access Journals (Sweden)

    Ruzica Livaja Koshiar

    Full Text Available Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte

  17. Point-of-Care Technologies for the Advancement of Precision Medicine in Heart, Lung, Blood, and Sleep Disorders.

    Science.gov (United States)

    Bigelow, Mary Emma Gorham; Jamieson, Brian G; Chui, Chi On; Mao, Yufei; Shin, Kyeong-Sik; Huang, Tony Jun; Huang, Po-Hsun; Ren, Liqiang; Adhikari, Bishow; Chen, Jue; Iturriaga, Erin

    2016-01-01

    The commercialization of new point of care technologies holds great potential in facilitating and advancing precision medicine in heart, lung, blood, and sleep (HLBS) disorders. The delivery of individually tailored health care to a patient depends on how well that patient's health condition can be interrogated and monitored. Point of care technologies may enable access to rapid and cost-effective interrogation of a patient's health condition in near real time. Currently, physiological data are largely limited to single-time-point collection at the hospital or clinic, whereas critical information on some conditions must be collected in the home, when symptoms occur, or at regular intervals over time. A variety of HLBS disorders are highly dependent on transient variables, such as patient activity level, environment, time of day, and so on. Consequently, the National Heart Lung and Blood Institute sponsored a request for applications to support the development and commercialization of novel point-of-care technologies through small businesses (RFA-HL-14-011 and RFA-HL-14-017). Three of the supported research projects are described to highlight particular point-of-care needs for HLBS disorders and the breadth of emerging technologies. While significant obstacles remain to the commercialization of such technologies, these advancements will be required to achieve precision medicine. PMID:27602308

  18. Plasma protein thiols, ceruloplasmin, C-reactive protein and red blood cell acetylcholinesterase in patients undergoing intrauterine insemination

    Directory of Open Access Journals (Sweden)

    Krishnananda Prabhu

    2009-01-01

    Full Text Available Objective: To estimate acetylcholinesterase (AChE, protein thiols (PT, ceruloplasmin (CP and C-reactive proteins (CRPs to assess any change in their levels following intrauterine insemination (IUI. Materials and Methods: Forty-two patients aged 31 ± 4.65 years (mean ± SD with primary infertility selected for IUI. All of them had induced ovulation with clomiphene citrate 50 mg from day 2 to day 6. After taking the consent, 2 ml of blood was withdrawn before and after 24 h of IUI for biochemical estimations. Results: We observed a significant decrease in plasma CP, PT and RBC AChE ( P < 0.001 following IUI compared with the respective pre-procedure levels. Highly sensitive CRP showed a marginal increase after IUI. Conclusion: Fluctuations in levels of the above parameters point to their role in the female reproductive system and in the outcome of the IUI.

  19. Study of p53 protein expression levels from irradiated peripheral blood lymphocytes for biodosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Cavalcanti, M.B.; Fernandes, T.S. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Amaral, A. [Universite Paris XII (UPXII) (France); Melo, J.A. [Centro de Radioterapia de Pernambuco (CERAPE), PE (Brazil); Neves, M.A.B.; Machado, C.G.F, E-mail: maribrayner@yahoo.com.br [Fundacao de Hematologia e Hemoterapia de Pernambuco, PE (Brazil)

    2005-07-01

    Biodosimetry can be defined as the investigation of radioinduced biological effects in order to correlate them with the absorbed dose. Scoring of unstable chromosomal aberrations and micronuclei, from in vitro irradiated peripheral blood lymphocytes, is commonly used for biodosimetry based on cytogenetic analysis. However, this method of analysis is time-consuming, which may represent a pitfall when fast investigation of a possible exposure to ionizing radiation (IR) is needed. The interaction of IR with the living cell can cause injuries in the DNA molecules. However, normal cells possess mechanisms of repair that are capable to correct those damages. During the repair process of the DNA various proteins are expressed. Among these proteins, p53 plays an important role. This protein is a transcription factor that helps in the maintenance of the genomic integrity. p53 protein is found into the cytoplasm in reduced concentrations and has a short average life. However, expression of p53 protein can be induced by DNA harmful radioinduced, which increases the concentration and the average life of this protein, making possible its detection. Thus, the correlation between the increasing of p53 expression and the irradiation may constitute a fast and reliable method of individual monitoring in cases of accidental or suspected exposures to IR. In this context, the objective of this research was to evaluate the p53 protein expression levels from lymphocytes of the human peripheral blood after in vitro irradiation. For this, samples of peripheral blood from healthy individuals were irradiated with known doses. Lymphocytes were separated on ficoll gradient by centrifugation and re-suspended at 1x 10{sub 6}/mL in RPMI medium enriched with fetal calf serum. Hence, lymphocytes were incubated in 5% CO{sub 2} at 37 deg C prior to the methodology of flow cytometry, using intranuclear antigens for the quantification of p53. In this report, the methodology performed and the results

  20. NMR contributions to structural dynamics studies of intrinsically disordered proteins

    OpenAIRE

    Konrat, Robert

    2014-01-01

    Intrinsically disordered proteins (IDPs) are characterized by substantial conformational plasticity. Given their inherent structural flexibility X-ray crystallography is not applicable to study these proteins. In contrast, NMR spectroscopy offers unique opportunities for structural and dynamic studies of IDPs. The past two decades have witnessed significant development of NMR spectroscopy that couples advances in spin physics and chemistry with a broad range of applications. This article will...

  1. In Silico Analysis of Correlations between Protein Disorder and Post-Translational Modifications in Algae

    OpenAIRE

    Atsushi Kurotani; Tetsuya Sakurai

    2015-01-01

    Recent proteome analyses have reported that intrinsically disordered regions (IDRs) of proteins play important roles in biological processes. In higher plants whose genomes have been sequenced, the correlation between IDRs and post-translational modifications (PTMs) has been reported. The genomes of various eukaryotic algae as common ancestors of plants have also been sequenced. However, no analysis of the relationship to protein properties such as structure and PTMs in algae has been reporte...

  2. The Specificity of Controlled Protein Disorder in the Photoprotection of Plants

    OpenAIRE

    Krüger, Tjaart P.J.; Ilioaia, Cristian; Johnson, Matthew P.; Belgio, Erica; Horton, Peter; Ruban, Alexander V.; van Grondelle, Rienk

    2013-01-01

    Light-harvesting pigment-protein complexes of photosystem II of plants have a dual function: they efficiently use absorbed energy for photosynthesis at limiting sunlight intensity and dissipate the excess energy at saturating intensity for photoprotection. Recent single-molecule spectroscopy studies on the trimeric LHCII complex showed that environmental control of the intrinsic protein disorder could in principle explain the switch between their light-harvesting and photoprotective conformat...

  3. Pharmaceutical protein production by yeast: towards production of human blood proteins by microbial fermentation

    OpenAIRE

    Martínez, José L.; Liu, Lifang; Petranovic, Dina; Nielsen, Jens

    2012-01-01

    Since the approval of recombinant insulin from Escherichia coli for its clinical use in the early 1980s, the amount of recombinant pharmaceutical proteins obtained by microbial fermentations has significantly increased. The recent advances in genomics together with high throughput analysis techniques (the so-called - omics approaches) and integrative approaches (systems biology) allow the development of novel microbial cell factories as valuable platforms for large scale production of therape...

  4. Regional blood flow in rats after a single low-protein, high-carbohydrate test meal.

    Science.gov (United States)

    Glick, Z; Wickler, S J; Stern, J S; Horwitz, B A

    1984-07-01

    It was previously observed that a single low-protein, high-carbohydrate test meal results in increased in vitro thermic activity of brown adipose tissue. In the present study, we have examined whether such a meal increases the in vivo thermic activity, estimated from measurement of the rate of blood flow. With radioactively labeled microspheres, blood flows into brown fat and several other tissues were determined in meal-deprived (n = 11) and meal-fed (n = 11) rats. The microspheres were injected into the heart of anesthetized animals about 2-2.5 h after the test meal, one injection in the resting state and one during maximal norepinephrine stimulation. In the resting state, blood flow per gram tissue more than doubled in the brown fat (P less than 0.05) and was increased more than 50% in the heart (P less than 0.01) of the fed group. Blood flows into liver and retroperitoneal white fat were reduced by 40 (P less than 0.01) and 30%, respectively, in the fed group. During norepinephrine infusion, significant meal-associated increases in blood flow were evident only in brown fat (P less than 0.05) and the soleus muscle (P less than 0.05), whereas a significant decrease was observed in the liver (P less than 0.05). No statistically significant meal-associated changes in norepinephrine-stimulated blood flow were found in the other tissues examined (i.e., heart, gastrocnemius, and diaphragm muscles, kidneys, white fat, spleen, and adrenals). Our in vivo data thus support the view that brown fat plays a role in the thermic effect of a meal. PMID:6742226

  5. Biophysical Methods to Investigate Intrinsically Disordered Proteins: Avoiding an "Elephant and Blind Men" Situation.

    Science.gov (United States)

    Uversky, Vladimir N

    2015-01-01

    Intrinsically disordered proteins (IDPs) and hybrid proteins possessing ordered domains and intrinsically disordered protein regions (IDPRs) are highly abundant in various proteomes. They are different from ordered proteins at many levels, and an unambiguous representation of an IDP structure is a difficult task. In fact, IDPs show an extremely wide diversity in their structural properties, being able to attain extended conformations (random coil-like) or to remain globally collapsed (molten globule-like). Disorder can differently affect different parts of a protein, with some regions being more ordered than others. IDPs and IDPRs exist as dynamic ensembles, resembling "protein-clouds". IDP structures are best presented as conformational ensembles that contain highly dynamic structures interconverting on a number of timescales. The determination of a unique high-resolution structure is not possible for an isolated IDP, and a detailed structural and dynamic characterization of IDPs cannot typically be provided by a single tool. Therefore, accurate descriptions of IDPs/IDPRs rely on a multiparametric approach that includes a host of biophysical methods that can provide information on the overall compactness of IDPs and their conformational stability, shape, residual secondary structure, transient long-range contacts, regions of restricted or enhanced mobility, etc. The goal of this chapter is to provide a brief overview of some of the components of this multiparametric approach. PMID:26387104

  6. DisPredict: A Predictor of Disordered Protein Using Optimized RBF Kernel

    Science.gov (United States)

    Iqbal, Sumaiya; Hoque, Md Tamjidul

    2015-01-01

    Intrinsically disordered proteins or, regions perform important biological functions through their dynamic conformations during binding. Thus accurate identification of these disordered regions have significant implications in proper annotation of function, induced fold prediction and drug design to combat critical diseases. We introduce DisPredict, a disorder predictor that employs a single support vector machine with RBF kernel and novel features for reliable characterization of protein structure. DisPredict yields effective performance. In addition to 10-fold cross validation, training and testing of DisPredict was conducted with independent test datasets. The results were consistent with both the training and test error minimal. The use of multiple data sources, makes the predictor generic. The datasets used in developing the model include disordered regions of various length which are categorized as short and long having different compositions, different types of disorder, ranging from fully to partially disordered regions as well as completely ordered regions. Through comparison with other state of the art approaches and case studies, DisPredict is found to be a useful tool with competitive performance. DisPredict is available at https://github.com/tamjidul/DisPredict_v1.0. PMID:26517719

  7. Postpartum Blood Clots

    Science.gov (United States)

    ... Infection Postpartum Blood Clots Postpartum Thyroid Disorders Postpartum Depression The risk of developing blood clots (thrombophlebitis) is increased for about 6 to 8 weeks after delivery (see Thromboembolic Disorders During Pregnancy ). Typically, blood clots occur in the deep veins ...

  8. High dimensional and high resolution pulse sequences for backbone resonance assignment of intrinsically disordered proteins

    Czech Academy of Sciences Publication Activity Database

    Zawadzka-Kazimierczuk, A.; Kozminski, W.; Šanderová, Hana; Krásný, Libor

    2012-01-01

    Roč. 52, č. 4 (2012), s. 329-337. ISSN 0925-2738 R&D Projects: GA ČR GA204/09/0583 Institutional research plan: CEZ:AV0Z50200510 Keywords : Intrinsically disordered proteins * Non-uniform sampling * Backbone assignment Subject RIV: EE - Microbiology, Virology Impact factor: 2.845, year: 2012

  9. Using NMR chemical shifts to calculate the propensity for structural order and disorder in proteins

    NARCIS (Netherlands)

    Tamiola, Kamil; Mulder, Frans A. A.

    2012-01-01

    NMR spectroscopy offers the unique possibility to relate the structural propensities of disordered proteins and loop segments of folded peptides to biological function and aggregation behaviour. Backbone chemical shifts are ideally suited for this task, provided that appropriate reference data are a

  10. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers

    Science.gov (United States)

    Quiroz, Felipe García; Chilkoti, Ashutosh

    2015-11-01

    Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level.

  11. Disorders of the colloid-osmotic blood condition and methods of their correction during angiography in children

    International Nuclear Information System (INIS)

    Results of angiography complication frequency reduction via patient preparation for osmotic stress (that is, introduction of radiopaque media bolus) are presented in the paper. Examination of children aged 5 monthes up to 14 years subjected to angiography under general anestesia has shown that during children preparation for angiography the specific infusion therapy corrects initial colloid-osmotic disorder in blood plasma and prevents action of hyperosmolalic radiopaque media. Occurance of critical values of hyperosmolality and hypooncia is not observed in contrast to control experiments, and it prevents development of some complications

  12. Relationship between changes in the cochlear blood flow and disorder of hearing function induced by blast injury in guinea pigs

    OpenAIRE

    Chen, Wei; Wang, Jianmin; Chen, Jing; Chen, Jichuan; Chen, Zhiqiang

    2013-01-01

    The auditory system is the most susceptible to damages from blast waves. Blast injuries always lead to varying degrees of hearing impairment. Although a disorder of the cochlear blood flow (CoBF) has been considered to be related to many pathological processes of the auditory system and to contribute to various types of hearing loss, changes in the CoBF induced by blast waves and the relationship between such changes and hearing impairment are undefined. To observe the changes in the cochlear...

  13. Blood serum components and serum protein test of Hybro-PG broilers of different ages

    Directory of Open Access Journals (Sweden)

    PRL Silva

    2007-12-01

    Full Text Available Blood serum samples of HYBRO PG broilers were analyzed, with 30 samples collected from 21-day-old broilers (G1, 30 from 35-day-old birds (G2, and 30 from 42-day-old birds (G3, with the aim of establishing normal values of some blood serum parameters. The activities of the enzymes gamma-glutamyl-transferase (GGT, aspartate aminotransferase (AST, creatine kinase (CK, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH, serum levels of total calcium, calcium ion, phosphorus, sodium, potassium, magnesium, chlorides, creatinine, uric acid, triglycerides, cholesterol, total protein, albumin, total and indirect and direct bilirubin, and electrophoretic profile of serum proteins in acrylamide (SDS-PAGE and agarose gel were determined. There was no influence of age on total bilirubin and albumin levels. All the other evaluated parameters presented differences in at least one age group. Protein electrophoretic profile also changed as a function of age. The obtained results can be considered as normal for the studied ages, and therefore be used as references for the interpretation of laboratory exams of broilers of this genetic line in the evaluated ages.

  14. Cord blood CD4+ T cells respond to self heat shock protein 60 (HSP60.

    Directory of Open Access Journals (Sweden)

    Joost A Aalberse

    Full Text Available BACKGROUND: To prevent harmful autoimmunity most immune responses to self proteins are controlled by central and peripheral tolerance. T cells specific for a limited set of self-proteins such as human heat shock protein 60 (HSP60 may contribute to peripheral tolerance. It is not known whether HSP60-specific T cells are present at birth and thus may play a role in neonatal tolerance. We studied whether self-HSP60 reactive T cells are present in cord blood, and if so, what phenotype these cells have. METHODOLOGY/PRINCIPAL FINDINGS: Cord blood mononuclear cells (CBMC of healthy, full term neonates (n = 21, were cultured with HSP60 and Tetanus Toxoid (TT to study antigen specific proliferation, cytokine secretion and up-regulation of surface markers. The functional capacity of HSP60-induced T cells was determined with in vitro suppression assays. Stimulation of CBMC with HSP60 led to CD4(+ T cell proliferation and the production of various cytokines, most notably IL-10, Interferon-gamma, and IL-6. HSP60-induced T cells expressed FOXP3 and suppressed effector T cell responses in vitro. CONCLUSION: Self-reactive HSP60 specific T cells are already present at birth. Upon stimulation with self-HSP60 these cells proliferate, produce cytokines and express FOXP3. These cells function as suppressor cells in vitro and thus they may be involved in the regulation of neonatal immune responses.

  15. Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria.

    Science.gov (United States)

    Beeson, James G; Drew, Damien R; Boyle, Michelle J; Feng, Gaoqian; Fowkes, Freya J I; Richards, Jack S

    2016-05-01

    Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities. PMID:26833236

  16. Proteins with Intrinsically Disordered Domains Are Preferentially Recruited to Polyglutamine Aggregates.

    Directory of Open Access Journals (Sweden)

    Maggie P Wear

    Full Text Available Intracellular protein aggregation is the hallmark of several neurodegenerative diseases. Aggregates formed by polyglutamine (polyQ-expanded proteins, such as Huntingtin, adopt amyloid-like structures that are resistant to denaturation. We used a novel purification strategy to isolate aggregates formed by human Huntingtin N-terminal fragments with expanded polyQ tracts from both yeast and mammalian (PC-12 cells. Using mass spectrometry we identified the protein species that are trapped within these polyQ aggregates. We found that proteins with very long intrinsically-disordered (ID domains (≥ 100 amino acids and RNA-binding proteins were disproportionately recruited into aggregates. The removal of the ID domains from selected proteins was sufficient to eliminate their recruitment into polyQ aggregates. We also observed that several neurodegenerative disease-linked proteins were reproducibly trapped within the polyQ aggregates purified from mammalian cells. Many of these proteins have large ID domains and are found in neuronal inclusions in their respective diseases. Our study indicates that neurodegenerative disease-associated proteins are particularly vulnerable to recruitment into polyQ aggregates via their ID domains. Also, the high frequency of ID domains in RNA-binding proteins may explain why RNA-binding proteins are frequently found in pathological inclusions in various neurodegenerative diseases.

  17. Gene Prioritization by Integrated Analysis of Protein Structural and Network Topological Properties for the Protein-Protein Interaction Network of Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Yashna Paul

    2016-01-01

    Full Text Available Neurological disorders are known to show similar phenotypic manifestations like anxiety, depression, and cognitive impairment. There is a need to identify shared genetic markers and molecular pathways in these diseases, which lead to such comorbid conditions. Our study aims to prioritize novel genetic markers that might increase the susceptibility of patients affected with one neurological disorder to other diseases with similar manifestations. Identification of pathways involving common candidate markers will help in the development of improved diagnosis and treatments strategies for patients affected with neurological disorders. This systems biology study for the first time integratively uses 3D-structural protein interface descriptors and network topological properties that characterize proteins in a neurological protein interaction network, to aid the identification of genes that are previously not known to be shared between these diseases. Results of protein prioritization by machine learning have identified known as well as new genetic markers which might have direct or indirect involvement in several neurological disorders. Important gene hubs have also been identified that provide an evidence for shared molecular pathways in the neurological disease network.

  18. Correlating Flavivirus virulence and levels of intrinsic disorder in shell proteins: protective roles vs. immune evasion.

    Science.gov (United States)

    Goh, Gerard Kian-Meng; Dunker, A Keith; Uversky, Vladimir N

    2016-05-24

    Computational analyses revealed correlations between the intrinsic disorder propensity of shell proteins and case fatality rates (CFRs) among Flaviviruses and within at least two Flavivirus species, such as tick-borne encephalitis virus (TBEV) and dengue virus (DENV). The shell proteins analyzed in this study are capsid (C) and membrane (PrM, Pr, and M) proteins. The highest correlations can be found when regression analyses were conducted using Pr (Flavivirus: r(2) = 0.78, p fever virus (YFV), which is the most virulent virus in the sample, has the highest PID levels, whereas the second most virulent TBEV FE subtype has the second highest PID score due to its C protein, and the least virulent West Nile virus (WNV) has the least disordered C protein. This knowledge can be used while working on the development and identification of attenuated strains for vaccine. Curiously, unlike Flaviviruses, a disordered outer shell was described for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human simplex virus 2 (HSV-2), which currently have no effective vaccine. PMID:27102744

  19. Personalized liposome-protein corona in the blood of breast, gastric and pancreatic cancer patients.

    Science.gov (United States)

    Colapicchioni, Valentina; Tilio, Martina; Digiacomo, Luca; Gambini, Valentina; Palchetti, Sara; Marchini, Cristina; Pozzi, Daniela; Occhipinti, Sergio; Amici, Augusto; Caracciolo, Giulio

    2016-06-01

    When nanoparticles (NPs) are dispersed in a biofluid, they are covered by a protein corona the composition of which strongly depends on the protein source. Recent studies demonstrated that the type of disease has a crucial role in the protein composition of the NP corona with relevant implications on personalized medicine. Proteomic variations frequently occur in cancer with the consequence that the bio-identity of NPs in the blood of cancer patients may differ from that acquired after administration to healthy volunteers. In this study we investigated the correlation between alterations of plasma proteins in breast, gastric and pancreatic cancer and the biological identity of clinically approved AmBisome-like liposomes as determined by a combination of dynamic light scattering, zeta potential analysis, one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) and semi-quantitative densitometry. While size of liposome-protein complexes was not significantly different between cancer groups, the hard corona from pancreatic cancer patients was significantly less negatively charged. Of note, the hard corona from pancreatic cancer patients was more enriched than those of other cancer types this enrichment being most likely due to IgA and IgG with possible correlations with the autoantibodies productions in cancer. Given the strict relationship between tumor antigen-specific autoantibodies and early cancer detection, our results could be the basis for the development of novel nanoparticle-corona-based screening tests of cancer. PMID:26369869

  20. Disorder in Milk Proteins: Formation, Structure, Function, Isolation and Applications of Casein Phosphopeptides.

    Science.gov (United States)

    Naqvi, Muhammad Ali; Irani, Kimia Anaraki; Katanishooshtari, Maryam; Rousseau, Dérick

    2016-01-01

    This article is a continuation of a series of reviews on the presence and the role of intrinsic disorder in milk proteins in the journal of Current Protein and Peptide Science. The focus of this article is on casein phosphopeptides, which are liberated during digestion of the milk protein casein. Structurally these phosphopeptides have multiphosphorylated regions making them highly charged. The high degree of charge coupled with relatively low instances of hydrophobic amino acids makes them intrinsically disordered. These peptides have anticariogenic, antimicrobial, immunomodulatory, and cytomodulatory properties. Recent work using in vivo and in vitro models suggests that in addition to transporting calcium, these peptides can also enhance its bioaccessibility. The mechanism of this enhancement has yet to be determined. We review the current state of their structure, function, and isolation of these peptides. PMID:26630980

  1. Effect of source and sex on blood protein fractions of West African Dwarf Goats (WADG

    Directory of Open Access Journals (Sweden)

    J. C. Okonkwo,

    2011-03-01

    Full Text Available Source and sex effects on the total blood protein and its various fractions were studied using juvenile West African Dwarf goats derived from Southern Nigeria. The goats were sourced from three distinct towns in the humid tropics namely, South-East (Umuahia, South-South (Ugheli and South-West (Akure at the rate of 6 males and 18 females per location. The mean values of the total blood plasma protein and its fractions obtained for the WADGs from different zones are 10.01±0.07 g/100ml, 10.07±0.08 g/100ml and 10.16±0.35 g/100ml (total plasma protein; 9.62±0.10 g/100ml, 9.68±0.08 g/100ml and 9.68±0.09 g/100ml (total serum protein, 0.38±0.03 g/100ml, 0.39±0.01 g/100ml, and 0.38±0.04 g/100ml (plasma fibrinogen, 5.62±0.23 g/100ml, 5.78±0.24 g/100ml and 5.45±0.26 g/100ml (serum albumin, 4.00±0.19 g/100ml, 3.89±0.29 g/100ml, and 4.12±0.25 g/100ml (serum globulin, and 1.41±0.27, 1.49±0.15 and 1.34±0.12 (albumin/globulin ratio for the goats from South-East (Umuahia, South-South (Ugheli and South-West (Akure respectively. The studies also indicate that albumin accounts for 53-58% of the total serum protein; globulin accounts for 42-47% serum protein, and the plasma fibrinogen 3.6-4% of the total plasma protein. sex and source interaction had no significant (P>0.05 effects on serum proteins; plasma fibrinogen is sex dependent, and the source of goat affects the proportions of the serum albumin, globulin, and albumin/globulin ratio characteristics of the experimental goats.

  2. Mapping the potential energy landscape of intrinsically disordered proteins at amino acid resolution.

    Science.gov (United States)

    Ozenne, Valéry; Schneider, Robert; Yao, Mingxi; Huang, Jie-rong; Salmon, Loïc; Zweckstetter, Markus; Jensen, Malene Ringkjøbing; Blackledge, Martin

    2012-09-12

    Intrinsically disordered regions are predicted to exist in a significant fraction of proteins encoded in eukaryotic genomes. The high levels of conformational plasticity of this class of proteins endows them with unique capacities to act in functional modes not achievable by folded proteins, but also places their molecular characterization beyond the reach of classical structural biology. New techniques are therefore required to understand the relationship between primary sequence and biological function in this class of proteins. Although dependences of some NMR parameters such as chemical shifts (CSs) or residual dipolar couplings (RDCs) on structural propensity are known, so that sampling regimes are often inferred from experimental observation, there is currently no framework that allows for a statistical mapping of the available Ramachandran space of each amino acid in terms of conformational propensity. In this study we develop such an approach, combining highly efficient conformational sampling with ensemble selection to map the backbone conformational sampling of IDPs on a residue specific level. By systematically analyzing the ability of NMR data to map the conformational landscape of disordered proteins, we identify combinations of RDCs and CSs that can be used to raise conformational degeneracies inherent to different data types, and apply these approaches to characterize the conformational behavior of two intrinsically disordered proteins, the K18 domain from Tau protein and N(TAIL) from measles virus nucleoprotein. In both cases, we identify the enhanced populations of turn and helical regions in key regions of the proteins, as well as contiguous strands that show clear and enhanced polyproline II sampling. PMID:22901047

  3. Acute responses of muscle protein metabolism to reduced blood flow reflect metabolic priorities for homeostasis.

    Science.gov (United States)

    Zhang, Xiao-Jun; Irtun, Oivind; Chinkes, David L; Wolfe, Robert R

    2008-03-01

    The present experiment was designed to measure the synthetic and breakdown rates of muscle protein in the hindlimb of rabbits with or without clamping the femoral artery. l-[ring-(13)C(6)]phenylalanine was infused as a tracer for measurement of muscle protein kinetics by means of an arteriovenous model, tracer incorporation, and tracee release methods. The ultrasonic flowmeter, dye dilution, and microsphere methods were used to determine the flow rates in the femoral artery, in the leg, and in muscle capillary, respectively. The femoral artery flow accounted for 65% of leg flow. A 50% reduction in the femoral artery flow reduced leg flow by 28% and nutritive flow by 26%, which did not change protein synthetic or breakdown rate in leg muscle. Full clamp of the femoral artery reduced leg flow by 42% and nutritive flow by 59%, which decreased (P < 0.05) both the fractional synthetic rate from 0.19 +/- 0.05 to 0.14 +/- 0.03%/day and fractional breakdown rate from 0.28 +/- 0.07 to 0.23 +/- 0.09%/day of muscle protein. Neither the partial nor full clamp reduced (P = 0.27-0.39) the intracellular phenylalanine concentration or net protein balance in leg muscle. We conclude that the flow threshold to cause a fall of protein turnover rate in leg muscle was a reduction of 30-40% of the leg flow. The acute responses of muscle protein kinetics to the reductions in blood flow reflected the metabolic priorities to maintain muscle homeostasis. These findings cannot be extrapolated to more chronic conditions without experimental validation. PMID:18089763

  4. Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins

    International Nuclear Information System (INIS)

    There has been a longstanding interest in being able to accurately predict NMR chemical shifts from structural data. Recent studies have focused on using molecular dynamics (MD) simulation data as input for improved prediction. Here we examine the accuracy of chemical shift prediction for intein systems, which have regions of intrinsic disorder. We find that using MD simulation data as input for chemical shift prediction does not consistently improve prediction accuracy over use of a static X-ray crystal structure. This appears to result from the complex conformational ensemble of the disordered protein segments. We show that using accelerated molecular dynamics (aMD) simulations improves chemical shift prediction, suggesting that methods which better sample the conformational ensemble like aMD are more appropriate tools for use in chemical shift prediction for proteins with disordered regions. Moreover, our study suggests that data accurately reflecting protein dynamics must be used as input for chemical shift prediction in order to correctly predict chemical shifts in systems with disorder

  5. A Novel Method of Predicting Protein Disordered Regions Based on Sequence Features

    Directory of Open Access Journals (Sweden)

    Tong-Hui Zhao

    2013-01-01

    Full Text Available With a large number of disordered proteins and their important functions discovered, it is highly desired to develop effective methods to computationally predict protein disordered regions. In this study, based on Random Forest (RF, Maximum Relevancy Minimum Redundancy (mRMR, and Incremental Feature Selection (IFS, we developed a new method to predict disordered regions in proteins. The mRMR criterion was used to rank the importance of all candidate features. Finally, top 128 features were selected from the ranked feature list to build the optimal model, including 92 Position Specific Scoring Matrix (PSSM conservation score features and 36 secondary structure features. As a result, Matthews correlation coefficient (MCC of 0.3895 was achieved on the training set by 10-fold cross-validation. On the basis of predicting results for each query sequence by using the method, we used the scanning and modification strategy to improve the performance. The accuracy (ACC and MCC were increased by 4% and almost 0.2%, respectively, compared with other three popular predictors: DISOPRED, DISOclust, and OnD-CRF. The selected features may shed some light on the understanding of the formation mechanism of disordered structures, providing guidelines for experimental validation.

  6. The change and significance of platelet parameters and blood coagulation function index in patients with hypertensive disorder complicating pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yu-Xia Shi; Yi-Xin Yang; Qian Xu; Yanhua Zhu

    2015-01-01

    Objective:To explore the change and significance of platelet parameters and blood coagulation function index in patients with hypertensive disorder complicating pregnancy.Methods: Chose 89 patients with HDCP, they were set as HDCP group, chose another 60 cases health late pregnancy women and 42 cases non pregnant female, they were set as late pregnant group and non-pregnant control group, detected the platelet parameters: the average blood platelet count (PLT), platelet volume (MPV), platelet distribution width (PDW) and blood coagulation indexes, plasma prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), D-dimer (D-D), activated partial blood coagulation time (APTT) live enzymes in three groups.Results: (1) Compared with the non-pregnant group and late pregnant group, PLT was significantly lower, while the MPV and PDW were significantly higher in HDCP group; PLT in late pregnant group was significantly lower than that in non-pregnant group, and there were no significantly difference of MPV and PDW in the two groups; (2) Compared with the non-pregnant group and late pregnant group, PT and APTT levels were significantly lower, while FIB and D-D were significantly higher in HDCP group; The level of PT and APTT in late pregnant group were significantly lower, and FIB and D-D levels were significantly higher than that in non-pregnant group, However, The level of TT were no statistical significance difference among the three groups.Conclusion: HDCP existence phenomenon of platelet activation and apparent high coagulation state, dynamic detection of HDCP patients platelet parameters and blood coagulation indexes to prevent related complications, improve obstetrics safety is of great significance.

  7. Vegetarian diet components, protein and blood pressure: which nutrients are important?

    Science.gov (United States)

    Beilin, L J; Burke, V

    1995-03-01

    1. Evidence that vegetarian dietary patterns lower blood pressure (BP) comes from both population studies and randomized controlled trials in normotensive and hypertensive subjects. 2. The effect has been shown most clearly in those who keep to a strict lacto-ovo vegetarian diet characterized by a relatively low intake of saturated fat, a high polyunsaturated/saturated fat ratio, and a high intake of fruit, vegetables and other fibre containing products. Randomized controlled dietary trials suggest the effects are independent of dietary sodium, additive to that of calorie restriction, and not due to the absence of meat protein per se. Indeed, recent population studies suggest an inverse relationship between dietary protein and BP. 4. Dietary fats, fibre, potassium, magnesium and calcium do not independently seem to account for the effects. A possible role for complex carbohydrate in conjunction with the other dietary factors has yet to be fully explored. PMID:7554413

  8. Prediction of Spontaneous Protein Deamidation from Sequence-Derived Secondary Structure and Intrinsic Disorder.

    Directory of Open Access Journals (Sweden)

    J Ramiro Lorenzo

    Full Text Available Asparagine residues in proteins undergo spontaneous deamidation, a post-translational modification that may act as a molecular clock for the regulation of protein function and turnover. Asparagine deamidation is modulated by protein local sequence, secondary structure and hydrogen bonding. We present NGOME, an algorithm able to predict non-enzymatic deamidation of internal asparagine residues in proteins in the absence of structural data, using sequence-based predictions of secondary structure and intrinsic disorder. Compared to previous algorithms, NGOME does not require three-dimensional structures yet yields better predictions than available sequence-only methods. Four case studies of specific proteins show how NGOME may help the user identify deamidation-prone asparagine residues, often related to protein gain of function, protein degradation or protein misfolding in pathological processes. A fifth case study applies NGOME at a proteomic scale and unveils a correlation between asparagine deamidation and protein degradation in yeast. NGOME is freely available as a webserver at the National EMBnet node Argentina, URL: http://www.embnet.qb.fcen.uba.ar/ in the subpage "Protein and nucleic acid structure and sequence analysis".

  9. Coagulation Factor and Hemostatic Protein Content of Canine Plasma after Storage of Whole Blood at Ambient Temperature

    OpenAIRE

    Walton, J.E.; Hale, A. S.; Brooks, M. B.; Boag, A.K.; Barnett, W.; Dean, R.

    2014-01-01

    Background Standard practice in canine blood banking is to produce fresh frozen plasma (FFP) by separating and freezing plasma produced from blood within 8 hours of collection. Within canine blood donation programs, this can limit the number of units collected. Hypothesis/Objectives The aim was to compare the coagulation factor and hemostatic protein content (CF&HPC) of plasma produced from blood stored at ambient temperature for 8, 12, and 24 hours. Another aim was to compare the CF&HPC betw...

  10. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, L; Vinberg, M;

    2015-01-01

    40 age- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with...... healthy control subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the...

  11. Interplay between Chaperones and Protein Disorder Promotes the Evolution of Protein Networks

    OpenAIRE

    Sebastian Pechmann; Judith Frydman

    2014-01-01

    Evolution is driven by mutations, which lead to new protein functions but come at a cost to protein stability. Non-conservative substitutions are of interest in this regard because they may most profoundly affect both function and stability. Accordingly, organisms must balance the benefit of accepting advantageous substitutions with the possible cost of deleterious effects on protein folding and stability. We here examine factors that systematically promote non-conservative mutations at the p...

  12. Expression of P53(v) protein of peripheral blood in patients with tumor and its relation with age

    International Nuclear Information System (INIS)

    To study the expression of P53(v) protein of peripheral blood monocytes in cancer patients and its relation with age, P53(v) proteins were determined in 88 cancer patients and 88 normals by flow cytometry. The levels of P53(v) were (7.76 +- 7.13)% in cancer group and (0.66 +- 0.5)% in normal group. Mean value of P53(v) in the cancers was higher than that in the controls (P<0.01). The expression of P53(v) of peripheral blood raised with age. Conclusion: P53(v) proteins can be detected in peripheral blood monocytes. The detection of P53 expression in human peripheral blood monocytes can be used to screen high risk population with tumor

  13. Child who presented with hematohidrosis (sweating blood) with oppositional defiant disorder

    OpenAIRE

    Deshpande, Manjiri; Indla, Vishal; Kumar, Varinder; Reddy, Indla Ramasubba

    2014-01-01

    Hematohidrosis is a very rare condition of sweating blood. A child's case who presented to us with hematohidrosis is reported. There are only few reports in the literature. A 10-year-old boy presented to our hospital with a history of repeated episodes of oozing of blood from navel, eyes, ear lobules, and nose. During the examination, it disappeared as soon as it was mopped leaving behind no sign of trauma only to reappear within a few seconds. Bleeding time, clotting time, and prothrombin ti...

  14. Effects of molecular crowding on the dynamics of intrinsically disordered proteins.

    Directory of Open Access Journals (Sweden)

    Elio A Cino

    Full Text Available Inside cells, the concentration of macromolecules can reach up to 400 g/L. In such crowded environments, proteins are expected to behave differently than in vitro. It has been shown that the stability and the folding rate of a globular protein can be altered by the excluded volume effect produced by a high density of macromolecules. However, macromolecular crowding effects on intrinsically disordered proteins (IDPs are less explored. These proteins can be extremely dynamic and potentially sample a wide ensemble of conformations under non-denaturing conditions. The dynamic properties of IDPs are intimately related to the timescale of conformational exchange within the ensemble, which govern target recognition and how these proteins function. In this work, we investigated the macromolecular crowding effects on the dynamics of several IDPs by measuring the NMR spin relaxation parameters of three disordered proteins (ProTα, TC1, and α-synuclein with different extents of residual structures. To aid the interpretation of experimental results, we also performed an MD simulation of ProTα. Based on the MD analysis, a simple model to correlate the observed changes in relaxation rates to the alteration in protein motions under crowding conditions was proposed. Our results show that 1 IDPs remain at least partially disordered despite the presence of high concentration of other macromolecules, 2 the crowded environment has differential effects on the conformational propensity of distinct regions of an IDP, which may lead to selective stabilization of certain target-binding motifs, and 3 the segmental motions of IDPs on the nanosecond timescale are retained under crowded conditions. These findings strongly suggest that IDPs function as dynamic structural ensembles in cellular environments.

  15. Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles

    Science.gov (United States)

    Hadjidemetriou, Marilena; Al-Ahmady, Zahraa; Kostarelos, Kostas

    2016-03-01

    Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the `protein corona' and it is considered to be a determinant factor for the pharmacological, toxicological and therapeutic profile of NPs. Protein exposure time is thought to greatly influence the composition of protein corona, however the dynamics of protein interactions under realistic, in vivo conditions remain unexplored. The aim of this study was to quantitatively and qualitatively investigate the time evolution of in vivo protein corona, formed onto blood circulating, clinically used, PEGylated liposomal doxorubicin. Protein adsorption profiles were determined 10 min, 1 h and 3 h post-injection of liposomes into CD-1 mice. The results demonstrated that a complex protein corona was formed as early as 10 min post-injection. Even though the total amount of protein adsorbed did not significantly change over time, the fluctuation of protein abundances observed indicated highly dynamic protein binding kinetics.Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their interaction with the blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the `protein corona' and it is considered to be a determinant factor for the pharmacological, toxicological and therapeutic profile of NPs. Protein exposure time is thought to greatly influence the composition of protein corona, however the dynamics of protein interactions under realistic, in vivo conditions remain unexplored. The aim of this study was to quantitatively and qualitatively investigate the time evolution of in vivo protein corona, formed onto blood circulating, clinically used, PEGylated liposomal doxorubicin. Protein adsorption profiles were determined 10 min, 1 h and 3 h post

  16. Sequence- and Temperature-Dependent Properties of Unfolded and Disordered Proteins from Atomistic Simulations.

    Science.gov (United States)

    Zerze, Gül H; Best, Robert B; Mittal, Jeetain

    2015-11-19

    We use all-atom molecular simulation with explicit solvent to study the properties of selected intrinsically disordered proteins and unfolded states of foldable proteins, which include chain dimensions and shape, secondary structure propensity, solvent accessible surface area, and contact formation. We find that the qualitative scaling behavior of the chains matches expectations from theory under ambient conditions. In particular, unfolded globular proteins tend to be more collapsed under the same conditions than charged disordered sequences of the same length. However, inclusion of explicit solvent in addition naturally captures temperature-dependent solvation effects, which results in an initial collapse of the chains as temperature is increased, in qualitative agreement with experiment. There is a universal origin to the collapse, revealed in the change of hydration of individual residues as a function of temperature: namely, that the initial collapse is driven by unfavorable solvation free energy of individual residues, which in turn has a strong temperature dependence. We also observe that in unfolded globular proteins, increased temperature also initially favors formation of native-like (rather than non-native-like) structure. Our results help to establish how sequence encodes the degree of intrinsic disorder or order as well as its response to changes in environmental conditions. PMID:26498157

  17. Knr4: a disordered hub protein at the heart of fungal cell wall signalling.

    Science.gov (United States)

    Martin-Yken, Hélène; François, Jean Marie; Zerbib, Didier

    2016-09-01

    The most highly connected proteins in protein-protein interactions networks are called hubs; they generally connect signalling pathways. In Saccharomyces cerevisiae, Knr4 constitutes a connecting node between the two main signal transmission pathways involved in cell wall maintenance upon stress: the cell wall integrity and the calcium-calcineurin pathway. Knr4 is required to enable the cells to resist many cell wall-affecting stresses, and KNR4 gene deletion is synthetic lethal with the simultaneous deletion of numerous other genes involved in morphogenesis and cell wall biogenesis. Knr4 has been shown to engage in multiple physical interactions, an ability conferred by the intrinsic structural adaptability of major disordered regions present in the N-terminal and C-terminal parts of the protein. Taking all together, Knr4 is an intrinsically disordered hub protein. Available data from other fungi indicate the conservation of Knr4 homologs cellular function and localization at sites of polarized growth among fungal species, including pathogenic species. Because of their particular role in morphogenesis control and of their fungal specificity, these proteins could constitute interesting new pharmaceutical drug targets for antifungal combination therapy. PMID:27199081

  18. Disruption in the Blood-Brain Barrier: The Missing Link between Brain and Body Inflammation in Bipolar Disorder?

    Directory of Open Access Journals (Sweden)

    Jay P. Patel

    2015-01-01

    Full Text Available The blood-brain barrier (BBB regulates the transport of micro- and macromolecules between the peripheral blood and the central nervous system (CNS in order to maintain optimal levels of essential nutrients and neurotransmitters in the brain. In addition, the BBB plays a critical role protecting the CNS against neurotoxins. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer’s disease and multiple sclerosis. Considering the increasing role of inflammation and oxidative stress in the pathophysiology of bipolar disorder (BD, here we propose a novel model wherein transient or persistent disruption of BBB integrity is associated with decreased CNS protection and increased permeability of proinflammatory (e.g., cytokines, reactive oxygen species substances from the peripheral blood into the brain. These events would trigger the activation of microglial cells and promote localized damage to oligodendrocytes and the myelin sheath, ultimately compromising myelination and the integrity of neural circuits. The potential implications for research in this area and directions for future studies are discussed.

  19. Myeloperoxidase activity and the oxidized proteins in blood neutrophils of patients with pneumonia.

    Science.gov (United States)

    Muravlyova, Larissa; Molotov-Luchanskiy, Vilen; Bakirova, Ryszhan; Klyuyev, Dmitriy; Demidchik, Ludmila; Kolesnikova, Yevgeniya

    2014-10-01

    The main purpose of our investigation was to study myeloperoxidase activity and concentration of oxidized proteins in blood neutrophils of patients with ambulant pneumonia and secondary pneumonia which has arisen on a background of chronic obstructive pulmonary disease (COPD). Patients were divided into 2 groups. 17 patients with ambulant pneumonia moderate severity and respiratory insufficiency of grade 2 were included in the 1-st group. 20 COPD patients with secondary pneumonia moderate severity and with respiratory insufficiency of grade 2 were included in the 2-nd group. The control group consisted of 15 healthy subjects. The reactive protein carbonyl derivates, advanced oxidation protein products (AOPP) and myeloperoxidase activity were detected in neutrophils. In neutrophils of 1-st group patients the augmentation of reactive protein carbonyl derivates was observed in comparison with healthy ones. In neutrophils of 2-nd group patients the slight decrease of reactive protein carbonyl derivates was observed in comparison with healthy ones (by 17%). In neutrophils of 2-nd group patients the significant increasing AOPP in comparison with healthy ones (p <0.01) and 1 group patients (p <0.05) was fixed. Myeloperoxidase activity was higher in neutrophils of 1-th group patients in comparison with healthy ones. In neutrophils of 2-nd group patients myeloperoxidase activity was higher in comparison with the same of 1 group patients (by 67%, p <0.05). Our results showed the different direction of oxidized proteins formation neutrophils of patients with primary and secondary pneumonia. Besides that the varied degree of myeloperoxidase activity was fixed. Our results require more detailed understanding because they can reflect peculiar mechanisms of pneumonia development and determine the characteristics of their progression. PMID:26461373

  20. CARDIO-PRED: an in silico tool for predicting cardiovascular-disorder associated proteins.

    Science.gov (United States)

    Jain, Prerna; Thukral, Nitin; Gahlot, Lokesh Kumar; Hasija, Yasha

    2015-06-01

    Interactions between proteins largely govern cellular processes and this has led to numerous efforts culminating in enormous information related to the proteins, their interactions and the function which is determined by their interactions. The main concern of the present study is to present interface analysis of cardiovascular-disorder (CVD) related proteins to shed lights on details of interactions and to emphasize the importance of using structures in network studies. This study combines the network-centred approach with three dimensional studies to comprehend the fundamentals of biology. Interface properties were used as descriptors to classify the CVD associated proteins and non-CVD associated proteins. Machine learning algorithm was used to generate a classifier based on the training set which was then used to predict potential CVD related proteins from a set of polymorphic proteins which are not known to be involved in any disease. Among several classifying algorithms applied to generate models, best performance was achieved using Random Forest with an accuracy of 69.5 %. The tool named CARDIO-PRED, based on the prediction model is present at http://www.genomeinformatics.dce.edu/CARDIO-PRED/. The predicted CVD related proteins may not be the causing factor of particular disease but can be involved in pathways and reactions yet unknown to us thus permitting a more rational analysis of disease mechanism. Study of their interactions with other proteins can significantly improve our understanding of the molecular mechanism of diseases. PMID:25972989

  1. Blood glucose regulation mechanism in depressive disorder animal model during hyperglycemic states.

    Science.gov (United States)

    Lim, Su-Min; Park, Soo-Hyun; Sharma, Naveen; Kim, Sung-Su; Lee, Jae-Ryeong; Jung, Jun-Sub; Suh, Hong-Won

    2016-06-01

    Depression is more common among diabetes people than in the general population. In the present study, blood glucose change in depression animal model was characterized by various types of hyperglycemia models such as d-glucose-fed-, immobilization stress-, and drug-induced hyperglycemia models. First, the ICR mice were enforced into chronic restraint stress for 2h daily for 2 weeks to produce depression animal model. The animals were fed with d-glucose (2g/kg), forced into restraint stress for 30min, or administered with clonidine (5μg/5μl) supraspinally or spinally to produce hyperglycemia. The blood glucose level in depression group was down-regulated compared to that observed in the normal group in d-glucose-fed-, restraint stress-, and clonidine-induced hyperglycemia models. The up-regulated corticosterone level induced by d-glucose feeding or restraint stress was reduced in the depression group while the up-regulation of plasma corticosterone level is further elevated after i.t. or i.c.v. clonidine administration in the depression group. The up-regulated insulin level induced by d-glucose feeding or restraint stress was reduced in the depression group. On the other hand, blood corticosterone level in depression group was up-regulated compared to the normal group after i.t. or i.c.v. clonidine administration. Whereas the insulin level in depression group was not altered when mice were administered clonidine i.t. or i.c.v. Our results suggest that the blood glucose level in depression group is down-regulated compared to the normal group during d-glucose-fed-, immobilization stress-, and clonidine-induced hyperglycemia in mice. The down-regulation of the blood glucose level might be one of the important pathophysiologic changes in depression. PMID:27034116

  2. Observational and mechanistic links between C-reactive protein and blood pressure in elderly women.

    Science.gov (United States)

    Hosford-Donovan, Adrian; Nilsson, Andreas; Wåhlin-Larsson, Britta; Kadi, Fawzi

    2016-07-01

    It is hypothesized that chronic systemic inflammation contributes to the age-related decline in cardiovascular function. The aim of the present study was to combine an assessment of the relationship between the serum level of C-reactive protein (CRP) and systolic and diastolic blood pressure in 108 elderly women (65 and 70 years) with an in-vitro exploration of the effects of CRP on the proliferative and angiogenic potential of endothelial cells exposed to serum in elderly women. Based on the median CRP level in our population, LowCRP (CRP1.3mg/L) groups were identified. Body mass index, waist circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in the HighCRP group than in the LowCRP group (pCRP on SBP and DBP remained significant after adjustments for BMI and use of antihypertensive medication (pCRP on SPB was attenuated (p=0.062). We next evaluated the ability to form capillary tubes (angiogenesis assay) and the proliferation rate of endothelial cells exposed to the sera of elderly women. Increased serum CRP levels were associated with an increased doubling time of endothelial cells (R(2)=0.39; p<0.05) and decreased capillary tube length (R(2)=0.30; p<0.05), indicating a reduction in the proliferation rate of endothelial cells and angiogenic potential. In conclusion, chronic inflammation influences blood pressure in elderly women and compromises endothelial cell function, thus contributing to the age-related decline in vascular health. PMID:27180160

  3. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Housing Travel Information Government Concierge View all meetings Publications Blood Current Issue First Edition Abstracts Blood Advances ... reflect the most recent scientific research View all publications For Patients Blood Basics Blood Disorders Anemia Bleeding ...

  4. Limbic system associated membrane protein as a potential target for neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Eero eVasar

    2013-03-01

    Full Text Available The studies performed in laboratory animals and psychiatric patients suggest a possible role of limbic system associated membrane protein (LAMP in the mechanisms of psychiatric disorders. Stressful manipulations and genetic invalidation have revealed a role of the Lsamp gene in the regulation of anxiety in rodents. Besides that, Lsamp deficient mice display reduced aggressiveness and impaired adaptation in novel and stressful environments. The behavioural effects of amphetamine were blunted in genetically modified mice. Recent pharmacological and biochemical studies point towards altered function of GABA-, 5-hydroxytryptamine- and dopaminergic systems in Lsamp deficient mice. Moreover, we found an association between the gene polymorphisms of LSAMP and major depressive disorder. Patients suffering from major depressive disorder had significantly increased ratio between risk and protective haplotypes of the LSAMP gene compared to healthy volunteers. However, the impact of these haplotypes for the function of LAMP is not clear and remains to be elucidated in future studies.

  5. Biochemical and Functional Analysis of Two Plasmodium falciparum Blood-Stage 6-Cys Proteins: P12 and P41

    OpenAIRE

    Tana Taechalertpaisarn; Cecile Crosnier; S Josefin Bartholdson; Hodder, Anthony N.; Jenny Thompson; Bustamante, Leyla Y.; Wilson, Danny W.; Sanders, Paul R.; Wright, Gavin J.; Rayner, Julian C.; Cowman, Alan F.; Gilson, Paul R.; Crabb, Brendan S

    2012-01-01

    The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here...

  6. Elucidation of binding mechanism and identification of binding site for an anti HIV drug, stavudine on human blood proteins.

    Science.gov (United States)

    Sandhya, B; Hegde, Ashwini H; Seetharamappa, J

    2013-05-01

    The binding of stavudine (STV) to two human blood proteins [human hemoglobin (HHb) and human serum albumin (HSA)] was studied in vitro under simulated physiological conditions by spectroscopic methods viz., fluorescence, UV absorption, resonance light scattering, synchronous fluorescence, circular dichroism (CD) and three-dimensional fluorescence. The binding parameters of STV-blood protein were determined from fluorescence quenching studies. Stern-Volmer plots indicated the presence of static quenching mechanism in the interaction of STV with blood proteins. The values of n close to unity indicated that one molecule of STV bound to one molecule of blood protein. The binding process was found to be spontaneous. Analysis of thermodynamic parameters revealed the presence of hydrogen bond and van der Waals forces between protein and STV. Displacement experiments indicated the binding of STV to Sudlow's site I on HSA. Secondary structures of blood proteins have undergone changes upon interaction with STV as evident from the reduction of α-helices (from 46.11% in free HHb to 38.34% in STV-HHb, and from 66.44% in free HSA to 52.26% in STV-HSA). Further, the alterations in secondary structures of proteins in the presence of STV were confirmed by synchronous and 3D-fluorescence spectral data. The distance between the blood protein (donor) and acceptor (STV) was found to be 5.211 and 5.402 nm for STV-HHb and STV-HSA, respectively based on Föster's non-radiative energy transfer theory. Effect of some metal ions was also investigated. The fraction of STV bound to HSA was found to be 87.8%. PMID:23275205

  7. Different Types of the Coagulation Disorders in Hamadan and A Comparison of the ABO & Rh Blood Group Distribution in the Patients and the Control Group

    Directory of Open Access Journals (Sweden)

    H. Pour-Jafari

    2003-10-01

    Full Text Available Patients with hemophilia and thalassemia are two groups of hereditary disorders that, periodically, use blood and blood substances. The aims of the present study are determination of the frequencies of different types of coagulation disorders, and a comparison of the frequencies of ABO & Rh phenotypes among affected individuals with the control group (blood donors. The subject group were all affected persons were referred to hemophilia and thalassemia centers in Hamadan. Primary information was collected from their files, then were classified and analyzed. The control group were blood donors that were registered in Hamadan blood bank. Results showed that the different types of coagulation disorders in affected individuals referred to the Hemophilia and thalassemia centers during 1998 were Hemophilia A (61.96%, Hemophilia B (20.86%, Von Willbrand (5.52%, Platelet deficiency (4.91%, Factor XIII deficiency (3.68% and Factor VII deficiency (3.07%. In general, results showed that in population with Hemophilia A, frequencies of A and O blood types were statistically different with the blood donors. The lowest rate of negative Rh, was in the population with thalassemia. The sex ratio of the affected persons was also different with control group.

  8. Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.

    Directory of Open Access Journals (Sweden)

    Elio A Cino

    Full Text Available Intrinsically disordered proteins (IDPs are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2, with a common binding partner, Kelch-like ECH-associated protein 1(Keap1, are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.

  9. Mutations in the selenocysteine insertion sequence–binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans

    Science.gov (United States)

    Schoenmakers, Erik; Agostini, Maura; Mitchell, Catherine; Schoenmakers, Nadia; Papp, Laura; Rajanayagam, Odelia; Padidela, Raja; Ceron-Gutierrez, Lourdes; Doffinger, Rainer; Prevosto, Claudia; Luan, Jian’an; Montano, Sergio; Lu, Jun; Castanet, Mireille; Clemons, Nick; Groeneveld, Matthijs; Castets, Perrine; Karbaschi, Mahsa; Aitken, Sri; Dixon, Adrian; Williams, Jane; Campi, Irene; Blount, Margaret; Burton, Hannah; Muntoni, Francesco; O’Donovan, Dominic; Dean, Andrew; Warren, Anne; Brierley, Charlotte; Baguley, David; Guicheney, Pascale; Fitzgerald, Rebecca; Coles, Alasdair; Gaston, Hill; Todd, Pamela; Holmgren, Arne; Khanna, Kum Kum; Cooke, Marcus; Semple, Robert; Halsall, David; Wareham, Nicholas; Schwabe, John; Grasso, Lucia; Beck-Peccoz, Paolo; Ogunko, Arthur; Dattani, Mehul; Gurnell, Mark; Chatterjee, Krishna

    2010-01-01

    Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence–binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of the latter stages of spermatogenesis, was associated with a lack of testis-enriched selenoproteins. An axial muscular dystrophy was also present, with features similar to myopathies caused by mutations in selenoprotein N (SEPN1). Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and susceptibility to ultraviolet radiation–induced oxidative damage may mediate the observed photosensitivity. Reduced levels of selenoproteins in peripheral blood cells were associated with impaired T lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, and telomere shortening. Paradoxically, raised ROS in affected subjects was associated with enhanced systemic and cellular insulin sensitivity, similar to findings in mice lacking the antioxidant selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is associated with a multisystem disorder with defective biosynthesis of many selenoproteins, highlighting their role in diverse biological processes. PMID:21084748

  10. Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children.

    Directory of Open Access Journals (Sweden)

    Paul R West

    Full Text Available The diagnosis of autism spectrum disorder (ASD at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age.To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment.Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD.A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set.This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1 determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2 gaining new insight into the biochemical mechanisms of various subtypes of ASD 3 identifying biomolecular targets for new modes of therapy, and 4 providing the basis for individualized treatment recommendations.

  11. A human phenome-interactome network of protein complexes implicated in genetic disorders

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Karlberg, Erik, Olof, Linnart; Størling, Zenia, Marian;

    2007-01-01

    We performed a systematic, large-scale analysis of human protein complexes comprising gene products implicated in many different categories of human disease to create a phenome-interactome network. This was done by integrating quality-controlled interactions of human proteins with a validated......, computationally derived phenotype similarity score, permitting identification of previously unknown complexes likely to be associated with disease. Using a phenomic ranking of protein complexes linked to human disease, we developed a Bayesian predictor that in 298 of 669 linkage intervals correctly ranks the...... known disease-causing protein as the top candidate, and in 870 intervals with no identified disease-causing gene, provides novel candidates implicated in disorders such as retinitis pigmentosa, epithelial ovarian cancer, inflammatory bowel disease, amyotrophic lateral sclerosis, Alzheimer disease, type...

  12. Cooperative folding of intrinsically disordered domains drives assembly of a strong elongated protein

    Science.gov (United States)

    Gruszka, Dominika T.; Whelan, Fiona; Farrance, Oliver E.; Fung, Herman K. H.; Paci, Emanuele; Jeffries, Cy M.; Svergun, Dmitri I.; Baldock, Clair; Baumann, Christoph G.; Brockwell, David J.; Potts, Jennifer R.; Clarke, Jane

    2015-06-01

    Bacteria exploit surface proteins to adhere to other bacteria, surfaces and host cells. Such proteins need to project away from the bacterial surface and resist significant mechanical forces. SasG is a protein that forms extended fibrils on the surface of Staphylococcus aureus and promotes host adherence and biofilm formation. Here we show that although monomeric and lacking covalent cross-links, SasG maintains a highly extended conformation in solution. This extension is mediated through obligate folding cooperativity of the intrinsically disordered E domains that couple non-adjacent G5 domains thermodynamically, forming interfaces that are more stable than the domains themselves. Thus, counterintuitively, the elongation of the protein appears to be dependent on the inherent instability of its domains. The remarkable mechanical strength of SasG arises from tandemly arrayed `clamp' motifs within the folded domains. Our findings reveal an elegant minimal solution for the assembly of monomeric mechano-resistant tethers of variable length.

  13. Food intake and blood cholesterol levels of community-based adults with mood disorders

    Directory of Open Access Journals (Sweden)

    Davison Karen M

    2012-02-01

    Full Text Available Abstract Background A growing body of literature links nutrition to mood, especially in epidemiological surveys, but there is little information characterizing food intake in people with diagnosed mood disorders. Methods Food intake obtained from 3-day food records was evaluated in 97 adults with mood disorders, whose diagnoses were confirmed in structured interviews. Information from a population nutrition survey, national guidelines for nutritional intakes (Eating Well with Canada's Food Guide and North American dietary guidelines (Dietary Reference Intakes was utilized to evaluate the quality of their food intake. Results Compared to the regional nutrition survey data and national guidelines, a greater proportion of study participants consumed fewer of the recommended servings of grains (p p p p p p 5.2 and ≤ 6.2 mmol/L and 21% had hypercholesterolemia (> 6.2 mmol/L. Conclusions Much research has proposed multiple ways in which healthier diets may exert protective effects on mental health. The results of this study suggest that adults with mood disorders could benefit from nutritional interventions to improve diet quality.

  14. Polymer scaling laws of unfolded and intrinsically disordered proteins quantified with single-molecule spectroscopy.

    OpenAIRE

    Hofmann H.; Soranno A; Borgia A; Gast K; Nettels D; Schuler B.

    2012-01-01

    The dimensions of unfolded and intrinsically disordered proteins are highly dependent on their amino acid composition and solution conditions, especially salt and denaturant concentration. However, the quantitative implications of this behavior have remained unclear, largely because the effective theta-state, the central reference point for the underlying polymer collapse transition, has eluded experimental determination. Here, we used single-molecule fluorescence spectroscopy and two-focus c...

  15. Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues

    OpenAIRE

    Das, Rahul K.; Pappu, Rohit V.

    2013-01-01

    The functions of intrinsically disordered proteins (IDPs) are governed by relationships between information encoded in their amino acid sequences and the ensembles of conformations that they sample as autonomous units. Most IDPs are polyampholytes, with sequences that include both positively and negatively charged residues. Accordingly, we focus here on the sequence–ensemble relationships of polyampholytic IDPs. The fraction of charged residues discriminates between weak and strong polyamphol...

  16. Hamiltonian Mapping Revisited: Calibrating Minimalist Models to Capture Molecular Recognition by Intrinsically Disordered Proteins

    OpenAIRE

    Law, Sean M.; Ahlstrom, Logan S.; Panahi, Afra; Brooks, Charles L.

    2014-01-01

    Molecular recognition by intrinsically disordered proteins (IDPs) plays a central role in many critical cellular processes. Toward achieving detailed mechanistic understanding of IDP–target interactions, here we employ the “Hamiltonian mapping” methodology, which is rooted in the weighted histogram analysis method (WHAM), for the fast and efficient calibration of structure-based models in studies of IDPs. By performing reference simulations on a given Hamiltonian, we illustrate for two model ...

  17. Deducing conformational variability of intrinsically disordered proteins from infrared spectroscopy with Bayesian statistics

    International Nuclear Information System (INIS)

    Highlights: • Deduce secondary structure content of intrinsically disordered proteins from IR spectra. • Bayesian analysis to infer conformations of disordered regions of proteins from IR. • Comparison of measured and calculated IR spectra to obtain thermodynamic weights. - Abstract: As it remains practically impossible to generate ergodic ensembles for large intrinsically disordered proteins (IDP) with molecular dynamics (MD) simulations, it becomes critical to compare spectroscopic characteristics of the theoretically generated ensembles to corresponding measurements. We develop a Bayesian framework to infer the ensemble properties of an IDP using a combination of conformations generated by MD simulations and its measured infrared spectrum. We performed 100 different MD simulations totaling more than 10 μs to characterize the conformational ensemble of α-synuclein, a prototypical IDP, in water. These conformations are clustered based on solvent accessibility and helical content. We compute the amide-I band for these clusters and predict the thermodynamic weights of each cluster given the measured amide-I band. Bayesian analysis produces a reproducible and non-redundant set of thermodynamic weights for each cluster, which can then be used to calculate the ensemble properties. In a rigorous validation, these weights reproduce measured chemical shifts

  18. [Dynamics of blood proteins spectra in normal and diarrheic long horn cattle during early ontogenesis].

    Science.gov (United States)

    Usatiuk, P V; Tsvilikhovs'kyĭ, M I; Aniiefiok, A; Mel'nychuk, D O

    2001-01-01

    The contains of blood plasma protein fractions and immunoglobulines were studied in adult cattle and in new born calves (just new born and age of 1, 2, 5 and 10 days) by the 10% PAAG EP (0.1% SDS) and radial immunodiffusion methods. It is shown that protein bands of 140-160 kD and immunoglobulines (G1, G2, M) are absent at the moment of birth. The physiology level of gamma-globulines and IgG1 reach at 1 day of life, while IgM--at second. After colostrum breeding of just new born calves the speed increasing of total plasma protein and gamma-globulines fraction are lowest (in 2.7 and 1.7 times respectively) in diarrhoea animals in compare to the health one. The maximum level of IgG1 concentration forms in disease animals only at 10 days of age. On the date obtained it is concluded the presence such new born calves which have low level of small intestine developing and disturbance of immunoglobulines absorption. PMID:11962094

  19. Localization of Cellular Retinol-Binding Protein and Retinol-Binding Protein in Cells Comprising the Blood-Brain Barrier of Rat and Human

    Science.gov (United States)

    MacDonald, Paul N.; Bok, Dean; Ong, David E.

    1990-06-01

    Brain is not generally recognized as an organ that requiries vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A-deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the endothelial cells of the brain microvasculature and within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur.

  20. Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, P.N.; Ong, D.E. (Vanderbilt Univ., Nashville, TN (USA)); Bok, D. (Univ. of California, Los Angeles (USA))

    1990-06-01

    Brain is not generally recognized as an organ that requires vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A-deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur.

  1. Extracorporeal irradiation of calves blood. Effects on: the lymphocytes, the blood-platelet function, seric proteins, and fibrinogen

    International Nuclear Information System (INIS)

    The present paper reports the results obtained after extracorporeal irradiation of circulating blood of calves. Animals are divided in 3 groups as follows: - control animals: blood circulation without irradiation; - calves which received 40000 rads during 24 hours of continuous irradiation; - calves which received the same dose, during a period of 5 days (5 hours every day). The more interesting results are: - the early lymphopenia which persists for 7 or 8 weeks and may be in relationship with the change of immunoglobulins; - a constant hyperfibrinemia (12 g/l) never reported, as far as we know, by authors using I.E.C. Several hypothesis are advanced to explain this phenomenon. (authors)

  2. Effect of peptides derived from food proteins on blood pressure – a meta-analysis of randomised controlled trials

    OpenAIRE

    Pripp, Are Hugo

    2008-01-01

    Background: Peptides derived from food proteins have in clinical trials shown an effect on blood pressure. Their biological mechanism is mainly due to inhibition of angiotensin-I-converting enzyme (ACE) and thereby regulation of blood pressure through the renin-angiotensin system. A meta-analysis of these trials is needed to better quantify their effect, sources of variation and possible publication bias. Objective: To perform a meta-analysis of placebo-controlled clinical trials on peptides ...

  3. Pathological Propagation through Cell-to-Cell Transmission of Non-Prion Protein Aggregates in Neurodegenerative Disorders

    Science.gov (United States)

    Lee, Seung-Jae; Desplats, Paula; Sigurdson, Christina; Tsigelny, Igor; Masliah, Eliezer

    2016-01-01

    Neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, fronto-temporal dementia, Huntington's Disease and Creutzfeldt-Jakob Disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. While protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has been reserved to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence suggests that prion-like spreading may occur in other neurodegenerative disorders, taking place with secreted proteins, such as amyloid-β,) and cytosolic proteins, such as tau, huntingtin and α-synuclein. Underlying molecular mechanisms and therapeutic implications are discussed. PMID:21045796

  4. Adsorption and adhesion of blood proteins and fibroblasts on multi-wall carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This article concerns the investigation of blood protein adsorption on carbon paper and multi-wall carbon nanotubes (MWCNTs). Mouse fibroblast cell adhesion and growth on MWCNTs was also studied. The results showed that fibrinogen adsorption on carbon paper was much lower than that on MWCNTs, which means that platelets readily aggregate on the surface of MWCNTs. Mouse fibroblast cells implanted on MWCNTs tended to grow more prolifically than those implanted on carbon paper. The cell concentration observed on MWCNTs increased from 1.2×105/mL for a single day culture to 2×105/mL for a 7-day culture. No toxicity reaction was observed during the culturing period. These results indicated that MWCNTs possessed excellent tissue compatibility.

  5. Residual nanoparticle label immunosensor for wash-free C-reactive protein detection in blood.

    Science.gov (United States)

    Huttunen, Roope J; Näreoja, Tuomas; Mariani, Laura; Härmä, Harri

    2016-09-15

    Current diagnostic immunotechnologies are universally based on the measurement of the bound label-antibody fraction in direct binding or sandwich-assay type approaches with various detection techniques (e.g. enzyme-linked immunosorbent assay or ELISA) on solid stationary phase surface. Here an alternative reciprocal approach is presented based on the detection of the non-bound fraction of nanoparticle-labelled antibodies using microparticles as solid support. The advantage of detecting the non-bound fraction of the labelled antibody instead of the bound fraction is the high dynamics and the suggested increased flexibility in the selection of the detection mode. No actual washing steps are required as the bound and non-bound fractions of the detection nanoparticle label are separated using physical separation rather than consecutive washing repeats. The quantitative proof-of-concept set-up was demonstrated through blood-based detection of C-reactive protein (CRP). A blood sample containing CRP was diluted 1/50 and measured in 15-min resulting in a linear response at a range from 1 to 30μg/ml. The lowest limit of detection was below 0.03μg/ml and the assay coefficient of variation ranged from 0.3 to 9%. The nanoparticle-based residual label detection outperformed the corresponding molecular label method providing wider applicability with nearly an order of magnitude higher signal-to-background ratio for novel assay configurations in clinical diagnostics practices. PMID:27104585

  6. Regulation of Exacerbated Immune Responses in Human Peripheral Blood Cells by Hydrolysed Egg White Proteins.

    Science.gov (United States)

    Lozano-Ojalvo, Daniel; Molina, Elena; López-Fandiño, Rosina

    2016-01-01

    The anti-allergic potential of egg white protein hydrolysates (from ovalbumin, lysozyme and ovomucoid) was evaluated as their ability to hinder cytokine and IgE production by Th2-skewed human peripheral blood mononuclear cells (PBMCs), as well as the release of pro-inflammatory factors and generation of reactive oxygen species from Th1-stimulated peripheral blood leukocytes (PBLs). The binding to IgE of egg allergic patients was determined and the peptides present in the hydrolysates were identified. The hydrolysates with alcalase down-regulated the production of Th2-biased cytokines and the secretion of IgE to the culture media of Th2-skewed PBMCs, and they significantly neutralized oxidative stress in PBLs. The hydrolysates of ovalbumin and ovomucoid with pepsin helped to re-establish the Th1/Th2 balance in Th2-biased PBMCs, while they also inhibited the release of pro-inflammatory mediators and reduced oxidative stress in PBLs treated with inflammatory stimuli. The hydrolysates with alcalase, in addition to equilibrating Th2 differentiation, exhibited a low IgE-binding. Therefore, they would elicit mild allergic reactions while retaining T cell-stimulating abilities, which might correlate with an anti-allergic benefit. PMID:27007699

  7. Regulation of Exacerbated Immune Responses in Human Peripheral Blood Cells by Hydrolysed Egg White Proteins.

    Directory of Open Access Journals (Sweden)

    Daniel Lozano-Ojalvo

    Full Text Available The anti-allergic potential of egg white protein hydrolysates (from ovalbumin, lysozyme and ovomucoid was evaluated as their ability to hinder cytokine and IgE production by Th2-skewed human peripheral blood mononuclear cells (PBMCs, as well as the release of pro-inflammatory factors and generation of reactive oxygen species from Th1-stimulated peripheral blood leukocytes (PBLs. The binding to IgE of egg allergic patients was determined and the peptides present in the hydrolysates were identified. The hydrolysates with alcalase down-regulated the production of Th2-biased cytokines and the secretion of IgE to the culture media of Th2-skewed PBMCs, and they significantly neutralized oxidative stress in PBLs. The hydrolysates of ovalbumin and ovomucoid with pepsin helped to re-establish the Th1/Th2 balance in Th2-biased PBMCs, while they also inhibited the release of pro-inflammatory mediators and reduced oxidative stress in PBLs treated with inflammatory stimuli. The hydrolysates with alcalase, in addition to equilibrating Th2 differentiation, exhibited a low IgE-binding. Therefore, they would elicit mild allergic reactions while retaining T cell-stimulating abilities, which might correlate with an anti-allergic benefit.

  8. Investigation of two blood proteins binding to Cantharidin and Norcantharidin by multispectroscopic and chemometrics methods

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Rong; Cheng, Zhengjun, E-mail: ncczj1112@126.com; Li, Tian; Jiang, Xiaohui

    2015-01-15

    The interactions of Cantharidin/Norcantharidin (CTD/NCTD) with two blood proteins, i.e., bovine serum albumin (BSA) and bovine hemoglobin (BHb), have been investigated by the fluorescence, UV–vis absorption, and FT-IR spectra under imitated physiological condition. The binding characteristics between CTD/NCTD and BSA/BHb were determined by fluorescence emission and resonance light scattering (RLS) spectra. The quenching mechanism of two blood proteins with CTD/NCTD is a static quenching. Moreover, the experimental data were further analyzed based on multivariate curve resolution-alternating least squares (MCR-ALS) technique to obtain the concentration profiles and pure spectra for three species (BSA/BHb, CTD/NCTD and CTD/NCTD–BSA/BHb complexes) which existed in the interaction procedure. The number of binding sites n and binding constants K{sub b} were calculated at various temperatures. The thermodynamic parameters (such as, ΔG, ΔH, and ΔS) for BSA–CTD/NCTD and BHb–CTD/NCTD systems were calculated by the Van’t Hoff equation and also discussed. The distance r between CTD/NCTD and BSA/BHb were evaluated according to Förster no-radiation energy transfer theory. The results of Fourier transform infrared (FT-IR), synchronous fluorescence and three-dimensional fluorescence spectra showed that the conformations of BSA/BHb altered with the addition of CTD/NCTD. In addition, the effects of common ions on the binding constants of BSA–CTD/NCTD and BHb–CTD/NCTD systems were also discussed.

  9. Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders.

    Science.gov (United States)

    Rusanov, Alexander L; Luzgina, Natalia G; Barreto, George E; Aliev, Gjumrakch

    2016-01-01

    In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions, including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the mutual influences of cells under normal conditions and when exposed to the test substance. New experimental possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in the practice for pre-clinical studies of novel drugs against neurodegenerative diseases. PMID:26831260

  10. Structure of an Intrinsically Disordered Stress Protein Alone and Bound to a Membrane Surface.

    Science.gov (United States)

    Atkinson, John; Clarke, Matthew W; Warnica, Josephine M; Boddington, Kelly F; Graether, Steffen P

    2016-08-01

    Dehydrins are a group of intrinsically disordered proteins that protect plants from damage caused by drought, cold, and high salinity. Like other intrinsically disordered proteins, dehydrins can gain structure when bound to a ligand. Previous studies have shown that dehydrins are able to protect liposomes from cold damage, but the interactions that drive membrane binding and the detailed structure of the bound and unbound forms are not known. We use an ensemble-structure approach to generate models of a dehydrin known as K2 in the presence and absence of sodium dodecyl sulfate micelles, and we docked the bound structure to the micelle. The collection of residual dipolar coupling data, amide protection factors, and paramagnetic relaxation enhancement distances, in combination with chemical shifts and relaxation measurements, allows for determining plausible structures that are not otherwise visible in time-averaged structural data. The results show that in the bound structure, the conserved lysines are important for membrane binding, whereas the flanking hydrophobic residues play a lesser role. The unbound structure shows a high level of disorder and an extended structure. We propose that the structural differences between bound and unbound forms allow dehydrins to act as molecular shields in their unbound state and as membrane protectants in their bound state. Unlike α-synuclein, the significant gain of α-helicity in K2 at low concentrations of sodium dodecyl sulfate is not due to a decrease in the critical micelle concentration. The study provides structural insight into how a disordered protein can interact with a membrane surface. PMID:27508433

  11. Effect of dietary protein sources of on blood or milk urea nitrogen of native cows

    International Nuclear Information System (INIS)

    When feed protein metabolism in ruminants produces urea in the liver and recycles or blood urea (BUN) filters into milk urea nitrogen (MUN), an indicator of protein status in diets or feeding urea as one of the non-protein nitrogen sources for ruminants is scientifically acceptable throughout the world; a section of environmentalists, policy makers or even professionals often raise question of residual effects in milk and/or meat of fattening and/or dairy cattle fed with diets containing urea. Keeping their views in consideration, a feeding trial on 30 Pabna milking cows of 2 to 4 parities dividing equally into 5 groups was arranged to determine the effect of feeding of different sources of protein on BUN and MUN, and milk yield or protein content. To achieve the objectives, a group of cows was fed a diet of rice straw and concentrate as the control (T0), two out of the rests was fed either with urea-molasses straw (UMS) (T1) or Matikalai (Vigna mungo) hay ( T2) as sources of basal roughage. The rest two groups of cows were fed the control diet replacing % of feed protein by the amount of urea and molasses fed to UMS group. The amount of urea and molasses was fed daily either in two meals (T3) or fed to cows mixing with other concentrate feed (T4). In addition, a concentrate mixture containing 45 % wheat bran, 24% Khesari bran, 12% Til oil cake, 12% soybean meal, 4% fishmeal, 2.0% oyster-shell, 0.5% DCP and 0.5% common salt, was supplied twice daily. Having adjusted the cows with the diets for 20 d, a 20 d feeding trial was conducted, when feed intake and samples of blood and milk were collected. Milk samples were collected from individual cow after feeding the experimental diets in the morning and evening milking. Samples were collected from milk bucket after complete milking and mixing thoroughly. Samples were analyzed for milk urea content (MUN) using a Colorimetric p-dimethylaminobenzaldehyde (DMAB) method as described by Bector et al. Concentration of MUN in

  12. The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder

    Energy Technology Data Exchange (ETDEWEB)

    Szobot, Claudia M.; Ketzer, Carla; Kapczinski, Flavio [Department of Psychiatry, Federal University of Rio Grande do Sul (Brazil); Cunha, Renato D. [Service of Nuclear Medicine, Hospital de Clinicas de Porto Alegre (Brazil); Parente, Maria A. [Department of Psychology, Federal University of Rio Grande do Sul (Brazil); Langleben, Daniel D. [Department of Psychiatry, University of Pennsylvania (United States); Acton, Paul D. [Department of Radiology, University of Pennsylvania (United States); Rohde, Luis A.P. [Department of Psychiatry, Federal University of Rio Grande do Sul (Brazil); Servico de Psiquiatria da Infancia e Adolescencia, Hospital de Clinicas de Porto Alegre (HCPA), Rua Ramiro Barcelos 2350, CEP 90035-003, RS Porto Alegre (Brazil)

    2003-03-01

    Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer ({sup 99m}Tc-ECD) and single-photon emission tomography (SPET). The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD. (orig.)

  13. The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder

    International Nuclear Information System (INIS)

    Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer (99mTc-ECD) and single-photon emission tomography (SPET). The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD. (orig.)

  14. Electrophoretic pattern of blood serum proteins and enzymes activity of house sparrow (Passer domesticus in Baghdad (Iraq

    Directory of Open Access Journals (Sweden)

    Faris A. Al-Obaidi

    2011-04-01

    Full Text Available The objective of this study was to determine the electrophoretic pattern of blood serum proteins and the activity of some blood serum enzymes included GOT, GPT and AP of house Sparrow (Passer domesticus in Baghdad, Iraq. Seventeen (9 males and 8 females individuals of house sparrow were collected from different regions of Baghdad. Samples of 1.0 ml of whole blood were taken from the wing vein from individuals to determined electrophoretic pattern of serum proteins and enzymes in three replicates for each sex within species. Results revealed that house sparrow blood serum proteins were separated into seven different regions, these bands were pre- albumen (3.68%, albumen (13.20%, post–albumen (8.37%, α–globulin (4.54%, β–globulin (27.49%, γ–globulin (30.15% and transferrin (12.59%. Electrophoretic pattern of serum proteins were differed due to sex: females dominated males in pre–albumen, γ–globulin and total albumens. House sparrow blood serum GOT, GPT and AP enzymes activity were 38.4, 10.9 and 42.05 U/L respectively. Males had higher activity of GOT and GPT enzymes compared to females.

  15. Correlations between regional cerebral blood flow and depression scale in the mood disorder. A study using 123I-IMP SPECT

    International Nuclear Information System (INIS)

    Regional cerebral blood flow (rCBF) was assessed on 26 mood disorder patients using 123I-iodoamphetamine and single photon emission computed tomography (SPECT), and their correlations to depression scores of Hamilton's Rating Scale for Depression were studied. Region of interest (ROI) was established on coronary images and used as an indicator. As a result, left hemisphere was suspected of a primary lesion in mood disorder, however, the relationship between clinical symptoms and various lesion areas were not clarified. Further studies with neuropsychological loading or pharmaceutical loading such as antidepressant are thus expected to clarify the etiology of mood disorders. (S.Y.)

  16. Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex.

    Science.gov (United States)

    Vovk, Andrei; Gu, Chad; Opferman, Michael G; Kapinos, Larisa E; Lim, Roderick Yh; Coalson, Rob D; Jasnow, David; Zilman, Anton

    2016-01-01

    Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function. PMID:27198189

  17. Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6-cys proteins: P12 and P41.

    Directory of Open Access Journals (Sweden)

    Tana Taechalertpaisarn

    Full Text Available The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here we investigate the biochemical nature and function of two blood-stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to afflict humans. We show that native P12 and P41 form a stable heterodimer on the infective merozoite surface and are secreted following invasion, but could find no evidence that this complex mediates erythrocyte-receptor binding. That P12 and P41 do not appear to have a major role as adhesins to erythrocyte receptors was supported by the observation that antisera to these proteins did not substantially inhibit erythrocyte invasion. To investigate other functional roles for these proteins their genes were successfully disrupted in P. falciparum, however P12 and P41 knockout parasites grew at normal rates in vitro and displayed no other obvious phenotypic changes. It now appears likely that these blood-stage 6-cys proteins operate as a pair and play redundant roles either in erythrocyte invasion or in host-immune interactions.

  18. Acute effects of electroconvulsive therapy on regional cerebral blood flow (rCBF) in psychiatric disorders

    International Nuclear Information System (INIS)

    Electroconvulsive therapy (ECT) is frequently used in the treatment of major depression and other psychiatric disorders; its mechanism of action is not established, but previous evidence suggests that it is associated with postictal metabolic suppression. The authors have used measurements of rCBF as an index of cortical metabolic activity to study the acute effects of ECT. Measurements of rCBF were made in 32 cortical regions in 10 patients (pts) following one minute breathing of Xe-133 (5mCi/L); the measurements were performed 30min before and 50min after ECT. Bilateral ECT was administered to six pts (five diagnosed as major depressives and one schizophrenic) and unilateral ECT to four (all diagnosed as unipolar or bipolar affective disorder). The total rCBF material consists of 52 measurements in these pts, made before and after 16 bilateral and 10 unilateral treatments. ECT was found to cause significant reduction of rCBF. Mean hemispheric flows (using the Initial Slope Index to measure grey-matter flow) were reduced by about 5% in both hemispheres following bilateral treatment. Unilateral treatment caused a 9% reduction of flow in the treated hemisphere, but only 2% contralaterally. Regional patterns of flow decreases also differed between the two treatment modes: bilateral frontal reductions were found after bilateral treatment, whereas unilateral ECT caused a widespread flow reduction in the treated hemisphere, and almost no effect contralaterally. These results suggest that rCBF studies are useful for assessing ECT, and indicate that the acute cerebral effects of ECT vary with the mode of treatment

  19. G Protein-Linked Signaling Pathways in Bipolar and Major Depressive Disorders

    Directory of Open Access Journals (Sweden)

    Hiroaki eTomita

    2013-12-01

    Full Text Available The G-protein linked signaling system (GPLS comprises a large number of G-proteins, G protein-coupled receptors (GPCRs, GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP, phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD and bipolar disorder (BPD. This study evaluated whether GPLS is altered at the transcript level. The gene expression in the dorsolateral prefrontal (DLPFC and anterior cingulate (ACC were compared from MDD, BPD, and control subjects using Affymetrix Gene Chips and real time quantitative PCR. High quality brain tissue was used in the study to control for confounding effects of agonal events, tissue pH, RNA integrity, gender, and age. GPLS signaling transcripts were altered especially in the ACC of BPD and MDD subjects. Transcript levels of molecules which repress cAMP activity were increased in BPD and decreased in MDD. Two orphan GPCRs, GPRC5B and GPR37, showed significantly decreased expression levels in MDD, and significantly increased expression levels in BPD. Our results suggest opposite changes in BPD and MDD in the GPLS, ‘activated’ cAMP signaling activity in BPD and ‘blunted’ cAMP signaling activity in MDD. GPRC5B and GPR37 both appear to have behavioral effects, and are also candidate genes for neurodegenerative disorders. In the context of the opposite changes observed in BPD and MDD, these GPCRs warrant further study of their brain effects.

  20. Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.

    Science.gov (United States)

    Kamat, Pradip K; Kyles, Philip; Kalani, Anuradha; Tyagi, Neetu

    2016-05-01

    Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation. Hcy intracerebral (IC) treatment significantly impaired cerebral blood flow (CBF), and cerebral circulation and memory function. Hcy treatment also decreases the expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) in the brain along with increased expression of NMDA-R (NR1) and synaptosomal Ca(2+) indicating excitotoxicity. Additionally, we found that Hcy treatment increased protein and mRNA expression of intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 and also increased MMP-2 and MMP-9 activity in the brain. The increased expression of ICAM-1, glial fibrillary acidic protein (GFAP), and the decreased expression of vascular endothelial (VE)-cadherin and claudin-5 indicates BBB disruption and vascular inflammation. Moreover, we also found decreased expression of microtubule-associated protein 2 (MAP-2), postsynaptic density protein 95 (PSD-95), synapse-associated protein 97 (SAP-97), synaptosomal-associated protein 25 (SNAP-25), synaptophysin, and brain-derived neurotrophic factor (BDNF) showing synapse dysfunction in the hippocampus. Furthermore, NaHS and MK801 treatment ameliorates BBB disruption, CBF, and synapse functions in the mice brain. These results demonstrate a neuro-protective effect of H2S over Hcy

  1. Plasma protein induced clustering of red blood cells in micro capillaries

    Science.gov (United States)

    Wagner, Christian; Brust, Mathias; Aouane, Othmane; Flormann, Daniel; Thiebaud, Marine; Verdier, Claude; Coupier, Gwennou; Podgorski, Thomas; Misbah, Chaouqi; Selmi, Hassib

    2013-11-01

    The plasma molecule fibrinogen induces aggregation of RBCs to clusters, the so called rouleaux. Higher shear rates in bulk flow can break them up which results in the pronounced shear thinning of blood. This led to the assumption that rouleaux formation does not take place in the microcapillaries of the vascular network where high shear rates are present. However, the question is of high medical relevance. Cardio vascular disorders are still the main cause of death in the western world and cardiac patients have often higher fibrinogen level. We performed AFM based single cell force spectroscopy to determine the work of separation. Measurements at low hematocrit in a microfluidic channel show that the number of size of clusters is determined by the adhesion strength and we found that cluster formation is strongly enhanced by fibrinogen at physiological concentrations, even at shear rate as high as 1000 1/s. Numerical simulations based on a boundary integral method confirm our findings and the clustering transition takes place both in the experiments and in the simulations at the same interaction energies. In vivo measurements with intravital fluorescence microscopy in a dorsal skin fold chamber in a mouse reveal that RBCs indeed form clusters in the micrcapillary flow. This work was supported by the German Science Foundation research imitative SFB1027.

  2. Impact of Exercise and Metabolic Disorders on Heat Shock Proteins and Vascular Inflammation

    Directory of Open Access Journals (Sweden)

    Earl G. Noble

    2012-01-01

    Full Text Available Heat shock proteins (Hsp play critical roles in the body’s self-defense under a variety of stresses, including heat shock, oxidative stress, radiation, and wounds, through the regulation of folding and functions of relevant cellular proteins. Exercise increases the levels of Hsp through elevated temperature, hormones, calcium fluxes, reactive oxygen species (ROS, or mechanical deformation of tissues. Isotonic contractions and endurance- type activities tend to increase Hsp60 and Hsp70. Eccentric muscle contractions lead to phosphorylation and translocation of Hsp25/27. Exercise-induced transient increases of Hsp inhibit the generation of inflammatory mediators and vascular inflammation. Metabolic disorders (hyperglycemia and dyslipidemia are associated with type 1 diabetes (an autoimmune disease, type 2 diabetes (the common type of diabetes usually associated with obesity, and atherosclerotic cardiovascular disease. Metabolic disorders activate HSF/Hsp pathway, which was associated with oxidative stress, increased generation of inflammatory mediators, vascular inflammation, and cell injury. Knock down of heat shock factor-1 (HSF1 reduced the activation of key inflammatory mediators in vascular cells. Accumulating lines of evidence suggest that the activation of HSF/Hsp induced by exercise or metabolic disorders may play a dual role in inflammation. The benefits of exercise on inflammation and metabolism depend on the type, intensity, and duration of physical activity.

  3. Detection of Antibodies in Blood Plasma Using Bioluminescent Sensor Proteins and a Smartphone.

    Science.gov (United States)

    Arts, Remco; den Hartog, Ilona; Zijlema, Stefan E; Thijssen, Vito; van der Beelen, Stan H E; Merkx, Maarten

    2016-04-19

    Antibody detection is of fundamental importance in many diagnostic and bioanalytical assays, yet current detection techniques tend to be laborious and/or expensive. We present a new sensor platform (LUMABS) based on bioluminescence resonance energy transfer (BRET) that allows detection of antibodies directly in solution using a smartphone as the sole piece of equipment. LUMABS are single-protein sensors that consist of the blue-light emitting luciferase NanoLuc connected via a semiflexible linker to the green fluorescent acceptor protein mNeonGreen, which are kept close together using helper domains. Binding of an antibody to epitope sequences flanking the linker disrupts the interaction between the helper domains, resulting in a large decrease in BRET efficiency. The resulting change in color of the emitted light from green-blue to blue can be detected directly in blood plasma, even at picomolar concentrations of antibody. Moreover, the modular architecture of LUMABS allows changing of target specificity by simple exchange of epitope sequences, as demonstrated here for antibodies against HIV1-p17, hemagglutinin (HA), and dengue virus type I. The combination of sensitive ratiometric bioluminescent detection and the intrinsic modularity of the LUMABS design provides an attractive generic platform for point-of-care antibody detection that avoids the complex liquid handling steps associated with conventional immunoassays. PMID:27018236

  4. NS3 Protease from Hepatitis C Virus: Biophysical Studies on an Intrinsically Disordered Protein Domain

    Directory of Open Access Journals (Sweden)

    Adrian Velazquez-Campoy

    2013-06-01

    Full Text Available The nonstructural protein 3 (NS3 from the hepatitis C virus (HCV is responsible for processing the non-structural region of the viral precursor polyprotein in infected hepatic cells. NS3 protease activity, located at the N-terminal domain, is a zinc-dependent serine protease. A zinc ion, required for the hydrolytic activity, has been considered as a structural metal ion essential for the structural integrity of the protein. In addition, NS3 interacts with another cofactor, NS4A, an accessory viral protein that induces a conformational change enhancing the hydrolytic activity. Biophysical studies on the isolated protease domain, whose behavior is similar to that of the full-length protein (e.g., catalytic activity, allosteric mechanism and susceptibility to inhibitors, suggest that a considerable global conformational change in the protein is coupled to zinc binding. Zinc binding to NS3 protease can be considered as a folding event, an extreme case of induced-fit binding. Therefore, NS3 protease is an intrinsically (partially disordered protein with a complex conformational landscape due to its inherent plasticity and to the interaction with its different effectors. Here we summarize the results from a detailed biophysical characterization of this enzyme and present new experimental data.

  5. Phagocytic and oxidative-burst activity of blood leukocytes in rats fed a protein-free diet

    DEFF Research Database (Denmark)

    Sawosz, Ewa; Winnicka, Anna; Chwalibog, André;

    2009-01-01

    The objective of this study was to evaluate the effects of two weeks' protein deprivation on the cellular parameters of non-specific immunity in rats. Wistar rats (200-250 g) were divided into two groups (2x12) and were fed two isoenergetic (control and protein-free) diets. The phagocytic activity...... of neutrophils and monocytes, and the oxidative-burst activity of neutrophils of peripheral blood, were determined by flow cytometry after stimulation with E. coli and phorbol 12-mirystate 13-acetate. Feeding the protein-free diet for two weeks did not influence the phagocytic activity of neutrophils......, monocytes or blood morphology. However, the oxidative burst of stimulated neutrophils was increased indicating that two weeks' protein deprivation does not depress the oxygen-dependent killing mechanism in neutrophils, but may lead to the overproduction of reactive oxygen species....

  6. Blood smear

    Science.gov (United States)

    ... osmotic fragility ) Deficiency of an enzyme called lecithin cholesterol acyl transferase Abnormalities of hemoglobin , the protein in ... sickle and Pappenheimer Red blood cells, target cells Formed elements of blood References Bain BJ. The peripheral ...

  7. Proteomic analysis of ERK1/2-mediated human sickle red blood cell membrane protein phosphorylation

    Directory of Open Access Journals (Sweden)

    Soderblom Erik J

    2013-01-01

    Full Text Available Abstract Background In sickle cell disease (SCD, the mitogen-activated protein kinase (MAPK ERK1/2 is constitutively active and can be inducible by agonist-stimulation only in sickle but not in normal human red blood cells (RBCs. ERK1/2 is involved in activation of ICAM-4-mediated sickle RBC adhesion to the endothelium. However, other effects of the ERK1/2 activation in sickle RBCs leading to the complex SCD pathophysiology, such as alteration of RBC hemorheology are unknown. Results To further characterize global ERK1/2-induced changes in membrane protein phosphorylation within human RBCs, a label-free quantitative phosphoproteomic analysis was applied to sickle and normal RBC membrane ghosts pre-treated with U0126, a specific inhibitor of MEK1/2, the upstream kinase of ERK1/2, in the presence or absence of recombinant active ERK2. Across eight unique treatment groups, 375 phosphopeptides from 155 phosphoproteins were quantified with an average technical coefficient of variation in peak intensity of 19.8%. Sickle RBC treatment with U0126 decreased thirty-six phosphopeptides from twenty-one phosphoproteins involved in regulation of not only RBC shape, flexibility, cell morphology maintenance and adhesion, but also glucose and glutamate transport, cAMP production, degradation of misfolded proteins and receptor ubiquitination. Glycophorin A was the most affected protein in sickle RBCs by this ERK1/2 pathway, which contained 12 unique phosphorylated peptides, suggesting that in addition to its effect on sickle RBC adhesion, increased glycophorin A phosphorylation via the ERK1/2 pathway may also affect glycophorin A interactions with band 3, which could result in decreases in both anion transport by band 3 and band 3 trafficking. The abundance of twelve of the thirty-six phosphopeptides were subsequently increased in normal RBCs co-incubated with recombinant ERK2 and therefore represent specific MEK1/2 phospho-inhibitory targets mediated via ERK2

  8. Effect of whey supplementation on blood markers of protein metabolism in young and elderly after resistance exercise

    OpenAIRE

    Holte, Kristin

    2014-01-01

    Abstract Introduction: Ingestion of whey protein has been shown to be superior to casein in the acute stimulation of anabolic responses in muscle. The composition of whey protein may alter how rapidly the amino acids are available after consumption, and thus affect acute anabolic responses in muscle and other tissues. Aims: To investigate how ingestion of different whey products, influences the acute changes in the blood amino acid and urea concentration following standardized resistance exer...

  9. Vector-host-parasite inter-relationships in leishmaniasis. IV. Electrophoretic studies on proteins of four vertebrate bloods with and without Leishmania infantum or L. major.

    Science.gov (United States)

    Daba, S; Mansour, N S; Youssef, F G; Shanbaky, N M; el Sawaf, B M

    1997-12-01

    Fifty five protein bands with relative mobilities of 8,954 to 245,471 kilo Daltons (kD) were electrophoretically separated from 12 feeding media of blood from 4 natural vertebrate hosts of Phlebotomus langeroni. The feeding media included human, dog (Canis familiaris), rat (Rattus rattus) and turkey (Melagris gallopava) bloods without or with Leishmania infantum or L. major promastigotes. Protein bands were identical among the feeding media of one host's blood but varied in number (24-28 bands) and relative mobilities among the various hosts' blood. Some protein fractions were common among the various hosts blood, others were only present in two or three hosts' blood and some were restricted to one host blood and were unique for each host. This study provides data which may help in understanding why blood from different natural hosts may variably influence the life cycle of Leishmania parasite in the sand fly gut. PMID:9425823

  10. Software tools for simultaneous data visualization and T cell epitopes and disorder prediction in proteins.

    Science.gov (United States)

    Jandrlić, Davorka R; Lazić, Goran M; Mitić, Nenad S; Pavlović, Mirjana D

    2016-04-01

    We have developed EpDis and MassPred, extendable open source software tools that support bioinformatic research and enable parallel use of different methods for the prediction of T cell epitopes, disorder and disordered binding regions and hydropathy calculation. These tools offer a semi-automated installation of chosen sets of external predictors and an interface allowing for easy application of the prediction methods, which can be applied either to individual proteins or to datasets of a large number of proteins. In addition to access to prediction methods, the tools also provide visualization of the obtained results, calculation of consensus from results of different methods, as well as import of experimental data and their comparison with results obtained with different predictors. The tools also offer a graphical user interface and the possibility to store data and the results obtained using all of the integrated methods in the relational database or flat file for further analysis. The MassPred part enables a massive parallel application of all integrated predictors to the set of proteins. Both tools can be downloaded from http://bioinfo.matf.bg.ac.rs/home/downloads.wafl?cat=Software. Appendix A includes the technical description of the created tools and a list of supported predictors. PMID:26851400

  11. Milk Proteins, Peptides, and Oligosaccharides: Effects against the 21st Century Disorders

    Directory of Open Access Journals (Sweden)

    Chia-Chien Hsieh

    2015-01-01

    Full Text Available Milk is the most complete food for mammals, as it supplies all the energy and nutrients needed for the proper growth and development of the neonate. Milk is a source of many bioactive components, which not only help meeting the nutritional requirements of the consumers, but also play a relevant role in preventing various disorders. Milk-derived proteins and peptides have the potential to act as coadjuvants in conventional therapies, addressing cardiovascular diseases, metabolic disorders, intestinal health, and chemopreventive properties. In addition to being a source of proteins and peptides, milk contains complex oligosaccharides that possess important functions related to the newborn’s development and health. Some of the health benefits attributed to milk oligosaccharides include prebiotic probifidogenic effects, antiadherence of pathogenic bacteria, and immunomodulation. This review focuses on recent findings demonstrating the biological activities of milk peptides, proteins, and oligosaccharides towards the prevention of diseases of the 21st century. Processing challenges hindering large-scale production and commercialization of those bioactive compounds have been also addressed.

  12. Concentration of total proteins in blood plasma of chickens hatched from irradiated eggs with low dose gamma radiation

    International Nuclear Information System (INIS)

    It is known that low-dose ionising radiation may have stimulating effects on chickens. Low doses may also cause changes in the concentration of blood plasma total proteins, glucose and cholesterol in chickens. This study investigates the effects of low dose gamma-radiation on the concentration of total proteins in the blood plasma of chickens hatched from eggs irradiated with a dose of 0.15 Gy on incubation days 7 and 19. Results were compared with the control group (chickens hatched from non-irradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from the heart, and later from the wing vein on days 1, 3, 5, 7,10, 20, 30 and 42. The concentration of total proteins was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 7 showed a statistically significant decrease on the sampling day 3 (P less than 0.05) and 7 (P less than 0.01). The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 19 showed a statistically significant increase only on sampling day 1 (P less than 0.05). These results suggest that exposure of eggs to 0.15 Gy of gamma-radiation on the 7th and 19th day of incubation could produce different effects on the protein metabolism in chickens.(author)

  13. Single-photon tomographic determination of regional cerebral blood flow in psychiatric disorders

    International Nuclear Information System (INIS)

    Regional cerebral blood flow (rCBF) was measured by single-photon emission computed tomography (SPECT) of 133-Xe washout in 29 normal volunteers, 22 unipolar endogenous depressives (UPE), 9 unipolar nonendogenous depressives (UPNE), 13 bipolar depressed patients (BPD), and 14 schizophrenic patients (SCHZ). RCBF was measured 2 and 6 cm above and parallel to the cantho-meatal line and quantitated in 14 gray matter regions. Most subjects were drug-free for 4-14 days. Diagnoses were made by experienced clinicians employing the Research Diagnostic Criteria, the Hamilton Rating Scale, and the dexamethasone suppression test. SCHZ were rated with the Brief Psychiatric Rating Scale. UPE had reduced flow compared to normals in the right parietal and temporal lobes and a nonsignificant trend toward left temporal flow reductions. UPNE were not different from normal or other patient groups. BPD had significant flow elevations in the left hemisphere relative to normal, and in both hemispheres relative to UPE. SCHZ were not significantly different from normal or other patient groups. Anterior-posterior flow shifts were evaluated by subtracting parietal or temporal flows from frontal flows. SCHZ demonstrated a greater posterior shift (lower relative frontal lobe flow) in comparison to both UPE and UPNE. The most significant regional flow abnormalities were observed as frontal flow reductions in individual SCHZ, although these were not significant in the whole group in comparison to normal

  14. Targeted mass spectrometry analysis of the proteins IGF1, IGF2, IBP2, IBP3 and A2GL by blood protein precipitation

    DEFF Research Database (Denmark)

    Such-Sanmartín, Gerard; Bache, Nicolai; Callesen, Anne K;

    2015-01-01

    aggravated when using fast high-throughput methods, which are necessary for analysis of hundreds and thousands of samples in clinical laboratories. The blood proteins IGF1, IGF2, IBP2, IBP3 and A2GL have been proposed as indirect biomarkers for detection of GH administration and as putative biomarkers for...

  15. On the importance of polar interactions for complexes containing intrinsically disordered proteins.

    Directory of Open Access Journals (Sweden)

    Eric T C Wong

    Full Text Available There is a growing recognition for the importance of proteins with large intrinsically disordered (ID segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions.

  16. Determination of olanzapine in whole blood using simple protein precipitation and liquid chromatography-tandem mass spectrometry

    DEFF Research Database (Denmark)

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe

    2009-01-01

    A simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of the antipsychotic drug olanzapine in whole blood using dibenzepine as internal standard (IS). After acidic methanol-induced protein precipitation of...

  17. C-reactive protein and white blood cell count do not improve clinical decision-making in acute appendicitis

    DEFF Research Database (Denmark)

    Tind, Sofie; Lassen, Annmarie Touborg; Zimmermann-Nielsen, Erik;

    2015-01-01

    INTRODUCTION: Acute appendicitis (AA) remains a diagnostic challenge as indicated by the high rate of unnecessary surgery. Blood samples, primarily C-reactive protein (CRP) and leucocyte counts, are used as a diagnostic supplement despite their relatively low sensitivities and specificities...... leucocyte counts did not influence clinical decision-making....

  18. The effect of varying protein levels on blood chemistry, food consumption, and behavior of captive seaducks

    Science.gov (United States)

    Wells-Berlin, A. M.; Perry, M.C.; Olsen, G.H.

    2005-01-01

    The Chesapeake Bay is a primary wintering area for scoters and the long-tailed ducks (Clangia hyemalis) that migrate along the Atlantic Flyway. Recently, the Chesapeake Bay had undergone an ecosystem shift and little is known about how this is affecting the seaduck populations. We are determining what are the preferred food sources of the seaducks wintering on the Bay and analyzing the factors influencing prey selection whether it is prey composition, energy assimilated, prey availability, or a combination of any or all of these factors. We have established a captive colony of surf (Melanitta perspicillata) and white-winged scoters (Melanitta fusca) as well as long-tailed ducks at Patuxent Wildlife Research Center to allow us to examine these factors in a more controlled environment. This project contains a multitude of experiments and the resultant data will be compiled into a compartmental model on the feeding ecology of seaducks wintering on the Bay. The first experiment entailed feeding groups of each species (four ducks per pen of equal sex ratio, if possible, and four pens per species) three diets varying in percent protein levels from November to February. Each diet was randomly assigned to each pen and the amount of food consumed was recorded each day. New feed was given when all existing food was consumed. Behavioral trials and blood profiles were completed on all study birds to determine the effects of the varying diets. There were no significant differences in food consumption, blood chemistry, and behavior detected at the 5% level among the diets for all three species of interest. There was a seasonal effect determined based on the food consumption data for white-winged scoters, but not for surf scoters or long-tailed ducks. The blood profiles of the surf scoters were compared to blood profiles of wild surf scoters and a there was no difference detected at the 5% level. As a health check of the ducks an aspergillosis test was run on the blood obtained

  19. Blood profile of proteins and steroid hormones predicts weight change after weight loss with interactions of dietary protein level and glycemic index.

    Directory of Open Access Journals (Sweden)

    Ping Wang

    Full Text Available BACKGROUND: Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI diet improved weight maintenance. OBJECTIVE: To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study. DESIGN: Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured. RESULTS: Angiotensin I converting enzyme (ACE was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24±1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%. CONCLUSIONS: A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss. REGISTRATION: ClinicalTrials.gov NCT00390637.

  20. Effect of Peumus boldus on the labeling of red blood cells and plasma proteins with Technetium-99m

    International Nuclear Information System (INIS)

    Peumus boldus is used in popular medicine in Brazil. The influence of Peumus boldus on the labeling of red blood cells and plasma proteins with 99mTc was studied. Stannous chloride and 99mTc pertechnetate were incubated with blood and a tincture of Peumus boldus. Aliquots of plasma and blood cells were isolated from the mixture and treated with trichloroacetic acid (TCA). After separation, analysis of the soluble and insoluble fractions showed a rapid uptake of the radioactivity by blood cells in the presence of the drug, whereas there was a slight decrease in the amount of 99mTc radioactivity in the TCA-insoluble fraction of plasma

  1. Effect of Peumus boldus on the labeling of red blood cells and plasma proteins with Technetium-99m

    Energy Technology Data Exchange (ETDEWEB)

    Wancke Reiniger, Ingrid; Fonseca de Oliveira, Joelma; Caldeira-de-Araujo, Adriano [Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Bernardo-Filho, Mario [Instituto Nacional de Cancer, Centro de Pesquisa Basica, Rio de Janeiro, RJ (Brazil)

    1999-08-01

    Peumus boldus is used in popular medicine in Brazil. The influence of Peumus boldus on the labeling of red blood cells and plasma proteins with {sup 99m}Tc was studied. Stannous chloride and {sup 99m}Tc pertechnetate were incubated with blood and a tincture of Peumus boldus. Aliquots of plasma and blood cells were isolated from the mixture and treated with trichloroacetic acid (TCA). After separation, analysis of the soluble and insoluble fractions showed a rapid uptake of the radioactivity by blood cells in the presence of the drug, whereas there was a slight decrease in the amount of {sup 99m}Tc radioactivity in the TCA-insoluble fraction of plasma.

  2. Effect of Peumus boldus on the labeling of red blood cells and plasma proteins with technetium-99m.

    Science.gov (United States)

    Reiniger, I W; de Oliveira, J F; Caldeira-de-Araújo, A; Bernardo-Filho, M

    1999-08-01

    Peumus boldus is used in popular medicine in Brazil. The influence of Peumus boldus on the labeling of red blood cells and plasma proteins with 99mTc was studied. Stannous chloride and 99mTc pertechnetate were incubated with blood and a tincture of Peumus boldus. Aliquots of plasma and blood cells were isolated from the mixture and treated with trichloroacetic acid (TCA). After separation, analysis of the soluble and insoluble fractions showed a rapid uptake of the radioactivity by blood cells in the presence of the drug, whereas there was a slight decrease in the amount of 99mTc radioactivity in the TCA-insoluble fraction of plasma. PMID:10376326

  3. Towards a Proteomic Catalogue and Differential Annotation of Salivary Gland Proteins in Blood Fed Malaria Vector Anopheles culicifacies by Mass Spectrometry.

    Science.gov (United States)

    Rawal, Ritu; Vijay, Sonam; Kadian, Kavita; Singh, Jagbir; Pande, Veena; Sharma, Arun

    2016-01-01

    In order to understand the importance of functional proteins in mosquito behavior, following blood meal, a baseline proteomic dataset is essential for providing insights into the physiology of blood feeding. Therefore, in this study as first step, in solution and 1-D electrophoresis digestion approach combined with tandem mass spectrometry (nano LC-MS/MS) and computational bioinformatics for data mining was used to prepare a baseline proteomic catalogue of salivary gland proteins of sugar fed An. culicifacies mosquitoes. A total of 106 proteins were identified and analyzed by SEQUEST algorithm against mosquito protein database from Uniprot/NCBI. Importantly, D7r1, D7r2, D7r4, salivary apyrase, anti-platelet protein, calreticulin, antigen 5 family proteins were identified and grouped on the basis of biological and functional roles. Secondly, differential protein expression and annotations between salivary glands of sugar fed vs blood fed mosquitoes was analyzed using 2-Delectrophoresis combined with MALDI-TOF mass spectrometry. The alterations in the differential expression of total 38 proteins was observed out of which 29 proteins like beclin-1, phosphorylating proteins, heme oxygenase 1, ferritin, apoptotic proteins, coagulation and immunity like, serine proteases, serpins, c-type lectin and protein in regulation of blood feeding behavior were found to be up regulated while 9 proteins related to blood feeding, juvenile hormone epoxide hydrolase ii, odorant binding proteins and energy metabolic enzymes were found to be down regulated. To our knowledge, this study provides a first time baseline proteomic dataset and functional annotations of An. culicifacies salivary gland proteins that may be involved during the blood feeding. Identification of differential salivary proteins between sugar fed and blood fed mosquitoes and their plausible role may provide insights into the physiological processes associated with feeding behavior and sporozoite transmission during the

  4. DMPD: Protein kinase C epsilon: a new target to control inflammation andimmune-mediated disorders. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14643884 Protein kinase C epsilon: a new target to control inflammation andimmune-mediated diso...g) (.html) (.csml) Show Protein kinase C epsilon: a new target to control inflammation andimmune-mediated diso...l inflammation andimmune-mediated disorders. Authors Aksoy E, Goldman M, Willems F. Publication Int J Bioche

  5. Platelet Disorders

    Science.gov (United States)

    ... higher risk of blood clots. With other platelet disorders, the platelets do not work as they should. ... This can cause excessive bleeding. Treatment of platelet disorders depends on the cause. NIH: National Heart, Lung, ...

  6. Prevalence of Sexually Transmitted Diseases and Blood-Borne Transmitted Infections among Male Patients with Antisocial Personality Disorder

    Directory of Open Access Journals (Sweden)

    Hamza Yıldız

    2015-03-01

    Full Text Available Objective: The aim of this study was to compare the patients who have antisocial personality disorder (ASPD and the healthy individuals in terms of sexually transmitted diseases (STDs and Blood-Borne Transmitted Infections (BTIs prevalences. Methods: This study is a prospective, single-center, open-label, non-randomized controlled clinical study. There were two groups in the study. The patient group consistsed of 100 males who were diagnosed as ASPD with a clinical interview form. The control group consisted of 98 healthy males who did not have any psychiatric disorder. Dermatologic examination was performed, and clinical findings were recorded. Results: The mean age of the patient group was 21.96±2.40 (range 20-37 years. The mean age of the control group was 24.20±2.88 (21-36 years. The most common disease was gonorrhea (25% followed by genital wart (11%, molluskum contagiosum (5%, HBsAg (4%, and HSV-2 seropositivity (4% in the patients group. In the control group, HSV-2 seropositivity (4.08%, genital wart (3.06%, molluskum contagiosum (3.06%, and gonorrhe (1.02% were commonly seen in the control group. STDs and/or BVTIs were found more common in the patients group (82% than that in the control group (45.91% (X2=30.62, p=0.000. Conclusions: The patients with ASPD are at greater risk than normal population to catch a STDs or BTIs because of their lower educational levels and riskier behaviors. This condition entertains a risk in the general population and the patients themselves.

  7. Changes in cerebral blood flow after cognitive behavior therapy in patients with panic disorder: a SPECT study

    Directory of Open Access Journals (Sweden)

    Seo HJ

    2014-04-01

    Full Text Available Ho-Jun Seo,1 Young Hee Choi,2 Yong-An Chung,3 Wangku Rho,1 Jeong-Ho Chae11Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Metta Institute of Cognitive Behavior Therapy, Seoul, South Korea; 3Department of Radiology, Nuclear Medicine, College of Medicine, The Catholic University of Korea, Seoul, South KoreaAim: Inconsistent results continue to be reported in studies that examine the neural correlates of cognitive behavioral therapy (CBT in patients with panic disorder. We examined the changes in regional cerebral blood flow (rCBF associated with the alleviation of anxiety by CBT in panic patients.Methods: The change in rCBF and clinical symptoms before and after CBT were assessed using single photon emission computed tomography and various clinical measures were analyzed.Results: Fourteen subjects who completed CBT showed significant improvements in symptoms on clinical measures, including the Panic and Agoraphobic Scale and the Anxiety Sensitivity Index-Revised. After CBT, increased rCBF was detected in the left postcentral gyrus (BA 43, left precentral gyrus (BA 4, and left inferior frontal gyrus (BA 9 and BA 47, whereas decreased rCBF was detected in the left pons. Correlation analysis of the association between the changes in rCBF and changes in each clinical measure did not show significant results.Conclusion: We found changes in the rCBF associated with the successful completion of CBT. The present findings may help clarify the effects of CBT on changes in brain activity in panic disorder.Keyword: single photon emission computed tomography (SPECT, anxiety, neural correlate, brain activity

  8. Attention deficit/hyperactivity disorder: is there a correlation between dopamine transporter density and cerebral blood flow?

    Science.gov (United States)

    da Silva, Neivo; Szobot, Claudia M; Anselmi, Carlos E; Jackowski, Andrea P; Chi, Shih M; Hoexter, Marcelo Q; Anselmi, Osvaldo E; Pechansky, Flavio; Bressan, Rodrigo A; Rohde, Luis A

    2011-08-01

    Attention deficit/hyperactivity disorder (ADHD) is one of the most frequent behavioral problems in school-age children. Although the etiology remains unclear, the involvement of the dopaminergic system has been suggested by genetic studies that report an overexpression of the dopamine transporter (DAT) gene. In spite of these abnormalities being directly related to the decrease of dopamine (DA) in the striatum (STR), abnormalities in brain perfusion have also been observed in cortical-subcortical structures. Functional neuroimaging studies have suggested that the DA concentration may cause changes in the cerebral blood flow (CBF). The objective of our study was to evaluate the relationship between DAT density in STR and cortical-subcortical impairment in CBF. Based on the hypothesis that there is a correlation between DA availability and brain perfusion, we postulated that individuals with ADHD, with a higher DAT density in the basal ganglia, will have lower perfusion in the fronto-striatal-cerebellar networks. We used Tc-99m TRODAT-1 SPECT to measure DAT density and Tc-99m ECD SPECT to assess brain perfusion. Ten adolescents diagnosed with ADHD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were investigated. Analysis with Statistical Parametric Mapping 5 corrected for multiple comparisons, using small volume correction, showed a significant negative correlation between the DAT density in the STR and CBF in the cingulate gyrus, frontal lobe, temporal lobe, and cerebellum (pFDR <0.01). Our findings suggest that higher DAT density in the STR was associated with a decrease in the regional CBF in the cortical and subcortical attention network. PMID:21716015

  9. FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

    International Nuclear Information System (INIS)

    Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples. The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders

  10. FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

    Directory of Open Access Journals (Sweden)

    Di Bonito Maurizio

    2007-01-01

    Full Text Available Abstract Background Fos-related antigen 1 (FRA-1 is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. Methods We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. Results FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB samples. Conclusion The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative

  11. Improving the chemical shift dispersion of multidimensional NMR spectra of intrinsically disordered proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bermel, Wolfgang [Bruker BioSpin GmbH (Germany); Bruix, Marta [Consejo Superior de Investigaciones Cientificas, Instituto de Quimica Fisica ' ' Rocasolano' ' (Spain); Felli, Isabella C., E-mail: felli@cerm.unifi.it [University of Florence, Department of Chemistry ' Ugo Shiff' (Italy); Kumar, M.V. Vasantha [University of Florence, Magnetic Resonance Center (Italy); Pierattelli, Roberta, E-mail: pierattelli@cerm.unifi.it [University of Florence, Department of Chemistry ' Ugo Shiff' (Italy); Serrano, Soraya [Consejo Superior de Investigaciones Cientificas, Instituto de Quimica Fisica ' ' Rocasolano' ' (Spain)

    2013-03-15

    Intrinsically disordered proteins (IDPs) have recently attracted the attention of the scientific community challenging the well accepted structure-function paradigm. In the characterization of the dynamic features of proteins nuclear magnetic resonance spectroscopy (NMR) is a strategic tool of investigation. However the peculiar properties of IDPs, with the lack of a unique 3D structure and their high flexibility, have a strong impact on NMR observables (low chemical shift dispersion, efficient solvent exchange broadening) and thus on the quality of NMR spectra. Key aspects to be considered in the design of new NMR experiments optimized for the study of IDPs are discussed. A new experiment, based on direct detection of {sup 13}C{sup {alpha}}, is proposed.

  12. Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder - Results from a prospective study

    DEFF Research Database (Denmark)

    Jacoby, Anne Sophie; Munkholm, Klaus; Vinberg, Maj;

    2016-01-01

    . Further, 69 blood samples were drawn from 35 healthy control subjects with three months apart. In unadjusted mixed-model analysis, levels of IL-6 and IL-8 were increased 64% (b=1.64, 95% CI: 1.31-2.05, p=<0.0001) and 24% (b=1.24, 95% CI: 1.05-1.47, p=0.013), respectively in patients with bipolar disorder......BACKGROUND: Peripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression. AIMS: To investigate whether neutrophins and inflammatory marker vary with mood...... states and are increased in patients with bipolar disorder type I during euthymia as well as in all affective states as a group, compared to levels in healthy control subjects. METHODS: In a prospective 6-12 months follow-up study, we investigated state specific, intra-individual alterations in levels of...

  13. SLiMPrints: conservation-based discovery of functional motif fingerprints in intrinsically disordered protein regions

    Science.gov (United States)

    Davey, Norman E.; Cowan, Joanne L.; Shields, Denis C.; Gibson, Toby J.; Coldwell, Mark J.; Edwards, Richard J.

    2012-01-01

    Large portions of higher eukaryotic proteomes are intrinsically disordered, and abundant evidence suggests that these unstructured regions of proteins are rich in regulatory interaction interfaces. A major class of disordered interaction interfaces are the compact and degenerate modules known as short linear motifs (SLiMs). As a result of the difficulties associated with the experimental identification and validation of SLiMs, our understanding of these modules is limited, advocating the use of computational methods to focus experimental discovery. This article evaluates the use of evolutionary conservation as a discriminatory technique for motif discovery. A statistical framework is introduced to assess the significance of relatively conserved residues, quantifying the likelihood a residue will have a particular level of conservation given the conservation of the surrounding residues. The framework is expanded to assess the significance of groupings of conserved residues, a metric that forms the basis of SLiMPrints (short linear motif fingerprints), a de novo motif discovery tool. SLiMPrints identifies relatively overconstrained proximal groupings of residues within intrinsically disordered regions, indicative of putatively functional motifs. Finally, the human proteome is analysed to create a set of highly conserved putative motif instances, including a novel site on translation initiation factor eIF2A that may regulate translation through binding of eIF4E. PMID:22977176

  14. The Pf332 gene codes for a megadalton protein of Plasmodium falciparum asexual blood stages

    Directory of Open Access Journals (Sweden)

    Denise Mattei

    1992-01-01

    Full Text Available We characterized the Plasmodium falciparum antigen 332 (Ag332 which is specifically expressed during the asexual intraerythrocytic cycle of the parasite. The corresponding Pf332 gene has been located in the subtelomeric region of chromosome 11. Furthermore, it is present in all strais so far analyzed and shows marked restriction length fragment polymorphism. Partial sequence and restriction endonuclease digestion of cloned fragments revealed that the Pf332 gene is composed of highly degenerated repeats rich is glutamic acid. Mung been nuclease digestion and Northern blot analysis suggested that Pf332 gene codes for a protein of about 700 kDa. These data were further confirmed by Western blot and immunoprecipitation of parasites extracts with an antiserum raised against a recombinant clone expressing part of the Ag332. Confocal immunofluorescence showed that Ag332 is translocated from the parasite to the surface of infected red blood cells within vesicle-like structures. In addition, Ag332 was detected on the surface of monkey erythrocytes infected with Plasmodium falciparum.

  15. [Genetic polymorphism of blood protein of six Passeriformes species in Zhalong National Nature Reserve].

    Science.gov (United States)

    Xu, Xing-Jun; Lü, Jian-Wei; Xuan, Li-Fang; Zhang, Dong-Yue; Zhou, Shuang-Tao; Zhao, Kan; Wang, Bin; Shao, Shu-Li

    2009-06-01

    The polymorphism of hemoglobin (Hb), serum albumin (Alb), trandferring (Tf) and adenosin deaminase (Ada) in the blood of Emberiza elegans, Phylloscopus inornatus, E. aureola, Lanius tigrinus, Passer montanus, and E. spodocephala in Zhalong National Nature Reserve were studied by SDS-polyacrylamide-gel electrophoresis. All the protein loci of the six Passeriformes species exhibited polymorphism, and Ada locus had a relatively high heterozygosity. The analysis of average heterozygosity demonstrated that P. inornatus had a higher population genetic variance, while E. spodocephala was relatively stable. The six species could be classified into two clusters. E. elegans, E. aureola, E. spodocephala and P. inornatus were clustered into one group, while P. montanus and L. tigrinus were clustered into another group. This clustering was consistent with the actual taxonomic status of the six species. The higher thermoregulation index and predation pressure of the study area did not lead to the substantial variation of hereditary constitution of the six species, possibly due to the gene intercommunion between the six species and the outside of the study area, which decreased the variance and differentiation of the population genetics of the six species. PMID:19795660

  16. Reduced mRNA expression of PTGDS in peripheral blood mononuclear cells of rapid-cycling bipolar disorder patients compared with healthy control subjects

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Peijs, Lone; Kessing, Lars Vedel;

    2015-01-01

    BACKGROUND: Disturbances related to the arachidonic acid cascade and prostaglandin metabolism may be involved in the pathophysiology of bipolar disorder, as supported by a recent genome-wide association study meta-analysis; however, evidence from clinical studies on a transcriptional level...... disorder. The sample size was limited; replication of the findings in larger, independent samples is warranted to further explore the role of the arachidonic acid cascade and prostaglandin metabolism as a potential therapeutic target in bipolar disorder....... that mRNA expression of PTGDS and AKR1C3 is deregulated in rapid-cycling disorder patients in a euthymic or current affective state compared with healthy control subjects, and that expression alters with affective states. METHODS: PTGDS and AKR1C3 mRNA expression in peripheral blood mononuclear cells...

  17. Effects of previous protein intake on rectal temperature, blood glucose, plasma thyroid hormone and minerals by laying hens during a forced molt

    International Nuclear Information System (INIS)

    The effects of forced molting on blood glucose, rectal temperature, plasma T4, T3 and minerals were studied in hens previously fed rations with different protein contents (14, 17 and 20% crude protein). Blood samples were obtained from brachial veins for blood glucose, T4 and T3 were measured by radioimmunoassay, and plasma minerals were determined by atomic absorption spectroscopy. Blood glucose and rectal temperature were reduced during fasting regardless of previous protein intake. Pre molting T4 plasma level was higher in laying hens fed higher protein ration, but feed deprivation reduced T4 and T3 concentrations irrespective of protein intake, except T4 level for 14% crude protein fed birds that increased during fasting. The data obtained in this experiment suggest that previous protein intake does not interfere with the metabolic changes during forced molt. (author). 19 refs, 1 fig, 4 tabs

  18. Combining predictors of natively unfolded proteins to detect a twilight zone between order and disorder in generic datasets

    OpenAIRE

    Deiana, Antonio; Giansanti, Andrea

    2009-01-01

    Natively unfolded proteins lack a well defined three dimensional structure but have important biological functions, suggesting a re-assignment of the structure-function paradigm. Many proteins have amino acidic compositions compatible both with the folded and unfolded status, and belong to a twilight zone between order and disorder. This makes difficult a dichotomic classification of protein sequences into folded and natively unfolded ones. In this methodological paper dichotomic folding inde...

  19. Blood smear

    Science.gov (United States)

    ... of RBCs due to body destroying them ( immune hemolytic anemia ) Low number of RBCs due to some red ... of Heinz bodies may indicate: Alpha thalassemia Congenital hemolytic anemia Disorder in which red blood cells break down ...

  20. Identifying intrinsically disordered protein regions likely to undergo binding-induced helical transitions.

    Science.gov (United States)

    Glover, Karen; Mei, Yang; Sinha, Sangita C

    2016-10-01

    Many proteins contain intrinsically disordered regions (IDRs) lacking stable secondary and ordered tertiary structure. IDRs are often implicated in macromolecular interactions, and may undergo structural transitions upon binding to interaction partners. However, as binding partners of many protein IDRs are unknown, these structural transitions are difficult to verify and often are poorly understood. In this study we describe a method to identify IDRs that are likely to undergo helical transitions upon binding. This method combines bioinformatics analyses followed by circular dichroism spectroscopy to monitor 2,2,2-trifluoroethanol (TFE)-induced changes in secondary structure content of these IDRs. Our results demonstrate that there is no significant change in the helicity of IDRs that are not predicted to fold upon binding. IDRs that are predicted to fold fall into two groups: one group does not become helical in the presence of TFE and includes examples of IDRs that form β-strands upon binding, while the other group becomes more helical and includes examples that are known to fold into helices upon binding. Therefore, we propose that bioinformatics analyses combined with experimental evaluation using TFE may provide a general method to identify IDRs that undergo binding-induced disorder-to-helix transitions. PMID:27179590

  1. A Method for Systematic Assessment of Intrinsically Disordered Protein Regions by NMR

    Directory of Open Access Journals (Sweden)

    Natsuko Goda

    2015-07-01

    Full Text Available Intrinsically disordered proteins (IDPs that lack stable conformations and are highly flexible have attracted the attention of biologists. Therefore, the development of a systematic method to identify polypeptide regions that are unstructured in solution is important. We have designed an “indirect/reflected” detection system for evaluating the physicochemical properties of IDPs using nuclear magnetic resonance (NMR. This approach employs a “chimeric membrane protein”-based method using the thermostable membrane protein PH0471. This protein contains two domains, a transmembrane helical region and a C-terminal OB (oligonucleotide/oligosaccharide binding-fold domain (named NfeDC domain, connected by a flexible linker. NMR signals of the OB-fold domain of detergent-solubilized PH0471 are observed because of the flexibility of the linker region. In this study, the linker region was substituted with target IDPs. Fifty-three candidates were selected using the prediction tool POODLE and 35 expression vectors were constructed. Subsequently, we obtained 15N-labeled chimeric PH0471 proteins with 25 IDPs as linkers. The NMR spectra allowed us to classify IDPs into three categories: flexible, moderately flexible, and inflexible. The inflexible IDPs contain membrane-associating or aggregation-prone sequences. This is the first attempt to use an indirect/reflected NMR method to evaluate IDPs and can verify the predictions derived from our computational tools.

  2. Calcium ion binding properties and the effect of phosphorylation on the intrinsically disordered Starmaker protein.

    Science.gov (United States)

    Wojtas, Magdalena; Hołubowicz, Rafał; Poznar, Monika; Maciejewska, Marta; Ożyhar, Andrzej; Dobryszycki, Piotr

    2015-10-27

    Starmaker (Stm) is an intrinsically disordered protein (IDP) involved in otolith biomineralization in Danio rerio. Stm controls calcium carbonate crystal formation in vivo and in vitro. Phosphorylation of Stm affects its biomineralization properties. This study examined the effects of calcium ions and phosphorylation on the structure of Stm. We have shown that CK2 kinase phosphorylates 25 or 26 residues in Stm. Furthermore, we have demonstrated that Stm's affinity for calcium binding is dependent on its phosphorylation state. Phosphorylated Stm (StmP) has an estimated 30 ± 1 calcium binding sites per protein molecule with a dissociation constant (KD) of 61 ± 4 μM, while the unphosphorylated protein has 28 ± 3 sites and a KD of 210 ± 22 μM. Calcium ion binding induces a compaction of the Stm molecule, causing a significant decrease in its hydrodynamic radius and the formation of a secondary structure. The screening effect of Na(+) ions on calcium binding was also observed. Analysis of the hydrodynamic properties of Stm and StmP showed that Stm and StmP molecules adopt the structure of native coil-like proteins. PMID:26445027

  3. Long-lasting hippocampal synaptic protein loss in a mouse model of posttraumatic stress disorder.

    Directory of Open Access Journals (Sweden)

    Leonie Herrmann

    Full Text Available Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expression levels of a set of neurostructural marker proteins between traumatized and control mice at different time points after their subjection to either an electric footshock or mock treatment which was followed by stressful re-exposure in several experimental groups. To our knowledge, this is the first systematic in vivo study analyzing the long-term neuromolecular sequelae of acute traumatic stress combined with re-exposure. We show here that a PTSD-like syndrome in mice is accompanied by a long-lasting reduction of hippocampal synaptic proteins which interestingly correlates with the strength of the generalized and conditioned fear response but not with the intensity of hyperarousal symptoms. Furthermore, we demonstrate that treatment with the serotonin reuptake inhibitor (SSRI fluoxetine is able to counteract both the PTSD-like syndrome and the posttraumatic synaptic protein loss. Taken together, this study demonstrates for the first time that a loss of hippocampal synaptic proteins is associated with a PTSD-like syndrome in mice. Further studies will have to reveal whether these findings are transferable to PTSD patients.

  4. Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly.

    Science.gov (United States)

    Fadda, Elisa

    2016-01-01

    Lack of structure is often an essential functional feature of protein domains. The coordination of macromolecular assemblies in DNA repair pathways is yet another task disordered protein regions are highly implicated in. Here I review the available experimental and computational data and within this context discuss the functional role of structure and disorder in one of the essential scaffolding proteins in the nucleotide excision repair (NER) pathway, namely Xeroderma pigmentosum complementation group A (XPA). From the analysis of the current knowledge, in addition to protein-protein docking and secondary structure prediction results presented for the first time herein, a mechanistic framework emerges, where XPA builds the NER pre-incision complex in a modular fashion, as "beads on a string", where the protein-protein interaction "beads", or modules, are interconnected by disordered link regions. This architecture is ideal to avoid the expected steric hindrance constraints of the DNA expanded bubble. Finally, the role of the XPA structural disorder in binding affinity modulation and in the sequential binding of NER core factors in the pre-incision complex is also discussed. PMID:26865925

  5. Analysis on blood glucose metabolic disorders in critically ill neonates%危重新生儿血糖代谢紊乱相关因素分析

    Institute of Scientific and Technical Information of China (English)

    李艳秋; 赵军

    2012-01-01

    目的:对危重新生儿血糖代谢紊乱的相关因素进行调查分析,为临床治疗提供参考依据.方法:分析2007年6月~2011年6月168例危重新生儿血糖代谢紊乱的形成原因.结果:168例血糖代谢紊乱患者中,低血糖症者97例,高血糖症者42例,二者兼有者29例.血糖代谢紊乱与胎龄和出生体重呈负相关,而且在轻度窒息的情形下低血糖症状较多,重度窒息的情况下高血糖症状较多.结论:对危重新生儿血糖代谢紊乱相关因素的分析,可以及时发现和治疗病症,减少患儿日后的痛苦.%Objective; To investigate and analyze the related factors of blood glucose metabolic disorders in critically ill neonates, provide reference for clinical treatment. Methods; The causes of blood glucose metabolic disorders in 168 critically ill neonates who were treated in the hospital from June 2007 to June 2011 were analyzed. Results; Among 168 neonates with blood glucose metabolic disorders, 97 neonates were found with hypoglycemia, 42 neonates were found with hyperglycemia, and 29 neonates were found with both of the above -mentioned diseases. There was a negative correlation between blood glucose metabolic disorders and birth weight, hypoglycemia was commonly found under the circumstance of mild asphyxia, and hyperglycemia was commonly found under the circumstance of severe asphyxia. Conclusion; Blood glucose metabolic disorders can be diagnosed and cured timely through analyzing the related factors of blood glucose metabolic disorders in critically ill neonates to reduce future pains of the neonates.

  6. Production of soluble recombinant proteins with Kell, Duffy and Lutheran blood group antigen activity, and their use in screening human sera for Kell, Duffy and Lutheran antibodies.

    Science.gov (United States)

    Ridgwell, K; Dixey, J; Scott, M L

    2007-10-01

    The aim of this study was to show that soluble recombinant (sr) proteins can mimic blood group antigens and be used to screen human sera for blood-group-specific antibodies. The blood of all pregnant women and pretransfusion patients should be screened for blood-group-specific antibodies to identify and monitor pregnancies at risk of haemolytic disease of the foetus and newborn (HDFN), and to prevent haemolytic transfusion reactions. Current antibody screening and identification methods use human red blood cell panels, which can complicate antibody identification if more than one antibody specificity is present. COS-7 cells were transfected to produce sr forms of the extracellular domains of the red blood cell membrane proteins that express Kell, Duffy or Lutheran blood group antigens. These sr proteins were used to screen for and identify anti-Kell, anti-Duffy or anti-Lutheran blood-group-specific allo-antibodies in human sera by haemagglutination inhibition and in solid-phase enzyme-linked immunosorbent assays (ELISAs). There is a positive correlation (correlation coefficient 0.605, P value 0.002) between antibody titre by standard indirect antiglobulin test (IAT) and signal intensity in the ELISA test. This work shows that sr proteins can mimic blood group antigens and react with human allogeneic antibodies, and that such proteins could be used to develop solid-phase, high-throughput blood group antibody screening and identification platforms. PMID:17725551

  7. Blood levels of critical amino acids in very low birthweight infants on a high human milk protein intake.

    Science.gov (United States)

    Lindblad, B S; Hagelberg, S; Lundsjö, A

    1982-01-01

    A method for a semi-industrial production of human milk subfractions (human milk protein and human milk fat isolates) is described. Four very low birthweight (VLBW) newborn were given a human milk protein isolate added to the mother's own fresh expressed milk in addition to sodium chloride up to 20 mEkv/liter. Growth followed the intrauterine growth curve. Urea levels did not increase in spite of providing a double-normal protein intake. There was no metabolic acidosis and the blood levels of free amino acids determined with a micro-method did not exceed those seen after a normal meal. The concentrated human milk protein product showed a considerable specific sIgA activity against E. coli 0-antigen. It seems possible to use similar "lacto-engineering"-techniques in order to satisfy the increased protein requirements of the VLBW infant, while providing the caloric requirements, without causing any visible disturbance of blood-homeostasis of urea, amino acids or base excess. The method could provide knowledge about the "human milk protein requirements" and a controlled study has been started. PMID:6961736

  8. Sleep, Plasticity and the Pathophysiology of Neurodevelopmental Disorders: The Potential Roles of Protein Synthesis and Other Cellular Processes

    Directory of Open Access Journals (Sweden)

    Dante Picchioni

    2014-03-01

    Full Text Available Sleep is important for neural plasticity, and plasticity underlies sleep-dependent memory consolidation. It is widely appreciated that protein synthesis plays an essential role in neural plasticity. Studies of sleep-dependent memory and sleep-dependent plasticity have begun to examine alterations in these functions in populations with neurological and psychiatric disorders. Such an approach acknowledges that disordered sleep may have functional consequences during wakefulness. Although neurodevelopmental disorders are not considered to be sleep disorders per se, recent data has revealed that sleep abnormalities are among the most prevalent and common symptoms and may contribute to the progression of these disorders. The main goal of this review is to highlight the role of disordered sleep in the pathology of neurodevelopmental disorders and to examine some potential mechanisms by which sleep-dependent plasticity may be altered. We will also briefly attempt to extend the same logic to the other end of the developmental spectrum and describe a potential role of disordered sleep in the pathology of neurodegenerative diseases. We conclude by discussing ongoing studies that might provide a more integrative approach to the study of sleep, plasticity, and neurodevelopmental disorders.

  9. Movement disorders.

    Science.gov (United States)

    Stoessl, A Jon; Mckeown, Martin J

    2016-01-01

    Movement disorders can be hypokinetic (e.g., parkinsonism), hyperkinetic, or dystonic in nature and commonly arise from altered function in nuclei of the basal ganglia or their connections. As obvious structural changes are often limited, standard imaging plays less of a role than in other neurologic disorders. However, structural imaging is indicated where clinical presentation is atypical, particularly if the disorder is abrupt in onset or remains strictly unilateral. More recent advances in magnetic resonance imaging (MRI) may allow for differentiation between Parkinson's disease and atypical forms of parkinsonism. Functional imaging can assess regional cerebral blood flow (functional MRI (fMRI), positron emission tomography (PET), or single-photon emission computed tomography (SPECT)), cerebral glucose metabolism (PET), neurochemical and neuroreceptor status (PET and SPECT), and pathologic processes such as inflammation or abnormal protein deposition (PET) (Table 49.1). Cerebral blood flow can be assessed at rest, during the performance of motor or cognitive tasks, or in response to a variety of stimuli. In appropriate situations, the correct imaging modality and/or combination of modalities can be used to detect early disease or even preclinical disease, and to monitor disease progression and the effects of disease-modifying interventions. Various approaches are reviewed here. PMID:27430452

  10. Phosphorylation Regulates the Bound Structure of an Intrinsically Disordered Protein: The p53-TAZ2 Case.

    Directory of Open Access Journals (Sweden)

    Raúl Esteban Ithuralde

    Full Text Available Disordered regions and Intrinsically Disordered Proteins (IDPs are involved in critical cellular processes and may acquire a stable three-dimensional structure only upon binding to their partners. IDPs may follow a folding-after-binding process, known as induced folding, or a folding-before-binding process, known as conformational selection. The transcription factor p53 is involved in the regulation of cellular events that arise upon stress or DNA damage. The p53 domain structure is composed of an N-terminal transactivation domain (p53TAD, a DNA Binding Domain and a tetramerization domain. The activity of TAD is tightly regulated by interactions with cofactors, inhibitors and phosphorylation. To initiate transcription, p53TAD binds to the TAZ2 domain of CBP, a co-transcription factor, and undergoes a folding and binding process, as revealed by the recent NMR structure of the complex. The activity of p53 is regulated by phosphorylation at multiple sites on the TAD domain and recent studies have shown that modifications at three residues affect the binding towards TAZ2. However, we still do not know how these phosphorylations affect the structure of the bound state and, therefore, how they regulate the p53 function. In this work, we have used computational simulations to understand how phosphorylation affects the structure of the p53TAD:TAZ2 complex and regulates the recognition mechanism. Phosphorylation has been proposed to enhance binding by direct interaction with the folded protein or by changing the unbound conformation of IDPs, for example by pre-folding the protein favoring the recognition mechanism. Here, we show an interesting turn in the p53 case: phosphorylation mainly affects the bound structure of p53TAD, highlighting the complexity of IDP protein-protein interactions. Our results are in agreement with previous experimental studies, allowing a clear picture of how p53 is regulated by phosphorylation and giving new insights into how

  11. Effect of an extract of Artemisia vulgaris L. (Mugwort) on the in vitro labeling of red blood cells and plasma proteins with technetium-99m

    International Nuclear Information System (INIS)

    The aim of this work was to evaluate the effect of an extract of the Artemisia vulgaris L. (mugwort) on the labeling of blood constituents with technetium-99m (99mTc). Blood samples from Wistar rats were incubated with a mugwort extract and the radiolabeling of blood constituents was carried out. Plasma and blood cells were separated by centrifugation. Aliquots of plasma and blood cells were also precipitated with trichloroacetic acid and centrifuged to isolate soluble and insoluble fractions of plasma and blood cells. Radioactivity in each fraction was counted and the percentages of radioactivity (%ATI) was calculated. Mugwort extract decreased significantly (p<0.05) the %ATI on the blood compartments and on the blood cells proteins (insoluble fraction). The analysis of the results indicates that the extract could have substances that could interfere on the transport of stannous through the erythrocyte membrane altering the labeling of blood cells with 99mTc. (author)

  12. Elevated C-reactive protein and late-onset bipolar disorder in 78 809 individuals from the general population

    DEFF Research Database (Denmark)

    Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne

    2016-01-01

    BACKGROUND: No prospective studies have examined the role of C-reactive protein (CRP) in late-onset bipolar disorder. AIMS: We tested the hypothesis that elevated levels of CRP are associated cross-sectionally and prospectively with late-onset bipolar disorder, and that such an association possibly...... levels of CRP were associated both cross-sectionally and prospectively with late-onset bipolar disorder. When CRP was on a continuous scale, a doubling in CRP yielded an observational odds ratio for late-onset bipolar disorder of 1.28 (1.08-1.52) with a corresponding causal odds ratio of 4.66 (0.......89-24.3). CONCLUSION: Elevated CRP is associated with increased risk of late-onset bipolar disorder in the general population which was supported by the genetic analysis....

  13. Enhanced neutralization potency of botulinum neurotoxin antibodies using a red blood cell-targeting fusion protein.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    Full Text Available Botulinum neurotoxin (BoNT potently inhibits cholinergic signaling at the neuromuscular junction. The ideal countermeasures for BoNT exposure are monoclonal antibodies or BoNT antisera, which form BoNT-containing immune complexes that are rapidly cleared from the general circulation. Clearance of opsonized toxins may involve complement receptor-mediated immunoadherence to red blood cells (RBC in primates or to platelets in rodents. Methods of enhancing immunoadherence of BoNT-specific antibodies may increase their potency in vivo. We designed a novel fusion protein (FP to link biotinylated molecules to glycophorin A (GPA on the RBC surface. The FP consists of an scFv specific for murine GPA fused to streptavidin. FP:mAb:BoNT complexes bound specifically to the RBC surface in vitro. In a mouse model of BoNT neutralization, the FP increased the potency of single and double antibody combinations in BoNT neutralization. A combination of two antibodies with the FP gave complete neutralization of 5,000 LD50 BoNT in mice. Neutralization in vivo was dependent on biotinylation of both antibodies and correlated with a reduction of plasma BoNT levels. In a post-exposure model of intoxication, FP:mAb complexes gave complete protection from a lethal BoNT/A1 dose when administered within 2 hours of toxin exposure. In a pre-exposure prophylaxis model, mice were fully protected for 72 hours following administration of the FP:mAb complex. These results demonstrate that RBC-targeted immunoadherence through the FP is a potent enhancer of BoNT neutralization by antibodies in vivo.

  14. Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex

    Science.gov (United States)

    Vovk, Andrei; Gu, Chad; Opferman, Michael G; Kapinos, Larisa E; Lim, Roderick YH; Coalson, Rob D; Jasnow, David; Zilman, Anton

    2016-01-01

    Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function. DOI: http://dx.doi.org/10.7554/eLife.10785.001 PMID:27198189

  15. Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder

    OpenAIRE

    Maria Jalbrzikowski; Maria T Lazaro; Fuying Gao; Alden Huang; Carolyn Chow; Geschwind, Daniel H.; Giovanni Coppola; Bearden, Carrie E.

    2015-01-01

    Background 22q11.2 Deletion Syndrome (22q11DS) represents one of the greatest known genetic risk factors for the development of psychotic illness, and is also associated with high rates of autistic spectrum disorders (ASD) in childhood. We performed integrated genomic analyses of 22q11DS to identify genes and pathways related to specific phenotypes. Methods We used a high-resolution aCGH array to precisely characterize deletion breakpoints. Using peripheral blood, we examined differential exp...

  16. Blood-based gene expression signatures of medication-free outpatients with major depressive disorder: integrative genome-wide and candidate gene analyses

    OpenAIRE

    Hiroaki Hori; Daimei Sasayama; Toshiya Teraishi; Noriko Yamamoto; Seiji Nakamura; Miho Ota; Kotaro Hattori; Yoshiharu Kim; Teruhiko Higuchi; Hiroshi Kunugi

    2016-01-01

    Several microarray-based studies have investigated gene expression profiles in major depressive disorder (MDD), yet with highly variable findings. We examined blood-based genome-wide expression signatures of MDD, focusing on molecular pathways and networks underlying differentially expressed genes (DEGs) and behaviours of hypothesis-driven, evidence-based candidate genes for depression. Agilent human whole-genome arrays were used to measure gene expression in 14 medication-free outpatients wi...

  17. Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Zuccala

    Full Text Available Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion.

  18. Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines.

    OpenAIRE

    Cole, J L; Housley, G A; Dykman, T R; MacDermott, R P; Atkinson, J P

    1985-01-01

    Proteins binding the third component of complement (C3) were isolated by affinity chromatography from surface-labeled solubilized membranes of human peripheral blood cells and cell lines. The isolated molecules were subjected to NaDodSO4/PAGE, and autoradiographs of these gels indicated that C3-binding proteins could be divided into three groups based on Mr: (i) gp200, an approximately 200,000 Mr molecule previously identified as the C3b/C4b receptor or CR1; (ii) gp140, an approximately 140,0...

  19. Protein-Based Blood Substitutes: Recent Attempts at Controlling Pro-Oxidant Reactivity with and Beyond Hemoglobin

    Directory of Open Access Journals (Sweden)

    Radu Silaghi-Dumitrescu

    2013-07-01

    Full Text Available Reviewed here are recent attempts to produce protein-based artificial oxygen carriers (“blood substitutes”. Most of these involve chemical or physical modifications on hemoglobin, although a recent line of research using hemerythrin instead of hemoglobin is also described. The focus is set on the extent to which these modifications alter the redox reactivity of the proteins, and on ways in which this can be done systematically and purposefully, within the framework of a working hypothesis where redox side-reactions hold an important role in the physiological outcome of experimental transfusions with artificial oxygen carriers.

  20. Serum, plasma, and dried blood spot high sensitivity C-reactive protein enzyme immunoassay for population research

    OpenAIRE

    Brindle, Eleanor; FUJITA, MASAKO; Shofer, Jane; O’Connor, Kathleen A.

    2010-01-01

    C-reactive protein (CRP) is used as a biomarker of morbidity and mortality risk in studies of population health, and is essential to interpretation of several micronutrient biomarkers. There is thus need for a robust high sensitivity CRP (hsCRP) measurement method for large-scale, non-clinical studies. We developed an efficient, inexpensive assay suitable for quantifying CRP across the physiological range using any blood specimen type. The ELISA uses readily available monoclonal antibodies to...

  1. Correlation of serum C-reactive protein, white blood count and neutrophil percentage with histopathology findings in acute appendicitis

    OpenAIRE

    Xharra Shefki; Gashi-Luci Lumturije; Xharra Kumrije; Veselaj Fahredin; Bicaj Besnik; Sada Fatos; Krasniqi Avdyl

    2012-01-01

    Abstract Background Acute appendicitis is one of the most common surgical emergencies. Accurate diagnosis of acute appendicitis is based on careful history, physical examination, laboratory and imaging investigation. The aim of the study is to analyze the role of C-reactive protein (CRP), white blood count (WBC) and Neutrophil percentage (NP) in improving the accuracy of diagnosis of acute appendicitis and to compare it with the intraoperative assessment and histopathology findings. Materials...

  2. Blood-brain barrier delivery of protein and non-viral gene therapeutics with molecular Trojan horses

    OpenAIRE

    Pardridge, William M

    2007-01-01

    The products of biotechnology, recombinant proteins, monoclonal antibodies, antisense, RNA interference, or non-viral gene transfer, cannot be developed as pharmaceuticals for the brain, unless these molecules are re-formulated to enable transport across the blood-brain barrier (BBB). Large molecule drugs, and plasmid DNA, can be delivered across the BBB with receptor-specific molecular Trojan horses. Trojan horse BBB delivery systems, coupled with one of 3 different technology platforms (fus...

  3. Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men

    OpenAIRE

    Fry, Christopher S.; Glynn, Erin L.; Drummond, Micah J.; Timmerman, Kyle L.; Fujita, Satoshi; Abe, Takashi; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B.

    2010-01-01

    The loss of skeletal muscle mass during aging, sarcopenia, increases the risk for falls and dependence. Resistance exercise (RE) is an effective rehabilitation technique that can improve muscle mass and strength; however, older individuals are resistant to the stimulation of muscle protein synthesis (MPS) with traditional high-intensity RE. Recently, a novel rehabilitation exercise method, low-intensity RE, combined with blood flow restriction (BFR), has been shown to stimulate mammalian targ...

  4. Extensive surface protein profiles of extracellular vesicles from cancer cells may provide diagnostic signatures from blood samples

    OpenAIRE

    Belov, Larissa; Matic, Kieran J.; Hallal, Susannah; Mulligan, Stephen P.; Best, O. Giles; Christopherson, Richard I

    2016-01-01

    Extracellular vesicles (EV) are membranous particles (30–1,000 nm in diameter) secreted by cells. Important biological functions have been attributed to 2 subsets of EV, the exosomes (bud from endosomal membranes) and the microvesicles (MV; bud from plasma membranes). Since both types of particles contain surface proteins derived from their cell of origin, their detection in blood may enable diagnosis and prognosis of disease. We have used an antibody microarray (DotScan) to compare the surfa...

  5. Phosphoproteomic analysis reveals major default phosphorylation sites outside long intrinsically disordered regions of Arabidopsis plasma membrane proteins

    Directory of Open Access Journals (Sweden)

    Nespoulous Claude

    2012-10-01

    Full Text Available Abstract Background Genome-wide statistics established that long intrinsically disordered regions (over 30 residues are predicted in a large part of proteins in all eukaryotes, with a higher ratio in trans-membrane proteins. At functional level, such unstructured and flexible regions were suggested for years to favour phosphorylation events. In plants, despite increasing evidence of the regulation of transport and signalling processes by phosphorylation events, only few data are available without specific information regarding plasma membrane proteins, especially at proteome scale. Results Using a dedicated phosphoproteomic workflow, 75 novel and unambiguous phosphorylation sites were identified in Arabidopsis plasma membrane. Bioinformatics analysis showed that this new dataset concerned mostly integral proteins involved in key functions of the plasma membrane (such as transport and signal transduction, including protein phosphorylation. It thus expanded by 15% the directory of phosphosites previously characterized in signalling and transport proteins. Unexpectedly, 66% of phosphorylation sites were predicted to be located outside long intrinsically disordered regions. This result was further corroborated by analysis of publicly available data for the plasma membrane. Conclusions The new phosphoproteomics data presented here, with published datasets and functional annotation, suggest a previously unexpected topology of phosphorylation in the plant plasma membrane proteins. The significance of these new insights into the so far overlooked properties of the plant plasma membrane phosphoproteome and the long disordered regions is discussed.

  6. Actin capping protein and its inhibitor CARMIL: how intrinsically disordered regions function

    International Nuclear Information System (INIS)

    The actin capping protein (CP) tightly binds to the barbed end of actin filaments to block further elongation. The β-tentacle in CP is an important region that ensures stable interaction with actin filaments. CARMIL inhibits the interaction of CP with actin filaments via the C-terminal portion containing the CP-binding motif, located in an intrinsically disordered region. We have proposed an allosteric inhibition model in which CARMIL suppresses CP by the population shift mechanism. Here, we solved a crystal structure of CP in complex with a CARMIL-derived peptide, CA32. The new structure clearly represents the α-helical form of the β-tentacle that was invisible in other CP/CARMIL peptide complex structures. In addition, we exhaustively performed a normal mode analysis with the elastic network model on all available crystal structures of the CP/CARMIL peptide complexes, including the new structure. We concluded that the CP-binding motif is necessary and sufficient for altering the fluctuation of CP, which is essential for attenuating the barbed-end-capping activity along the population shift mechanism. The roles and functions of the β-tentacle and the CP-binding motif are discussed in terms of their intrinsically disordered nature

  7. Whole blood BDNF levels in healthy twins discordant for affective disorder: association to life events and neuroticism

    DEFF Research Database (Denmark)

    Trajkovska, V.; Vinberg, M.; Aznar, S.;

    2008-01-01

    BACKGROUND: Depression has been associated with decreased blood BDNF concentrations; but it is unclear if low blood BDNF levels are a state or a trait marker of depression. METHODS: We investigated blood BDNF concentrations in a twin population including both subjects highly predisposed and prote...

  8. Disorder and structure in the Rab11 binding domain of Rab11 family interacting protein 2.

    Science.gov (United States)

    Wei, Jie; Liu, Yuqi; Bose, Kakoli; Henry, Gillian D; Baleja, James D

    2009-01-27

    Rab11 plays a central role in plasma membrane recycling which returns cellular receptors for reuse at the cell surface. A recently identified family of Rab11 interacting proteins (FIP) includes FIP2. The C-terminal region of FIP2 is essential for colocalization with Rab11 on early endosomes and for enabling formation of higher-order oligomers. Rab11 binding and oligomerization of FIP2 are separable. Here we have determined the three-dimensional structure of the 40-residue coiled-coil oligomerization domain of FIP2 in the absence of Rab11 using NMR methods. The N-terminal half showed strong NOE cross-peaks and well-dispersed NMR resonances, whereas the C-terminal half had fewer NOE cross-peaks and less chemical shift dispersion. The 10 C-terminal residues were mostly disordered. The final structures of the dimer had favorable Ramachandran angles and a root-mean-square deviation of 0.59 +/- 0.13 A over superimposed backbone residues. The structure allows a comparison to a structure of FIP2 in complex with Rab11 that was determined crystallographically. In complex with Rab11, the C-terminal residues are not disordered but have a helical structure that predicts residual dipolar coupling constants that are incompatible with those measured on the unbound FIP2. In both structures, a histidine residue is found at the normally hydrophobic position of the heptad repeat of the coiled coil, and here we show its ionization destabilizes the coiled-coil structure. Together, these data allow us to build a model in which the binding of FIP family proteins to Rab11 can be described in terms of conformational changes and that suggests new modes of regulation. PMID:19119858

  9. Monitoring structural changes in intrinsically disordered proteins using QCM-D: application to the bacterial cell division protein ZipA.

    Science.gov (United States)

    Mateos-Gil, Pablo; Tsortos, Achilleas; Vélez, Marisela; Gizeli, Electra

    2016-05-01

    The sensitivity of QCM-D to molecular hydrodynamic properties is applied in this work to study conformational changes of the intrinsically disordered protein ZipA. Acoustic measurements can clearly follow ZipA's unstructured domain expansion and contraction with salt content and be correlated with changes in the hydrodynamic radius of 1.8 nm or less. PMID:27109863

  10. Chemical composition and biological value of spray dried porcine blood by-products and bone protein hydrolysate for young chickens.

    Science.gov (United States)

    Jamroz, D; Wiliczkiewicz, A; Orda, J; Skorupińska, J; Słupczyńska, M; Kuryszko, J

    2011-10-01

    The chemical composition of spray dried porcine blood by-products is characterised by wide variation in crude protein contents. In spray dried porcine blood plasma (SDBP) it varied between 670-780 g/kg, in spray dried blood cells (SDBC) between 830-930 g/kg, and in bone protein hydrolysate (BPH) in a range of 740-780 g/kg. Compared with fish meal, these feeds are poor in Met and Lys. Moreover, in BPH deep deficits of Met, Cys, Thr and other amino acids were found. The experiment comprised 7 dietary treatments: SDBP, SDBC, and BPH, each at an inclusion rate of 20 or 40 g/kg diet, plus a control. The addition of 20 or 40 g/kg of the analysed meals into feeds for very young chickens (1-28 d post hatch) significantly decreased the body weight (BW) of birds. Only the treatments with 40 g/kg of SDBP and SDBC showed no significant difference in BW as compared with the control. There were no significant differences between treatments and type of meal for feed intake, haematocrit and haemoglobin concentrations in blood. Addition of bone protein and blood cell meals to feed decreased the IgG concentration in blood and caused shortening of the femur and tibia bones. However, changes in the mineral composition of bones were not significantly affected by the type of meal used. The blood by-products, which are rich in microelements, improved retention of Ca and Cu only. In comparison to control chickens, significantly better accretion of these minerals was found in treatments containing 20 g/kg of SDBP or 40 g/kg of SDBC. Great variability in apparent ileal amino acid digestibility in chickens was determined. In this respect, some significant differences related to the type of meal fed were confirmed for Asp, Pro, Val, Tyr and His. In general, the apparent ileal digestibility of amino acids was about 2-3 percentage units better in chickens fed on diets containing the animal by products than in control birds. PMID:22029787

  11. Combining a PagP fusion protein system with nickel ion-catalyzed cleavage to produce intrinsically disordered proteins in E. coli.

    Science.gov (United States)

    Zahran, Somaya; Pan, Jonathan S; Liu, Philip B; Hwang, Peter M

    2015-12-01

    Many proteins contain intrinsically disordered regions that are highly solvent-exposed and susceptible to post-translational modifications. Studying these protein segments is critical to understanding their physiologic regulation, but proteolytic degradation can make them difficult to express and purify. We have designed a new protein expression vector that fuses the target protein to the N-terminus of the integral membrane protein, PagP. The two proteins are connected by a short linker containing the sequence SRHW, previously shown to be optimal for nickel ion-catalyzed cleavage. The methodology is demonstrated for an intrinsically disordered segment of cardiac troponin I. cTnI[135-209]-SRHW-PagP-His6 fusion protein was overexpressed in Escherichia coli, accumulating in insoluble inclusion bodies. The protein was solubilized, purified using nickel affinity chromatography, and then cleaved with 0.5mM NiSO4 at pH 9.0 and 45 °C, all in 6M guanidine-HCl. Nickel ion-catalyzed peptide bond hydrolysis is an effective chemical cleavage technique under denaturing conditions that preclude the use of proteases. Moreover, nickel-catalyzed cleavage is more specific than the most commonly used agent, cyanogen bromide, which cleaves C-terminal to methionine residues. We were able to produce 15 mg of purified cTnI[135-209] from 1L of M9 minimal media using this protocol. The methodology is more generally applicable to the production of intrinsically disordered protein segments. PMID:26297994

  12. Effect of a high-protein diet on maintenance of blood pressure levels achieved after initial weight loss

    DEFF Research Database (Denmark)

    Engberink, M F; Geleijnse, J M; Bakker, S J L;

    2015-01-01

    Randomized trials have shown significant blood pressure (BP) reductions after increased protein compared with carbohydrate intake, but the effect on BP maintenance after initial weight loss is unclear. We examined the effect of a high-protein diet on the maintenance of reduced BP after weight loss...... in 420 overweight adults from the Diet, Obesity and Genes study. After an 8-week weight-loss period (>8% BW), subjects (42±6 years) were randomized to either a high-protein diet (23-28 en% protein) or a lower-protein control diet (10-15 en% protein) for 26 weeks. BMI after weight loss was 30.3±4.3 kg...... m(-2), BP was 118/73 mm Hg and 28 subjects (6.5%) used antihypertensive agents. Systolic BP during 26 weeks of weight maintenance dietary intervention increased in both treatment groups, but it was 2.2 mm Hg less (95% CI: -4.6 to 0.2 mm Hg, P=0.08) in the high-protein group than in the lower...

  13. Standardization for cortisol determination in human blood by competitive protein-binding

    International Nuclear Information System (INIS)

    Standardization for determination of cortisol from human plasma (17-hydroxycorticosteroids) using competitive protein-binding method is presented. Activated carbon coated with dextrans is used for separation of the hormone-protein complexe and hormone labelled free

  14. Changing optical properties of blood serum proteins in case of oncological diseases

    Science.gov (United States)

    Petrova, G. P.; Petrusevich, Yu. M.; Boiko, A. V.; Ivanov, A. V.; Papish, E. A.; Khlapov, V. P.; Fedorova, K. V.

    2007-03-01

    Molecular methods of diagnostics of widespread diseases including oncological pathology on the base static and dynamic laser light scattering in serum blood solution are testified. Rayleigh - Debye laser light scattering method are used to measure molecular parameters of blood serum. Dynamical parameters of macromolecules can be measured by photon correlation spectroscopy method. We obtained that the parameter of intermolecular interaction B for serum blood solution of oncological patients is considerably less then B for serum blood solution of healthy persons and in a number of cases has even a negative value. The effective mass of scattering particles in serum water solutions for samples of oncology diseases patients increase in comparison to control samples. As follows from our experimental results, there is the difference between dynamic molecular parameters for control samples and ones with oncological pathology.

  15. Homocysteine induces production of monocyte chemoattractant protein-1 and interleukin-8 in cultured human whole blood

    Institute of Scientific and Technical Information of China (English)

    Xiao-kunZENG; DanielGREMICK; XianWANG

    2004-01-01

    AIM: To investigate whether increased plasma L-homocysteine (Hcy) level could promote monocyte chemoattract antprotein-1 (MCP-1) and interleukin-8 (IL-8) in cultured whole blood. METHODS: Human whole blood or differenttype of peripheral blood cells from health volunteers were incubated with Hcy and/or the inhibitors. MCP-1 and IL-8 level were measured by ELISA assay. RESULTS: Hcy 10-1000 μmol/L induced production of MCP-1and IL-8 in cultured human whole blood (P<0.05). The major cellular source of these chemokines comed from monocytes. Meanwhile,Hcy also promoted the upregulation of MPO level even at the 10 μmol/L in the cultured whole blood.The intracellular ROS, particular the OH radicals, play extremely important role in the Hcy-induced MCP-1 and IL-8 production. CONCLUSION: Increased Hcy level in plasma (hyperhomocysteinemia) induced MCP-1 and IL-8secretion in cultured human whole blood, especially in monocytes via oxidative stress mechanism,

  16. Revealing the role of oxidation state in interaction between nitro/amino-derived particulate matter and blood proteins

    Science.gov (United States)

    Liu, Zhen; Li, Ping; Bian, Weiwei; Yu, Jingkai; Zhan, Jinhua

    2016-05-01

    Surface oxidation states of ultrafine particulate matter can influence the proinflammatory responses and reactive oxygen species levels in tissue. Surface active species of vehicle-emission soot can serve as electron transfer-mediators in mitochondrion. Revealing the role of surface oxidation state in particles-proteins interaction will promote the understanding on metabolism and toxicity. Here, the surface oxidation state was modeled by nitro/amino ligands on nanoparticles, the interaction with blood proteins were evaluated by capillary electrophoresis quantitatively. The nitro shown larger affinity than amino. On the other hand, the affinity to hemoglobin is 103 times larger than that to BSA. Further, molecular docking indicated the difference of binding intensity were mainly determined by hydrophobic forces and hydrogen bonds. These will deepen the quantitative understanding of protein-nanoparticles interaction from the perspective of surface chemical state.

  17. Hepatitis C virus core protein induces energy metabolism disorders of hepatocytes by down-regulation of silent mating type information regulation 2 homolog-1 and adenosine monophosphate-acti vated protein kinase signaling pathway

    Institute of Scientific and Technical Information of China (English)

    于建武

    2013-01-01

    Objective To study the role of silent mating type information regulation2homotog-1(SIRT1)-adenosine monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway in hepatitis C virus core protein(HCV-core)induced energy metabolism disorders

  18. Disordered nano-wrinkle substrates for inducing crystallization over a wide range of concentration of protein and precipitant

    CERN Document Server

    Ghatak, Anindita Sengupta

    2015-01-01

    There are large number of proteins, the existence of which are known but not their crystal structure, because of difficulty in finding the exact condition for their crystallization. Heterogeneous nucleation on disordered porous substrates with small yet large distribution of pores is considered a panacea for this problem, but a universal nucleant, suitable for crystallizing large variety of proteins does not really exist. To this end, we report here a nano-wrinkled substrate which displays remarkable ability and control over protein crystallization. Experiments with different proteins show that on these substrates, crystals nucleate even at very low protein concentration in buffer. Small number of very large crystals appear for precipitant concentrations varied over orders of magnitude ~0.003-0.3M; for some proteins, crystals appear even without addition of any precipitant, not seen with any other heterogeneous substrates. In essence, these substrates significantly diminish the influence of the above two para...

  19. Characterization of the deleted in autism 1 protein family: implications for studying cognitive disorders.

    Directory of Open Access Journals (Sweden)

    Azhari Aziz

    Full Text Available Autism spectrum disorders (ASDs are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1 and cXorf36 or Deleted in Autism-1 Related (DIA1R are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L, lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental

  20. A group 6 late embryogenesis abundant protein from common bean is a disordered protein with extended helical structure and oligomer-forming properties.

    Science.gov (United States)

    Rivera-Najera, Lucero Y; Saab-Rincón, Gloria; Battaglia, Marina; Amero, Carlos; Pulido, Nancy O; García-Hernández, Enrique; Solórzano, Rosa M; Reyes, José L; Covarrubias, Alejandra A

    2014-11-14

    Late embryogenesis-abundant proteins accumulate to high levels in dry seeds. Some of them also accumulate in response to water deficit in vegetative tissues, which leads to a remarkable association between their presence and low water availability conditions. A major sub-group of these proteins, also known as typical LEA proteins, shows high hydrophilicity and a high percentage of glycine and other small amino acid residues, distinctive physicochemical properties that predict a high content of structural disorder. Although all typical LEA proteins share these characteristics, seven groups can be distinguished by sequence similarity, indicating structural and functional diversity among them. Some of these groups have been extensively studied; however, others require a more detailed analysis to advance in their functional understanding. In this work, we report the structural characterization of a group 6 LEA protein from a common bean (Phaseolus vulgaris L.) (PvLEA6) by circular dichroism and nuclear magnetic resonance showing that it is a disordered protein in aqueous solution. Using the same techniques, we show that despite its unstructured nature, the addition of trifluoroethanol exhibited an intrinsic potential in this protein to gain helicity. This property was also promoted by high osmotic potentials or molecular crowding. Furthermore, we demonstrate that PvLEA6 protein is able to form soluble homo-oligomeric complexes that also show high levels of structural disorder. The association between PvLEA6 monomers to form dimers was shown to occur in plant cells by bimolecular fluorescence complementation, pointing to the in vivo functional relevance of this association. PMID:25271167

  1. Studies on Some Biophysical Properties of the Serum Protein of Mice blood exposed to an electric field

    International Nuclear Information System (INIS)

    As an indication of the effect of the electric field on each of the dielectric properties and the molecular structure of the serum protein of the mice blood, an electric field of a 6 kv/m strength and 50 Hz frequency was directed to three groups of mice for exposure periods 30, 45 and 60 days respectively, and investigated directly. Another group was exposed to also 60 days, but investigated after 30 days from switching off the electric field for delayed effect studies. The molecular structure of the serum protein was studied by measuring each of the dielectric relaxation and the electric conductivity in the frequency range 0.15 MHz at 4 ± 0.5 degree C and the dielectric increment (Δ), relaxation time (τ) and average molecular radii (τ) were calculated for all groups. The absorption spectra of the extracted protein were also measured in the wavelength range 200 600 nm. Moreover, electrophoresis of enzymes B-esterase, lactate and Malate dehydrogenase extracted from the blood serum of exposed mice were taken by using the gel electrophoresis technique. The results indicated that exposure of the animals to 50 H, 6 kv/m electric field resulted in the decrease of serum protein permittivity values and increase its conductivity a fact that indicates pronounced changes in the molecular structure of total serum protein the exposed mice. In addition, the intensity of the absorption spectral bands of serum protein of exposed mice were found to decrease relative to unexposed mice. Also the enzymes B-esterase and lactate dehydrogenase were slightly affected by exposing to the electric field whereas their number of bands and their intensities changed relative to the unexposed mice but the malate dehydrogenase was not affected

  2. Team-based learning on a third-year pediatric clerkship improves NBME subject exam blood disorder scores

    Directory of Open Access Journals (Sweden)

    Kris Saudek

    2015-10-01

    Full Text Available Purpose: At our institution, speculation amongst medical students and faculty exists as to whether team-based learning (TBL can improve scores on high-stakes examinations over traditional didactic lectures. Faculty with experience using TBL developed and piloted a required TBL blood disorders (BD module for third-year medical students on their pediatric clerkship. The purpose of this study is to analyze the BD scores from the NBME subject exams before and after the introduction of the module. Methods: We analyzed institutional and national item difficulties for BD items from the NBME pediatrics content area item analysis reports from 2011 to 2014 before (pre and after (post the pilot (October 2012. Total scores of 590 NBME subject examination students from examinee performance profiles were analyzed pre/post. t-Tests and Cohen's d effect sizes were used to analyze item difficulties for institutional versus national scores and pre/post comparisons of item difficulties and total scores. Results: BD scores for our institution were 0.65 (±0.19 compared to 0.62 (±0.15 nationally (P=0.346; Cohen's d=0.15. The average of post-consecutive BD scores for our students was 0.70(±0.21 compared to examinees nationally [0.64 (±0.15] with a significant mean difference (P=0.031; Cohen's d=0.43. The difference in our institutions pre [0.65 (±0.19] and post [0.70 (±0.21] BD scores trended higher (P=0.391; Cohen's d=0.27. Institutional BD scores were higher than national BD scores for both pre and post, with an effect size that tripled from pre to post scores. Institutional BD scores increased after the use of the TBL module, while overall exam scores remained steadily above national norms. Conclusions: Institutional BD scores were higher than national BD scores for both pre and post, with an effect size that tripled from pre to post scores. Institutional BD scores increased after the use of the TBL module, while overall exam scores remained steadily above

  3. Team-based learning on a third-year pediatric clerkship improves NBME subject exam blood disorder scores

    Science.gov (United States)

    Saudek, Kris; Treat, Robert

    2015-01-01

    Purpose At our institution, speculation amongst medical students and faculty exists as to whether team-based learning (TBL) can improve scores on high-stakes examinations over traditional didactic lectures. Faculty with experience using TBL developed and piloted a required TBL blood disorders (BD) module for third-year medical students on their pediatric clerkship. The purpose of this study is to analyze the BD scores from the NBME subject exams before and after the introduction of the module. Methods We analyzed institutional and national item difficulties for BD items from the NBME pediatrics content area item analysis reports from 2011 to 2014 before (pre) and after (post) the pilot (October 2012). Total scores of 590 NBME subject examination students from examinee performance profiles were analyzed pre/post. t-Tests and Cohen's d effect sizes were used to analyze item difficulties for institutional versus national scores and pre/post comparisons of item difficulties and total scores. Results BD scores for our institution were 0.65 (±0.19) compared to 0.62 (±0.15) nationally (P=0.346; Cohen's d=0.15). The average of post-consecutive BD scores for our students was 0.70 (±0.21) compared to examinees nationally [0.64 (±0.15)] with a significant mean difference (P=0.031; Cohen's d=0.43). The difference in our institutions pre [0.65 (±0.19)] and post [0.70 (±0.21)] BD scores trended higher (P=0.391; Cohen's d=0.27). Institutional BD scores were higher than national BD scores for both pre and post, with an effect size that tripled from pre to post scores. Institutional BD scores increased after the use of the TBL module, while overall exam scores remained steadily above national norms. Conclusions Institutional BD scores were higher than national BD scores for both pre and post, with an effect size that tripled from pre to post scores. Institutional BD scores increased after the use of the TBL module, while overall exam scores remained steadily above national

  4. Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder

    Science.gov (United States)

    Cai, Zhiyou; Yan, Yong; Wang, Yonglong

    2013-01-01

    Background Compelling evidence has shown that diabetic metabolic disorder plays a critical role in the pathogenesis of Alzheimer’s disease, including increased expression of β-amyloid protein (Aβ) and tau protein. Evidence has supported that minocycline, a tetracycline derivative, protects against neuroinflammation induced by neurodegenerative disorders or cerebral ischemia. This study has evaluated minocycline influence on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the brain of diabetic rats to clarify neuroprotection by minocycline under diabetic metabolic disorder. Method An animal model of diabetes was established by high fat diet and intraperitoneal injection of streptozocin. In this study, we investigated the effect of minocycline on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α) in the hippocampus of diabetic rats via immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. Results These results showed that minocycline decreased expression of Aβ protein and lowered the phosphorylation of tau protein, and retarded the proinflammatory cytokines, but not amyloid precursor protein. Conclusion On the basis of the finding that minocycline had no influence on amyloid precursor protein and beta-site amyloid precursor protein cleaving enzyme 1 which determines the speed of Aβ generation, the decreases in Aβ production and tau hyperphosphorylation by minocycline are through inhibiting neuroinflammation, which contributes to Aβ production and tau hyperphosphorylation. Minocycline may also lower the self-perpetuating cycle between neuroinflammation and the pathogenesis of tau and Aβ to act as a neuroprotector. Therefore, the ability of minocycline to modulate inflammatory reactions may be of great importance in the selection of neuroprotective agents, especially in chronic conditions

  5. Disorder in Milk Proteins: α-Lactalbumin. Part B. A Multifunctional Whey Protein Acting as an Oligomeric Molten Globular "Oil Container" in the Anti-Tumorigenic Drugs, Liprotides.

    Science.gov (United States)

    Uversky, Vladimir N; Permyakov, Serge E; Breydo, Leonid; Redwan, Elrashdy M; Almehdar, Hussein A; Permyakov, Eugene A

    2016-07-15

    This is a second part of the three-part article from a series of reviews on the abundance and roles of intrinsic disorder in milk proteins. We continue to describe α-lactalbumin, a small globular Ca2+-binding protein, which besides being one of the two components of lactose synthase that catalyzes the final step of the lactose biosynthesis in the lactating mammary gland, possesses a multitude of other functions. In fact, recent studies indicated that some partially folded forms of this protein possess noticeable bactericidal activity and other forms might be related to induction of the apoptosis of tumor cells. In its anti-tumorigenic function, oligomeric α-lactalbumin serves as a founding member of a new family of anticancer drugs termed liprotides (for lipids and partially denatured proteins), where an oligomeric molten globular protein acts as an "oil container" or cargo for the delivery of oleic acid to the cell membranes. PMID:26916155

  6. The effects of protein, amino acid, and dietary electrolyte balance on broiler chicken performance and blood parameters under heat stress

    Directory of Open Access Journals (Sweden)

    Ali Asghar Saki

    2016-08-01

    Full Text Available The effect of crude protein (CP, amino acid (AA, and dietary electrolyte balance (DEB were evaluated on blood parameters, carcass traits, and broiler performance under heat stress (29-34°C. A total of 540 male chickens (Ross 308 were allocated to 12 diets with factorial arrangement 2 × 2 × 3, using a completely randomized design with three replicates of 15 chickens in grower (13 to 26 days and finisher (27 to 42 days periods. and 120, 220, and 320 mEq kg-1 DEB. The level of 21% CP increased body weight gain (BWG and decreased feed conversion ratio (FCR at grower period (p < 0.05. In contrast, 20% CP level decreased BWG and increased FCR at finisher period (p < 0.05. Further, 20% CP level reduced blood sodium and blood electrolyte balance (p < 0.05. The highest blood electrolyte balance was achieved by DEB 320 mEq kg-1 diet (p < 0.05. Broiler response to DEB in heat stress depended on the age of bird, length of exposure to high temperature and CP level of the diet. Under heat stress (29-34°C, the 21% CP level at grower period and 17% CP level at finisher period improved broiler BWG and FCR.

  7. CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation.

    Science.gov (United States)

    Jansen, Jos C; Cirak, Sebahattin; van Scherpenzeel, Monique; Timal, Sharita; Reunert, Janine; Rust, Stephan; Pérez, Belén; Vicogne, Dorothée; Krawitz, Peter; Wada, Yoshinao; Ashikov, Angel; Pérez-Cerdá, Celia; Medrano, Celia; Arnoldy, Andrea; Hoischen, Alexander; Huijben, Karin; Steenbergen, Gerry; Quelhas, Dulce; Diogo, Luisa; Rymen, Daisy; Jaeken, Jaak; Guffon, Nathalie; Cheillan, David; van den Heuvel, Lambertus P; Maeda, Yusuke; Kaiser, Olaf; Schara, Ulrike; Gerner, Patrick; van den Boogert, Marjolein A W; Holleboom, Adriaan G; Nassogne, Marie-Cécile; Sokal, Etienne; Salomon, Jody; van den Bogaart, Geert; Drenth, Joost P H; Huynen, Martijn A; Veltman, Joris A; Wevers, Ron A; Morava, Eva; Matthijs, Gert; Foulquier, François; Marquardt, Thorsten; Lefeber, Dirk J

    2016-02-01

    Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V-ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal

  8. A catalog for the transcripts from the venomous structures of the caterpillar Lonomia obliqua: identification of the proteins potentially involved in the coagulation disorder and hemorrhagic syndrome.

    Science.gov (United States)

    Veiga, Ana B G; Ribeiro, José M C; Guimarães, Jorge A; Francischetti, Ivo M B

    2005-08-01

    Accidents with the caterpillar Lonomia obliqua are often associated with a coagulation disorder and hemorrhagic syndrome in humans. In the present study, we have constructed cDNA libraries from two venomous structures of the caterpillar, namely the tegument and the bristle. High-throughput sequencing and bioinformatics analyses were performed in parallel. Over one thousand cDNAs were obtained and clustered to produce a database of 538 contigs and singletons (clusters) for the tegument library and 368 for the bristle library. We have thus identified dozens of full-length cDNAs coding for proteins with sequence homology to snake venom prothrombin activator, trypsin-like enzymes, blood coagulation factors and prophenoloxidase cascade activators. We also report cDNA coding for cysteine proteases, Group III phospholipase A2, C-type lectins, lipocalins, in addition to protease inhibitors including serpins, Kazal-type inhibitors, cystatins and trypsin inhibitor-like molecules. Antibacterial proteins and housekeeping genes are also described. A significant number of sequences were devoid of database matches, suggesting that their biologic function remains to be defined. We also report the N-terminus of the most abundant proteins present in the bristle, tegument, hemolymph, and "cryosecretion". Thus, we have created a catalog that contains the predicted molecular weight, isoelectric point, accession number, and putative function for each selected molecule from the venomous structures of L. obliqua. The role of these molecules in the coagulation disorder and hemorrhagic syndrome caused by envenomation with this caterpillar is discussed. All sequence information and the , including figures and tables with hyperlinks to FASTA-formatted files for each contig and the best match to the databases, are available at http://www.ncbi.nih.gov/projects/omes. PMID:16023793

  9. The Expression Level and Clinical Significance of MMP-7 Protein 
in Peripheral Blood in the Patients with Lung Cancer

    OpenAIRE

    SUN, XIAOLIANG; Ting XIAO; Yang, Lei; Gao, Yanning; Guiyu CHENG; Kelin SUN

    2012-01-01

    Background and objective Matrix metalloproteinase 7 (MMP-7), also known as matrilysin, is a member of the MMP family. The objectives of this study were to test MMP-7 protein levels in the peripheral blood of lung cancer patients and healthy control subjects and to determine their corresponding clinical significance. Methods Peripheral blood samples were obtained from 114 lung cancer patients and 100 healthy control subjects. MMP-7 protein levels in the plasma were measured by enzyme-linked im...

  10. Magnetic permeability based diagnostic test for the determination of the canine C-reactive protein concentration in undiluted whole blood

    Energy Technology Data Exchange (ETDEWEB)

    Ibraimi, Filiz; Kriz, Kirstin [Department of Pure and Applied Biochemistry, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); LifeAssays AB, IDEON Science Park, SE-223 70 Lund (Sweden); Merin, Henrik [Malmoe Animal Hospital, P.O. Box 9090, SE-213 63 Malmoe (Sweden); Kriz, Dario [Department of Pure and Applied Biochemistry, Lund University, P.O. Box 124, SE-221 00 Lund (Sweden); LifeAssays AB, IDEON Science Park, SE-223 70 Lund (Sweden)], E-mail: dario.kriz@euris.org

    2009-05-15

    We describe an one-step 11-min magnetic permeability based two-site immunoassay for C-reactive protein (CRP) utilizing polyclonal anti-canine CRP antibody conjugated dextran iron oxide nanoparticles (79 nm) as superparamagnetic labels and polyclonal anti-canine CRP conjugated silica microparticles (15 to 40 {mu}m) as carriers. An inductance based magnetic permeability reader was used to detect the target analyte, CRP, in 10 {mu}L whole blood samples, by measuring the magnetic permeability increase of the silica microparticle sediment due to immuno complex superparamagnetic nanoparticles. Measurements on standards showed a linear response between 0 and 17.5 mg/L CRP. Measurements performed on 16 whole blood samples from mixed breeds showed good correlation with a commercially available ELISA assay.

  11. Magnetic permeability based diagnostic test for the determination of the canine C-reactive protein concentration in undiluted whole blood

    International Nuclear Information System (INIS)

    We describe an one-step 11-min magnetic permeability based two-site immunoassay for C-reactive protein (CRP) utilizing polyclonal anti-canine CRP antibody conjugated dextran iron oxide nanoparticles (79 nm) as superparamagnetic labels and polyclonal anti-canine CRP conjugated silica microparticles (15 to 40 μm) as carriers. An inductance based magnetic permeability reader was used to detect the target analyte, CRP, in 10 μL whole blood samples, by measuring the magnetic permeability increase of the silica microparticle sediment due to immuno complex superparamagnetic nanoparticles. Measurements on standards showed a linear response between 0 and 17.5 mg/L CRP. Measurements performed on 16 whole blood samples from mixed breeds showed good correlation with a commercially available ELISA assay.

  12. Pattern recognition of monocyte chemoattractant protein-1 (MCP-1) in whole blood samples using new platforms based on nanostructured materials

    Science.gov (United States)

    Stefan-van Staden, Raluca-Ioana; Gugoasa, Livia Alexandra; Biris, Alexandru Radu

    2015-09-01

    Four stochastic microsensors based on nanostructured materials (graphene, maltodextrin (MD), and diamond) integrated in miniaturized platforms were proposed. Monocyte chemoattractant protein-1 (MCP-1) is a pro-inflammatory cytokine whose main function is to regulate cell trafficking. It is correlated with the incidence of cardiovascular diseases and obesity, and was used as the model analyte in this study. The screening of whole blood samples for MCP-1 can be done for concentrations ranging from 10-12 to 10-8 g mL-1. The method was used for both qualitative and quantitative assessments of MCP-1 in whole blood samples. The lowest quantification limits for the assay of MCP-1 (1 pg mL-1) were reached when the microsensors based on protoporphyrin IX/Graphene-Au-3 and on MD/Graphene were employed in the platform design.

  13. Predictors of natively unfolded proteins: unanimous consensus score to detect a twilight zone between order and disorder in generic datasets

    Directory of Open Access Journals (Sweden)

    Deiana Antonio

    2010-04-01

    Full Text Available Abstract Background Natively unfolded proteins lack a well defined three dimensional structure but have important biological functions, suggesting a re-assignment of the structure-function paradigm. To assess that a given protein is natively unfolded requires laborious experimental investigations, then reliable sequence-only methods for predicting whether a sequence corresponds to a folded or to an unfolded protein are of interest in fundamental and applicative studies. Many proteins have amino acidic compositions compatible both with the folded and unfolded status, and belong to a twilight zone between order and disorder. This makes difficult a dichotomic classification of protein sequences into folded and natively unfolded ones. In this work we propose an operational method to identify proteins belonging to the twilight zone by combining into a consensus score good performing single predictors of folding. Results In this methodological paper dichotomic folding indexes are considered: hydrophobicity-charge, mean packing, mean pairwise energy, Poodle-W and a new global index, that is called here gVSL2, based on the local disorder predictor VSL2. The performance of these indexes is evaluated on different datasets, in particular on a new dataset composed by 2369 folded and 81 natively unfolded proteins. Poodle-W, gVSL2 and mean pairwise energy have good performance and stability in all the datasets considered and are combined into a strictly unanimous combination score SSU, that leaves proteins unclassified when the consensus of all combined indexes is not reached. The unclassified proteins: i belong to an overlap region in the vector space of amino acidic compositions occupied by both folded and unfolded proteins; ii are composed by approximately the same number of order-promoting and disorder-promoting amino acids; iii have a mean flexibility intermediate between that of folded and that of unfolded proteins. Conclusions Our results show that

  14. Idiopathic Brainstem Neuronal Chromatolysis (IBNC: a novel prion protein related disorder of cattle?

    Directory of Open Access Journals (Sweden)

    Martin Stuart

    2008-09-01

    Full Text Available Abstract Background The epidemic form of Bovine Spongiform Encephalopathy (BSE is generally considered to have been caused by a single prion strain but at least two strain variants of cattle prion disorders have recently been recognized. An additional neurodegenerative condition, idiopathic brainstem neuronal chromatolysis and hippocampal sclerosis (IBNC, a rare neurological disease of adult cattle, was also recognised in a sub-set of cattle submitted under the BSE Orders in which lesions of BSE were absent. Between the years of 1988 and 1991 IBNC occurred in Scotland with an incidence of 7 cases per 100,000 beef suckler cows over the age of 6 years. Results When the brains of 15 IBNC cases were each tested by immunohistochemistry, all showed abnormal labelling for prion protein (PrP. Immunohistological labelling for PrP was also present in the retina of a single case available for examination. The pattern of PrP labelling in brain is distinct from that seen in other ruminant prion diseases and is absent from brains with other inflammatory conditions and from normal control brains. Brains of IBNC cattle do not reveal abnormal PrP isoforms when tested by the commercial BioRad or Idexx test kits and do not reveal PrPres when tested by Western blotting using stringent proteinase digestion methods. However, some weakly protease resistant isoforms of PrP may be detected when tissues are examined using mild proteinase digestion techniques. Conclusion The study shows that a distinctive neurological disorder of cattle, which has some clinical similarities to BSE, is associated with abnormal PrP labelling in brain but the pathology and biochemistry of IBNC are distinct from BSE. The study is important either because it raises the possibility of a significant increase in the scope of prion disease or because it demonstrates that widespread and consistent PrP alterations may not be confined to prion diseases. Further studies, including transmission

  15. Blood and Milk Protein Polymorphism and Their Effects on Various Production Traits in Simmental Cows

    OpenAIRE

    ŞEKERDEN, Özel

    1998-01-01

    This research was carried out to determine the transferrin (Tf) and haemoglobine (Hb) and milk protein (alfa-S1-casein, beta casein, capa casein, beta lactoglobuline) types, and relationships between Tf and Hb types and milk protein genotypes with various characteristics. The relationship between Tf types and milk yields of control milking and control day were only statistically significant (P0.05). None of the investigated characteristics were effected by milk protein genetic variants at sta...

  16. Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.

    Science.gov (United States)

    Ma, Yingying; Sun, Zeyu; de Matos, Ricardo; Zhang, Jing; Odunsi, Kunle; Lin, Biaoyang

    2014-05-01

    Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here

  17. Biophysical characterization of the structural change of Nopp140, an intrinsically disordered protein, in the interaction with CK2α.

    Science.gov (United States)

    Na, Jung-Hyun; Lee, Won-Kyu; Kim, Yuyoung; Jeong, Cherlhyun; Song, Seung Soo; Cha, Sun-Shin; Han, Kyou-Hoon; Shin, Yeon-Kyun; Yu, Yeon Gyu

    2016-08-19

    Nucleolar phosphoprotein 140 (Nopp140) is a nucleolar protein, more than 80% of which is disordered. Previous studies have shown that the C-terminal region of Nopp140 (residues 568-596) interacts with protein kinase CK2α, and inhibits the catalytic activity of CK2. Although the region of Nopp140 responsible for the interaction with CK2α was identified, the structural features and the effect of this interaction on the structure of Nopp140 have not been defined due to the difficulty of structural characterization of disordered protein. In this study, the disordered feature of Nopp140 and the effect of CK2α on the structure of Nopp140 were examined using single-molecule fluorescence resonance energy transfer (smFRET) and electron paramagnetic resonance (EPR). The interaction with CK2α was increased conformational rigidity of the CK2α-interacting region of Nopp140 (Nopp140C), suggesting that the disordered and flexible conformation of Nopp140C became more rigid conformation as it binds to CK2α. In addition, site specific spin labeling and EPR analysis confirmed that the residues 574-589 of Nopp140 are critical for binding to CK2α. Similar technical approaches can be applied to analyze the conformational changes in other IDPs during their interactions with binding partners. PMID:27297113

  18. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding.

    Science.gov (United States)

    Nakamura, T; Lipton, S A

    2007-07-01

    Although activation of glutamate receptors is essential for normal brain function, excessive activity leads to a form of neurotoxicity known as excitotoxicity. Key mediators of excitotoxic damage include overactivation of N-methyl-D-aspartate (NMDA) receptors, resulting in excessive Ca(2+) influx with production of free radicals and other injurious pathways. Overproduction of free radical nitric oxide (NO) contributes to acute and chronic neurodegenerative disorders. NO can react with cysteine thiol groups to form S-nitrosothiols and thus change protein function. S-nitrosylation can result in neuroprotective or neurodestructive consequences depending on the protein involved. Many neurodegenerative diseases manifest conformational changes in proteins that result in misfolding and aggregation. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. Molecular chaperones - such as protein-disulfide isomerase, glucose-regulated protein 78, and heat-shock proteins - can provide neuroprotection by facilitating proper protein folding. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence that NO contributes to degenerative conditions by S-nitrosylating-specific chaperones that would otherwise prevent accumulation of misfolded proteins and neuronal cell death. In contrast, we also review therapeutics that can abrogate excitotoxic damage by preventing excessive NMDA receptor activity, in part via S-nitrosylation of this receptor to curtail excessive activity. PMID:17431424

  19. Cloning, expression and characterization of a gene from earthworm Eisenia fetida encoding a blood-clot dissolving protein.

    Science.gov (United States)

    Li, GangQiang; Wang, Kevin Yueju; Li, DaHui; Wang, Nan; Liu, DeHu

    2012-01-01

    A lumbrokinase gene encoding a blood-clot dissolving protein was cloned from earthworm (Eisenia fetida) by RT-PCR amplification. The gene designated as CST1 (GenBank No. AY840996) was sequence analyzed. The cDNA consists of 888 bp with an open reading frame of 729 bp, which encodes 242 amino acid residues. Multiple sequence alignments revealed that CST1 shares similarities and conserved amino acids with other reported lumbrokinases. The amino acid sequence of CST1 exhibits structural features similar to those found in other serine proteases, including human tissue-type (tPA), urokinase (uPA), and vampire bat (DSPAα1) plasminogen activators. CST1 has a conserved catalytic triad, found in the active sites of protease enzymes, which are important residues involved in polypeptide catalysis. CST1 was expressed as inclusion bodies in Escherichia coli BL21(DE3). The molecular mass of recombinant CST1 (rCST) was 25 kDa as estimated by SDS-PAGE, and further confirmed by Western Blot analysis. His-tagged rCST1 was purified and renatured using nickel-chelating resin with a recovery rate of 50% and a purity of 95%. The purified, renatured rCST1 showed fibrinolytic activity evaluated by both a fibrin plate and a blood clot lysis assay. rCST1 degraded fibrin on the fibrin plate. A significant percentage (65.7%) of blood clot lysis was observed when blood clot was treated with 80 mg/mL of rCST1 in vitro. The antithrombotic activity of rCST1 was 912 units/mg calculated by comparison with the activity of a lumbrokinase standard. These findings indicate that rCST1 has potential as a potent blood-clot treatment. Therefore, the expression and purification of a single lumbrokinase represents an important improvement in the use of lumbrokinases. PMID:23300872

  20. Proteins involved in the Vroman effect during exposure of human blood plasma to glass and polyethylene

    NARCIS (Netherlands)

    Turbill, P.; Beugeling, T.; Poot, A.A.

    1996-01-01

    The amounts of fibrinogen adsorbed to glass from various human blood plasmas have been measured as a function of time. The plasmas were 11 single donor plasmas, pooled plasma, a single donor high molecular weight kininogen (HMWK)-deficient plasma and HMWK-deficient plasma, which had been reconstitut

  1. Immunomodulatory capacity of fungal proteins on the cytokine production of human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Jeurink, P.V.; Lull Noguera, C.; Savelkoul, H.F.J.; Wichers, H.J.

    2008-01-01

    Immunomodulation by fungal compounds can be determined by the capacity of the compounds to influence the cytokine production by human peripheral blood mononuclear cells (hPBMC). These activities include mitogenicity, stimulation and activation of immune effector cells. Eight mushroom strains (Agaric

  2. High-protein and high-carbohydrate breakfasts differentially change the transcriptome of human blood cells

    NARCIS (Netherlands)

    Erk, M.J. van; Blom, W.A.M.; Ommen, B. van; Hendriks, H.F.J.

    2006-01-01

    Background: Application of transcriptomics technology in human nutrition intervention studies would allow for genome-wide screening of the effects of specific diets or nutrients and result in biomarker profiles. Objective: The aim was to evaluate the potential of gene expression profiling in blood c

  3. SDS-PAGE Patterns of Blood Serum Proteins in some Species of the Genus Meriones (Mammalia: Rodentia)

    OpenAIRE

    ÇOLAK, Reyhan; Nuri YİĞİT; ÇOLAK, Ercüment

    2002-01-01

    The blood serum proteins of Meriones meridianus, Meriones crassus, Meriones persicus and Meriones tristrami, all found in Turkey, along with domestic Meriones unguiculatus, which originated in Mongolia, were examined for the first time by SDS-PAGE. In the globulin zone, seven to ten bands were identified, one band in the post-albumin and albumin zones and one or two bands in the pre-albumin zone of five species of the genus Meriones. There was no diagnostic difference in the pattern of serum ...

  4. Structural Ensembles of Intrinsically Disordered Proteins Depend Strongly on Force Field: A Comparison to Experiment.

    Science.gov (United States)

    Rauscher, Sarah; Gapsys, Vytautas; Gajda, Michal J; Zweckstetter, Markus; de Groot, Bert L; Grubmüller, Helmut

    2015-11-10

    Intrinsically disordered proteins (IDPs) are notoriously challenging to study both experimentally and computationally. The structure of IDPs cannot be described by a single conformation but must instead be described as an ensemble of interconverting conformations. Atomistic simulations are increasingly used to obtain such IDP conformational ensembles. Here, we have compared the IDP ensembles generated by eight all-atom empirical force fields against primary small-angle X-ray scattering (SAXS) and NMR data. Ensembles obtained with different force fields exhibit marked differences in chain dimensions, hydrogen bonding, and secondary structure content. These differences are unexpectedly large: changing the force field is found to have a stronger effect on secondary structure content than changing the entire peptide sequence. The CHARMM 22* ensemble performs best in this force field comparison: it has the lowest error in chemical shifts and J-couplings and agrees well with the SAXS data. A high population of left-handed α-helix is present in the CHARMM 36 ensemble, which is inconsistent with measured scalar couplings. To eliminate inadequate sampling as a reason for differences between force fields, extensive simulations were carried out (0.964 ms in total); the remaining small sampling uncertainty is shown to be much smaller than the observed differences. Our findings highlight how IDPs, with their rugged energy landscapes, are highly sensitive test systems that are capable of revealing force field deficiencies and, therefore, contributing to force field development. PMID:26574339

  5. Hyperphosphorylation of intrinsically disordered tau protein induces an amyloidogenic shift in its conformational ensemble.

    Directory of Open Access Journals (Sweden)

    Shaolong Zhu

    Full Text Available Tau is an intrinsically disordered protein (IDP whose primary physiological role is to stabilize microtubules in neuronal axons at all stages of development. In Alzheimer's and other tauopathies, tau forms intracellular insoluble amyloid aggregates known as neurofibrillary tangles, a process that appears in many cases to be preceded by hyperphosphorylation of tau monomers. Understanding the shift in conformational bias induced by hyperphosphorylation is key to elucidating the structural factors that drive tau pathology, however, as an IDP, tau is not amenable to conventional structural characterization. In this work, we employ a straightforward technique based on Time-Resolved ElectroSpray Ionization Mass Spectrometry (TRESI-MS and Hydrogen/Deuterium Exchange (HDX to provide a detailed picture of residual structure in tau, and the shifts in conformational bias induced by hyperphosphorylation. By comparing the native and hyperphosphorylated ensembles, we are able to define specific conformational biases that can easily be rationalized as enhancing amyloidogenic propensity. Representative structures for the native and hyperphosphorylated tau ensembles were generated by refinement of a broad sample of conformations generated by low-computational complexity modeling, based on agreement with the TRESI-HDX profiles.

  6. Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and Attention-Deficit/Hyperactivity Disorder in Children

    Science.gov (United States)

    Nigg, Joel T.; Elmore, Alexis L.; Natarajan, Neil; Friderici, Karen H.; Nikolas, Molly A.

    2016-01-01

    Although attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental condition, there is also considerable scientific and public interest in environmental modulators of its etiology. Exposure to neurotoxins is one potential source of perturbation of neural, and hence psychological, development. Exposure to lead in particular has been widely investigated and is correlated with neurodevelopmental outcomes, including ADHD. To investigate whether this effect is likely to be causal, we used a Mendelian randomization design with a functional gene variant. In a case-control study, we examined the association between ADHD symptoms in children and blood lead level as moderated by variants in the hemochromatosis (HFE) gene. The HFE gene regulates iron uptake and secondarily modulates lead metabolism. Statistical moderation was observed: The magnitude of the association of blood lead with symptoms of ADHD was altered by functional HFE genotype, which is consistent with a causal hypothesis. PMID:26710823

  7. MERA: a webserver for evaluating backbone torsion angle distributions in dynamic and disordered proteins from NMR data

    Energy Technology Data Exchange (ETDEWEB)

    Mantsyzov, Alexey B. [M.V. Lomonosov Moscow State University, Faculty of Fundamental Medicine (Russian Federation); Shen, Yang; Lee, Jung Ho [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Hummer, Gerhard [Max Planck Institute of Biophysics (Germany); Bax, Ad, E-mail: bax@nih.gov [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)

    2015-09-15

    MERA (Maximum Entropy Ramachandran map Analysis from NMR data) is a new webserver that generates residue-by-residue Ramachandran map distributions for disordered proteins or disordered regions in proteins on the basis of experimental NMR parameters. As input data, the program currently utilizes up to 12 different parameters. These include three different types of short-range NOEs, three types of backbone chemical shifts ({sup 15}N, {sup 13}C{sup α}, and {sup 13}C′), six types of J couplings ({sup 3}J{sub HNHα}, {sup 3}J{sub C′C′}, {sup 3}J{sub C′Hα}, {sup 1}J{sub HαCα}, {sup 2}J{sub CαN} and {sup 1}J{sub CαN}), as well as the {sup 15}N-relaxation derived J(0) spectral density. The Ramachandran map distributions are reported in terms of populations of their 15° × 15° voxels, and an adjustable maximum entropy weight factor is available to ensure that the obtained distributions will not deviate more from a newly derived coil library distribution than required to account for the experimental data. MERA output includes the agreement between each input parameter and its distribution-derived value. As an application, we demonstrate performance of the program for several residues in the intrinsically disordered protein α-synuclein, as well as for several static and dynamic residues in the folded protein GB3.

  8. MERA: a webserver for evaluating backbone torsion angle distributions in dynamic and disordered proteins from NMR data

    International Nuclear Information System (INIS)

    MERA (Maximum Entropy Ramachandran map Analysis from NMR data) is a new webserver that generates residue-by-residue Ramachandran map distributions for disordered proteins or disordered regions in proteins on the basis of experimental NMR parameters. As input data, the program currently utilizes up to 12 different parameters. These include three different types of short-range NOEs, three types of backbone chemical shifts (15N, 13Cα, and 13C′), six types of J couplings (3JHNHα, 3JC′C′, 3JC′Hα, 1JHαCα, 2JCαN and 1JCαN), as well as the 15N-relaxation derived J(0) spectral density. The Ramachandran map distributions are reported in terms of populations of their 15° × 15° voxels, and an adjustable maximum entropy weight factor is available to ensure that the obtained distributions will not deviate more from a newly derived coil library distribution than required to account for the experimental data. MERA output includes the agreement between each input parameter and its distribution-derived value. As an application, we demonstrate performance of the program for several residues in the intrinsically disordered protein α-synuclein, as well as for several static and dynamic residues in the folded protein GB3

  9. An occludin-focal adhesion kinase protein complex at the blood-testis barrier: a study using the cadmium model.

    Science.gov (United States)

    Siu, Erica R; Wong, Elissa W P; Mruk, Dolores D; Sze, K L; Porto, Catarina S; Cheng, C Yan

    2009-07-01

    Several integral membrane proteins that constitute the blood-testis barrier (BTB) in mammalian testes, in particular rodents, are known to date. These include tight junction (TJ) proteins (e.g. occludin, junctional adhesion molecule-A, claudins), basal ectoplasmic specialization proteins (e.g. N-cadherin), and gap junction proteins (e.g. connexin43). However, the regulators (e.g. protein kinases and phosphatases) that affect these proteins, such as their interaction with the cytoskeletal actin, which in turn confer cell adhesion at the TJ, remain largely unknown. We report herein that focal adhesion kinase (FAK) is a putative interacting partner of occludin, but not claudin-11 or junctional adhesion molecule-A. Immunohistochemistry and fluorescence microscopy studies illustrated that the expression of FAK in the seminiferous epithelium of adult rat testes was stage specific. FAK colocalized with occludin at the BTB in virtually all stages of the seminiferous epithelial cycle but considerably diminished in stages VIII-IX, at the time of BTB restructuring to facilitate the transit of primary leptotene spermatocytes. Using Sertoli cells cultured in vitro with established TJ-permeability barrier and ultrastructures of TJ, basal ectoplasmic specialization and desmosome-like junction that mimicked the BTB in vivo, FAK was shown to colocalize with occludin and zonula occludens-1 (ZO-1) at the Sertoli-Sertoli cell interface. When these Sertoli cell cultures were treated with CdCl(2) to perturb the TJ-barrier function, occludin underwent endocytic-mediated internalization in parallel with FAK and ZO-1. Thus, these findings demonstrate that FAK is an integrated regulatory component of the occludin-ZO-1 protein complex, suggesting that functional studies can be performed to study the role of FAK in BTB dynamics. PMID:19213829

  10. Actinidia DRM1 - An Intrinsically Disordered Protein Whose mRNA Expression Is Inversely Correlated with Spring Budbreak in Kiwifruit

    Science.gov (United States)

    Wood, Marion; Rae, Georgina M.; Wu, Rong-Mei; Walton, Eric F.; Xue, Bin; Hellens, Roger P.; Uversky, Vladimir N.

    2013-01-01

    Intrinsically disordered proteins (IDPs) are a relatively recently defined class of proteins which, under native conditions, lack a unique tertiary structure whilst maintaining essential biological functions. Functional classification of IDPs have implicated such proteins as being involved in various physiological processes including transcription and translation regulation, signal transduction and protein modification. Actinidia DRM1 (Ade DORMANCY ASSOCIATED GENE 1), represents a robust dormancy marker whose mRNA transcript expression exhibits a strong inverse correlation with the onset of growth following periods of physiological dormancy. Bioinformatic analyses suggest that DRM1 is plant specific and highly conserved at both the nucleotide and protein levels. It is predicted to be an intrinsically disordered protein with two distinct highly conserved domains. Several Actinidia DRM1 homologues, which align into two distinct Actinidia-specific families, Type I and Type II, have been identified. No candidates for the Arabidopsis DRM1-Homologue (AtDRM2) an additional family member, has been identified in Actinidia. PMID:23516402

  11. Effect of Buddhist meditation on serum cortisol and total protein levels, blood pressure, pulse rate, lung volume and reaction time.

    Science.gov (United States)

    Sudsuang, R; Chentanez, V; Veluvan, K

    1991-09-01

    Serum cortisol and total protein levels, blood pressure, heart rate, lung volume, and reaction time were studied in 52 males 20-25 years of age practicing Dhammakaya Buddhist meditation, and in 30 males of the same age group not practicing meditation. It was found that after meditation, serum cortisol levels were significantly reduced, serum total protein level significantly increased, and systolic pressure, diastolic pressure and pulse rate significantly reduced. Vital capacity, tidal volume and maximal voluntary ventilation were significantly lower after meditation than before. There were also significant decreases in reaction time after mediation practice. The percentage decrease in reaction time during meditation was 22%, while in subjects untrained in meditation, the percentage decrease was only 7%. Results from these studies indicate that practising Dhammakaya Buddhist meditation produces biochemical and physiological changes and reduces the reaction time. PMID:1801007

  12. Differences in abundances of cell-signalling proteins in blood reveal novel biomarkers for early detection of clinical Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Mateus Rocha de Paula

    Full Text Available BACKGROUND: In November 2007 a study published in Nature Medicine proposed a simple test based on the abundance of 18 proteins in blood to predict the onset of clinical symptoms of Alzheimer's Disease (AD two to six years before these symptoms manifest. Later, another study, published in PLoS ONE, showed that only five proteins (IL-1, IL-3, EGF, TNF- and G-CSF have overall better prediction accuracy. These classifiers are based on the abundance of 120 proteins. Such values were standardised by a Z-score transformation, which means that their values are relative to the average of all others. METHODOLOGY: The original datasets from the Nature Medicine paper are further studied using methods from combinatorial optimisation and Information Theory. We expand the original dataset by also including all pair-wise differences of z-score values of the original dataset ("metafeatures". Using an exact algorithm to solve the resulting Feature Set problem, used to tackle the feature selection problem, we found signatures that contain either only features, metafeatures or both, and evaluated their predictive performance on the independent test set. CONCLUSIONS: It was possible to show that a specific pattern of cell signalling imbalance in blood plasma has valuable information to distinguish between NDC and AD samples. The obtained signatures were able to predict AD in patients that already had a Mild Cognitive Impairment (MCI with up to 84% of sensitivity, while maintaining also a strong prediction accuracy of 90% on a independent dataset with Non Demented Controls (NDC and AD samples. The novel biomarkers uncovered with this method now confirms ANG-2, IL-11, PDGF-BB, CCL15/MIP-1; and supports the joint measurement of other signalling proteins not previously discussed: GM-CSF, NT-3, IGFBP-2 and VEGF-B.

  13. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Current Issue First Edition Abstracts Blood Advances A peer-reviewed, online only, open access journal with a ... If you find that you are interested in learning more about blood diseases and disorders, here are ...

  14. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... Hematologist Clinical Trials Talking with Your Doctor Patient Group Links Advocacy Toolkit Home For Patients Blood Disorders ... a request to the Blood Publishing Office . Patient Groups A list of Web links to patient groups ...

  15. Blood Clotting and Pregnancy

    Medline Plus

    Full Text Available ... pregnancy: Be aware of risk factors. Know your family history. Make sure your doctor knows about any ... blood clots or blood clotting disorders in your family. Remain active, with your doctor's approval. Be aware ...

  16. Tether Extrusion from Red Blood Cells: Integral Proteins Unbinding from Cytoskeleton

    OpenAIRE

    Borghi, N.; Brochard-Wyart, F.

    2007-01-01

    We investigate the mechanical strength of adhesion and the dynamics of detachment of the membrane from the cytoskeleton of red blood cells (RBCs). Using hydrodynamical flows, we extract membrane tethers from RBCs locally attached to the tip of a microneedle. We monitor their extrusion and retraction dynamics versus flow velocity (i.e., extrusion force) over successive extrusion-retraction cycles. Membrane tether extrusion is carried out on healthy RBCs and ATP-depleted or -inhibited RBCs. For...

  17. [Present situation and question and prospect of study on kidney-supplementing and blood-activating method in treating ovaries functional disorders (infertility with dysfunctional ovulation) for stimulating ovaries reactive mechanism to gonadotropic hormones].

    Science.gov (United States)

    Ma, Kun

    2011-09-01

    To summarize present situation of a study on kidney-supplementing and blood-activating method in treating ovaries functional disorders (infertility with dysfunctional ovulation) for stimulating ovaries reactive mechanism to gonadotropic hormones. Refer to correlative articles and combine clinical experience to report. Kidney-supplementing and blood-activating method have obvious therapeutic effect and no side effect and no adverse reaction. More attention are paid on influence factors and contribution about kidney-supplementing and blood-activating method in treating ovaries functional disorders especially on sex hormones, ovulating, corpora luteuman and implantation factors. Indicate the necessarity to develop polycentric kidney-supplementing and blood-activating method in treating ovaries functional disorders (infertility with dysfunctional ovulation) evaluation research. PMID:22121820

  18. Effect of a high-protein diet on maintenance of blood pressure levels achieved after initial weight loss: the DiOGenes randomized study

    NARCIS (Netherlands)

    Engberink, M.F.; Geleijnse, J.M.; Bakker, S.J.L.; Larsen, T.

    2015-01-01

    Randomized trials have shown significant blood pressure (BP) reductions after increased protein compared with carbohydrate intake, but the effect on BP maintenance after initial weight loss is unclear. We examined the effect of a high-protein diet on the maintenance of reduced BP after weight loss i

  19. Effect of a high-protein diet on maintenance of blood pressure levels achieved after initial weight loss : the DiOGenes randomized study

    NARCIS (Netherlands)

    Engberink, M. F.; Geleijnse, J. M.; Bakker, S. J. L.; Larsen, T. M.; Handjieva-Darlesnka, T.; Kafatos, A.; Martinez, J. A.; Pfeiffer, A. F. H.; Kunesova, M.; Jebb, S. A.; Holst, C.; Astrup, A.; Saris, W. H. M.; Brink, E. J.; van Baak, M. A.

    2015-01-01

    Randomized trials have shown significant blood pressure (BP) reductions after increased protein compared with carbohydrate intake, but the effect on BP maintenance after initial weight loss is unclear. We examined the effect of a high-protein diet on the maintenance of reduced BP after weight loss i

  20. Minocycline alleviates beta-amyloid protein and tau pathology via restraining neuroinflammation induced by diabetic metabolic disorder

    Directory of Open Access Journals (Sweden)

    Cai Z

    2013-08-01

    Full Text Available Zhiyou Cai,1 Yong Yan,2 Yonglong Wang2 1Department of Neurology, the Lu’an Affiliated Hospital of Anhui Medical University, Lu’an People’s Hospital, Lu’an, Anhui Province, People’s Republic of China; 2Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, People’s Republic of China Background: Compelling evidence has shown that diabetic metabolic disorder plays a critical role in the pathogenesis of Alzheimer’s disease, including increased expression of β-amyloid protein (Aβ and tau protein. Evidence has supported that minocycline, a tetracycline derivative, protects against neuroinflammation induced by neurodegenerative disorders or cerebral ischemia. This study has evaluated minocycline influence on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α in the brain of diabetic rats to clarify neuroprotection by minocycline under diabetic metabolic disorder. Method: An animal model of diabetes was established by high fat diet and intraperitoneal injection of streptozocin. In this study, we investigated the effect of minocycline on expression of Aβ protein, tau phosphorylation, and inflammatory cytokines (interleukin-1β and tumor necrosis factor-α in the hippocampus of diabetic rats via immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. Results: These results showed that minocycline decreased expression of Aβ protein and lowered the phosphorylation of tau protein, and retarded the proinflammatory cytokines, but not amyloid precursor protein. Conclusion: On the basis of the finding that minocycline had no influence on amyloid precursor protein and beta-site amyloid precursor protein cleaving enzyme 1 which determines the speed of Aβ generation, the decreases in Aβ production and tau hyperphosphorylation by minocycline are through inhibiting

  1. SU-E-T-45: Antibody Mean Residence Time in Blood and Its Correlation with Protein Molecular Weight

    International Nuclear Information System (INIS)

    Purpose: Animal biodistribution data are required prior to introducing a new radiopharmaceutical into clinical trials. Protein engineering, using recombinant DNA techniques can produce a large number of related (cognate) antibodies to a given molecular target. Thus, it is important that these constructs be numerically related to one another via a single criterion. In the following, we use the mean residence time (MRT) in murine blood as this criterion. Methods: Five cognate anti-CEA (Carcinoembryonic Antigen) antibodies were compared with regard to their MRT in whole blood of CEA-positive tumor-bearing (LS174T) mice. MRT was defined by blood AUC (area under the curve) divided by the initial blood uptake value; all in units of percent injected dose per gram (%ID/g). Cognates included single chain scFv (25 kDa), diabody (50 kDa), minibody (80 kDa), F(ab')2 (120 kDa), and intact (155 kDa) forms of the murine cT84.66 antibody against CEA. All were labeled with radioactive iodine. Results: The agents, in the sequence listed, exhibited MRT values of 1.16 +/- 0.01 h, 0.99 h, 5.06 +/- 0.70 h, 6.61 +/- 0.36 h, and 59.3 +/- 2.4 h respectively. Because of the monotonic nature of the sequence, a linear correlation analysis was performed between molecular weight (MW) and MRT or ln(MRT) of the 5 proteins. Probability of random correlation was 0.10 for MRT and 0.01 for ln(MRT). Conclusion: MRT values of cognate anti-CEA antibodies were found to be a monotonically increasing sequence with respect to MW. Cognate MW values correlated best to ln(MRT) of the protein species. Thus MRT was proportional to an exponential function of molecular weight. The extended intact antibody circulation time presumably reflected its relatively maximal MW. Presence of an intact FC segment on this native antibody may also have influenced these results

  2. SU-E-T-45: Antibody Mean Residence Time in Blood and Its Correlation with Protein Molecular Weight

    Energy Technology Data Exchange (ETDEWEB)

    Kwok, C; Williams, L [Retired from City of Hope Medical Center, Arcadia, CA (United States)

    2014-06-01

    Purpose: Animal biodistribution data are required prior to introducing a new radiopharmaceutical into clinical trials. Protein engineering, using recombinant DNA techniques can produce a large number of related (cognate) antibodies to a given molecular target. Thus, it is important that these constructs be numerically related to one another via a single criterion. In the following, we use the mean residence time (MRT) in murine blood as this criterion. Methods: Five cognate anti-CEA (Carcinoembryonic Antigen) antibodies were compared with regard to their MRT in whole blood of CEA-positive tumor-bearing (LS174T) mice. MRT was defined by blood AUC (area under the curve) divided by the initial blood uptake value; all in units of percent injected dose per gram (%ID/g). Cognates included single chain scFv (25 kDa), diabody (50 kDa), minibody (80 kDa), F(ab')2 (120 kDa), and intact (155 kDa) forms of the murine cT84.66 antibody against CEA. All were labeled with radioactive iodine. Results: The agents, in the sequence listed, exhibited MRT values of 1.16 +/- 0.01 h, 0.99 h, 5.06 +/- 0.70 h, 6.61 +/- 0.36 h, and 59.3 +/- 2.4 h respectively. Because of the monotonic nature of the sequence, a linear correlation analysis was performed between molecular weight (MW) and MRT or ln(MRT) of the 5 proteins. Probability of random correlation was 0.10 for MRT and 0.01 for ln(MRT). Conclusion: MRT values of cognate anti-CEA antibodies were found to be a monotonically increasing sequence with respect to MW. Cognate MW values correlated best to ln(MRT) of the protein species. Thus MRT was proportional to an exponential function of molecular weight. The extended intact antibody circulation time presumably reflected its relatively maximal MW. Presence of an intact FC segment on this native antibody may also have influenced these results.

  3. The effects of stress-induced blood components on protein synthesis and secretion in isolated rat hepatocytes

    International Nuclear Information System (INIS)

    The effect of stress-induced blood components were examined, specifically adrenaline and noradrenaline, in the presence and absence of rabbit serum or foetal calf serum, on soluble protein synthesis and secretion by isolated hepatocytes maintained in monolayer culture. Rabbit serum and low doses of adrenaline stimulated soluble protein synthesis and secretion whereas foetal calf serum and high doses of noradrenaline were inhibitory. The effect of noradrenaline on soluble protein synthesis and secretion ocurred in the first 12 hours of incubation. The stimulatory effect of adrenaline was still present after 24 hours of incubation. Preloading of the medium with [3H]-leucine i.e. before the addition of sera and/or catecholamines, showed the [3H]-leucine uptake to have occured to a large extent within the first hour of incubation. Noradrenaline supplementation of the medium at two hourly intervals showed no effect on protein synthesis and secretion. The stability of the cetecholamines and the status of the receptors need to be determined for the effective analysis of the results at any point during the incubation. 17 figs., 15 tabs., 83 refs

  4. Proteomic analysis of blood level of proteins before and after operation in patients with esophageal squamous cell carcinoma at high-incidence area in Henan Province

    Institute of Scientific and Technical Information of China (English)

    Ji-Ye An; Zong-Min Fan; Ze-Hao Zhuang; Yan-Ru Qin; Shan-Shan Gao; Ji-Lin Li; Li-Dong Wang

    2004-01-01

    AIM: To characterize the protein files in blood from same patients with esophageal squamous cell carcinoma (ESCC)before and after operation at the high-incidence area for ESCC in Henan Province, China.METHODS: Two-dimensional electrophoresis, silver staining and ImageMaster 2-DE analysis software were applied to the determination of protein files in the blood obtained from normal controls and ESCC patients before and after operation.RESULTS: A total of 655, 662 and 677 protein spots were identified, respectively, from the normal controls and ESCC patients before and after operation. No significant difference in the number of protein spots was observed between the normal group and ESCC patients. A total of seven protein spots were identified with a dramatic difference among the samples before and after operation. Six protein spots were up-regulated and one protein spot was down-regulated in the group after operation compared with those in normal and before operation. Three protein spots were further characterized by matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS). The proteins from these three spots were identified as serum amyloid A(SAA), amyloid related serum protein and haptoglobin.CONCLUSION: Serum amyloid A, amyloid related serum protein and haptoglobin may be related with ESCC and/or surgery. The significance of these proteins needs to be further characterized. The present study provides informative data for the establishment of serum protein profiles related with ESCC.

  5. Effect of advanced glycosylation end products on activity of protein kinase C in human peripheral blood mononuclear cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objectives TO investigate the effect of advanced glycosylation end products (AGEs) on the activity of protein kinese C (PKC) in human peripheral bloodmononuclear Cells (PBMC) and to observe whether aminoguanidine (AG) can influence the effect of AGEs. Methods After PBMC were isoiated from human peripheral blood and incubated with different concentrations of AGEs-BSA for various periods, total PKC activity in PBMC was determined by measuring the incorporation of 32P from [γ-32P] ATP=into a special substrate using Prornega PKC assay kit. Results AGEs-BSA increased the total PKC activity in PBMC from 83.43±6.57 pmol/min/mg protein to 116.8±13.82 pmol/min/mg protein with a peak at 15 min.AGEs-BSA also increased the total PKC activity in a concentration-dependent manner from 83.1±6.4 pmol/min/mg protein(control) to 119.1±13.3 pmol/min/mg protein (control vs AGEs-BSA 400 mg/L, P<0.01). Furthermore, AGEs-BSA induced an elevation of PKC activity in a glycosylating time-related manner,from 80.9±8.2 (control) to 118.3±11.5 pmol/min/mg protein (glycasytation for 12 wk, P<0.01). The total PKC activity stimulated by AGEs-BSA pretreated with AG (100, 200 mg/L) was markedly lower than that of AGEs-BSA group not pretreated with AG ( P<0.05, P<0.01). Conclusions AGEs-BSA increased the total PKC activity in PBMC in a concentration and incubation time dependent manner. The ability of AGEs-B.SA to stimulate PKC activity was markedly decreased by pretreatment of AGEs-BSA with AG.

  6. Influence of sinomenine on protein profiles of peripheral blood mononuclear cells from ankylosing spondylitis patients: a pharmacoproteomics study

    Institute of Scientific and Technical Information of China (English)

    HUANG Zhi-xiang; TAN Jin-hui; LI Tian-wang; DENG Wei-ming; QIU Ke-wei; LIAO Ze-tao; ZENG Zhao-qiu

    2013-01-01

    Background Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease which lacks satisfactory treatment so far.Sinomenine (SIN) is an alkaloid and has recently been utilized in treating multiple rheumatic diseases including AS in China,but its exact mechanism remains to be explored.This study investigated the alteration of proteome in peripheral blood mononuclear cells (PBMCs) from AS patients.Methods Thirty AS patients were enrolled in this study.PBMCs from each AS patient were cultured in medium with or without SIN respectively.Then PBMCs proteins from both groups were separated by two-dimensional electrophoresis (2-DE) and analyzed by mass spectrometry (MS).Two differentially expressed proteins were then chosen to be verified using Western blotting.Results Seven proteins,including α-synuclein (SNCA),calmodulin (CALM),acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A),chloride intracellular channel protein 1 (CLIC1),guanine nucleotide-binding protein G(I)/G(S)/ G(T) subunit beta-1 (GNB1),gelsolin (GSN) and histone H2B type 1-M (HISTH2BM)were over-expressed,while coronin1A (CORO1A) was under-expressed in the SIN-treated PBMCs.Further bioinformatics search indicated that the changes of SNCA,ANP32A and CLIC1 pertained to apoptosis,while changes of GSN and CORO1A were associated with both apoptosis and inhibition of immunological function.Subsequently GSN and CORO1A were selected to validate by Western blotting and the results were consistent with those of 2-DE.Conclusion There were 8 differentially expressed proteins in the SIN-treated PBMCs,which might shed some light on the mechanism of SIN in the treatment of AS.

  7. Association between the Regulator of G-protein Signaling 9 Gene and Patients with Methamphetamine Use Disorder and Schizophrenia

    Science.gov (United States)

    Okahisa, Y; Kodama, M; Takaki, M; Inada, T; Uchimura, N; Yamada, M; Iwata, N; Iyo, M; Sora, I; Ozaki, N; Ujike, H

    2011-01-01

    The regulator of G-protein signaling (RGS) modulates the functioning of heterotrimeric G protein. RGS9-2 is highly expressed in the striatum and plays a role in modulating dopaminergic receptor-mediated signaling cascades. Previous studies suggested that the RGS9 gene might contribute to the susceptibility to psychotic diseases. Therefore, we investigated the association between the RGS9 gene and two related dopamine psychoses, schizophrenia and methamphetamine use disorders. The subjects comprised 487 patients of schizophrenia and 464 age- and sex-matched healthy controls and 220 patients of methamphetamine use disorder and 289 controls. We genotyped two nonsynonymous polymorphisms, rs12452285 (Leu225Ser) and rs34797451 (His498Arg), of the RGS9 gene. Rs34797451 showed monomorphism in the present Japanese population, but rs12452285 showed polymorphism. There were no significant differences in genotypic or allelic distributions of rs12452285 between patients with schizophrenia and the corresponding control or between patients with methamphetamine use disorder and the corresponding control. We also analyzed the clinical features of methamphetamine use disorder. We found a significant association in allelic distribution with the phenotypes of age at first consumption (p=0.047). The present study suggested that the RGS9 gene is unlikely to play a major role in schizophrenia and methamphetamine dependence liability and/or the development of methamphetamine induced psychosis, at least in a Japanese population. PMID:21886588

  8. Tick receptor for outer surface protein A from Ixodes ricinus — the first intrinsically disordered protein involved in vector-microbe recognition

    Science.gov (United States)

    Urbanowicz, Anna; Lewandowski, Dominik; Szpotkowski, Kamil; Figlerowicz, Marek

    2016-04-01

    The tick receptor for outer surface protein A (TROSPA) is the only identified factor involved in tick gut colonization by various Borrelia species. TROSPA is localized in the gut epithelium and can recognize and bind the outer surface bacterial protein OspA via an unknown mechanism. Based on earlier reports and our latest observations, we considered that TROSPA would be the first identified intrinsically disordered protein (IDP) involved in the interaction between a vector and a pathogenic microbe. To verify this hypothesis, we performed structural studies of a TROSPA mutant from Ixodes ricinus using both computational and experimental approaches. Irrespective of the method used, we observed that the secondary structure content of the TROSPA polypeptide chain is low. In addition, the collected SAXS data indicated that this protein is highly extended and exists in solution as a set of numerous conformers. These features are all commonly considered hallmarks of IDPs. Taking advantage of our SAXS data, we created structural models of TROSPA and proposed a putative mechanism for the TROSPA-OspA interaction. The disordered nature of TROSPA may explain the ability of a wide spectrum of Borrelia species to colonize the tick gut.

  9. Ellipsometric studies of synthetic albumin-binding chitosan-derivatives and selected blood plasma proteins

    Science.gov (United States)

    Sarkar, Sabyasachi

    This dissertation summarizes work on the synthesis of chitosan-derivatives and the development of ellipsometric methods to characterize materials of biological origin. Albumin-binding chitosan-derivatives were synthesized via addition reactions that involve amine groups naturally present in chitosan. These surfaces were shown to have an affinity towards human serum albumin via ELISA, UV spectroscopy and SDS PAGE. Modified surfaces were characterized with IR ellipsometry at various stages of their synthesis using appropriate optical models. It was found that spin cast chitosan films were anisotropic in nature. All optical models used for characterizing chitosan-derivatives were thus anisotropic. Chemical signal dependence on molecular structure and composition was illustrated via IR spectroscopic ellipsometry (IRSE). An anisotropic optical model of an ensemble of Lorentz oscillators were used to approximate material behavior. The presence of acetic acid in spin-cast non-neutralized chitosan samples was thus shown. IRSE application to biomaterials was also demonstrated by performing a step-wise chemical characterizations during synthesis stages. Protein adsorbed from single protein solutions on these modified surfaces was monitored by visible in-situ variable wavelength ellipsometry. Based on adsorption profiles obtained from single protein adsorption onto silicon surfaces, lumped parameter kinetic models were developed. These models were used to fit experimental data of immunoglobulin-G of different concentrations and approximate conformational changes in fibrinogen adsorption. Biomaterial characterization by ellipsometry was further extended to include characterization of individual protein solutions in the IR range. Proteins in an aqueous environment were characterized by attenuated total internal reflection (ATR) IR ellipsometry using a ZnSe prism. Parameterized dielectric functions were created for individual proteins using Lorentz oscillators. These

  10. Biochemical and Molecular Characterization of a Novel Cu/Zn Superoxide Dismutase from Amaranthus hypochondriacus L.: an Intrinsically Disordered Protein.

    Science.gov (United States)

    Montero-Morán, Gabriela M; Sampedro, José G; Saab-Rincón, Gloria; Cervantes-González, Miguel A; Huerta-Ocampo, José Á; De León-Rodríguez, Antonio; Barba de la Rosa, Ana P

    2015-08-01

    A novel Cu/ZnSOD from Amaranthus hypochondriacus was cloned, expressed, and characterized. Nucleotide sequence analysis showed an open reading frame (ORF) of 456 bp, which was predicted to encode a 15.6-kDa molecular weight protein with a pI of 5.4. Structural analysis showed highly conserved amino acid residues involved in Cu/Zn binding. Recombinant amaranth superoxide dismutase (rAhSOD) displayed more than 50 % of catalytic activity after incubation at 100 °C for 30 min. In silico analysis of Amaranthus hypochondriacus SOD (AhSOD) amino acid sequence for globularity and disorder suggested that this protein is mainly disordered; this was confirmed by circular dichroism, which showed the lack of secondary structure. Intrinsic fluorescence studies showed that rAhSOD undergoes conformational changes in two steps by the presence of Cu/Zn, which indicates the presence of two binding sites displaying different affinities for metals ions. Our results show that AhSOD could be classified as an intrinsically disordered protein (IDP) that is folded when metals are bound and with high thermal stability. PMID:26129702

  11. Conformations of intrinsically disordered proteins are influenced by linear sequence distributions of oppositely charged residues.

    Science.gov (United States)

    Das, Rahul K; Pappu, Rohit V

    2013-08-13

    The functions of intrinsically disordered proteins (IDPs) are governed by relationships between information encoded in their amino acid sequences and the ensembles of conformations that they sample as autonomous units. Most IDPs are polyampholytes, with sequences that include both positively and negatively charged residues. Accordingly, we focus here on the sequence-ensemble relationships of polyampholytic IDPs. The fraction of charged residues discriminates between weak and strong polyampholytes. Using atomistic simulations, we show that weak polyampholytes form globules, whereas the conformational preferences of strong polyampholytes are determined by a combination of fraction of charged residues values and the linear sequence distributions of oppositely charged residues. We quantify the latter using a patterning parameter κ that lies between zero and one. The value of κ is low for well-mixed sequences, and in these sequences, intrachain electrostatic repulsions and attractions are counterbalanced, leading to the unmasking of preferences for conformations that resemble either self-avoiding random walks or generic Flory random coils. Segregation of oppositely charged residues within linear sequences leads to high κ-values and preferences for hairpin-like conformations caused by long-range electrostatic attractions induced by conformational fluctuations. We propose a scaling theory to explain the sequence-encoded conformational properties of strong polyampholytes. We show that naturally occurring strong polyampholytes have low κ-values, and this feature implies a selection for random coil ensembles. The design of sequences with different κ-values demonstrably alters the conformational preferences of polyampholytic IDPs, and this ability could become a useful tool for enabling direct inquiries into connections between sequence-ensemble relationships and functions of IDPs. PMID:23901099

  12. Effect of dietary protein content on animal production and blood metabolites of dairy cows during lactation.

    Science.gov (United States)

    Law, R A; Young, F J; Patterson, D C; Kilpatrick, D J; Wylie, A R G; Mayne, C S

    2009-03-01

    Ninety autumn-calving Holstein dairy cows [45 primiparous and 45 multiparous (mean parity, 3.1)] were allocated to 1 of 3 dietary crude protein (CP) concentrations: 173, 144, or 114 g of CP/kg of DM, from calving until d 150 of lactation. On d 151, half of the animals in each treatment were allocated an alternative dietary protein concentration. Half of the animals receiving 114 g of CP/kg of DM went onto 144 g of CP/kg of DM; half of the animals receiving 144 g of CP/kg of DM went onto 173 g of CP/kg of DM; and half of the animals receiving 173 g of CP/kg of DM went onto 144 g of CP/kg of DM, with the remaining animals staying on their original treatment. This resulted in 6 treatments in the mid to late lactation period: 114/114, 144/144, 173/173, 114/144, 144/173, and 173/144 g of CP/kg of DM. An increase in dietary CP concentration significantly increased milk, fat, and protein yield in early lactation (d 1 to 150). Dry matter intake was also increased with increased dietary protein concentration; however, this was not significant between 144 and 173 g of CP/kg of DM. Increased dietary CP significantly increased plasma urea, albumin, and total protein concentrations but had no significant effect on NEFA, leptin, or IGF-1 concentrations. Decreasing the dietary CP concentration in mid-late lactation (d 151 to 305) from 173 to 144 g/kg of DM had no significant effect on milk yield, dry matter intake, or milk fat and protein yield, compared with animals that remained on 173 g of CP/kg of DM throughout lactation. Increasing dietary CP concentration from 144 to 173 g/kg of DM significantly increased dry matter intake compared with animals that remained on the 144 g of CP/kg of DM throughout lactation. There were no significant dietary treatment effects on live weight or body condition score change throughout the experiment. Results of this study indicate that high protein diets (up to 173 g of CP/kg of DM) improved feed intake and animal performance in early lactation

  13. The Effect of 60Co Gamma Irradiation on Various Fractions of Human Blood-Plasma Proteins

    International Nuclear Information System (INIS)

    The potential usefulness of employing ionizing radiation to cold-sterilize biomedical products has stimulated interest in characterizing the radiation sensitivity of various biologicals like vitamins, antibiotics, enzymes, antibodies and blood plasma fractions. This report presents findings on the sensitivity of haemagglutinin activity in human sera exposed to cobalt-60 gamma radiation. At doses tested between 0.2 and 5.0 Mrad, α-isohaemagglutinins were found to be more readily inactivated than ß-isohaemagglutinins, but neither was completely inactivated in this range. Sterility, clotting and antihaemophilic activity were also assessed on irradiated and freeze-dried preparations of human plasma with no significant differences in response detected. (author)

  14. Ontogeny and characterization of blood leukocyte subsets and serum proteins in piglets before and after weaning

    DEFF Research Database (Denmark)

    Juul-Madsen, H.R.; Jensen, K.H.; Nielsen, Jens;

    2010-01-01

    Existing knowledge about the development of the porcine immune system was extended by phenotypic characterization of leukocyte subsets and with assessment of Mannan-Binding Lectin (MBL) and immunoglobulin concentrations in peripheral blood of healthy piglets. Single-color and/or double-color flow...... immune system seem to be stimulated immediately after weaning. At the time considered to have the highest infection pressure T-cells and TLR4+ cells were markedly enhanced, whereas the expression of SLA I did not seem to be affected by weaning....

  15. C-14-activity incorporation into the protein of fetal organs of guinea pigs with different maternal placental blood flow and fetal arterial O2-saturation

    International Nuclear Information System (INIS)

    In anaesthesised gravid guinea-pigs the dilate, end section of a placental radial artery was connected to the A.carotis via a flow meter and a throttle in order to measure and widely alter the maternal placental blood flow. Blood samples are taken from the fetal A.carotis, the fetal arterial O2-saturation and the Hb-content were determined. By altering the maternal placental blood circulation the fetal arterial O2-concentration can stabilised at various levels. In order to study the protein synthesis, under these conditions one infused 185 kBq C-14-leucine over a period of 3 hours into the jugular vein of the fetus. During infusion the radioactive concentrations in whole plasma and plasma water were measured. After the infusion the radioactive concentrations in the tissue fluid, the intracellular fluid and the acid-insoluble tissue fraction (protein) of the heart, kidenys, liver, the muscles of the upper end lower part of the body, the brain and the placenta were measured. The following deductions were drawn from the findings: The maternal placental blood flow vitally influences the activity incorporation per activity concentration in the plasma water. These findings agree with the hypotheses that the maternal blood circulation has an essential influence on the fetal proteins synthesis and that this influence can be attributed to the connection between placenta connection blood flow and oxygen saturation of fetal arterial blood. (orig.)

  16. The structure of multilayer protein/polyelectrolyte coatings and its effect on blood compatibility

    Czech Academy of Sciences Publication Activity Database

    Houska, Milan; Brynda, Eduard; Broučková, A.; Dyr, J. E.

    Praha : Institute of Macromolecular Chemistry, AS CR, 2004 - (Kahovec, J.). s. PC38 ISBN 80-85009-49-8. [Microsymposium on Polymer Biomaterials: Biomimetic and Bioanalogous systems /43./. 11.07.2004-15.07.2004, Prague] R&D Projects: GA AV ČR KSK4050111 Keywords : protein/ polyelectrolyte assemblies * heparin * albumin Subject RIV: CD - Macromolecular Chemistry

  17. Trace elements studies on Karachi population part IV: blood copper, zinc, magnesium and lead levels in psychiatric patients with depression, mental retardation and seizure disorder

    International Nuclear Information System (INIS)

    Blood copper, zinc, magnesium and lead levels were determined by atomic absorption spectroscopy for 15 males and 16 female suffering from depression, 6 males and 1 female with mental retardation and 3 males and 4 females with seizure disorders. They were all under no medication and belong to low income groups. No difference in copper levels was found between the sexes in any of the groups. The levels in all the groups were significantly higher than in the normals. In depressives, males had significantly higher zinc levels than females and only female depressives had lower levels from normals. In both depressives and normals, males had higher magnesium levels than females but no group of patients had significantly different levels from normals. Lead levels were significantly higher in female depressives and for those with seizure disorders than for controls. At least one metal abnormality was found in 21 (67.7%) depressive, 5 (71.4%) of those with mental retardation and 6 (85.7%) with seizure disorders. (author)

  18. Beta-propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation

    Science.gov (United States)

    Hayflick, Susan J.; Kruer, Michael C.; Gregory, Allison; Haack, Tobias B.; Kurian, Manju A.; Houlden, Henry H.; Anderson, James; Boddaert, Nathalie; Sanford, Lynn; Harik, Sami I.; Dandu, Vasuki H.; Nardocci, Nardo; Zorzi, Giovanna; Dunaway, Todd; Tarnopolsky, Mark; Skinner, Steven; Holden, Kenton R.; Frucht, Steven; Hanspal, Era; Schrander-Stumpel, Connie; Mignot, Cyril; Héron, Delphine; Saunders, Dawn E.; Kaminska, Margaret; Lin, Jean-Pierre; Lascelles, Karine; Cuno, Stephan M.; Meyer, Esther; Garavaglia, Barbara; Bhatia, Kailash; de Silva, Rajith; Crisp, Sarah; Lunt, Peter; Carey, Martyn; Hardy, John; Meitinger, Thomas; Prokisch, Holger; Hogarth, Penelope

    2013-01-01

    Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a ‘halo’ of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features. PMID:23687123

  19. Blood protein polymorphism in three sheep breeds from the south of Tunisia

    Directory of Open Access Journals (Sweden)

    Khaldi Zahrane,

    2011-02-01

    Full Text Available Biochemical polymorphism was studied in the native ovine Barbarine (BAR and Queue Fine de l’Ouest (QF breeds as well as in the exotic D’man (DMN breed in the South of Tunisia using a panel of six protein coding loci: Haemoglobin (Hb, Carbonic anhydrase (Ca, Albumin (Al, Transferrin (Tf, X-protein (X-p and Arylesterase A (EsA. Polymorphic loci were detected by means of horizontal starch gel electrophoresis. All tested loci were polymorphic. The Tf locus exhibited the highest number of alleles while the other loci showed two alleles in all sampled breeds. Estimates of expected heterozygosity were almost twice those of observed heterosigositiy in all sheep populations and the high level of heterozygosity was observed in DMN breed. Genetic distances observed between BAR-DMN and between QF-DMN were larger than those found between BAR-QF breeds.

  20. Thermodiffusion as a close-to-interface effect that matters in non-isothermal (dis)orderly protein aggregations

    International Nuclear Information System (INIS)

    The goal of this discussion letter is to argue how and why an inherent nanoscale thermodiffusion (Soret-type) effect can be relevant in (dis)orderly protein aggregation. We propose a model in which the aggregation of proteins, in the presence of temperature gradient, is described in terms of Smoluchowski dynamics in the phase space of nuclei sizes. The Soret coefficient of the aggregation is proportional to the variations of the aggregation free energy over temperature. The free energy is related to the (interface) boundary condition of the system. When boundary condition is of equilibrium Gibbs–Thomson type, with a well-stated surface tension of the nucleus, to the system can be assigned a negative Soret effect. On the contrary, when a non-equilibrium perturbing (salting-out) term enters the boundary condition, a positive Soret effect may manifest. A zero-value Soret regime is expected to occur in between, yielding very soft (“fragile”) non-Kossel protein-type crystals. - Highlights: • Comprehension for non-isothermal formation of (dis)orderly protein aggregation. • Classification of temperature-sensitive morphologies in colloid-type aggregation. • Morphologies split into near-equilibrium and nonequilibrium structural outcomes. • Classification on mesoscopic nonequilibrium thermodynamics near local equilibrium

  1. Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

    Energy Technology Data Exchange (ETDEWEB)

    Knott, Michael [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Best, Robert B., E-mail: robertbe@helix.nih.gov [Department of Chemistry, Cambridge University, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520 (United States)

    2014-05-07

    Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an “induced fit” or “conformational selection” mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD.

  2. Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

    Science.gov (United States)

    Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

    2016-05-01

    Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. PMID:26924758

  3. Assessing brain immune activation in psychiatric disorders: clinical and preclinical PET imaging studies of the 18-kDa translocator protein

    OpenAIRE

    van der Doef, Thalia F; Doorduin, Janine; Berckel, Bart Nm; Cervenka, Simon

    2015-01-01

    Accumulating evidence from different lines of research suggests an involvement of the immune system in the pathophysiology of several psychiatric disorders. During recent years, a series of positron emission tomography (PET) studies have been published using radioligands for the translocator protein (TSPO) to study microglia activation in schizophrenia, bipolar I disorder, major depression, autism spectrum disorder, and drug abuse. The results have been somewhat conflicting, which could be du...

  4. Genetic and protein biomarkers in blood for the improved detection of GH abuse.

    Science.gov (United States)

    Ferro, P; Ventura, R; Pérez-Mañá, C; Farré, M; Segura, J

    2016-09-01

    Human Growth Hormone (hGH, somatotropin) is one of the relevant forbidden substances to be detected in sport drug testing. Since the appearance of recombinant hGH (rhGH) in the 80's, its expansion and availability through the black market have increased, so the detection of its abuse continues to be a challenge at present. New techniques or biomarkers that are robust, reliable, sensitive and allowing a large detection time window are welcome. rhGH produces an increase of insulin-like growth factor 1 (IGF-1). FN1 (fibronectin 1) and RAB31 (member of RAS oncogene family) genes have been suggested as two potential biomarkers for IGF-1 abuse. Following this line, in the present study some genetic and proteomic approaches have been performed with fourteen healthy male subjects treated with rhGH (which produces increase of IGF-1 concentrations) to study FN1 gene, FN1 protein, RAB31 gene and RAB31 protein as potential biomarkers for rhGH abuse. The results showed that both, RAB31 and FN1 genes and FN1 protein could be potential biomarkers for rhGH administration. Preliminary assessments of gender, age, acute sport activities and GHRP-2 (pralmorelin, a rhGH releasing peptide) influence suggest they are not relevant confounding factors. Thus, the selected markers present high sensitivity and a larger detection window for rhGH detection than IGF-1 itself. PMID:27243825

  5. The interplay between transient a-helix formation and side chain rotamer distributions in disordered proteins probed by methyl chemical shifts

    DEFF Research Database (Denmark)

    Kjærgaard, Magnus; Iesmantavicius, Vytautas; Poulsen, Flemming M

    2011-01-01

    shifts can in principle report the conformations of aliphatic side chains in disordered proteins and in order to examine this two model systems were chosen: the acid denatured state of acyl-CoA binding protein (ACBP) and the intrinsically disordered activation domain of the activator for thyroid hormone...... allow a quantitative analysis of the ensemble of ¿(2)-angles of especially leucine residues in disordered proteins. The changes in the rotamer distributions upon denaturation correlate to the changes upon helix induction by the co-solvent trifluoroethanol, suggesting that the side chain conformers are......The peptide backbones of disordered proteins are routinely characterized by NMR with respect to transient structure and dynamics. Little experimental information is, however, available about the side chain conformations and how structure in the backbone affects the side chains. Methyl chemical...

  6. The use of blood protein polymorphism to estimate genetic distance among populations of Indonesian native sheep, St. Croix and Merino

    Directory of Open Access Journals (Sweden)

    Agus Suparyanto

    2002-03-01

    Full Text Available The genetic distance among populations of Indonesia native sheep (Ciamis, Garut, Sumatera and Garahan, St. Croix and Merino were estimated to investigate the genetic relationship among those breeds. Blood protein polymorphism of transferin (Tf, post-transferin (PTf, albumin (Alb, post-albumin (PAlb were detected from blood plasma, while haemoglobine (Hb was detected from erythrocyte using Polyacrylamide Gel Electrophoresis (PAGE. Results of PAGE showed that Tf was controlled by 6 alleles, while Alb by 4 alleles, PTf by 3 Alleles and PAlb and Hb by 2 alleles. Value of breeding coefficient within individual subpopulations (FIS for Tf (-0,0014, Alb (-0,0046 and Hb (0,0256 were not significantly different by noel. These results show that data of gene frequency are still following Hardy-Weinberg Equilibrium and inbreeding inside the sub population did not occur. The closest distance among the native breeds is the subpopulations of Ciamis and Garut due to neighboring area and similar traits of Thin Tail Sheep. The genetic distance of both population to Sumatera Thin Tail Sheep and Garahan Fat Tail are quite far. In addition to that results all Indonesian native breed were distinctly different from St. Croix and Merino.

  7. Detection of Homocysteine and C-Reactive Protein in the Saliva of Healthy Adults: Comparison with Blood Levels

    Directory of Open Access Journals (Sweden)

    Michael C. Dillon

    2010-07-01

    Full Text Available Inflammation and cardiovascular disease are associated with elevated serum levels of C-Reactive Protein (CRP and homocysteine. The presence of both molecules in saliva provides an opportunity for development of non-invasive assessments of disease risk. However, salivary CRP and homocysteine reference ranges and their correlation with serum levels are unknown. This study investigated if CRP and homocysteine could be routinely detected in the saliva of healthy adults and the relationship between salivary and blood levels. CRP and homocysteine concentrations were determined using ELISA and enzymatic assays respectively. Homocysteine was detected in only two saliva samples (n = 55. CRP was measurable in all saliva samples (range: 0.05 to 64.3 µg/L; median = 1.2 µg/L and plasma samples (range: 0.14 to 31.1 mg/L; median = 2.0 mg/L. Regression analysis demonstrated no relation- ship between CRP concentration in saliva and plasma (R2 = 0.001. Generalized linear models including variables such as saliva flow rate and time since eating or drinking also did not pass lack of fit testing. Therefore, a relationship between CRP concentration in saliva and blood could not be established in this group of subjects. More sensitive detection methods are needed to determine if a correlation between salivary and serum homocysteine levels exists.

  8. Studies of blood groups and protein polymorphisms in the Brazilian horse breeds Mangalarga Marchador and Mangalarga (Equus caballus

    Directory of Open Access Journals (Sweden)

    Andréia Samaha Lippi

    2003-12-01

    Full Text Available Allelic frequencies at 12 loci (five blood groups: C, D, K, P, and U; and seven protein polymorphisms: Al, A1B, Es, Gc, Hb, PGD, and Tf, are given for two Brazilian horse breeds: Mangalarga Marchador and Mangalarga. The high genetic identity value found (96.0% is consistent with their common origin, although, at some point of the development of Mangalarga Marchador, Mangalarga separated from the original stock. The expected average heterozygosity was higher in Mangalarga Marchador. The populations presented genetic differentiation, as shown by the statistically significant value of F ST. The nonsignificant F IS values showed that there was no appreciable consanguineous mating in any of the two populations. Exclusion probability calculated for the 12 loci was 87.0% and 86.5% for Mangalarga Marchador and Mangalarga, respectively. No genetic equilibrium was observed in the A1B, Tf, and Es loci of Mangalarga Marchador. The frequencies of blood factors A, Q, and T were calculated.

  9. Detecting remote sequence homology in disordered proteins: discovery of conserved motifs in the N-termini of Mononegavirales phosphoproteins.

    Directory of Open Access Journals (Sweden)

    David Karlin

    Full Text Available Paramyxovirinae are a large group of viruses that includes measles virus and parainfluenza viruses. The viral Phosphoprotein (P plays a central role in viral replication. It is composed of a highly variable, disordered N-terminus and a conserved C-terminus. A second viral protein alternatively expressed, the V protein, also contains the N-terminus of P, fused to a zinc finger. We suspected that, despite their high variability, the N-termini of P/V might all be homologous; however, using standard approaches, we could previously identify sequence conservation only in some Paramyxovirinae. We now compared the N-termini using sensitive sequence similarity search programs, able to detect residual similarities unnoticeable by conventional approaches. We discovered that all Paramyxovirinae share a short sequence motif in their first 40 amino acids, which we called soyuz1. Despite its short length (11-16aa, several arguments allow us to conclude that soyuz1 probably evolved by homologous descent, unlike linear motifs. Conservation across such evolutionary distances suggests that soyuz1 plays a crucial role and experimental data suggest that it binds the viral nucleoprotein to prevent its illegitimate self-assembly. In some Paramyxovirinae, the N-terminus of P/V contains a second motif, soyuz2, which might play a role in blocking interferon signaling. Finally, we discovered that the P of related Mononegavirales contain similarly overlooked motifs in their N-termini, and that their C-termini share a previously unnoticed structural similarity suggesting a common origin. Our results suggest several testable hypotheses regarding the replication of Mononegavirales and suggest that disordered regions with little overall sequence similarity, common in viral and eukaryotic proteins, might contain currently overlooked motifs (intermediate in length between linear motifs and disordered domains that could be detected simply by comparing orthologous proteins.

  10. Effect of whey protein on blood lipid profiles: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhang, J-W; Tong, X; Wan, Z; Wang, Y; Qin, L-Q; Szeto, I M Y

    2016-08-01

    Previous studies have suggested that whey supplementation may have beneficial effects on lipid profiles, although results were inconsistent. A literature search was performed in March 2015 for randomized controlled trials observing the effects of whey protein and its derivatives on circulating levels of triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). A meta-analysis was subsequently conducted. The meta-analysis results of 13 trials showed that whey supplementation significantly reduced the circulating TG level by 0.11 mmol/l (95% CI: -0.21, 0 mmol/l), whereas the whey protein had no effects on circulating TC (-0.11 mmol/l, 95% CI: -0.27, 0.05 mmol/l), LDL-C (-0.08 mmol/l, 95% CI: -0.23, 0.07 mmol/l) and HDL-C (0.01 mmol/l, 95% CI: -0.04, 0.05 mmol/l). Subgroup analysis showed that significant TG reduction disappeared in participants with low body mass index, low supplemental whey dose or under exercise training/energy restriction during the trial. No evidence of heterogeneity across studies and publication bias was observed. In conclusion, our findings demonstrated that the effects of whey protein supplementation were modest, with an overall lowering effect on TG but no effect on TC, LDL-C and HDL-C. PMID:27026427

  11. [The response of the blood proteins to ablation of the capsaicin-sensitive nerves].

    Science.gov (United States)

    Kostina, N E; Spiridonov, V K

    2005-07-01

    Effects of neurotoxic doses of capsaicin (150 mg/kg) on the protein content in electrophoretic fractions (PAAG) in the Wistar rat plasma were studied. In early period (7 days) after administration of capsaicin, an increase of the alpha1-, alpha2-globulins and a decrease of the albumin, gamma-globulins, were observed. After 14-30 days, increase of the albumin and decrease of the alpha1-, gammay-globulins were detected. The ablation of the capsaicin-sensitive nerves abrogated the changes of positive and negative acute phase reactants induced by zymosan and diminished the content of gamma-globulins. PMID:16206619

  12. C-reactive protein is produced by a small number of normal human peripheral blood lymphocytes

    OpenAIRE

    1986-01-01

    Biosynthetic labeling with [35S]met and immunoprecipitation with anti-C- reactive protein (CRP) antibodies and Staphylococcus aureus indicate that cell surface CRP is produced by lymphocytes. The ability of anti- CRP to reduce NK activity, and the demonstration that 125I-anti-CRP- labeled PBL are found in low-density Percoll fractions associated with large granular lymphocyte (LGL) and NK activity suggest that S-CRP- bearing cells are NK effectors. The production of S-CRP by LGL supports this...

  13. Relationship between blood urea, protein, creatinine, triglycerides and macro-mineral concentrations with the quality and quantity of milk in dairy Holstein cows

    OpenAIRE

    Azadeh Babapour; Siamak Asri-Rezaei; Gholamali Moghadam; Ali-Gholi Ramin; Shahram Nozad; Sina Ramin

    2012-01-01

    Seventy six high and low producer cows were selected to determine the composition of the blood and milk parameters, and their interrelationships to determine the indices which could be useful to improve the milk yield. The highest mean blood concentrations were found in high producer cows. Mean values for blood urea nitrogen (BUN), serum protein (SPtn), creatinine, triglycerides (TGs), cholesterol, and beta-hydroxybutyric acid (BHB) were 25.10 mg dL-1, 10.15 g dL-1, 0.81, 62.30, 177.10 and 0....

  14. Appetite Sensations, Appetite Signaling Proteins, and Glucose in Obese Adolescents with Subclinical Binge Eating Disorder

    OpenAIRE

    Adamo, Kristi B; Wilson, Shanna L.; Ferraro, Zachary M.; Hadjiyannakis, Stasia; Doucet, Éric; Gary S. Goldfield

    2014-01-01

    Objective. This study aimed to investigate potential differences in appetite sensations, ghrelin, peptide YY, and glucose and their relationship with energy and macronutrient intake in obese adolescents with subclinical binge eating disorder. Methods. Fifteen obese adolescents (six and nine individuals with and without subclinical binge eating disorder, resp.) qualified for this study. Visual analog scales and Three-Factor Eating Questionnaires were used to assess eating behaviours. Circulati...

  15. Transporter protein and drug-conjugated gold nanoparticles capable of bypassing the blood-brain barrier.

    Science.gov (United States)

    Zhang, Yanhua; Walker, Janelle Buttry; Minic, Zeljka; Liu, Fangchao; Goshgarian, Harry; Mao, Guangzhao

    2016-01-01

    Drug delivery to the central nervous system (CNS) is challenging due to the inability of many drugs to cross the blood-brain barrier (BBB). Here, we show that wheat germ agglutinin horse radish peroxidase (WGA-HRP) chemically conjugated to gold nanoparticles (AuNPs) can be transported to the spinal cord and brainstem following intramuscular injection into the diaphragm of rats. We synthesized and determined the size and chemical composition of a three-part nanoconjugate consisting of WGA-HRP, AuNPs, and drugs for the treatment of diaphragm paralysis associated with high cervical spinal cord injury (SCI). Upon injection into the diaphragm muscle of rats, we show that the nanoconjugate is capable of delivering the drug at a much lower dose than the unconjugated drug injected systemically to effectively induce respiratory recovery in rats following SCI. This study not only demonstrates a promising strategy to deliver drugs to the CNS bypassing the BBB but also contributes a potential nanotherapy for the treatment of respiratory muscle paralysis resulted from cervical SCI. PMID:27180729

  16. SLC9A9 mutations, gene expression and protein-protein interactions in rat models of attention-deficit/hyperactivity disorder

    OpenAIRE

    Zhang-James, Yanli; DasBanerjee, Tania; Sagvolden, Terje; Middleton, Frank A.; Stephen V Faraone

    2011-01-01

    SLC9A9 (solute carrier family 9, member 9, also known as Na+/H+ exchanger member (NHE9)) is a membrane protein that regulates the luminal pH of the recycling endosome, an essential organelle for synaptic transmission and plasticity. SLC9A9 has been implicated in human attention deficit hyperactivity disorder (ADHD) and in rat studies of hyperactivity. We examined the SLC9A9 gene sequence and expression profile in prefrontal cortex, dorsal striatum and hippocampus in two genetic rat models of ...

  17. Wine grape pomace flour improves blood pressure, fasting glucose and protein damage in humans: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Inés Urquiaga

    2015-01-01

    Full Text Available BACKGROUND: The Mediterranean diet is a healthy diet with positive scientific evidence of preventing chronic diseases. Bioactive components support the healthy properties of the Mediterranean diet. Antioxidants and fiber, two components of the Mediterranean diet, are key functional nutrients for healthy eating and nutrition. Wine grape pomace is a rich source of these dietary constituents and may be beneficial for human health. Our hypothesis was that the intake of red wine grape pomace flour (WGPF prepared from red wine grapes (Cabernet Sauvignon variety reduced the metabolic syndrome in humans. To evaluate the effect of WGPF on components of metabolic syndrome we design a 16-week longitudinal intervention study. Thirty-eight males, 30-65 years of age, with at least one component of metabolic syndrome, were randomly assigned to either the intervention group (n = 25 or the control group (n = 13. At lunch, the intervention group was given 20 g of WGPF per day, which contained 10 g of dietary fiber, 822 mg of polyphenols and an antioxidant capacity of 7258 ORAC units. Both groups were asked to maintain their regular eating habits and lifestyles. Clinical evaluation, anthropometric measurements and biochemical blood analyses were done at the beginning and the end of the study. RESULTS: WGPF intake significantly decreased systolic and diastolic blood pressure as well as fasting glucose levels. Plasma γ-tocopherol and δ-tocopherol increased and carbonyl group in plasma protein decreased in WGPT group, significantly. No significant effect was observed for waist circumference, HDL cholesterol, triglycerides, total antioxidant capacity and vitamin C in and between groups. The group-dependent magnitude of the differences between the baseline and final postprandial insulin values and γ-tocopherol concentrations was statistically significant. CONCLUSIONS: The consumption of WGPF-rich in fiber and polyphenol antioxidants, as a food supplement in a

  18. Identification of multiple novel protein biomarkers shed by human serous ovarian tumors into the blood of immunocompromised mice and verified in patient sera.

    Directory of Open Access Journals (Sweden)

    Lynn A Beer

    Full Text Available The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples.

  19. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders

    DEFF Research Database (Denmark)

    Gregersen, N; Bross, P; Jørgensen, M M;

    2000-01-01

    Many disease-causing point mutations do not seriously compromise synthesis of the affected polypeptide but rather exert their effects by impairing subsequent protein folding or stability of the folded protein. This often results in rapid degradation of the affected protein. The concepts...

  20. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter; Jørgensen, Malene Munk;

    2000-01-01

    Many disease-causing point mutations do not seriously compromise synthesis of the affected polypeptides but rather exert their effects by impairing subsequent protein folding or stability of the folded protein. This often results in rapid degradation of the affected protein. The concepts...

  1. Comparison Of Blood Proteins And Some Hormonal Levels In Pregnant And Non-Pregnant Cows

    International Nuclear Information System (INIS)

    The aim of this study is to determine the changes in serum protein and its fractions by using electrophoresis in Holstein cows during different months of pregnancy in comparison with non-pregnant cows and to determine hormonal levels including T4, T3 and progesterone hormones. The samples were taken from 40 pregnant cows during deferent months and 10 non-pregnant cows. Significant decrease in the levels of total protein, albumin and globulin were observed in the third and late month of pregnancy than in mid pregnancy where the values were 6.5, 3.1 and 3.4 g/dl for early months and 6.5, 3.2 and 3.3 g/dl for late month as compared to the non-pregnant cows. Significant increase in α-1globulin was observed during months of pregnancy by about 33.3%. The decrease in the levels of α-2, β and γ-globulins were recorded by about 10%, 45.3% and 21.6%, respectively. A marked decrease in T4 hormone (5.0 μg/dl) was observed in pregnant cows than in non-pregnant ones (7.1 μg/dl). Also, a decreasing T3 level (169 ng/dl) was recorded as compared to non-pregnant cows (221 ng/dl). High significant increase in progesterone level was recorded in the mid pregnancy until reached the maximum value (49.94 ng/ml) at the 7th month of pregnancy then declined (2.42 ng/ml) at the late month of pregnancy. In conclusion, during pregnancy of Holstein dairy cows, a decline in protein fractions and thyroid hormonal levels were recorded during different months as compared to non- pregnant cows. The opposite trend was observed in progesterone levels. The increasing progesterone level at the mid pregnancy indicated its importance in the continuation of pregnancy and maintenance of fetus against maternal rejection.

  2. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain

    International Nuclear Information System (INIS)

    Utilizing 125I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated 125I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and 125I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of 125I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs

  3. Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain

    Energy Technology Data Exchange (ETDEWEB)

    Markowitz, S.; Saito, K.; Moskowitz, M.A.

    1987-12-01

    Utilizing /sup 125/I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated /sup 125/I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and /sup 125/I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of /sup 125/I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.

  4. Strategy for complete NMR assignment of disordered proteins with highly repetitive sequences based on resolution-enhanced 5D experiments

    International Nuclear Information System (INIS)

    A strategy for complete backbone and side-chain resonance assignment of disordered proteins with highly repetitive sequence is presented. The protocol is based on three resolution-enhanced NMR experiments: 5D HN(CA)CONH provides sequential connectivity, 5D HabCabCONH is utilized to identify amino acid types, and 5D HC(CC-TOCSY)CONH is used to assign the side-chain resonances. The improved resolution was achieved by a combination of high dimensionality and long evolution times, allowed by non-uniform sampling in the indirect dimensions. Random distribution of the data points and Sparse Multidimensional Fourier Transform processing were used. Successful application of the assignment procedure to a particularly difficult protein, δ subunit of RNA polymerase from Bacillus subtilis, is shown to prove the efficiency of the strategy. The studied protein contains a disordered C-terminal region of 81 amino acids with a highly repetitive sequence. While the conventional assignment methods completely failed due to a very small differences in chemical shifts, the presented strategy provided a complete backbone and side-chain assignment.

  5. Blood-Brain Barrier and Breast Cancer Resistance Protein: A Limit to the Therapy of CNS Tumors and Neurodegenerative Diseases

    Science.gov (United States)

    Iorio, Anna Lisa; da Ros, Martina; Fantappiè, Ornella; Lucchesi, Maurizio; Facchini, Ludovica; Stival, Alessia; Becciani, Sabrina; Guidi, Milena; Favre, Claudio; de Martino, Maurizio; Genitori, Lorenzo; Sardi, Iacopo

    2016-01-01

    The treatment of brain tumors and neurodegenerative diseases, represents an ongoing challenge. In Central Nervous System (CNS) the achievement of therapeutic concentration of chemical agents is complicated by the presence of distinct set of efflux proteins, such as ATP-Binding Cassette (ABC) transporters localized on the Blood-Brain Barrier (BBB). The activity of ABC transporters seems to be a common mechanism that underlies the poor response of CNS diseases to therapies. The molecular characterization of Breast Cancer Resistance Protein (BCRP/ABCG2), as an ABC transporter conferring multidrug resistance (MDR), has stimulated many studies to investigate its activity on the BBB, its involvement in physiology and CNS diseases and its role in limiting the delivery of drugs in CNS. In this review, we highlight the activity and localization of BCRP on the BBB and the action that this efflux pump has on many conventional drugs or latest generation molecules used for the treatment of CNS tumors and other neurodegenerative diseases. PMID:26584727

  6. Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

    Science.gov (United States)

    Diez-Silva, Monica; Park, Yongkeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

    2012-08-01

    Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.

  7. Expression of the antiviral protein Mx in peripheral blood mononuclear cells of pregnant and bred, non-pregnant ewes.

    Science.gov (United States)

    Yankey, S J; Hicks, B A; Carnahan, K G; Assiri, A M; Sinor, S J; Kodali, K; Stellflug, J N; Stellflug, J N; Ott, T L

    2001-08-01

    Interferon-tau (IFN tau) acts locally on the endometrium to suppress estrogen and oxytocin receptor expression and block luteolysis in ruminants. Systemic administration of conceptus homogenates or recombinant ovine IFN tau does not block luteolysis or enhance pregnancy rates in sheep or cattle, respectively. However, IFN tau up-regulates expression of the antiviral protein Mx throughout the entire uterine wall during early pregnancy. These studies determined if conceptus-derived IFN tau also up-regulates Mx expression in components of the circulating immune system that migrate through the endometrial wall. In experiment one, peripheral blood mononuclear cells (PBMC) were isolated from ewes at D26 post-artificial insemination (AI) and Mx mRNA levels examined by Northern and slot-blot hybridization. Pregnancy resulted in a two-fold increase in Mx mRNA levels compared to bred, non-pregnant ewes at D26. In experiment two, PBMC were isolated from ewes at AI, and every three days from D9 to D30. Results showed a four-fold increase in Mx mRNA levels in PBMC from pregnant versus bred, non-pregnant ewes at D15. Increased Mx mRNA, which remained elevated through D30, was accompanied by increased levels of Mx protein. These results show that pregnancy recognition signaling rapidly induces Mx gene expression in PBMC, and are the first to suggest that IFN tau activates gene expression in components of the circulating immune system. PMID:11479146

  8. Structure and Ligand-Binding Mechanism of a Cysteinyl Leukotriene-Binding Protein from a Blood-Feeding Disease Vector.

    Science.gov (United States)

    Jablonka, Willy; Pham, Van; Nardone, Glenn; Gittis, Apostolos; Silva-Cardoso, Lívia; Atella, Georgia C; Ribeiro, José M C; Andersen, John F

    2016-07-15

    Blood-feeding disease vectors mitigate the negative effects of hemostasis and inflammation through the binding of small-molecule agonists of these processes by salivary proteins. In this study, a lipocalin protein family member (LTBP1) from the saliva of Rhodnius prolixus, a vector of the pathogen Trypanosoma cruzi, is shown to sequester cysteinyl leukotrienes during feeding to inhibit immediate inflammatory responses. Calorimetric binding experiments showed that LTBP1 binds leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4) but not biogenic amines, adenosine diphosphate, or other eicosanoid compounds. Crystal structures of ligand-free LTBP1 and its complexes with LTC4 and LTD4 reveal a conformational change during binding that brings Tyr114 into close contact with the ligand. LTC4 is cleaved in the complex, leaving free glutathione and a C20 fatty acid. Chromatographic analysis of bound ligands showed only intact LTC4, suggesting that cleavage could be radiation-mediated. PMID:27124118

  9. Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

    Directory of Open Access Journals (Sweden)

    Olgun eGuvench

    2015-06-01

    Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

  10. Improved Methodology for Assessment of mRNA Levels in Blood of Patients with FMR1 Related Disorders

    Directory of Open Access Journals (Sweden)

    Godler David E

    2009-06-01

    Full Text Available Abstract Background Elevated levels of FMR1 mRNA in blood have been implicated in RNA toxicity associated with a number of clinical conditions. Due to the extensive inter-sample variation in the time lapse between the blood collection and RNA extraction in clinical practice, the resulting variation in mRNA quality significantly confounds mRNA analysis by real-time PCR. Methods Here, we developed an improved method to normalize for mRNA degradation in a sample set with large variation in rRNA quality, without sample omission. Initially, RNA samples were artificially degraded, and analyzed using capillary electrophoresis and real-time PCR standard curve method, with the aim of defining the best predictors of total RNA and mRNA degradation. Results We found that: (i the 28S:18S ratio and RNA quality indicator (RQI were good predictors of severe total RNA degradation, however, the greatest changes in the quantity of different mRNAs (FMR1, DNMT1, GUS, B2M and GAPDH occurred during the early to moderate stages of degradation; (ii chromatographic features for the 18S, 28S and the inter-peak region were the most reliable predictors of total RNA degradation, however their use for target gene normalization was inferior to internal control genes, of which GUS was the most appropriate. Using GUS for normalization, we examined in the whole blood the relationship between the FMR1 mRNA and CGG expansion in a non-coding portion of this gene, in a sample set (n = 30 with the large variation in rRNA quality. By combining FMR1 3' and 5' mRNA analyses the confounding impact of mRNA degradation on the correlation between FMR1 expression and CGG size was minimized, and the biological significance increased from p = 0.046 for the 5' FMR1 assay, to p = 0.018 for the combined FMR1 3' and 5' mRNA analysis. Conclusion Our observations demonstrate that, through the use of an appropriate internal control and the direct analysis of multiple sites of target mRNA, samples that

  11. Fetal Genotyping in Maternal Blood by Digital PCR: Towards NIPD of Monogenic Disorders Independently of Parental Origin

    Science.gov (United States)

    Perlado, Sara; Bustamante-Aragonés, Ana; Donas, Marta; Lorda-Sánchez, Isabel; Plaza, Javier; Rodríguez de Alba, Marta

    2016-01-01

    Purpose To date, non-invasive prenatal diagnosis (NIPD) of monogenic disorders has been limited to cases with a paternal origin. This work shows a validation study of the Droplet Digital PCR (ddPCR) technology for analysis of both paternally and maternally inherited fetal alleles. For the purpose, single nucleotide polymorphisms (SNPs) were studied with the only intention to mimic monogenic disorders. Methods NIPD SNP genotyping was performed by ddPCR in 55 maternal plasma samples. In 19 out of 55 cases, inheritance of the paternal allele was determined by presence/absence criteria. In the remaining 36, determination of the maternally inherited fetal allele was performed by relative mutation dosage (RMD) analysis. Results ddPCR exhibited 100% accuracy for detection of paternal alleles. For diagnosis of fetal alleles with maternal origin by RMD analysis, the technology showed an accuracy of 96%. Twenty-nine out of 36 were correctly diagnosed. There was one FP and six maternal plasma samples that could not be diagnosed. Discussion In this study, ddPCR has shown to be capable to detect both paternal and maternal fetal alleles in maternal plasma. This represents a step forward towards the introduction of NIPD for all pregnancies independently of the parental origin of the disease. PMID:27078875

  12. Correlation between the level of microRNA expression in peripheral blood mononuclear cells and symptomatology in patients with generalized anxiety disorder.

    Science.gov (United States)

    Chen, Sheng-Dong; Sun, Xin-Yang; Niu, Wei; Kong, Ling-Ming; He, Ming-Jun; Fan, Hui-Min; Li, Wan-Shuai; Zhong, Ai-Fang; Zhang, Li-Yi; Lu, Jim

    2016-08-01

    This study investigated the correlation between the level of microRNA expression in peripheral blood mononuclear cells (PBMCs) and symptomatology in patients with generalized anxiety disorder (GAD). MicroRNA array was performed in peripheral blood mononuclear cells (PBMCs) obtained from GAD patients with gender, age, ethnicity-matched healthy controls. Then real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the top 7 miRNAs with the highest fold-change values in 76 GAD patients and 39 healthy controls. It demonstrated that 5 miRNAs showed significantly differences in expression levels (Ppsychic anxiety symptomatology scores, and it could explain 5.3% of the HAMA total scores and 15.3% of the anxiety symptomatology scores. This study analyzed preliminarily possible circulating miRNAs expression changes in GAD patients, and the expression level of miR-663 highly correlated with psychic anxiety symptoms, further molecular mechanism of which needs to be explored. PMID:27423364

  13. 15N-enrichments of ammonia and glutamine in blood after infusion of 15N-ammonia in chickens fed low or high protein diet

    International Nuclear Information System (INIS)

    In this experment, the blood ammonia and glutamine amide came from infused ammonia were determined when N-15 labeled ammonium acetate was intraportally infused into the chickens fed 5 or 20 % protein diet. The data obtained indicated that the infused ammonia was taken into blood glutamine amide, and also accumulated in blood as it is, in both dietary groups. 10 to 12 months old White Leghorn male birds were used. The experimental diet was fed once a day for 5 days to the birds weighting about 1.2 kg by 35 g per kg body weight. The experimental diet was consumed within 40 min in all cases. Cardiac and portal catheterization were performed for blood collection and ammonia infusion, respectively. After finishing the infusion, blood samples were taken to analyze the ammonia and glutamine contents and their N-15 enrichment. Statistical difference was not observed in the appearance of N-15 in ammonia and glutamine amide between two dietary groups. The N-15 enrichment in blood ammonia and the amide of plasma glutamine, and the calculated exogenous nitrogen in the ammonia and glutamine amide tended to be more in the 5 % protein diet group than the other. (Kako, I.)

  14. Intrinsically disordered regions may lower the hydration free energy in proteins: a case study of nudix hydrolase in the bacterium Deinococcus radiodurans.

    Directory of Open Access Journals (Sweden)

    Omar Awile

    Full Text Available The proteome of the radiation- and desiccation-resistant bacterium D. radiodurans features a group of proteins that contain significant intrinsically disordered regions that are not present in non-extremophile homologues. Interestingly, this group includes a number of housekeeping and repair proteins such as DNA polymerase III, nudix hydrolase and rotamase. Here, we focus on a member of the nudix hydrolase family from D. radiodurans possessing low-complexity N- and C-terminal tails, which exhibit sequence signatures of intrinsic disorder and have unknown function. The enzyme catalyzes the hydrolysis of oxidatively damaged and mutagenic nucleotides, and it is thought to play an important role in D. radiodurans during the recovery phase after exposure to ionizing radiation or desiccation. We use molecular dynamics simulations to study the dynamics of the protein, and study its hydration free energy using the GB/SA formalism. We show that the presence of disordered tails significantly decreases the hydration free energy of the whole protein. We hypothesize that the tails increase the chances of the protein to be located in the remaining water patches in the desiccated cell, where it is protected from the desiccation effects and can function normally. We extrapolate this to other intrinsically disordered regions in proteins, and propose a novel function for them: intrinsically disordered regions increase the "surface-properties" of the folded domains they are attached to, making them on the whole more hydrophilic and potentially influencing, in this way, their localization and cellular activity.

  15. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    International Nuclear Information System (INIS)

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity

  16. Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xueqing; Chang, Bianca W. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Mans, Ben J. [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States); Agricultural Research Council, Onderstepoort 0110 (South Africa); Ribeiro, Jose M. C.; Andersen, John F., E-mail: jandersen@niaid.nih.gov [NIH/NIAID, 12735 Twinbrook Parkway, Rockville, MD 20852 (United States)

    2013-01-01

    Biogenic amine-binding proteins mediate the anti-inflammatory and antihemostatic activities of blood-feeding insect saliva. The structure of the amine-binding protein from R. prolixus reveals the interaction of biogenic amine ligands with the protein. Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the β-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity.

  17. Effects of dermatan sulfate derivatives on platelet surface P-selectin expression and protein C activity in blood of inflammatory bowel disease patients

    OpenAIRE

    Ji, Sheng-Li; Du, Hai-Yan; Chi, Yan-Qing; Cui, Hui-Fei; Cao, Ji-Chao; Geng, Mei-yu; Guan, Hua-Shi

    2004-01-01

    AIM: To investigate the effect of dermatan sulfate (DS) derivatives on platelet surface P-selectin expression and blood activated protein C (APC) activity in patients with inflammatory bowel disease (IBD), and to clarity the anti-inflammatory mechanism of DS derivatives.

  18. Comparison of usefulness of C-reactive protein versus white blood cell count to predict outcome after primary percutaneous coronary intervention for ST elevation myocardial infarction

    NARCIS (Netherlands)

    Smit, Jaap Jan J.; Ottervanger, Jan Paul; Slingerland, Robbert J.; Kolkman, J. J. Evelien; Suryapranata, Harry; Hoorntje, Jan C. A.; Dambrink, Jan-Henk E.; Gosselink, A. T. Marcel; de Boer, Menko-Jan; Zijlstra, Felix; van 't Hof, Arnoud W. J.

    2008-01-01

    White blood cell (WBC) count and high-sensitive C-reactive protein (hs-CRP) are both used as markers of inflammation and prognosis after an ST elevation myocardial infarction (STEMI), but it is unknown whether they have independent prognostic value. We investigated the association and independent pr

  19. Renin-angiotensin-aldosterone responsiveness to low sodium and blood pressure reactivity to angiotensin-II are unrelated to cholesteryl ester transfer protein mass in healthy subjects

    NARCIS (Netherlands)

    Krikken, Jan A.; Dallinga-Thie, Geesje M.; Navis, Gerjan; Dullaart, Robin P. F.

    2008-01-01

    Background: The blood pressure increase associated with the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib is probably attributable to an off-target effect but it is unknown whether activation of the renin-angiotensin-aldosterone system (RAAS) may be related to variation in the pla

  20. Protein intrinsic disorder in Arabidopsis NAC transcription factors

    DEFF Research Database (Denmark)

    O'Shea, Charlotte; Jensen, Mikael Kryger; Stender, Emil G.P.;

    2015-01-01

    transcription activation factor), cup-shaped cotyledon] TFs shows that the domains are present in similar average pre-molten or molten globule-like states, but have different patterns of order/disorder and MoRFs (molecular recognition features). ANAC046 (Arabidopsis NAC 046) was selected for further studies...

  1. Cytoplasmic dynein and its regulatory proteins in Golgi pathology in nervous system disorders

    NARCIS (Netherlands)

    D. Jaarsma (Dick); C.C. Hoogenraad (Casper)

    2015-01-01

    textabstractThe Golgi apparatus is a dynamic organelle involved in processing and sorting of lipids and proteins. In neurons, the Golgi apparatus is important for the development of axons and dendrites and maintenance of their highly complex polarized morphology. The motor protein complex cytoplasmi

  2. Cytoplasmic dynein and its regulatory proteins in Golgi pathology in nervous system disorders

    NARCIS (Netherlands)

    Jaarsma, Dick; Hoogenraad, Casper C

    2015-01-01

    The Golgi apparatus is a dynamic organelle involved in processing and sorting of lipids and proteins. In neurons, the Golgi apparatus is important for the development of axons and dendrites and maintenance of their highly complex polarized morphology. The motor protein complex cytoplasmic dynein has

  3. Identification of an additional class of C3-binding membrane proteins of human peripheral blood leukocytes and cell lines.

    Science.gov (United States)

    Cole, J L; Housley, G A; Dykman, T R; MacDermott, R P; Atkinson, J P

    1985-02-01

    Proteins binding the third component of complement (C3) were isolated by affinity chromatography from surface-labeled solubilized membranes of human peripheral blood cells and cell lines. The isolated molecules were subjected to NaDodSO4/PAGE, and autoradiographs of these gels indicated that C3-binding proteins could be divided into three groups based on Mr: (i) gp200, an approximately 200,000 Mr molecule previously identified as the C3b/C4b receptor or CR1; (ii) gp140, an approximately 140,000 Mr molecule previously identified as the C3d receptor or CR2; and (iii) gp45-70, a heretofore unrecognized group of 45,000-70,000 Mr C3-binding molecules. The cell distribution, Mr, antigenic cross-reactivity, and specificity of gp45-70 were examined. Erythrocytes have no detectable gp45-70, but all leukocyte populations examined possess this group of molecules. On neutrophils and mononuclear phagocytes, CR1 is the predominant C3-binding glycoprotein, but gp45-70 is present on both cell populations and on macrophage and neutrophil cell lines. B plus null cells, chronic lymphocytic leukemia cells, and an Epstein-Barr virus-transformed B-cell line possess CR1, CR2, and gp45-70. On T cells and T-cell lines gp45-70 is the predominant or, in some cases, the only C3-binding protein isolated. gp45-70 is structurally characterized as a broad band or doublet with a mean Mr that is slightly different for each cell population. gp45-70 binds iC3, C3b, and C4b, but not C3d, indicating that the binding region is probably within the C3c portion of C3b. A polyclonal antibody to CR1 and monoclonal antibodies to CR1 and CR2 do not immunoprecipitate gp45-70. While gp45-70 has not been previously characterized on human cells, a C3b-binding glycoprotein of similar Mr is present on rabbit alveolar macrophages. We conclude that gp45-70 is an additional group of membrane proteins present on human leukocytes that possess ligand-binding activity for C3b. PMID:3871945

  4. IDPT: Insights into potential intrinsically disordered proteins through transcriptomic analysis of genes for prostate carcinoma epigenetic data.

    Science.gov (United States)

    Mallik, Saurav; Sen, Sagnik; Maulik, Ujjwal

    2016-07-15

    Involvement of intrinsically disordered proteins (IDPs) with various dreadful diseases like cancer is an interesting research topic. In order to gain novel insights into the regulation of IDPs, in this article, we perform a transcriptomic analysis of mRNAs (genes) for transcripts encoding IDPs on a human multi-omics prostate carcinoma dataset having both gene expression and methylation data. In this regard, firstly the genes that consist of both the expression and methylation data, and that are corresponding to the cancer-related prostate-tissue-specific disordered proteins of MobiDb database, are selected. We apply standard t-test for determining differentially expressed genes as well as differentially methylated genes. A network having these genes and their targeter miRNAs from Diana Tarbase v7.0 database and corresponding Transcription Factors from TRANSFAC and ITFP databases, is then built. Thereafter, we perform literature search, and KEGG pathway and Gene Ontology analyses using DAVID database. Finally, we report several significant potential gene-markers (with the corresponding IDPs) that have inverse relationship between differential expression and methylation patterns, and that are hub genes of the TF-miRNA-gene network. PMID:27060408

  5. Involvement of senescence marker protein-30 in glucose metabolism disorder and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kondo, Yoshitaka; Ishigami, Akihito

    2016-03-01

    Senescence marker protein-30 (SMP30) was found to decrease in the liver, kidneys and lungs of mice during aging. SMP30 is a pleiotropic protein that acts to protect cells from apoptosis by enhancing plasma membrane Ca(2+) -pump activity and is bona fide gluconolactonase (EC 3.1.1.17) that participates in the penultimate step of the vitamin C biosynthetic pathway. For the past several years, we have obtained strong evidence showing the close relationship between SMP30, glucose metabolism disorder and non-alchoholic fatty liver disease in experiments with SMP30 knockout mice. Emerging proof links the following abnormalities: (i) the reduction of SMP30 by aging and/or excessive dietary fat or genetic deficiency causes a loss of Ca(2+) pumping activity, which impairs acute insulin release in pancreatic β-cells, initiates inflammatory responses with oxidative stress and endoplasmic reticulum stress in non-alchoholic steatohepatitis, exacerbates renal tubule damage, and introduces tubulointerstitial inflammation and fibrosis in diabetic nephropathy; (ii) vitamin C insufficiency also impairs acute insulin secretion in pancreatic β-cells by a mechanism distinct from that of the SMP30 deficiency; and (iii) the increased oxidative stress by concomitant deficiencies of SMP30, superoxide dismutase 1 and vitamin C similarly causes hepatic steatosis. Here, we review recent advances in our understanding of SMP30 in glucose metabolism disorder and non-alchoholic fatty liver disease. PMID:27018279

  6. Regional cerebral blood flow in children with autism spectrum disorders: a quantitative 99mTc-ECD brain SPECT study with statistical parametric mapping evaluation

    Institute of Scientific and Technical Information of China (English)

    YANG Wen-han; JING Jin; XIU Li-juan; CHENG Mu-hua; WANG Xin; BAO Peng; WANG Qing-xiong

    2011-01-01

    Background Autism spectrum disorders (ASD), which include autism, asperger syndrome (AS) and pervasive developmental disorder-not otherwise specified (PDD-NOS), are devastating neurodevelopmental disorders of childhood resulting in deficits in social interaction, repetitive patterns of behaviors, and restricted interests and activities. Single photon emission computed tomography (SPECT) is a common technique used to measure regional cerebral blood flow (rCBF). Several studies have measured rCBF in children with ASD using SPECT, however, findings are discordant. In addition, the majority of subjects used in these studies were autistic. In this study, we aimed to investigate changes in rCBF in children with ASD using SPECT.Methods A Technetium-99m-ethyl cysteinate dimmer (99mTc-ECD) brain SPECT study was performed on an ASD group consisting of 23 children (3 girls and 20 boys; mean age (7.2±3.0) years) who were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-Ⅳ) criteria and an age-matched control group with 8children (1 girl and 7 boys, mean age (5.5±2.4) years). Image data were evaluated with Statistical Parametric Mapping,5th version (SPM5). A Student's t test for unpaired data was used to compare rCBF and asymmetry in the autism and corresponding control group. The covariance analysis, taking age as covariance, was performed between the ASD and control group.Results There was a significant reduction in rCBF in the bilateral frontal lobe (frontal poles, arcula frontal gyrus) and the bilateral basal ganglia in the autism group, and a reduction in the bilateral frontal, temporal, parietal, legumina nucleus and cerebellum in the AS group compared to the control. In addition, asymmetry of hemispheric hypoperfusion in the ASD group was observed. Inner-group comparison analysis revealed that rCBF decreased significantly in the bilateral frontal lobe (42.7%), basal nucleus (24.9%) and temporal lobe (22.8%) in the autism

  7. Knockout studies reveal an important role of Plasmodium lipoic acid protein ligase A1 for asexual blood stage parasite survival.

    Directory of Open Access Journals (Sweden)

    Svenja Günther

    Full Text Available Lipoic acid (LA is a dithiol-containing cofactor that is essential for the function of alpha-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl: N-octanoyl (lipoyl transferase (LipB or lipoic acid protein ligases (LplA. Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that LplA1 plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite P. falciparum consistently were unsuccessful while in the rodent malaria model parasite P. berghei the LplA1 gene locus was targeted by knock-in and knockout constructs. However, the LplA1((- mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth in vitro and in vivo. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite.

  8. Effects of nitrogen and irrigation on gluten protein composition and their relationship to yellow berry disorder in wheat (triticum aestivum)

    International Nuclear Information System (INIS)

    In Mexico and the rest of the world, the presence of yellow berry (YB) in wheat grains (Triticum aestivum) has been related with poor quality, this defect is associated with low protein content in the grains. However, the quality of the wheat depends not only on the protein content, but also on the composition of the gluten proteins. The effect of the various agronomic factors on the composition of wheat gluten has been a subject of study worldwide. However, in Mexico, wheat quality still remains an issue, as there is a lack of knowledge regarding the optimal agronomic conditions to produce wheat with good-quality gluten. For this reason, the effects of nitrogen (N) rates and irrigations on the amount of gliadin subclasses, glutenin subunits (two main groups) and grain protein content as well as the relation of these proteins to the YB content in wheat grains were investigated. The experiment was conducted on arable farmland in the Valley of Empalme, Sonora, Mexico (27 degree 58' N, 110 degree 49' W; 10 m altitude), during the fall-winter period of 2009-2010. Tarachi, the hard wheat cultivar studied, was selected for its relative susceptibility to the presence of elevated YB content in mature wheat kernels. Three levels of N (75, 150 or 250 kg ha-1) and three levels of irrigation (1, 2 or 3 auxiliary irrigations) were studied. Using a N rate of 150 kg ha-1 with 3 auxiliary irrigations, wheat with good-quality gluten was obtained. The results suggest that the YB disorder is primarily related to the amount of protein in the wheat grain. (author)

  9. Effects of medium-chain fatty acids and oleic acid on blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities

    DEFF Research Database (Denmark)

    Tholstrup, T.; Ehnholm, C.; Jauhiainen, M.;

    2004-01-01

    cholesterol, although this claim is poorly documented. Objective: We compared the effects of a diet rich in either MCFAs or oleic acid on fasting blood lipids, lipoproteins, glucose, insulin, and lipid transfer protein activities in healthy men. Design: In a study with a double-blind, randomized, crossover...... design, 17 healthy young men replaced part of their habitual dietary fat intake with 70 g MCTs (66% 8:0 and 34% 10:0) or high-oleic sunflower oil (89.4% 18:1). Each intervention period lasted 21 d, and the 2 periods were separated by a washout period of 2 wk. Blood samples were taken before and after the...... oleic acid, MCT fat unfavorably affected lipid profiles in healthy young men by increasing plasma LDL cholesterol and triacylglycerol. No changes in the activities of phospholipid transfer protein and cholesterol ester transfer protein were evident....

  10. Determinants of resistance to radiation injury in blood granulocytes from normal donors and from patients with myeloproliferative disorders

    International Nuclear Information System (INIS)

    Dose-dependent injury to human blood granulocytes was measured within 2 hr of x irradiation, as changes in net 22Na influx and phagocytosing O2 consumption. Among samples from normal donors and patients with chronic myeloproliferative diseases, samples from 10 to 12 patients with chronic granulocytic leukemia exhibited increased sensitivity to injury by radiation. Selected granulocyte constituents which may contribute to inactivation of oxidant and free-radical products of radiation-activated H2O were also measured. These included glutathione and ascorbate contents; superoxide dismutase, catalase, glutathione proxidase, and glutathione reductase activities; and capacity to take up and reduce dehydroascorbate. Catalase activity was irregularly higher in radiation-sensitive than in radiation-resistant granulocytes (P = < 0.05). Dehydroascorbate uptake and reduction was consistently low in radiation-sensitive cells (P = < 0.001). We propose that cell capacity to maintain ascorbate in reduced form against oxidant and free-radical stress is a part of mechanisms which determine resistance to injury by ionizing radiation in human granulocytes

  11. Proton-decoupled CPMG: A better experiment for measuring 15N R2 relaxation in disordered proteins

    Science.gov (United States)

    Yuwen, Tairan; Skrynnikov, Nikolai R.

    2014-04-01

    15N R2 relaxation is one of the most informative experiments for characterization of intrinsically disordered proteins (IDPs). Small changes in nitrogen R2 rates are often used to determine how IDPs respond to various biologically relevant perturbations such as point mutations, posttranslational modifications and weak ligand interactions. However collecting high-quality 15N relaxation data can be difficult. Of necessity, the samples of IDPs are often prepared with low protein concentration and the measurement time can be limited because of rapid sample degradation. Furthermore, due to hardware limitations standard experiments such as 15N spin-lock and CPMG can sample the relaxation decay only to ca. 150 ms. This is much shorter than 15N T2 times in disordered proteins at or near physiological temperature. As a result, the sampling of relaxation decay profiles in these experiments is suboptimal, which further lowers the precision of the measurements. Here we report a new implementation of the proton-decoupled (PD) CPMG experiment which allows one to sample 15N R2 relaxation decay up to ca. 0.5-1 s. The new experiment has been validated through comparison with the well-established spin-lock measurement. Using dilute samples of denatured ubiquitin, we have demonstrated that PD-CPMG produces up to 3-fold improvement in the precision of the data. It is expected that for intrinsically disordered proteins the gains may be even more substantial. We have also shown that this sequence has a number of favorable properties: (i) the spectra are recorded with narrow linewidth in nitrogen dimension; (ii) 15N offset correction is small and easy to calculate; (iii) the experiment is immune to various spurious effects arising from solvent exchange; (iv) the results are stable with respect to pulse miscalibration and rf field inhomogeneity; (v) with minimal change, the pulse sequence can also be used to measure R2 relaxation of 15Nε spins in arginine side chains. We anticipate that

  12. Ozonation of Human Blood Induces a Remarkable Upregulation of Heme Oxygenase-1 and Heat Stress Protein-70

    Directory of Open Access Journals (Sweden)

    Velio Bocci

    2007-01-01

    Full Text Available Heme oxygenase-I (HO-1 has emerged as one of the most protective enzymes and its pleiotropic activities have been demonstrated in a variety of human pathologies. Unpublished observations have shown that HO-1 is induced after the infusion of ozonated blood into the respective donors, and many other experimental observations have demonstrated the efficacy of oxidizing agents. It appeared worthwhile to evaluate whether we could better define the activity of potential inducers such as hydrogen peroxide and ozonated human plasma. Human vascular endothelial cells at confluence were challenged with different concentrations of these inducers and the simultaneous production of nitric oxide (NO; and HO-1 was measured by either measuring nitrite, or bilirubin formation, or/and the immune reactivity of the protein by Western blot using a rabbit antihuman HO-1 and Hsp-70. The results show that production of both NO and HO-1 is fairly dose dependent but is particularly elevated using human plasma after transient exposure to a medium ozone concentration. At this concentration, there is also induction of Hsp-70. The results clarify another positive effect achievable by the use of ozone therapy.

  13. Effects of alcohol-induced human peripheral blood mononuclear cell (PBMC) pretreated whey protein concentrate (WPC) on oxidative damage.

    Science.gov (United States)

    Tseng, Yang-Ming; Chen, Sheng-Yi; Chen, Chien-Hung; Jin, Yi-Ru; Tsai, Shih-Meng; Chen, Ing-Jun; Lee, Jang-Hwa; Chiu, Chzng-Cheng; Tsai, Li-Yu

    2008-09-10

    Excessive alcohol consumption can induce apoptosis in a variety of tissues and influence the antioxidant status in peripheral blood mononuclear cells (PBMC). This paper investigates the effects of whey protein concentrate (WPC) pretreated in PBMC on the apoptosis and antioxidant status after the treatment of alcohol. The results show that the percentages of apoptotic cells in the alcohol-treated group were higher than those in the group without alcohol treatment. Additionally, there was higher glutathione (GSH) peroxidase (GPx) activity when the PBMC were treated with 300 mg/dL of alcohol. With regard to the activity of GSH reductase (GRx), there was higher activity in the group pretreated with WPC than in the group with the treatment of alcohol only. On the contrary, the levels of GSH were reduced after the treatment of alcohol, but there was a higher level of GSH in the group pretreated with WPC. In this study, it was found that the increased level of GSH in PBMC might not be attributed to the effect of GRx because there was still a higher level of GSH in the group with the treatment of WPC and BCNU (a GRx inhibitor) in this study. The results indicated that PBMC pretreated with WPC might ameliorate alcohol-induced effects such as imbalance of the antioxidant status. PMID:18700777

  14. The Changes of Protein Kinase C Activity in Peripheral Blood Lymphocytes in the Patients with Obstructive Jaundice and the Implication

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The roles of protein kinase C (PKC) signal pathway in the pathogenesis of obstructive jaundice were studied. PKC from cytosolic and membrane fractions of peripheral blood lymphocytes (PBL) in 51 patients with obstructive jaundice and 16 cases of normal controls was isolated and purified. The activities of PKC were determined by radioactive isotope γ-32P-ATP-catalyzing assay. The results showed that the total PKC activities in PBL in the patients with obstructive jaundice were significantly increased as compared with those in the normal controls (P<0.01). Moreover, the membrane PKC activities and their percentages of the total PKC activities were higher in obstructive jaundice group than in those in the normal controls (P<0.05). The total PKC activities in PBL in the patients with obstructive jaundice were significantly positively correlated with the levels of soluble IL-2 receptor (sIL-2R) (r=0.58, P<0.01) and the degree of jaundice (T-BIL) (r=0.67, P<0.01) in serum. It was concluded that the activities of PKC signal pathway was related with the degree of T-BIL. PKC signal pathway might took part in the activation of T-lymphocytes in the patients with obstructive jaundice and play an important role in the immune regulation and the assessment of pathosis in the patients with obstructive jaundice.

  15. Long-Lasting Hippocampal Synaptic Protein Loss in a Mouse Model of Posttraumatic Stress Disorder

    OpenAIRE

    Herrmann, Leonie; Ionescu, Irina A.; Henes, Kathrin; Golub, Yulia; Wang, Nancy Xin Ru; Buell, Dominik R.; Holsboer, Florian; Wotjak, Carsten T.; Schmidt, Ulrike

    2012-01-01

    Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD) and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expres...

  16. Thermolability of mutant MMACHC protein in the vitamin B12-responsive cblC disorder

    OpenAIRE

    Froese, D.S.; Healy, S.; McDonald, M; Kochan, G; Oppermann, U.; Niesen, F.H.; Gravel, R. A.

    2010-01-01

    Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of cellular vitamin B12 metabolism. We previously showed that the protein carrying the mutation responsible for late-onset cblC (MMACHC-R161Q), treatable with high dose OHCbl, is able to bind OHCbl with wild-type affinity, leaving undetermined the disease mechanism involved [Froese et al., Mechanism of responsiveness, Mol. Genet. Metab. (2009).]. To assess whether the mutation renders the protein unstable, w...

  17. From the Black Widow Spider to Human Behavior: Latrophilins, a Relatively Unknown Class of G Protein-Coupled Receptors, Are Implicated in Psychiatric Disorders

    OpenAIRE

    Martinez, Ariel F; Muenke, Maximilian; Arcos-Burgos, Mauricio

    2010-01-01

    The findings of a recent study associate LPHN3, a member of the latrophilin family, with an increased risk of developing attention deficit/hyperactivity disorder (ADHD), the most common psychiatric disorder in childhood and adolescence. Latrophilins comprise a new family of G protein-coupled receptors of unknown native physiological function that mediate the neurotoxic effects of α-latrotoxin, a potent toxin found in black widow spider venom. This receptor–toxin interaction has helped to eluc...

  18. Preferential binding of 4-hydroxynonenal to lysine residues in specific parasite proteins in plakortin-treated Plasmodium falciparum-parasitized red blood cells

    Directory of Open Access Journals (Sweden)

    Evelin Schwarzer

    2015-12-01

    Full Text Available The data show the frequencies by which the amino acid residues lysine, histidine and cysteine of six proteins of the malaria parasite Plasmodium falciparum are post-translationally modified by the lipoperoxydation endproduct 4-hydroxynonenal after challenging the parasitized red blood cell with plakortin. Plakortin is an antimalarial endoperoxide whose molecular anti-parasitic effect is described in Skorokhod et al. (2015 [1]. Plakortin did not elicit hemoglobin leakage from host red blood cells and did not oxidize reduced glutathione.

  19. Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder.

    Directory of Open Access Journals (Sweden)

    Maria Jalbrzikowski

    Full Text Available 22q11.2 Deletion Syndrome (22q11DS represents one of the greatest known genetic risk factors for the development of psychotic illness, and is also associated with high rates of autistic spectrum disorders (ASD in childhood. We performed integrated genomic analyses of 22q11DS to identify genes and pathways related to specific phenotypes.We used a high-resolution aCGH array to precisely characterize deletion breakpoints. Using peripheral blood, we examined differential expression (DE and networks of co-expressed genes related to phenotypic variation within 22q11DS patients. Whole-genome transcriptional profiling was performed using Illumina Human HT-12 microarrays. Data mining techniques were used to validate our results against independent samples of both peripheral blood and brain tissue from idiopathic psychosis and ASD cases.Eighty-five percent of 22q11DS individuals (N = 39 carried the typical 3 Mb deletion, with significant variability in deletion characteristics in the remainder of the sample (N = 7. DE analysis and weighted gene co-expression network analysis (WGCNA identified expression changes related to psychotic symptoms in patients, including a module of co-expressed genes which was associated with psychosis in 22q11DS and involved in pathways associated with transcriptional regulation. This module was enriched for brain-expressed genes, was not related to antipsychotic medication use, and significantly overlapped with transcriptional changes in idiopathic schizophrenia. In 22q11DS-ASD, both DE and WGCNA analyses implicated dysregulation of immune response pathways. The ASD-associated module showed significant overlap with genes previously associated with idiopathic ASD.These findings further support the use of peripheral tissue in the study of major mutational models of diseases affecting the brain, and point towards specific pathways dysregulated in 22q11DS carriers with psychosis and ASD.

  20. Solvent effects in the helix-coil transition model can explain the unusual biophysics of intrinsically disordered proteins

    Science.gov (United States)

    Badasyan, Artem; Mamasakhlisov, Yevgeni Sh.; Podgornik, Rudolf; Parsegian, V. Adrian

    2015-07-01

    We analyze a model statistical description of the polypeptide chain helix-coil transition, where we take into account the specificity of its primary sequence, as quantified by the phase space volume ratio of the number of all accessible states to the number corresponding to a helical conformation. The resulting transition phase diagram is then juxtaposed with the unusual behavior of the secondary structures in Intrinsically Disordered Proteins (IDPs) and a number of similarities are observed, even if the protein folding is a more complex transition than the helix-coil transition. In fact, the deficit in bulky and hydrophobic amino acids observed in IDPs, translated into larger values of phase space volume, allows us to locate the region in parameter space of the helix-coil transition that would correspond to the secondary structure transformations that are intrinsic to conformational transitions in IDPs and that is characterized by a modified phase diagram when compared to globular proteins. Here, we argue how the nature of this modified phase diagram, obtained from a model of the helix-coil transition in a solvent, would illuminate the turned-out response of IDPs to the changes in the environment conditions that follow straightforwardly from the re-entrant (cold denaturation) branch in their folding phase diagram.