Playground Designs to Increase Physical Activity Levels during School Recess: A Systematic Review

ERIC Educational Resources Information Center

Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M.

2014-01-01

School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A…

The Language Laboratory and Modern Language Teaching. Revised Edition.

ERIC Educational Resources Information Center

Stack, Edward M.

Since the audiolingual forms of a foreign language (hearing and speaking) must be controlled before the graphic skills (reading and writing) are taught, exercises in a language laboratory, which affords students intensive, active, individual drill, ought to precede written exercises on the same material. The three major forms of language…

Workplace Incivility and Commitment in Student Affairs

ERIC Educational Resources Information Center

Pantano, Laura Christine

2017-01-01

Over the past two decades there has been an increased interest in research on interpersonal mistreatment in the workplace and its influence on organizations (Schilpzand, De Pater, & Erez, 2016). The majority of research has focused on physical, active and direct forms of inappropriate behaviors at work, however, the most prominent form of…

Mechanisms of action of light on circadian rhythms in the monkey

NASA Technical Reports Server (NTRS)

Winget, C. M.; Rosenblatt, L. S.; DeRoshia, C. W.; Hetherington, N. W.

1970-01-01

Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr.

Comparison of authigenic carbonates formation at mud volcanoes and pockmarks in the Portuguese Margin vs. at the Yinazao serpentinite mud volcano in the Marianas forearc

NASA Astrophysics Data System (ADS)

Magalhaes, V. H.; Freitas, M.; Azevedo, M. R.; Pinheiro, L. M.; Salgueiro, E.; Abrantes, F. F. G.

2017-12-01

On the Portuguese passive continental margin, active and past seepage processes form mud volcanoes and pockmarks at the seafloor. Often associated with these structures are extensive methane-derived authigenic carbonates that form from deep-sourced methane-rich fluids that ascend from deep to the upper sedimentary column and often discharge at the seafloor. These carbonates form within the sediments and are either dominated by dolomite and high-Mg calcites, when formed under a restricted seawater circulation environment, anoxic and low sulphate conditions; or by aragonite and calcite when formed close to or at the seafloor in a high sulphate system. The δ13C values (-56.2‰ VPDB) found on the carbonate-cemented material clearly indicates methane as the major carbon source. On the Yinazao serpentinite mud volcano at an active, non-accretionary, convergent margin, sediment samples from IODP Sites U1491 and U1492 (Exp. 366) contain authigenic minerals such as aragonite, calcite, brucite, gypsum among others. Authigenic aragonite occurs predominantly within the top meters of the cores where both oxidation and seawater circulation in the sedimentary column are higher. In this system, initial results indicate that the major carbon source is most probably not methane but seawater related. This work discusses and compares the major carbon sources in both systems: sedimentary mud volcanoes and pockmarks of a passive margin vs. a serpentinite mud volcano of an active, non-accretionary, convergent margin. We acknowledge the support from the PES project - Pockmarks and fluid seepage in the Estremadura Spur: implications for regional geology, biology, and petroleum systems (PTDC/GEOFIQ/5162/2014) financed by the Portuguese Foundation for Science and Technology (FCT).

Major Appliance Repair. Teacher Edition and Student Edition. Second Edition.

ERIC Educational Resources Information Center

Smreker, Gene; Calvert, King

This second edition contains teacher and student guides for 14 units of instruction in major appliance repair. Each unit in the teacher edition includes some or all of the following basic components: objective sheet, suggested activities, answers to assignment sheets, answers to the written test, written test, a unit evaluation form, teacher…

Professionals' Perception of Quality Physical Education Learning in Selected Asian Cities

ERIC Educational Resources Information Center

Ho, Walter King Yan; Ahmed, Md. Dilsad; Keh, Nyit Chin; Khoo, Selina; Tan, Cheehian; Dehkordi, Mitra Rouhi; Gallardo, Mila; Lee, Kicheon; Yamaguchi, Yasuo; Wang, Jian; Liu, Min; Huang, Fan

2017-01-01

Numerous studies have been published heralding the benefits of physical education in school education. Sport and physical activities form the major content in learning and the arrangement serves as the major source of development in students. This paper identifies "quality" as an internationally concerned issue and within the concept,…

Investigating Ocean Pollution.

ERIC Educational Resources Information Center

LeBeau, Sue

1998-01-01

Describes a fifth-grade class project to investigate two major forms of ocean pollution: plastics and oil. Students work in groups and read, discuss, speculate, offer opinions, and participate in activities such as keeping a plastics journal, testing the biodegradability of plastics, and simulating oil spills. Activities culminate in…

The Formation and Development of Cognitive Activity of Students in the Learning Process

ERIC Educational Resources Information Center

Saparkyzy, Zhannat; Isatayeva, Gulzhan; Kozhabekova, Zahida; Zhakesheva, Aimzhan; Koptayeva, Gulzhamal; Agabekova, Gulzhan; Agabekova, Sholpan

2016-01-01

In this article we will discuss how the holding of a special and dedicated work helped to change the levels of formation of the major components of cognitive activity. Cognitive activity with the content aspect is a system of perceptual, mnemonic and intellectual activity and from the form--as an individual, joint, or pseudo-individual pseudo…

INTERINDIVIDUAL VARIANCE OF CYTOCHROME P450 FORMS IN HUMAN HEPATIC MICROSOMES: CORRELATION OF INDIVIDUAL FORMS WITH XENOBIOTIC METABOLISM AND IMPLICATIONS IN RISK ASSESSMENT

EPA Science Inventory

Differences in biotransformation activities may alter the bioavailability or efficacy of drugs, provide protection from certain xenobiotic and environmental agents, or increase toxicity of others. Cytochrome P450 (CYP450) enzymes are responsible for the majority of oxidation reac...

Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers

DTIC Science & Technology

2015-10-01

inhibitor, chromatin, x-ray crystallography , pre-clinical 3. ACCOMPLISHMENTS a. Major goals of the project as outlined in the approved Statement of...modeling of derivatives of our current lead VPC-14228 (months 1-30) 3.2. Synthesis of derivatives of our lead compounds (months 6-30). 3.3.Experimental...Activities for Vancouver Prostate Centre Site (Rennie, PI) In the first reporting period, the major activities consisted of a) design and synthesis of

Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration-Resistant Prostate Cancers

DTIC Science & Technology

2015-10-01

chromatin, x-ray crystallography , pre-clinical 3. ACCOMPLISHMENTS a. Major goals of the project as outlined in the approved Statement of Work (SOW...derivatives of our current lead VPC-14228 (months 1-30) 3.2. Synthesis of derivatives of our lead compounds (months 6-30). 3.3.Experimental evaluation...Activities for Vancouver Prostate Centre Site (Rennie, PI) In the first reporting period, the major activities consisted of a) design and synthesis

Lymphocyte changes in beta-thalassaemia major.

PubMed Central

Musumeci, S; Schiliro, G; Romeo, M A; Sciotto, A; Rosalba, A; Pizzarelli, G

1979-01-01

Lymphocyte subpopulations were studied in 20 hypertransfused patients with beta-thalassaemia major, some of whom had been splenectomised. B-lymphocytes were normal but T-lymphocytes were decreased in all patients. The T-cell count was lower in the splenectomised patients than in the nonsplenectomised ones. In the former, the active rosette-forming lymphocytes were also diminished, but the difference was not significant. In all patients the percentage of null cells was greater and the activity of K-cells increased compared with controls. PMID:316991

Purification and characterization of multiple forms of the pineapple-stem-derived cysteine proteinases ananain and comosain.

PubMed Central

Napper, A D; Bennett, S P; Borowski, M; Holdridge, M B; Leonard, M J; Rogers, E E; Duan, Y; Laursen, R A; Reinhold, B; Shames, S L

1994-01-01

A mixture of ananain (EC 3.4.22.31) and comosain purified from crude pineapple stem extract was found to contain numerous closely related enzyme forms. Chromatographic separation of the major enzyme forms was achieved after treatment of the mixture with thiol-modifying reagents: reversible modification with 2-hydroxyethyl disulphide provided enzyme for kinetic studies, and irreversible alkylation with bromotrifluoroacetone or iodoacetamide gave enzyme for structural analyses by 19F-n.m.r. and electrospray mass spectrometry respectively. Structural and kinetic analyses revealed comosain to be closely related to stem bromelain (EC 3.4.22.32), whereas ananain differed markedly from both comosain and stem bromelain. Nevertheless, differences were seen between comosain and stem bromelain in amino acid composition and kinetic specificity towards the epoxide inhibitor E-64. Differences between five isolatable alternative forms of ananain were characterized by amidolytic activity, thiol stoichiometry and accurate mass determinations. Three of the enzyme forms displayed ananain-like amidolytic activity, whereas the other two forms were inactive. Thiol-stoichiometry determinations revealed that the active enzyme forms contained one free thiol, whereas the inactive forms lacked the reactive thiol required for enzyme activity. M.s. provided direct evidence for oxidation of the active-site thiol to the corresponding sulphinic acid. Images Figure 3 Figure 4 PMID:8053898

The Prescribed Amount of Physical Activity in Randomized Clinical Trials in Older Adults

ERIC Educational Resources Information Center

Kruger, Judy; Buchner, David M.; Prohaska, Thomas R.

2009-01-01

Purpose: Over the past two decades, a consensus has formed that increasing physical activity and reducing sedentary behavior in older adults are important for physical and cognitive health. Although there is strong evidence that regular physical activity can prevent or delay the onset of many chronic diseases, a major concern is ensuring that…

Preliminary Assessment/Site Investigation: Tooele Army Depot, Utah. Volume 1. North Area and Facilities at Hill Air Force Base. Appendixes

DTIC Science & Technology

1988-12-01

the number of 2) Facilities occunied b, Army activities other than DA forms are prohibited without copies requested in Blocks 356 of the sub-e o e...scriber’s DA Form 12-QA-R. AR 420-76as tenants when reai property control is pr i o r approv al from HQDA distrbution is C for Active Army. ARNG. uner...quality 9 3-5 Records and reporting requirements (RCS Chief of Engineers * 2-1 Nonapproprnated fund activities * 3-6 DD-M (A&AR) 1080) • 4-4 Major Army

The Principal and Religious Activity.

ERIC Educational Resources Information Center

Mawdsley, Ralph D.

1998-01-01

Religious activity in public schools has become a major issue, thanks to the Equal Access Act and "Lamb's Chapel," but neither has eliminated the Establishment Clause as a feasible concern for school officials. Protecting student religious expression to the same extent as other forms of free speech raises legitimate concerns regarding…

Identification of novel superoxide dismutase isoenzymes in the olive (Olea europaea L.) pollen.

PubMed

Zafra, Adoración; Castro, Antonio Jesús; Alché, Juan de Dios

2018-06-08

Among antioxidant enzymes, the superoxide dismutase (SOD) family is a major actor in catalysing the disproportionation of superoxide. Apart from its role as antioxidant, these enzymes have a role in cell signalling, and Cu,Zn-SOD proteins are also major pollen allergens. In order to deepen our understanding of the SOD isoenzymes present in olive pollen and to analyse the molecular variability of the pollen Cu,Zn-SOD family, we carried out biochemical, transcriptomic and localization studies of pollen grains from different olive cultivars and other allergenic species. Olive pollen showed a high rate of total SOD activity in all cultivars assayed, which did not correlate with pollen viability. Mass spectrometry analysis together with activity assays and Western blotting experiments enabled us to identify new forms of Cu,Zn-SOD enzyme (including chloroplastidic and peroxisomal forms) as well as differentially expressed Mn-, Fe- and Cu,Zn-SOD isoenzymes among the pollen of different olive cultivars and allergenic species. Ultrastructural localization of Cu,Zn-SOD revealed its plastidial localization in the pollen grain. We also identified the occurrence of a shorter form of one of the cytosolic Cu,Zn-SOD enzymes, likely as the result of alternative splicing. This shorter enzyme showed lower SOD activity as compared to the full length form. The presence of multiple SOD isoenzymes in the olive pollen could be related to the need of finely tuning the ROS metabolism during the transition from its quiescent condition at maturity to a highly metabolically active state at germination.

Evidence of a major locus for lipoprotein lipase (LPL) activity in addition to a pleiotropic locus for both LPL and fasting insulin: results from the HERITAGE Family Study.

PubMed

Hong, Y; Rice, T; Després, J P; Gagnon, J; Nadeau, A; Bergeron, J; Pérusse, L; Bouchard, C; Leon, A S; Skinner, J S; Wilmore, J H; Rao, D C

1999-06-01

A major gene hypothesis for heparin releasable plasma lipoprotein lipase (PH-LPL) activity was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of Caucasian descent who participated in the HERITAGE Family Study. Segregation analyses were performed on PH-LPL adjusted for age, and on PH-LPL activity adjusted for age and fasting insulin. Prior to adjustment for insulin, neither a major gene effect nor a multifactorial component could be rejected, and support for a major gene was equivocal i.e. neither the Mendelian transmission nor the no transmission (equal tau s) models were rejected. However, after adjusting for the effects of insulin, a major gene effect on PH-LPL activity was unambiguous. The putative locus accounted for 60% of the total phenotypic variance, and the homozygous recessive form affected 10% (q2) of the sample (i.e. gene frequency (q) = 0.31), and led to a low PH-LPL value. The lack of a significant multifactorial effect suggested that the familial etiology of PH-LPL activity adjusted for insulin was likely to be primarily a function of the major locus. In conclusion, the present study is the first to report segregation analyses on PH-LPL activity prior to and after adjusting for insulin, and suggests that there is an indication of a pleiotropic genetic effect on PH-LPL activity and insulin, in addition to a major gene effect on PH-LPL activity alone.

Disruption of the Crithidia fasciculata RNH1 gene results in the loss of two active forms of ribonuclease H.

PubMed Central

Ray, D S; Hines, J C

1995-01-01

Both prokaryotic and eukaryotic cells contain multiple forms of ribonuclease H, a ribonuclease that specifically degrades the RNA strand of RNA-DNA hybrids and which has been implicated in the processing of initiator RNAs and in the removal of RNA primers from Okazaki fragments. The Crithidia fasciculata RNH1 gene encodes an RNase H and was shown to be a single-copy gene in this diploid trypanosomatid. The RNH1 gene has been disrupted by targeted gene disruption using hygromycin or G418 drug-resistance cassettes. Major active forms of RNase H (38 and 45 kDa) were observed on activity gels of extracts of wild-type cells or cells in which one allele of RNH1 was disrupted. Both the 38 and 45 kDa activities were absent in extracts of cells in which both alleles of RNH1 were disrupted indicating that both forms of the C.fasciculata RNase H are encoded by the RNH1 gene. Images PMID:7630731

Cellulose promotes extracellular assembly of Clostridium cellulovorans cellulosomes.

PubMed Central

Matano, Y; Park, J S; Goldstein, M A; Doi, R H

1994-01-01

Cellulosome synthesis by Clostridium cellulovorans was investigated by growing the cells in media containing different carbon sources. Supernatant from cells grown with cellobiose contained no cellulosomes and only the free forms of cellulosomal major subunits CbpA, P100, and P70 and the minor subunits with enzymatic activity. Supernatant from cells grown on pebble-milled cellulose and Avicel contained cellulosomes capable of degrading crystalline cellulose. Supernatants from cells grown with cellobiose, pebble-milled cellulose, and Avicel contained about the same amount of carboxymethyl cellulase activity. Although the supernatant from the medium containing cellobiose did not initially contain active cellulosomes, the addition of crystalline cellulose to the cell-free supernatant fraction converted the free major forms to cellulosomes with the ability to degrade crystalline cellulose. The binding of P100 and P70 to crystalline cellulose was dependent on their attachment to the endoglucanase-binding domains of CbpA. These data strongly indicate that crystalline cellulose promotes cellulosome assembly. Images PMID:7961457

Magnet Coil Test Facility for Researching Magnetic Activity of Pico/Nano/Micro Satellites (PNMSats)

DTIC Science & Technology

2017-05-16

research involving the College of Agriculture was initiated as a major activity of this research. Specific Objectives: The specific objectives...from the College of Agriculture and another form College of Arts and Science - may be benefitted by it. It is an asset to showcase to visitors and

Accumulation of sphingolipid activator proteins (SAPs) A and D in granular osmiophilic deposits in miniature Schnauzer dogs with ceroid-lipofuscinosis.

PubMed

Palmer, D N; Tyynelä, J; van Mil, H C; Westlake, V J; Jolly, R D

1997-03-01

The neuronal ceroid-lipofuscinoses (NCL, Batten disease) are fatal inherited neurodegenerative diseases of children characterized by retinal and brain atrophy and the accumulation of electron-dense storage bodies in cells. Mutations in different genes underlie different major forms. The infantile disease (CLN-1, McKusick 256730) is distinguished by the storage of the sphingolipid activator proteins (SAPs) A and D in distinctive granular osmiophilic deposits (GRODs). This contrasts with the other major forms, where subunit c of mitochondrial ATP synthase is stored in various multilamellar profiles. Ceroid-lipofuscinoses also occur in dogs, including a form in miniature Schnauzers with distinctive granular osmiophilic deposit-like storage bodies. Antisera to SAPs A and D reacted to these storage bodies in situ. The presence of SAP D was confirmed by Western blotting and of SAP A by protein sequencing. Neither subunit c of mitochondrial ATP synthase nor of vacuolar ATPase is stored. This suggests that there are two families of ceroid-lipofuscinoses, the subunit c-storing forms, and those in which SAPs A and D, and perhaps other proteins, accumulate. Further work is required to determine whether other forms with granular osmiophilic deposits belong to the latter class and the genetic relationships between them and the human infantile disease.

Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis with β-glucuronidase and sufatase: a review of bio-analytical methods.

PubMed

Ding, Yue; Peng, Ming; Zhang, Tong; Tao, Jian-Sheng; Cai, Zhen-Zhen; Zhang, Yong

2013-10-01

Glucuronidation and sulfation represent two major pathways in phase II drug metabolism in humans and other mammalian species. The great majority of drugs, for example, polyphenols, flavonoids and anthraquinones, could be transformed into sulfated and glucuronidated conjugates simultaneously and extensively in vivo. The pharmacological activities of drug conjugations are normally decreased compared with those of their free forms. However, some drug conjugates may either bear biological activities themselves or serve as excellent sources of biologically active compounds. As the bioactivities of drugs are thought to be relevant to the kinetics of their conjugates, it is essential to study the pharmacokinetic behaviors of the conjugates in more detail. Unfortunately, the free forms of drugs cannot be detected directly in most cases if their glucuronides and sulfates are the predominant forms in biological samples. Nevertheless, an initial enzymatic hydrolysis step using β-glucuronidase and/or sulfatase is usually performed to convert the glucuronidated and/or sulfated conjugates to their free forms prior to the extraction, purification and other subsequent analysis steps in the literature. This review provides fundamental information on drug metabolism pathways, the bio-analytical strategies for the quantification of various drug conjugates, and the applications of the analytical methods to pharmacokinetic studies. Copyright © 2013 John Wiley & Sons, Ltd.

Selected International Definitions about Young Students' Leisure Time: Theoretical and Practical Background in Poland

ERIC Educational Resources Information Center

Janicka-Panek, Teresa

2017-01-01

Terms such as recreation, leisure, functions of spare time, physical hygiene, mental hygiene or forms of spare time are among the issues discussed in the branch of educational science. The majority of educationalists are convinced that the issue of active leisure should form part of the core curriculum and should be an objective of education in…

Testing the Role of p21 Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

DTIC Science & Technology

2017-06-01

Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease The views, opinions and...Role of p21 Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease Form...NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. The major goal of this research project was to genetically and pharmacologically test the requirement of PAK

Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells.

PubMed Central

Takeuchi, M; Inoue, N; Strickland, T W; Kubota, M; Wada, M; Shimizu, R; Hoshi, S; Kozutsumi, H; Takasaki, S; Kobata, A

1989-01-01

Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. PMID:2813359

Structural and Functional Insights into the Catalytic Inactivity of the Major Fraction of Buffalo Milk Xanthine Oxidoreductase

PubMed Central

Gadave, Kaustubh S.; Panda, Santanu; Singh, Surender; Kalra, Shalini; Malakar, Dhruba; Mohanty, Ashok K.; Kaushik, Jai K.

2014-01-01

Background Xanthine oxidoreductase (XOR) existing in two interconvertible forms, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), catabolises xanthine to uric acid that is further broken down to antioxidative agent allantoin. XOR also produces free radicals serving as second messenger and microbicidal agent. Large variation in the XO activity has been observed among various species. Both hypo and hyper activity of XOR leads to pathophysiological conditions. Given the important nutritional role of buffalo milk in human health especially in south Asia, it is crucial to understand the functional properties of buffalo XOR and the underlying structural basis of variations in comparison to other species. Methods and Findings Buffalo XO activity of 0.75 U/mg was almost half of cattle XO activity. Enzymatic efficiency (k cat/K m) of 0.11 sec−1 µM−1 of buffalo XO was 8–10 times smaller than that of cattle XO. Buffalo XOR also showed lower antibacterial activity than cattle XOR. A CD value (Δε430 nm) of 46,000 M−1 cm−1 suggested occupancy of 77.4% at Fe/S I centre. Buffalo XOR contained 0.31 molybdenum atom/subunit of which 48% existed in active sulfo form. The active form of XO in buffalo was only 16% in comparison to ∼30% in cattle. Sequencing revealed 97.4% similarity between buffalo and cattle XOR. FAD domain was least conserved, while metal binding domains (Fe/S and Molybdenum) were highly conserved. Homology modelling of buffalo XOR showed several variations occurring in clusters, especially close to FAD binding pocket which could affect NAD+ entry in the FAD centre. The difference in XO activity seems to be originating from cofactor deficiency, especially molybdenum. Conclusion A major fraction of buffalo milk XOR exists in a catalytically inactive form due to high content of demolybdo and desulfo forms. Lower Fe/S content and structural factors might be contributing to lower enzymatic efficiency of buffalo XOR in a minor way. PMID:24498153

Problems of College Students' Adaptation to Professional Activity While in College

ERIC Educational Resources Information Center

Federova, E. E.

2008-01-01

Today's specialists are required to be actively involved, independent, flexible, original thinkers, and well trained both generally and professionally. Results of a sociological survey of 2,000 students at Urals State University indicate that a majority of students are at an average level of well-formed professional competence, and less than 1…

In Search of the Environmentalist Way: Beyond Mending the Machine

ERIC Educational Resources Information Center

Stables, Andrew

2017-01-01

In this essay, Andrew Stables notes that philosophies such as existentialism, humanism, and environmentalism come in either exploratory or active forms: that is, one can study the nature of existence or the human, or one can ascribe to a way of life in an attempt to improve the world. Among the major influences on active environmentalist thought…

Teaching Speaking Skills in English Language Using Classroom Activities in Secondary School Level in Eldoret Municipality, Kenya

ERIC Educational Resources Information Center

Gudu, Benter Oseno

2015-01-01

There is a general public concern in Kenya that majority of Form Four school leavers lack communicative and linguistic competence and thus cannot sustain conversation in English language without occasionally code switching to "Sheng" or Kiswahili. This study sought to find out the classroom activities used by teachers to promote…

The Development of Strategic Thinking: Learning to Impact Human Systems in a Youth Activism Program

ERIC Educational Resources Information Center

Larson, Reed; Hansen, David

2005-01-01

Human systems, including institutional systems and informal social networks, are a major arena of modern life. We argue that distinct forms of pragmatic reasoning or "strategic thinking" are required to exercise agency within such systems. This article explores the development of strategic thinking in a youth activism program in which young people…

Nano Engineered Energetic Materials (NEEM)

DTIC Science & Technology

2011-01-12

Al nanoparticles, owing to the surface oxidation of the unpassivated particles. The major drawback with utilizing organic capping groups is the...increases seen with nano-sized aluminum are promising, there are certain drawbacks . A thin layer of alumina (Al2O3) usually forms on the exterior...rocket motor by lowering the active aluminum content of the particles. Because of these drawbacks , surface protection in the form of coatings is

A study of solar magnetic fields below the surface, at the surface, and in the solar atmosphere - understanding the cause of major solar activity

NASA Astrophysics Data System (ADS)

Chintzoglou, Georgios

2016-04-01

Magnetic fields govern all aspects of solar activity from the 11-year solar cycle to the most energetic events in the solar system, such as solar flares and Coronal Mass Ejections (CMEs). As seen on the surface of the sun, this activity emanates from localized concentrations of magnetic fields emerging sporadically from the solar interior. These locations are called solar Active Regions (ARs). However, the fundamental processes regarding the origin, emergence and evolution of solar magnetic fields as well as the generation of solar activity are largely unknown or remain controversial. In this dissertation, multiple important issues regarding solar magnetism and activities are addressed, based on advanced observations obtained by AIA and HMI instruments aboard the SDO spacecraft. First, this work investigates the formation of coronal magnetic flux ropes (MFRs), structures associated with major solar activity such as CMEs. In the past, several theories have been proposed to explain the cause of this major activity, which can be categorized in two contrasting groups (a) the MFR is formed in the eruption, and (b) the MFR pre-exists the eruption. This remains a topic of heated debate in modern solar physics. This dissertation provides a complete treatment of the role of MFRs from their genesis all the way to their eruption and even destruction. The study has uncovered the pre-existence of two weakly twisted MFRs, which formed during confined flaring 12 hours before their associated CMEs. Thus, it provides unambiguous evidence for MFRs truly existing before the CME eruptions, resolving the pre-existing MFR controversy. Second, this dissertation addresses the 3-D magnetic structure of complex emerging ARs. In ARs the photospheric fields might show all aspects of complexity, from simple bipolar regions to extremely complex multi-polar surface magnetic distributions. In this thesis, we introduce a novel technique to infer the subphotospheric configuration of emerging magnetic flux tubes while forming ARs on the surface. Using advanced 3D visualization tools and applying this technique on a complex flare and CME productive AR, we found that the magnetic flux tubes involved in forming the complex AR may originate from a single progenitor flux tube in the SCZ. The complexity can be explained as a result of vertical and horizontal bifurcations that occurred on the progenitor flux tube. Third, this dissertation proposes a new scenario on the origin of major solar activity. When more than one flux tubes are in close proximity to each other while they break through the photospheric surface, collision and shearing may occur as they emerge. Once this collisional shearing occurs between nonconjugated sunspots (opposite polarities not belonging to the same bipole), major solar activity is triggered. The collision and the shearing occur due to the natural separation of polarities in emerging bipoles. This is forcing changes in the connectivity close to the photosphere (up to a few local pressure scale heights above the surface) by means of photospheric reconnection and subsequent submergence of small bipoles at the collision interface (polarity inversion line; PIL). In this continuous collision, more poloidal flux is added to the system effectively creating an expanding MFR into the corona, explaining the observation of filament formation above the PIL together with flare activity and CMEs. Our results reject two popular scenarios on the possible cause of solar eruptions (1) eruption occurs due to shearing motion between conjugate polarities, and, (2) bodily emergence of an MFR.

In Vitro Activity of Rifampicin Combined with Daptomycin or Tigecycline on Staphylococcus haemolyticus Biofilms.

PubMed

Szczuka, Ewa; Grabska, Katarzyna; Kaznowski, Adam

2015-08-01

Staphylococcus haemolyticus is of increasing concern as a cause of several biofilm-associated infections, and today, it represents the second most common organism among clinical isolates of coagulase-negative staphylococci. However, little is known regarding the treatment of infections caused by these bacteria. In this study, we characterize the biofilm formed by S. haemolyticus strains isolated from bloodstream infections and assess in vitro the activity of rifampicin combined with daptomycin or tigecycline against bacteria growing in a biofilm. The results of our studies indicated that the majority (78 %) of methicillin-resistant Staphylococcus haemolyticus strains have the ability to form a biofilm in vitro. None of these strains carried icaADBC genes indicating that they form biofilm via ica-independent mechanisms. The molecular characterization of the biofilm showed that proteins are the predominant matrix component and play a major role in biofilm structure. Extracellular DNA and polysaccharides, other than polysaccharide intercellular adhesin, are also present in the biofilm matrix, but they play a minor role. The images obtained by confocal laser scanning microscopy showed that most S. haemolyticus strains formed a dense biofilm with a low number of dead cells. In vitro study demonstrated excellent activity of tigecycline in combination with rifampicin against cell growth in the proteinous biofilm. The BIC (biofilm inhibitory concentration) value for tigecycline/rifampicin ranged from 0.062 to 1 µg/ml, whereas for daptomycin/rifampicin from 0.125 to 2 µg/ml. These results indicated that the tigecycline/rifampicin combination was more effective against ica-independent biofilm, formed by S. haemolyticus strains, than the daptomycin/rifampicin combination.

Comparative analysis of activator-Eσ54 complexes formed with nucleotide-metal fluoride analogues

PubMed Central

Burrows, Patricia C.; Joly, Nicolas; Nixon, B. Tracy; Buck, Martin

2009-01-01

Bacterial RNA polymerase (RNAP) containing the major variant σ54 factor forms open promoter complexes in a reaction in which specialized activator proteins hydrolyse ATP. Here we probe binding interactions between σ54-RNAP (Eσ54) and the ATPases associated with various cellular activities (AAA+) domain of the Escherichia coli activator protein, PspF, using nucleotide-metal fluoride (BeF and AlF) analogues representing ground and transition states of ATP, which allow complexes (that are otherwise too transient with ATP) to be captured. We show that the organization and functionality of the ADP–BeF- and ADP–AlF-dependent complexes greatly overlap. Our data support an activation pathway in which the initial ATP-dependent binding of the activator to the Eσ54 closed complex results in the re-organization of Eσ54 with respect to the transcription start-site. However, the nucleotide-dependent binding interactions between the activator and the Eσ54 closed complex are in themselves insufficient for forming open promoter complexes when linear double-stranded DNA is present in the initial closed complex. PMID:19553192

Heat Resistant Characteristics of Major Royal Jelly Protein 1 (MRJP1) Oligomer

PubMed Central

Moriyama, Takanori; Ito, Aimi; Omote, Sumire; Miura, Yuri; Tsumoto, Hiroki

2015-01-01

Soluble royal jelly protein is a candidate factor responsible for mammiferous cell proliferation. Major royal jelly protein 1 (MRJP1), which consists of oligomeric and monomeric forms, is an abundant proliferative protein in royal jelly. We previously reported that MRJP1 oligomer has biochemical heat resistance. Therefore, in the present study, we investigated the effects of several heat treatments (56, 65 and 96°C) on the proliferative activity of MRJP1 oligomer. Heat resistance studies showed that the oligomer molecular forms were slightly maintained until 56℃, but the molecular forms were converted to macromolecular heat-aggregated MRJP1 oligomer at 65℃ and 96℃. But, the growth activity of MRJP1 oligomer treated with 96°C was slightly attenuated when compared to unheated MRJP1 oligomer. On the other hand, the cell proliferation activity was preserved until 96℃ by the cell culture analysis of Jurkat cells. In contrast, those of IEC-6 cells were not preserved even at 56°C. The present observations suggest that the bioactive heat-resistance properties were different by the origin of the cells. The cell proliferation analysis showed that MRJP1 oligomer, but not MRJP2 and MRJP3, significantly increased cell numbers, suggesting that MRJP1 oligomer is the predominant proliferation factor for mammiferous cells. PMID:26020775

Heat Resistant Characteristics of Major Royal Jelly Protein 1 (MRJP1) Oligomer.

PubMed

Moriyama, Takanori; Ito, Aimi; Omote, Sumire; Miura, Yuri; Tsumoto, Hiroki

2015-01-01

Soluble royal jelly protein is a candidate factor responsible for mammiferous cell proliferation. Major royal jelly protein 1 (MRJP1), which consists of oligomeric and monomeric forms, is an abundant proliferative protein in royal jelly. We previously reported that MRJP1 oligomer has biochemical heat resistance. Therefore, in the present study, we investigated the effects of several heat treatments (56, 65 and 96°C) on the proliferative activity of MRJP1 oligomer. Heat resistance studies showed that the oligomer molecular forms were slightly maintained until 56℃, but the molecular forms were converted to macromolecular heat-aggregated MRJP1 oligomer at 65℃ and 96℃. But, the growth activity of MRJP1 oligomer treated with 96°C was slightly attenuated when compared to unheated MRJP1 oligomer. On the other hand, the cell proliferation activity was preserved until 96℃ by the cell culture analysis of Jurkat cells. In contrast, those of IEC-6 cells were not preserved even at 56°C. The present observations suggest that the bioactive heat-resistance properties were different by the origin of the cells. The cell proliferation analysis showed that MRJP1 oligomer, but not MRJP2 and MRJP3, significantly increased cell numbers, suggesting that MRJP1 oligomer is the predominant proliferation factor for mammiferous cells.

Chemical Composition of the Essential Oil from the Fresh Fruits of Xylopia laevigata and its Cytotoxic Evaluation.

PubMed

Costa, Emmanoel Vilaça; da Silva, Thanany Brasil; Costa, Cinara Oliveira D'Souza; Soares, Milena Botelho Pereira; Bezerra, Daniel Pereira

2016-03-01

The essential oil obtained by hydrodistillation from the fresh fruits of Xylopia laevigata was analyzed by gas chromatography using a flame ionization detector (GC-FID) coupled to a mass spectrometer (GC-MS). Monoterpenes predominated, forming 95.0% of the total essential oil. The major constituents identified were limonene (56.2%), α-pinene (28.0%), and β-pinene (5.5%). Cytotoxic activity against tumor cell lines and non-tumor cells was also investigated; however, neither the essential oil nor its major constituents evaluated presented any cytotoxic activity (IC₅₀ > 25.0 µg mL⁻¹).

ATP sulfurylase from higher plants: kinetic and structural characterization of the chloroplast and cytosol enzymes from spinach leaf.

PubMed

Renosto, F; Patel, H C; Martin, R L; Thomassian, C; Zimmerman, G; Segel, I H

1993-12-01

Two forms of ATP sulfurylase were purified from spinach leaf. The major (chloroplast) form accounts for 85 to 90% of the total leaf activity (0.03 +/- 0.01 adenosine-5'-phosphosulfate (APS) synthesis units x gram fresh weight-1). Both enzyme forms appear to be tetramers composed of 49- to 50-kDa subunits with the minor (cytosolic) form being slightly larger than the chloroplast form. The specific activities (units x milligram protein-1) of the chloroplast form at pH 8.0, 30 degrees C, were as follows: APS synthesis, 16; molybdolysis, 229; ATP synthesis, 267; selenolysis, 4.1; fluorophosphate activation, 11. Kinetic constants for the physiological reaction were as follows: KmA = 0.046 mM, K(ia) = 0.85 mM, KmB = 0.25 mM, KmQ = 0.37 microM, K(iq) = 64-85 nM, and KmP = 10 microM, where A = MgATP, B = SO4(2-), P = total PPi at 5 mM Mg2+, and Q = APS. The kinetic constants for molybdolysis were similar to those of the APS synthesis reaction. The kinetic constants of the minor (cytosol) form were similar to those of the major form with two exceptions: (a) The molybdolysis activity was 120 units x milligram protein-1, yielding a Vmax (ATP synthesis)/Vmax (molybdolysis) ratio close to 2 (compared to about unity for the chloroplast form) and (b) KmA was greater (0.24 and 0.15 mM for APS synthesis and molybdolysis, respectively). Initial velocity measurements (made over an extended range of MgATP and SO4(2-) concentrations), product inhibition studies (by initial velocity methods and by reaction progress curve analyses), dead end inhibition studies (with monovalent and divalent oxyanions), and kcat/Km comparisons (for SO4(2-) and MoO4(2-) support a random AB-ordered PQ kinetic mechanism in which MgATP and SO4(2-) bind in a highly synergistic manner. Equilibrium binding studies indicated the presence of one APS site per subunit. HPLC elution profiles of chymotryptic and tryptic peptides were essentially the same for both enzyme forms. The N-terminal sequence of residues 5-20 of the cytosol enzyme was identical to residues 1-16 of the chloroplast enzyme.

Termiticidal activity of chitosan against the subterranean termites Reticulitermes flavipes and Reticulitermes virginicus

Treesearch

Olanrewaju Raji; Juliet D Tang; Telmah Telmadarrehei; Dragica Jeremic

2018-01-01

BACKGROUND: Chitosan is a derivative form of chitin, which is the major component of exoskeletons of arthropods and the cell walls of fungi. The antimicrobial activity of chitosan against lepidopterans, aphids, fungi and bacteria has been extensively investigated, but only one report on the termiticidal effect of chitosan on termites has been published. In this study,...

Preventing Obesity among Preschool Children: How Can Child-Care Settings Promote Healthy Eating and Physical Activity? Research Synthesis

ERIC Educational Resources Information Center

Larson, Nicole; Ward, Dianne; Neelon, Sara Benjamin; Story, Mary

2011-01-01

Child-care settings provide numerous opportunities to promote healthy eating and physical activity behaviors among preschool children. The majority of U.S. children are placed in some form of non-parental care during their preschool years. While approximately 15 percent of preschool children are primarily cared for by their relatives, most…

Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates

PubMed Central

Chen, Miao-Hsueh; Li, Ya-Jun; Kawakami, Takatoshi; Xu, Shan-Mei; Chuang, Pao-Tien

2004-01-01

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue in Hh signaling is to elucidate the molecular mechanism by which a Hh protein morphogen gradient is formed despite its membrane association. In this study, we used a combination of genetic, cellular, and biochemical approaches to address the role of lipid modifications in long-range vertebrate Hh signaling. Our molecular analysis of knockout mice deficient in Skn, the murine homolog of the Drosophila ski gene, which catalyzes Hh palmitoylation, and gene-targeted mice producing a nonpalmitoylated form of Shh indicates that Hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos. Furthermore, our biochemical data show that Hh lipid modifications are required for producing a soluble multimeric protein complex, which constitutes the major active component for Hh signaling. These results suggest that soluble Hh multimeric complex travels in the morphogenetic field to activate Hh signaling in distant Hh-responsive cells. PMID:15075292

Inhibitory effects of different forms of tocopherols, tocopherol phosphates and tocopherol quinones on growth of colon cancer cells

PubMed Central

Dolfi, Sonia C.; Yang, Zhihong; Lee, Mao-Jung; Guan, Fei; Hong, Jungil; Yang, Chung S.

2013-01-01

Tocopherols are the major source of dietary vitamin E. In this study, the growth inhibitory effects of different forms of tocopherols, tocopheryl phosphates (TP) and tocopherol quinones (TQ) on human colon cancer HCT116 and HT29 cells were investigated. δ-T was more active than γ-T in inhibiting colon cancer cell growth, decreasing cancer cell colony formation and inducing apoptosis; however α-T was rather ineffective. Similarly, the rate of cellular uptake also followed the ranking order δ-T > γ-T ≫ α-T. TP and TQ generally had higher inhibitory activities than their parent compounds. Interestingly, the γ-forms of TP and TQ were more active than the δ-forms in inhibiting cancer cell growth; whereas the α-forms were the least effective. The potencies of γ-TQ and δ-TQ (showing IC50 of ~0.8 and ~2 μM on HCT116 cells after a 72-h incubation, respectively) were >100 and >20 fold higher, respectively, than those of their parent tocopherols. Induction of cancer cell apoptosis by δ-T, γ-TP and γ-TQ was characterized by the cleavage of caspase 3 and PARP1 and DNA fragmentation. These studies demonstrated the higher growth inhibitory activity of δ-T than γ-T, the even higher activities of the γ-forms of TP and TQ, and the ineffectiveness of the α-forms of tocopherol and their metabolites against colon cancer cells. PMID:23898832

Inhibitory effects of different forms of tocopherols, tocopherol phosphates, and tocopherol quinones on growth of colon cancer cells.

PubMed

Dolfi, Sonia C; Yang, Zhihong; Lee, Mao-Jung; Guan, Fei; Hong, Jungil; Yang, Chung S

2013-09-11

Tocopherols are the major source of dietary vitamin E. In this study, the growth inhibitory effects of different forms of tocopherols (T), tocopheryl phosphates (TP), and tocopherol quinones (TQ) on human colon cancer HCT116 and HT29 cells were investigated. δ-T was more active than γ-T in inhibiting colon cancer cell growth, decreasing cancer cell colony formation, and inducing apoptosis; however, α-T was rather ineffective. Similarly, the rate of cellular uptake also followed the ranking order δ-T > γ-T ≫ α-T. TP and TQ generally had higher inhibitory activities than their parent compounds. Interestingly, the γ forms of TP and TQ were more active than the δ forms in inhibiting cancer cell growth, whereas the α forms were the least effective. The potencies of γ-TQ and δ-TQ (showing IC50 values of ∼0.8 and ∼2 μM on HCT116 cells after a 72 h incubation, respectively) were greater than 100-fold and greater than 20-fold higher, respectively, than those of their parent tocopherols. Induction of cancer cell apoptosis by δ-T, γ-TP, and γ-TQ was characterized by the cleavage of caspase 3 and PARP1 and DNA fragmentation. These studies demonstrated the higher growth inhibitory activity of δ-T than γ-T, the even higher activities of the γ forms of TP and TQ, and the ineffectiveness of the α forms of tocopherol and their metabolites against colon cancer cells.

The 29-kDa proteins phosphorylated ion thrombin-activated human platelets are forms of the estrogen receptor-related 27-kDa heat shock protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mendelsohn, M.E.; Yan Zhu; O'Neill, S.

Thrombin plays a critical role in platelet activation, hemostasis, and thrombosis. Cellular activation by thrombin leads to the phosphorylation of multiple proteins, most of which are unidentified. The authors have characterized several 29-kDa proteins that are rapidly phosphorylated following exposure of intact human platelets to thrombin. A murine monoclonal antibody raised to an unidentified estrogen receptor-related 29-kDa protein selectively recognized these proteins as well as a more basic, unphosphorylated 27-kDa protein. Cellular activation by thrombin led to a marked shift in the proportion of protein from the 27-kDa unphosphorylated form to the 29-kDa phosphoprotein species. Using this antibody, they isolatedmore » and sequenced a human cDNA clone encoding a protein that was identical to the mammalian 27-kDa heat shock protein (HSP27), a protein of uncertain function that is known to be phosphorylated to several forms and to be transcriptionally induced by estrogen. The 29-kDa proteins were confirmed to be phosphorylated forms of HSP27 by immunoprecipitation studies. Thus, the estrogen receptor-related protein is HSP27, and the three major 20-kDa proteins phosphorylated in thrombin-activated platelets are forms of HSP27. These data suggest a role for HSP27 in the signal transduction events of platelet activation.« less

Isozymes of lignin peroxidase and manganese(II) peroxidase from the white-rot basidiomycete Trametes versicolor. I. Isolation of enzyme forms and characterization of physical and catalytic properties.

PubMed

Johansson, T; Nyman, P O

1993-01-01

The basidiomycete Trametes versicolor is a white-rot fungus and a potent degrader of lignin. The development of extracellular enzyme activities in the fungal culture under physiological conditions of secondary metabolism was investigated. Using the culture medium as starting material a large number of peroxidase forms were purified by the use of chromatographic techniques. Sixteen forms of lignin peroxidase and five forms of manganese(II) peroxidase were separated and the majority of these enzymes was characterized with respect to isoelectric point, molecular mass, and specific enzyme activity. The manganese(II) peroxidases showed a lower isoelectric point (pI 3.2-2.9) and a slightly higher molecular mass (44-45 kDa) than the lignin peroxidases (pI 3.7-3.1, and 41-43 kDa). Specific enzyme activities for the forms of lignin peroxidase, using veratryl alcohol as the substrate, were found to differ considerably. Certain differences in the specific enzyme activity were also observed among the forms of manganese(II) peroxidase. A multitude of peroxidase forms has previously been encountered in another white-rot fungus, Phanerochaete chrysosporium. The discovery that it also occurs in T. versicolor would suggest that this multiplicity could be a common feature among white-rot fungi and may be essential for the biodegradation of lignin.

Plants as sources of airborne bacteria, including ice nucleation-active bacteria.

PubMed

Lindemann, J; Constantinidou, H A; Barchet, W R; Upper, C D

1982-11-01

Vertical wind shear and concentration gradients of viable, airborne bacteria were used to calculate the upward flux of viable cells above bare soil and canopies of several crops. Concentrations at soil or canopy height varied from 46 colony-forming units per m over young corn and wet soil to 663 colony-forming units per m over dry soil and 6,500 colony-forming units per m over a closed wheat canopy. In simultaneous samples, concentrations of viable bacteria in the air 10 m inside an alfalfa field were fourfold higher than those over a field with dry, bare soil immediately upwind. The upward flux of viable bacteria over alfalfa was three- to fourfold greater than over dry soil. Concentrations of ice nucleation-active bacteria were higher over plants than over soil. Thus, plant canopies may constitute a major source of bacteria, including ice nucleation-active bacteria, in the air.

Physical activity level and fall risk among community-dwelling older adults.

PubMed

Low, Sok Teng; Balaraman, Thirumalaya

2017-07-01

[Purpose] To find the physical activity level and fall risk among the community-dwelling Malaysian older adults and determine the correlation between them. [Subjects and Methods] A cross-sectional study was conducted in which, the physical activity level was evaluated using the Rapid Assessment of Physical Activity questionnaire and fall risk with Fall Risk Assessment Tool. Subjects recruited were 132 community-dwelling Malaysian older adults using the convenience sampling method. [Results] The majority of the participants were under the category of under-active regular light-activities and most of them reported low fall risk. The statistical analysis using Fisher's exact test did not show a significant correlation between physical activity level and fall risk. [Conclusion] The majority of community-dwelling Malaysian older adults are performing some form of physical activity and in low fall risk category. But this study did not find any significant correlation between physical activity level and fall risk among community-dwelling older adults in Malaysia.

The stigmatisation of pregnancy: societal influences on pregnant women's physical activity Behaviour.

PubMed

van Mulken, Michelle R H; McAllister, Margaret; Lowe, John B

2016-08-01

Many women going through the major life transition of pregnancy experience decreases in physical activity behaviour, which may compromise maternal and infant health and wellbeing. Although research suggests that the social environment plays a large role in influencing women's physical activity behaviour, little is known about the association between societal attitudes and physical activity behaviour during the course of pregnancy. Through a qualitative longitudinal study, we explored women's physical activity experiences throughout pregnancy and how these were formed, supported and/or opposed by their social environment. This research included telephone interviews with 30 pregnant participants, recruited via a regional public hospital. Using a feminist standpoint analysis incorporating modern dialectics, three major tensions were identified, reflecting dominant societal discourses around physical activity and pregnancy: (1) engaging in physical activity and keeping the baby safe, (2) engaging in physical activity and obtaining social approval and (3) listening to oneself and to others. These findings present previously unrecognised opportunities for developing tailored and effective physical activity interventions among pregnant women.

Purification and properties of a novel ferricyanide-linked xanthine dehydrogenase from Pseudomonas putida 40.

PubMed Central

Woolfolk, C A

1985-01-01

The isolation of a xanthine dehydrogenase from Pseudomonas putida 40 which utilizes ferricyanide as an electron acceptor at high efficiency is presented. The new activity is separate from the NAD+ and oxygen-utilizing activities of the same organism but displays a broad pattern for reducing substrates typical of those of previously studied xanthine-oxidizing enzymes. Unlike the previously studied enzymes, the new enzyme appears to lack flavin but possess heme and is resistant to cyanide treatment. However, sensitivity of the purified enzyme to methanol and the selective elimination of the activity when tungstate is added to certain growth media suggest a role for molybdenum. The enzyme is subject to a selective proteolytic action during processing which is not accompanied by denaturation or loss of activity and which is minimized by the continuous exposure of the activity to EDTA and phenylmethylsulfonyl fluoride. Electrophoresis of the denatured enzyme in the presence of sodium dodecyl sulfate suggests that the enzyme is constructed of subunits with a molecular weight of approximately 72,000. Electrophoresis under native conditions of a purified enzyme previously exposed to magnesium ion reveals a series of major and minor activity bands which display some selectivity toward both electron donors and acceptors. An analysis of the effect of gel concentration on this pattern suggests that the enzyme forms a series of charge and size isomers with a pair of trimeric forms predominating. Comparison of the rate of sedimentation of the enzyme in sucrose gradients with its elution profile from standardized Sepharose 6B columns suggests a molecular weight of 255,000 for the major form of the native enzyme. Images PMID:3860496

Fiber Optic Chemical Sensors

DTIC Science & Technology

1993-10-01

patent rights. A major problem was identification of the property of ST&E vs LLNL ST&E was formed to manage the activities of Dr. Hirschfeld and Dr...positions of the fields defined in a fixed format to allow its importation into file management programs both in the microcomputer and the minicomputer...Systems Inc., Perry, Florida. askSam is a free-form information manager . A few basic elements of structure can be used to create a highly structured

Antileishmanial compounds from Cordia fragrantissima collected in Burma (Myanmar).

PubMed

Mori, Kanami; Kawano, Marii; Fuchino, Hiroyuki; Ooi, Takashi; Satake, Motoyoshi; Agatsuma, Yutaka; Kusumi, Takenori; Sekita, Setsuko

2008-01-01

A methanol extract of the wood of Cordia fragrantissima, collected in Burma (Myanmar), was found to exhibit significant activity against Leishmania major. Bioassay-guided fractionation of this extract using several chromatographic techniques afforded three new compounds (1-3) and five known compounds (4-8). The structures of the new compounds were revealed on the basis of spectroscopic data interpretation and by X-ray crystallographic analysis. Interestingly, the new compounds, despite the presence of asymmetric carbons, were found to be racemates. The activities of the isolates from C. fragrantissima and several derivatives were evaluated against the promastigote forms of Leishmania major, L. panamensis, and L. guyanensis.

DoD Science and Engineering Apprenticeship Program for High School Students, 1995-󈨤 Activities

DTIC Science & Technology

1996-06-01

University of Florida Sports Medicine Honor Roll Weightlifting , Swimming NAME: RACE: SEX: HIGH SCHOOL: ANTICIPATED COLLEGE: ANTICIPATED MAJOR...program. Three of the students took a Psychology course, one took a Nutritional Science class, one a Math course and two of them took a Meteorology...Awards and Scholarships: Honor Roll 13. Activities/Hobbies: Weightlifting , Swimming (Suggested Form) INFORMATION FOR EACH APPRENTICE

Gap-junctional channel and hemichannel activity of two recently identified connexin 26 mutants associated with deafness.

PubMed

Dalamon, Viviana; Fiori, Mariana C; Figueroa, Vania A; Oliva, Carolina A; Del Rio, Rodrigo; Gonzalez, Wendy; Canan, Jonathan; Elgoyhen, Ana B; Altenberg, Guillermo A; Retamal, Mauricio A

2016-05-01

Gap-junction channels (GJCs) are formed by head-to-head association of two hemichannels (HCs, connexin hexamers). HCs and GJCs are permeable to ions and hydrophilic molecules of up to Mr ~1 kDa. Hearing impairment of genetic origin is common, and mutations of connexin 26 (Cx26) are its major cause. We recently identified two novel Cx26 mutations in hearing-impaired subjects, L10P and G109V. L10P forms functional GJCs with slightly altered voltage dependence and HCs with decrease ATP/cationic dye selectivity. G109V does not form functional GJCs, but forms functional HCs with enhanced extracellular Ca(2+) sensitivity and subtle alterations in voltage dependence and ATP/cationic dye selectivity. Deafness associated with G109V could result from decreased GJCs activity, whereas deafness associated to L10P may have a more complex mechanism that involves changes in HC permeability.

Shocking Tails in the Major Merger Abell 2744

NASA Astrophysics Data System (ADS)

Owers, Matt S.; Couch, Warrick J.; Nulsen, Paul E. J.; Randall, Scott W.

2012-05-01

We identify four rare "jellyfish" galaxies in Hubble Space Telescope imagery of the major merger cluster Abell 2744. These galaxies harbor trails of star-forming knots and filaments which have formed in situ in gas tails stripped from the parent galaxies, indicating they are in the process of being transformed by the environment. Further evidence for rapid transformation in these galaxies comes from their optical spectra, which reveal starburst, poststarburst, and active galactic nucleus features. Most intriguingly, three of the jellyfish galaxies lie near intracluster medium features associated with a merging "Bullet-like" subcluster and its shock front detected in Chandra X-ray images. We suggest that the high-pressure merger environment may be responsible for the star formation in the gaseous tails. This provides observational evidence for the rapid transformation of galaxies during the violent core passage phase of a major cluster merger.

SHOCKING TAILS IN THE MAJOR MERGER ABELL 2744

DOE Office of Scientific and Technical Information (OSTI.GOV)

Owers, Matt S.; Couch, Warrick J.; Nulsen, Paul E. J.

We identify four rare 'jellyfish' galaxies in Hubble Space Telescope imagery of the major merger cluster Abell 2744. These galaxies harbor trails of star-forming knots and filaments which have formed in situ in gas tails stripped from the parent galaxies, indicating they are in the process of being transformed by the environment. Further evidence for rapid transformation in these galaxies comes from their optical spectra, which reveal starburst, poststarburst, and active galactic nucleus features. Most intriguingly, three of the jellyfish galaxies lie near intracluster medium features associated with a merging 'Bullet-like' subcluster and its shock front detected in Chandra X-raymore » images. We suggest that the high-pressure merger environment may be responsible for the star formation in the gaseous tails. This provides observational evidence for the rapid transformation of galaxies during the violent core passage phase of a major cluster merger.« less

The glycoprotein character of multiple forms of Aspergillus polygalacturonase.

PubMed

Stratilová, E; Mislovicová, D; Kacuráková, M; Machová, E; Kolarová, N; Markovic, O; Jörnvall, H

1998-02-01

Comparisons of known primary structures of polygalacturonases show that extent and localization of potential N-glycosylation sites differ. Some sites are similar in position and adjacent to strictly conserved residues at the potential active site. The presence of N-acetylglucosamine and mannose in the molecules of two homogeneous, major Aspergillus sp. polygalacturonase forms was confirmed by IR spectroscopy. The purification method, based on interaction of the carbohydrate part with concanavalin A immobilized on chlorotriazine bead cellulose, was optimized. Deglycosylation with N-glycosidase F under denaturating and nondenaturating conditions led to molecular mass decreases followed by complete inactivation of the polygalacturonase enzyme activity. These results show the importance of glycosylation in these protein forms, while the comparative patterns establish both variability and some similarities in overall glycosylation architectures.

Realizing the Potential of Community-University Partnerships

ERIC Educational Resources Information Center

Anyon, Yolanda; Fernandez, Maria A.

2007-01-01

Universities across the nation are expected to contribute to their neighboring communities. Responses to this charge come in many forms: college students volunteering in neighborhood schools, faculty conducting research activities to support local evaluation efforts, and university centers and civic leaders launching major community-development…

Steroselective Potencies and Relative Toxicities of Coniine Enantiomers

USDA-ARS?s Scientific Manuscript database

Coniine, one of the major toxic alkaloids present in poison hemlock (Conium maculatum), occurs in two optically active forms. A comparison of the relative potencies of (+)- and (-)-coniine enantiomers has not been previously reported. In this study, we separated the enantiomers of coniine and dete...

Programming that Takes Stress Out of the Military.

ERIC Educational Resources Information Center

Caverly, Mary

1980-01-01

A major form of stress often found in today's military service is that of boredom. Military recreation centers must provide a variety of challenging activities to meet the needs of bored military personnel. The challenge lies in motivating and stimulating military personnel to participate. (JN)

The influence of differential processing of procathepsin H on its aminopeptidase activity, secretion and subcellular localization in human cell lines.

PubMed

Rojnik, Matija; Jevnikar, Zala R; Doljak, Bojan; Turk, Samo; Zidar, Nace; Kos, Janko

2012-10-01

Cathepsin H is a unique member of the cysteine cathepsins that acts primarily as an aminopeptidase. Like other cysteine cathepsins, it is synthesized as an inactive precursor and activated by proteolytic removal of its propeptide. Here we demonstrate that, in human cells, the processing of the propeptide is an autocatalytic, multistep process proceeding from an inactive 41kDa pro-form, through a 30kDa intermediate form, to the 28kDa mature form. Tyr87P and Gly90P were identified as the two major endopeptidase cleavage sites, converting the 30kDa form into the mature 28kDa form. The level of processing differs significantly in different human cell lines. In monocyte-derived macrophages U937 and prostate cancer cells PC-3, the 28kDa form is predominant, whereas in osteoblasts HOS the processing from the 30kDa form to the 28kDa form is significantly lower. The aminopeptidase activity of the enzyme and its subcellular localization are independent of the product, however the 30kDa form was not secreted in HOS cells. The activity of the resulting cathepsin H in U937 cells was significantly lower than that in HOS cells, presumably due to the high levels of endogenous cysteine protease inhibitor cystatin F present specifically in this cell line. These results provide an insight into the dependence of human cathepsin H processing and regulation on cell type. Copyright © 2012 Elsevier GmbH. All rights reserved.

Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells

PubMed Central

Lefrançais, Emma; Duval, Anais; Mirey, Emilie; Roga, Stéphane; Espinosa, Eric; Cayrol, Corinne; Girard, Jean-Philippe

2014-01-01

Interleukin-33 (IL-33) is an alarmin cytokine from the IL-1 family. IL-33 activates many immune cell types expressing the interleukin 1 receptor-like 1 (IL1RL1) receptor ST2, including group-2 innate lymphoid cells (ILC2s, natural helper cells, nuocytes), the major producers of IL-5 and IL-13 during type-2 innate immune responses and allergic airway inflammation. IL-33 is likely to play a critical role in asthma because the IL33 and ST2/IL1RL1 genes have been reproducibly identified as major susceptibility loci in large-scale genome-wide association studies. A better understanding of the mechanisms regulating IL-33 activity is thus urgently needed. Here, we investigated the role of mast cells, critical effector cells in allergic disorders, known to interact with ILC2s in vivo. We found that serine proteases secreted by activated mast cells (chymase and tryptase) generate mature forms of IL-33 with potent activity on ILC2s. The major forms produced by mast cell proteases, IL-3395–270, IL-33107–270, and IL-33109–270, were 30-fold more potent than full-length human IL-331–270 for activation of ILC2s ex vivo. They induced a strong expansion of ILC2s and eosinophils in vivo, associated with elevated concentrations of IL-5 and IL-13. Murine IL-33 is also cleaved by mast cell tryptase, and a tryptase inhibitor reduced IL-33–dependent allergic airway inflammation in vivo. Our study identifies the central cleavage/activation domain of IL-33 (amino acids 66–111) as an important functional domain of the protein and suggests that interference with IL-33 cleavage and activation by mast cell and other inflammatory proteases could be useful to reduce IL-33–mediated responses in allergic asthma and other inflammatory diseases. PMID:25313073

Accelerated aging: prediction of chemical stability of pharmaceuticals.

PubMed

Waterman, Kenneth C; Adami, Roger C

2005-04-11

Methods of rapidly and accurately assessing the chemical stability of pharmaceutical dosage forms are reviewed with respect to the major degradation mechanisms generally observed in pharmaceutical development. Methods are discussed, with the appropriate caveats, for accelerated aging of liquid and solid dosage forms, including small and large molecule active pharmaceutical ingredients. In particular, this review covers general thermal methods, as well as accelerated aging methods appropriate to oxidation, hydrolysis, reaction with reactive excipient impurities, photolysis and protein denaturation.

Expression of a major surface protein of Trypanosoma brucei insect forms is controlled by the activity of mitochondrial enzymes.

PubMed

Vassella, Erik; Probst, Matthias; Schneider, André; Studer, Erwin; Renggli, Christina Kunz; Roditi, Isabel

2004-09-01

In cycling between the mammalian host and the tsetse fly vector, trypanosomes undergo major changes in energy metabolism and surface coat composition. Early procyclic (insect) forms in the tsetse fly midgut are coated by glycoproteins known as EP and GPEET procyclins. EP expression continues in late procyclic forms, whereas GPEET is down-regulated. In culture, expression of GPEET is modulated by glycerol or glucose. Here, we demonstrate that a glycerol-responsive element of 25 nucleotides within the 3' untranslated region of GPEET mRNA also controls expression by glucose and during development in the fly. In trypanosomes, mitochondrial ATP is produced mainly by the acetate: succinate-CoA transferase/succinyl-CoA synthetase (ASCT) cycle, the citric acid cycle, and the cytochromes. Silencing of the pyruvate dehydrogenase or succinyl-CoA synthetase from the ASCT cycle by RNA interference induces reexpression of GPEET in late procyclic forms, whereas inhibition of the citric acid cycle or the cytochromes has no effect. In contrast, inhibition of the alternative oxidase, the second branch of the electron transport chain, with salicylhydroxamic acid overrides the effect of glucose or glycerol and causes a reduction in the level of GPEET mRNA. Our results reveal a new mechanism by which expression of a surface glycoprotein is controlled by the activity of mitochondrial enzymes.

Conformational antigenic determinants generated by interactions between a bacterially expressed recombinant peptide of the hepatitis E virus structural protein.

PubMed

Zhang, J Z; Ng, M H; Xia, N S; Lau, S H; Che, X Y; Chau, T N; Lai, S T; Im, S W

2001-06-01

A 23 kDa peptide locating to amino acid residues 394 to 604 of the major Hepatitis E Virus (HEV) structural protein was expressed in E. coli. This peptide was found to interact naturally with one another to form homodimers and it was recognized strongly and commonly in its dimeric form by HEV reactive human sera. The antigenic activity associated with the dimeric form was abrogated when the dimer was dissociated into monomer and the activity was reconstituted after the monomer was re-associated into dimer again. The dimeric form of the peptide elicited a vigorous antibody response in experimental animals and the resulting antisera were found to cross-react against HEV, effecting an efficient immune capture of the virus. These results attributed the antigenic activity associated with the dimeric form of the peptide to conformational antigenic determinants generated as a result of interaction between the peptide molecules. It is suggested that some of these antigenic determinants may be expressed by the HEV capsid and raised the possibility of this bacterially expressed peptide as an HEV vaccine candidate. Copyright 2001 Wiley-Liss, Inc.

Information, Education, Communication in Population.

ERIC Educational Resources Information Center

Hawaii Univ., Honolulu. East-West Center.

Programs and services of the Swedish International Development Authority (SIDA) are reviewed in this report on resources available for the support of population information, education, and communication activities. Four major sections describe in concise, outline form: (1) the agency and its programs, (2) the specific program in population/family…

The research infrastructure of Chinese foundations, a database for Chinese civil society studies

PubMed Central

Ma, Ji; Wang, Qun; Dong, Chao; Li, Huafang

2017-01-01

This paper provides technical details and user guidance on the Research Infrastructure of Chinese Foundations (RICF), a database of Chinese foundations, civil society, and social development in general. The structure of the RICF is deliberately designed and normalized according to the Three Normal Forms. The database schema consists of three major themes: foundations’ basic organizational profile (i.e., basic profile, board member, supervisor, staff, and related party tables), program information (i.e., program information, major program, program relationship, and major recipient tables), and financial information (i.e., financial position, financial activities, cash flow, activity overview, and large donation tables). The RICF’s data quality can be measured by four criteria: data source reputation and credibility, completeness, accuracy, and timeliness. Data records are properly versioned, allowing verification and replication for research purposes. PMID:28742065

Morphological changes and fusogenic activity of influenza virus hemagglutinin.

PubMed Central

Shangguan, T; Siegel, D P; Lear, J D; Axelsen, P H; Alford, D; Bentz, J

1998-01-01

The kinetics of low-pH induced fusion of influenza virus with liposomes have been compared to changes in the morphology of influenza hemagglutinin (HA). At pH 4.9 and 30 degrees C, the fusion of influenza A/PR/8/34 virus with ganglioside-bearing liposomes was complete within 6 min. Virus preincubated at pH 4.9 and 30 degrees C in the absence of liposomes for 2 or 10 min retained most of its fusion activity. However, fusion activity was dramatically reduced after 30 min, and virtually abolished after a 60-min preincubation. Cryo-electron microscopy showed that the hemagglutinin spikes of virions exposed to pH 4.9 at 30 degrees C for 10 min underwent no major morphological changes. After 30 min, however, the spike morphology changed dramatically, and further changes occurred for up to 60 min after exposure to low pH. Because the morphological changes occur at a rate corresponding to the loss of fusion activity, and because these changes are much slower than the rate at which fusion occurs, we conclude that the morphologically altered HA is inactive with respect to fusion-promoting activity. Molecular modeling studies indicate that the formation of an extended coiled coil within the HA trimer, as proposed for HA at low pH, requires a major conformational change in HA, and that the morphological changes we observe are consistent with the formation of an extended coiled coil. These results imply that the crystallographically determined low-pH form of HA does occur in the intact virus, but that this form is not a precursor of viral fusion. It is speculated that the motion to the low-pH form may be responsible for the membrane destabilization leading to fusion. PMID:9449309

Isolation and characterization of diadenosine tetraphosphate (Ap4A) hydrolase from Schizosaccharomyces pombe.

PubMed

Robinson, A K; de la Peña, C E; Barnes, L D

1993-02-13

An enzyme that catalyzes the asymmetric hydrolysis of Ap4A has been partially purified from the fission yeast, Schizosaccharomyces pombe. The crude supernatant fraction from log-phase cells was fractionated by (NH4)2SO4 precipitation followed by chromatography on DEAE-cellulose, Red A dye-ligand and QAE-Sepharose resins. Two peaks of Ap4A hydrolase activity, designated major and minor, were separated on the Red A dye-ligand resin. Both the major and minor Ap4A hydrolase have an apparent molecular mass of 49 kDa based on gel filtration chromatography. On a SDS polyacrylamide gel, a protein of 22 kDa exhibited Ap4A hydrolase activity. Both forms of the enzyme have a Km value in the range of 22 to 36 microM for Ap4A. Both forms of the enzyme asymmetrically hydrolyze Ap4A to AMP and ATP as determined by HPLC. Ap4A is the optimal substrate among several nucleotides and dinucleoside polyphosphates tested at 10 microM. A divalent metal cation is required for activity. Concentrations of Pi below 30 mM stimulate Ap4A hydrolase while higher concentrations inhibit the activity. Pi is not a substrate for this Ap4A-degradative enzyme. Fluoride, from 50 microM to 20 mM, has no significant effect on Ap4A hydrolase activity.

A comprehensive review of chalcone derivatives as antileishmanial agents.

PubMed

de Mello, Marcos Vinícius Palmeira; Abrahim-Vieira, Barbara de Azevedo; Domingos, Thaisa Francielle Souza; de Jesus, Jessica Barbosa; de Sousa, Ana Carolina Corrêa; Rodrigues, Carlos Rangel; Souza, Alessandra M Teles de

2018-04-25

Leishmaniasis is a group of infectious neglected tropical diseases caused by more than 20 pathogenic species of Leishmania sp. Due to the limitations of the current treatments available, chalcone moiety has been drawn with a lot of attention due to the simple chemistry and synthesis, being reported with antileishmanial activity in particular against amastigote form. This review aims to provide an overview towards antileishmanial activity of chalcones derivatives against amastigote form for Leishmania major, L. amazonensis, L. panamensis, L. donovani and L. infantum as well as their structure-activity relationship (SAR), molecular targets and in silico ADMET evaluation. In this way, it is expected that this review may support the research and development of new promising chalcones candidates a leishmanicidal drugs. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Sleep-Active Neurons: Conserved Motors of Sleep

PubMed Central

Bringmann, Henrik

2018-01-01

Sleep is crucial for survival and well-being. This behavioral and physiological state has been studied in all major genetically accessible model animals, including rodents, fish, flies, and worms. Genetic and optogenetic studies have identified several neurons that control sleep, making it now possible to compare circuit mechanisms across species. The “motor” of sleep across animal species is formed by neurons that depolarize at the onset of sleep to actively induce this state by directly inhibiting wakefulness. These sleep-inducing neurons are themselves controlled by inhibitory or activating upstream pathways, which act as the “drivers” of the sleep motor: arousal inhibits “sleep-active” neurons whereas various sleep-promoting “tiredness” pathways converge onto sleep-active neurons to depolarize them. This review provides the first overview of sleep-active neurons across the major model animals. The occurrence of sleep-active neurons and their regulation by upstream pathways in both vertebrate and invertebrate species suggests that these neurons are general and ancient components that evolved early in the history of nervous systems. PMID:29618588

Visual design for the user interface, Part 1: Design fundamentals.

PubMed

Lynch, P J

1994-01-01

Digital audiovisual media and computer-based documents will be the dominant forms of professional communication in both clinical medicine and the biomedical sciences. The design of highly interactive multimedia systems will shortly become a major activity for biocommunications professionals. The problems of human-computer interface design are intimately linked with graphic design for multimedia presentations and on-line document systems. This article outlines the history of graphic interface design and the theories that have influenced the development of today's major graphic user interfaces.

Magnetohydrodynamic (MHD) analyses of various forms of activity and their propagation through helio spheric space

NASA Technical Reports Server (NTRS)

Wu, S. T.

1987-01-01

Theoretical and numerical modeling of solar activity and its effects on the solar atmosphere within the context of magnetohydrodynamics were examined. Specifically, the scientific objectives were concerned with the physical mechanisms for the flare energy build-up and subsequent release. In addition, transport of this energy to the corona and solar wind was also investigated. Well-posed, physically self-consistent, numerical simulation models that are based upon magnetohydrodynamics were sought. A systematic investigation of the basic processes that determine the macroscopic dynamic behavior of solar and heliospheric phenomena was conducted. A total of twenty-three articles were accepted and published in major journals. The major achievements are summarized.

Biological Effects of Directed Energy

NASA Astrophysics Data System (ADS)

Dayton, Thomas; Beason, Charles; Hitt, M. K.; Rogers, Walter; Cook, Michael

2002-11-01

This Final Report summarizes the biological effects research conducted by Veridian Engineering personnel under contract F41624-96-C-9009 in support of the Air Force Research Laboratory's Radio Frequency Radiation Branch from April 1997 to April 2002. Biological effects research and consultation were provided in five major areas: Active Denial System (also known as Vehicle Mounted Active Denial System), radio frequency radiation (RFR) health and safety, non-lethal weapon biological effects research, the newly formed Joint Non-Lethal Weapons Human Effects Center of Excellence, and Biotechnology. The report is organized by research efforts within the major research areas, providing title, objective, a brief description, relevance to the AF or DoD, funding, and products.

Characterization of aroma-active compounds in raw and cooked pine-mushrooms (Tricholoma matsutake Sing.).

PubMed

Cho, In Hee; Kim, Se Young; Choi, Hyung-Kyoon; Kim, Young-Suk

2006-08-23

The characteristic aroma-active compounds in raw and cooked pine-mushrooms (Tricholoma matsutake Sing.) were investigated by gas chromatography-olfactometry using aroma extract dilution analysis. 1-Octen-3-one (mushroom-like) was the major aroma-active compound in raw pine-mushrooms; this compound had the highest flavor dilution factor, followed by ethyl 2-methylbutyrate (floral and sweet), linalool (citrus-like), methional (boiled potato-like), 3-octanol (mushroom-like and buttery), 1-octen-3-ol (mushroom-like), (E)-2-octen-1-ol (mushroom-like), and 3-octanone (mushroom-like and buttery). By contrast, methional, 2-acetylthiazole (roasted), an unknown compound (chocolate-like), 3-hydroxy-2-butanone (buttery), and phenylacetaldehyde (floral and sweet), which could be formed by diverse thermal reactions during the cooking process, together with C8 compounds, were identified as the major aroma-active compounds in cooked pine-mushrooms.

Two Isoforms of Dihydroxyacetone Phosphate Reductase from the Chloroplasts of Dunaliella tertiolecta.

PubMed

Gee, R.; Goyal, A.; Byerrum, R. U.; Tolbert, N. E.

1993-09-01

Three isoforms of dihydroxyacetone phosphate reductase in extracts from Dunaliella tertiolecta have been separated by a diethylaminoethyl cellulose column chromatography with a shallow NaCl gradient. The chloroplasts contained the two major isoforms, and the third, minor form was in the cytosol. The isoforms are unstable in the absence of glycerol and they are cold labile, but they may be partially reactivated at 35[deg]C. The first chloroplast form to elute from the DEAE cellulose column was the major form when the cells were grown on high NaCl and it has been referred to as the form for glycerol production for osmoregulation or "osmoregulator form." The second form increased in specific activity when inorganic phosphate was increased in the growth media to stimulate growth, and it has been given the designation for the form for glyceride synthesis, "glyceride form." The osmoregulator form was stimulated by NaCl added to the enzyme assay, but not by reduced Escherichia coli thioredoxin. The glyceride form had properties similar to the enzyme in leaf chloroplast, such as inhibition by NaCl and by fatty acyl-coenzyme A derivatives and some stimulation by dithiothreitol, uridine diphosphate galactose, cyti-dine diphosphate dipalmatoyl diglyceride, and reduced E. coli thioredoxin. Thus, Dunaliella chloroplasts have a salt-stimulated osmoregulatory form of dihydroxyacetone phosphate reductase, which seems to have a role in glycerol production, and an isoform, which may be involved in glyceride synthesis and which has properties similar to the enzyme in chloroplasts of higher plants.

Two Isoforms of Dihydroxyacetone Phosphate Reductase from the Chloroplasts of Dunaliella tertiolecta.

PubMed Central

Gee, R.; Goyal, A.; Byerrum, R. U.; Tolbert, N. E.

1993-01-01

Three isoforms of dihydroxyacetone phosphate reductase in extracts from Dunaliella tertiolecta have been separated by a diethylaminoethyl cellulose column chromatography with a shallow NaCl gradient. The chloroplasts contained the two major isoforms, and the third, minor form was in the cytosol. The isoforms are unstable in the absence of glycerol and they are cold labile, but they may be partially reactivated at 35[deg]C. The first chloroplast form to elute from the DEAE cellulose column was the major form when the cells were grown on high NaCl and it has been referred to as the form for glycerol production for osmoregulation or "osmoregulator form." The second form increased in specific activity when inorganic phosphate was increased in the growth media to stimulate growth, and it has been given the designation for the form for glyceride synthesis, "glyceride form." The osmoregulator form was stimulated by NaCl added to the enzyme assay, but not by reduced Escherichia coli thioredoxin. The glyceride form had properties similar to the enzyme in leaf chloroplast, such as inhibition by NaCl and by fatty acyl-coenzyme A derivatives and some stimulation by dithiothreitol, uridine diphosphate galactose, cyti-dine diphosphate dipalmatoyl diglyceride, and reduced E. coli thioredoxin. Thus, Dunaliella chloroplasts have a salt-stimulated osmoregulatory form of dihydroxyacetone phosphate reductase, which seems to have a role in glycerol production, and an isoform, which may be involved in glyceride synthesis and which has properties similar to the enzyme in chloroplasts of higher plants. PMID:12231930

Coal and Energy.

ERIC Educational Resources Information Center

Bryant, Reba; And Others

This teaching unit explores coal as an energy resource. Goals, student objectives, background information, and activity options are presented for each major section. The sections are: (1) an introduction to coal (which describes how and where coal was formed and explains the types of coal); (2) the mining of coal (including the methods and ways of…

Electricity. Electrical Appliance Serviceman (Major Resistive Type).

ERIC Educational Resources Information Center

Moughan, John P.; And Others

Two types of materials comprise the curriculum guide: descriptive information about student, job and individualized instruction techniques for use by the instructor and a set of 10 learning activity packages for the student. Together, these form a work unit which, when successfully completed by the student, provides the necessary skills for an…

Biocidal Energetic Materials for the Destruction of Spore Forming Bacteria

DTIC Science & Technology

2015-07-01

Bacteria Spore Gas Antibacterial Thermal Unclassified Unclassified Unclassified SAR 47 Suhithi Peiris...naturally antibacterial and biocidal properties using combustion synthesis of mildly energetic reactants; and, (2) engineering an aerosolized spray...of biocidal gases using unique a deflagration synthesis approach. Accomplishments for all years: Major Activity 1: Creating highly porous

LMOOCs, Classifying Design: Survey Findings from LMOOC Providers

ERIC Educational Resources Information Center

Beirne, Elaine; Mhichíl, Mairéad Nic Giolla; Cleircín, Gearóid Ó

2017-01-01

Many of the major Massive Open Online Course (MOOC) platforms support learning approaches which can be roughly categorised as transmission-based and asynchronous (Morris & Lambe, 2014), with limited forms of interactive elements. Language learning is viewed within this study as an active process which includes knowledge, skills, and cultural…

Home Education in Russia

ERIC Educational Resources Information Center

Staroverova, T. I.

2011-01-01

From the eighteenth through the early twentieth centuries, home education (home schooling) by tutors and governesses in Russia was a customary form of schooling for an overwhelming majority of members of the nobility. Social and political transformations of the twentieth century led to substantial changes as the state got actively involved with…

Suppression or activation of immune responses by predicted secreted proteins of the soybean rust pathogen Phakopsora pachyrhizi

USDA-ARS?s Scientific Manuscript database

Rust fungi, such as Phakopsora pachyrhizi, are major threats to crop production. They form specialized haustoria that are intimately associated with plant cells. These haustoria have roles in acquiring nutrients and secreting effector proteins that manipulate host immune systems. Functional characte...

Characterization of Mercury Emissions from ASGM Goldshop Activities in Peru

EPA Science Inventory

Mercury (Hg), used in artisanal small-scale gold mining (ASGM) practices, is recognized as a significant source of Hg release to the environment and is a major area of focus of the United Nations Environment Programme (UNEP) Global Mercury Partnership. Hg is used to bind (form a...

COLBALT-MEDIATED ACTIVATION OF PEROXYMONOSULFATE AND SULFATE RADICAL ATTACK ON PHENOLIC COMPOUNDS, IMPLICATIONS OF CHLORIDE IONS

EPA Science Inventory

This study reports on the sulfate radical pathway of room temperature degradation of two phenolic compounds in water. The radicals were produced by the cobalt-mediated decomposition of peroxymonosulfate (Oxone) in an aqueous homogeneous system. The major intermediates formed from...

SMART Teaching in New and Old Classrooms

ERIC Educational Resources Information Center

Saunders, Gunter; Oradini, Federica; Clements, Mark

2017-01-01

The University of Westminster is undertaking a major classroom refurbishment program that is linked to a new approach to staff development in mobile learning. Feedback obtained from academic staff and students previously highlighted how classrooms should be changed so as to promote more active forms of curriculum delivery. Both technology and…

Community input requested

NASA Astrophysics Data System (ADS)

Fine, Rana A.; Walker, Dan

In June 1996, the National Research Council (NRC) formed the Committee on Major U.S. Oceanographic Research Programs to foster coordination among the large programs (e.g., World Ocean Circulation Experiment, Ocean Drilling Program, Ridge Interdisciplinary Global Experiment, and others) and examine their role in ocean research. In particular, the committee is charged with (1) enhancing information sharing and the coordinated implementation of the research plans of the major ongoing and future programs; (2) assisting the federal agencies and ocean sciences community in identifying gaps, as well as appropriate followon activities to existing programs; (3) making recommendations on how future major ocean programs should be planned, structured and organized; and (4) evaluating the impact of major ocean programs on the understanding of the oceans, development of research facilities, education, and collegiality in the academic community. The activity was initiated at the request of the National Science Foundation (NSF) Division of Ocean Sciences, is overseen by the NRC's Ocean Studies Board (OSB), and is funded by both NSF and the Office of Naval Research.

In vitro anti-leishmanial activity of methanolic extracts of Calendula officinalis flowers, Datura stramonium seeds, and Salvia officinalis leaves.

PubMed

Nikmehr, Banafsheh; Ghaznavi, Habib; Rahbar, Amir; Sadr, Samira; Mehrzadi, Saeed

2014-06-01

The anti-leishmanial activity of methanolic extracts of Calendula officinalis flowers, Datura stramonium seeds, and Salvia officinalis leaves against extracellular (promastigote) and intracellular (amastigote) forms of Leishmania major were evaluated in this study. In the first stage, promastigote forms of L. major, were treated with different doses of the plant extracts in a 96-well tissue-culture microplate and IC50 values for each extract were measured with colorimetric MTT assay. In the second stage, macrophage cells were infected with L. major promastigotes. Infected macrophages were treated with plant extracts. Then the macrophages were stained with Gimsa and the number of infected macrophages and amastigotes were counted with a light microscope. The results indicated that the plant extracts inhibited the growth of promastigotes and amastigotes of L. major. Inhibitory concentrations (IC50) for promastigote assay were 108.19, 155.15, and 184.32 μgmL(-1) for C. officinalis flowers, D. stramonium seeds and S. officinalis, respectively. The extracts also reduced the number of amastigotes in macrophage cells from 264 for control group to 88, 97, and 102 for test groups. Although the anti-leishmanial activity of the extracts were not comparable with the standard drug, miltefosine; but they showed significant efficiency in reducing the number of amastigotes in macrophages, in comparison with the control group (P < 0.001). These plant extracts had lower toxicity compared with miltefosine. This study demonstrates the potential efficacy of the methanolic extracts of C. officinalis flowers, D. stramonium seeds, and S. officinalis leaves to control of cutaneous leishmaniasis. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Potential applications of silk sericin, a natural protein from textile industry by-products.

PubMed

Aramwit, Pornanong; Siritientong, Tippawan; Srichana, Teerapol

2012-03-01

Silk is composed of two major proteins, fibroin (fibrous protein) and sericin (globular, gumming protein). Fibroin has been used in textile manufacturing and for several biomaterial applications, whereas sericin is considered a waste material in the textile industry. Sericin has recently been found to activate the proliferation of several cell-lines and has also shown various biological activities. Sericin can form a gel by itself; however, after mixing with other polymers and cross-linking it can form a film or a scaffold with good characteristics that can be used in the cosmetic and pharmaceutical industries. Sericin is proven to cause no immunological responses, which has resulted in a more acceptable material for biological applications.

Neuroimmune Interactions, Low-Dose Sarin Inhalation, and Gulf War Syndrome

DTIC Science & Technology

2012-10-01

antibody-forming cell qPCR real-time PCR CORT corticosterone Introduction Cigarette smoking is a major health risk factor and contributes to over...and PTK activities in splenic T cells One of the earliest effects of TCR ligation is the activation of PTK, including Src-like kinases Fyn and Lck...development of Clara and goblet cells without causing significant lung inflammation, and the SS-induced effects on alveolar architecture are

Investigations of Martian history

NASA Technical Reports Server (NTRS)

Hartmann, W. K.

1976-01-01

Geologic and stratigraphic analyses of Martian channels were accomplished using Mariner frames of high resolution. Crater counts were made to determine which forms had the least relative age. Results indicate that major channel and chaotic systems were relatively young, and that Mars experienced periods of enhanced erosive activity during a period of early dense atmospheric activity with rain. The problem of absolute age determination is discussed and geomorphological studies of selected Local Martian Regions are presented.

2-Nitrosoamino-3-methylimidazo[4,5-f]quinoline activated by the inflammatory response forms nucleotide adducts.

PubMed

Lakshmi, Vijaya M; Schut, Herman A J; Zenser, Terry V

2005-11-01

Heterocyclic amines and inflammation have been implicated in the etiology of colon cancer. We have recently demonstrated that during autoxidation of the inflammatory mediator nitric oxide 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) undergoes nitrosation to form 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO-IQ). This study evaluates the genotoxicity of N-NO-IQ and compares the adducts it forms to those of 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-OH-IQ). N-NO-IQ was incubated with 2'-deoxyguanosine 3'-monophosphate (dGp) under a variety of inflammatory conditions. 32P-Postlabeling demonstrated the presence of multiple adducts. Incubation of N-OH-IQ with dGp at pH 7.4, 5.5, or 2.0 resulted in the formation of a single major adduct, N-(deoxyguanosin-8-yl)-IQ (dG-C8-IQ). Using a combination of 32P-postlabeling, HPLC, and nuclease P1 treatment, N-NO-IQ was shown to produce dG-C8-IQ under several different conditions. HOCl oxidation of N-NO-IQ increased dG-C8-IQ formation, and this was further increased as pH decreased from 7.4 to 5.5. Oxidation of N-NO-IQ formed a new adduct, adduct 2, while in the absence of oxidants adduct m was the major adduct. Adducts 2 and m were not formed by N-OH-IQ and not further identified. The results demonstrate that N-NO-IQ forms N-(deoxyguanosin-8-yl)-IQ, is genotoxic, is activated by conditions that mediate inflammatory responses, and is a possible cancer risk factor for individuals with colitis, inflammation of the colon.

Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome.

PubMed

Al Khatib, Shadi; Keles, Sevgi; Garcia-Lloret, Maria; Karakoc-Aydiner, Elif; Reisli, Ismail; Artac, Hasibe; Camcioglu, Yildiz; Cokugras, Haluk; Somer, Ayper; Kutukculer, Necil; Yilmaz, Mustafa; Ikinciogullari, Aydan; Yegin, Olcay; Yüksek, Mutlu; Genel, Ferah; Kucukosmanoglu, Ercan; Baki, Ali; Bahceciler, Nerin N; Rambhatla, Anupama; Nickerson, Derek W; McGhee, Sean; Barlan, Isil B; Chatila, Talal

2009-08-01

The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired T(H)17 differentiation. To elucidate mechanisms underlying different forms of HIES. A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, respectively. Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired T(H)17 responses, but whereas STAT3 mutations abrogated early steps in T(H)17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired T(H)17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome.

Cosmic web and star formation activity in galaxies at z ∼ 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darvish, B.; Mobasher, B.; Sales, L. V.

We investigate the role of the delineated cosmic web/filaments on star formation activity by exploring a sample of 425 narrow-band selected Hα emitters, as well as 2846 color-color selected underlying star-forming galaxies for a large-scale structure at z = 0.84 in the COSMOS field from the HiZELS survey. Using the scale-independent Multi-scale Morphology Filter algorithm, we are able to quantitatively describe the density field and disentangle it into its major components: fields, filaments, and clusters. We show that the observed median star formation rate (SFR), stellar mass, specific SFR, the mean SFR-mass relation, and its scatter for both Hα emittersmore » and underlying star-forming galaxies do not strongly depend on different classes of environment, in agreement with previous studies. However, the fraction of Hα emitters varies with environment and is enhanced in filamentary structures at z ∼ 1. We propose mild galaxy-galaxy interactions as the possible physical agent for the elevation of the fraction of Hα star-forming galaxies in filaments. Our results show that filaments are the likely physical environments that are often classed as the 'intermediate' densities and that the cosmic web likely plays a major role in galaxy formation and evolution which has so far been poorly investigated.« less

Identification of Ser-543 as the major regulatory phosphorylation site in spinach leaf nitrate reductase

NASA Technical Reports Server (NTRS)

Bachmann, M.; Shiraishi, N.; Campbell, W. H.; Yoo, B. C.; Harmon, A. C.; Huber, S. C.; Davies, E. (Principal Investigator)

1996-01-01

Spinach leaf NADH:nitrate reductase (NR) responds to light/dark signals and photosynthetic activity in part as a result of rapid regulation by reversible protein phosphorylation. We have identified the major regulatory phosphorylation site as Ser-543, which is located in the hinge 1 region connecting the cytochrome b domain with the molybdenum-pterin cofactor binding domain of NR, using recombinant NR fragments containing or lacking the phosphorylation site sequence. Studies with NR partial reactions indicated that the block in electron flow caused by phosphorylation also could be localized to the hinge 1 region. A synthetic peptide (NR6) based on the phosphorylation site sequence was phosphorylated readily by NR kinase (NRk) in vitro. NR6 kinase activity tracked the ATP-dependent inactivation of NR during several chromatographic steps and completely inhibited inactivation/phosphorylation of native NR in vitro. Two forms of NRk were resolved by using anion exchange chromatography. Studies with synthetic peptide analogs indicated that both forms of NRk had similar specificity determinants, requiring a basic residue at P-3 (i.e., three amino acids N-terminal to the phosphorylated serine) and a hydrophobic residue at P-5. Both forms are strictly calcium dependent but belong to distinct families of protein kinases because they are distinct immunochemically.

Comprehensive review on additives of topical dosage forms for drug delivery.

PubMed

Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-12-01

Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

A model of EcoRII restriction endonuclease action: the active complex is most likely formed by one protein subunit and one DNA recognition site

NASA Technical Reports Server (NTRS)

Karpova, E. A.; Kubareva, E. A.; Shabarova, Z. A.

1999-01-01

To elucidate the mechanism of interaction of restriction endonuclease EcoRII with DNA, we studied by native gel electrophoresis the binding of this endonuclease to a set of synthetic DNA-duplexes containing the modified or canonical recognition sequence 5'-d(CCA/TGG)-3'. All binding substrate or substrate analogues tested could be divided into two major groups: (i) duplexes that, at the interaction with endonuclease EcoRII, form two types of stable complexes on native gel in the absence of Mg2+ cofactor; (ii) duplexes that form only one type of complex, observed both in the presence and absence of Mg2+. Unlike the latter, duplexes under the first group can be hydrolyzed by endonuclease. Data obtained suggest that the active complex is most likely formed by one protein subunit and one DNA recognition sequence. A model of EcoRII endonuclease action is presented.

History of Persecution and Health Outcomes Among U.S. Refugees.

PubMed

Yun, Katherine; Mohamad, Zeinab; Kiss, Ligia; Annamalai, Aniyizhai; Zimmerman, Cathy

2016-02-01

Our goal was to describe the forms of persecution reported by adult refugees in the U.S. and the relationships between persecution and health status among this population. Data were derived from the 2003 New Immigrant Survey, a representative sample of new U.S. lawful permanent residents. Major depression, impairment in daily activities due to pain, poor self-reported health, and declining health were described for refugees who had and had not reported persecution prior to arrival in the U.S. Health status was also examined for refugees who reported different forms of persecution. Half of refugees (46.7 %) in this sample reported that they or an immediate family member had been persecuted. One in three persecuted refugees (31.8 %) reported both incarceration and physical punishment. Major depression, pain-related impairment, poor health, and declining health were twice as common among persecuted refugees than among non persecuted refugees. Notably, despite these adverse experiences, the majority of persecuted refugees did not report poor health outcomes.

Volcanic geology of Furnas Volcano, São Miguel, Azores

NASA Astrophysics Data System (ADS)

Guest, J. E.; Gaspar, J. L.; Cole, P. D.; Queiroz, G.; Duncan, A. M.; Wallenstein, N.; Ferreira, T.; Pacheco, J.-M.

1999-09-01

Furnas is the easternmost of the three active central volcanoes on the island of São Miguel in the Azores. Unlike the other two central volcanoes, Sete Cidades and Fogo, Furnas does not have a well-developed edifice, but consists of a steep-sided caldera complex 8×5 km across. It is built on the outer flanks of the Povoação/Nordeste lava complex that forms the eastern end of São Miguel. Constructive flanks to the volcano exist on the southern side where they form the coastal cliffs, and to the west. The caldera margins tend to reflect the regional/local tectonic pattern which has also controlled the distribution of vents within the caldera and areas of thermal springs. Activity at Furnas has been essentially explosive, erupting materials of trachytic composition. Products associated with the volcano include plinian and sub-plinian pumice deposits, ignimbrites and surge deposits, phreatomagmatic ashes, block and ash deposits and dome materials. Most of the activity has occurred from vents within the caldera, or on the caldera margin, although strombolian eruptions with aa flows of ankaramite and hawaiite have occurred outside the caldera. The eruptive history consists of at least two major caldera collapses, followed by caldera infilling. Based on 14C dates, it appears that the youngest major collapse occurred about 12,000-10,000 years BP. New 14C dates for a densely welded ignimbrite suggest that a potential caldera-forming eruption occurred at about 30,000 years BP. Recent eruptions (<5000 years old) were mainly characterised by alternating episodes of magmatic and phreatomagmatic activity of plinian and sub-plinian magnitude, forming deposits of interbedded ash and lapilli. An historical eruption is documented in 1630 AD; new evidence suggests that another occurred during the early occupation of the area at about 1440 AD.

Ion-exchange chromatography separates activities synthesizing and degrading fructose 2,6-bisphosphate from C3 and C4 leaves but not from rat liver

NASA Technical Reports Server (NTRS)

Macdonald, F. D.; Chou, Q.; Buchanan, B. B.

1987-01-01

Fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase were separated on the basis of charge from leaves of C3 (spinach, lettuce, and pea) and C4 (sorghum and amaranthus) plants but not from rat liver--a tissue known to contain a bifunctional enzyme with both activities. [2-32P]Fructose 2,6-bisphosphate binding experiments also suggest that the major forms of these activities reside on different proteins in leaves.

Carcinogenicity and mutagenicity of chromium.

PubMed

Léonard, A; Lauwerys, R R

1980-11-01

Occupational exposure represents the main source of human contamination by chromium. For non-occupationally exposed people the major environmental exposure to chromium occurs as a consequence of its presence in food. Chromium must be considered as an essential element. Its deficiency impairs glucose metabolism. Trivalent chromium salts are poorly absorbed through the gastro-intestinal and respiratory tracts because they do not cross membranes easily. Hexavalent chromium can be absorbed by the oral and pulmonary routes and probably also through the skin. After its absorption, hexavalent chromium is rapidly reduced to the trivalent form which is probably the only form to be found in biological material. Epidemiological studies have shown that some chromium salts (mainly the slightly soluble hexavalent salts) are carcinogens. Lung cancers have, indeed, often been reported among workers in chromate-producing industry and, to a lesser extent, in workers from the chrome-pigment industry. The first attempts to produce cancers in experimental animals by inhalation or parenteral introduction gave negative or equivocal results but, from 1960, positive results have been obtained with various chromium compounds. As for the carcinogenic activity, the mutagenicity of chromium has mainly been found with hexavalent salts. In the majority of assay systems used, trivalent chromium appears inactive. It can be considered as evident, however, that the ultimate mutagen which binds to the genetic material is the trivalent form produced intracellularly from hexavalent chromium, the apparent lack of activity of the trivalent form being due to its poor cellular uptake.

Profiling primaquine metabolites in primary human hepatocytes by UPLC-QTOF-MS with 13c stable isotope labeling

USDA-ARS?s Scientific Manuscript database

Primaquine (PQ) is an important antimalarial agent because of its activity against exoerythrocytic forms of Plasmodium spp. However, hemolytic anemia is a dose-limiting side effect of primaquine therapy that limits its widespread use. The major plasma metabolite identified in humans and animals, car...

76 FR 13403 - Agency Information Collection Activities: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-11

... insurance programs. We have revised the following question: ``Indicate (Not Required) if owned by a woman or an ethnic minority, describe'' To this question: ``Is the majority ownership of your business represented by: women or minority?'' This form can be reviewed at http://www.exim.gov/pub/pending/EIB 92--79...

Over Land and Sea: Intermediate Science through Children's Literature.

ERIC Educational Resources Information Center

Butzow, Carol M.; Butzow, John W.

This book suggests an approach to science instruction that integrates literature as an alternative form of instruction or to enrich textbook instruction. It uses conceptually and factually correct works of fiction and outlines activities where students are allowed to do the majority of the work and the teachers act as facilitators. Though the…

National boating trends

Treesearch

Albert J. Marmo

1980-01-01

This paper examines the characteristics of recreational boats and boaters in the United States and the nature and extent of boating activities. The primary sources of the information presented are the United States Coast Guard's Nationwide Boating Surveys conducted in 1973 and 1976. The evidence indicates that boating is a major form of outdoor recreation with a...

Using Telestrations™ to Illustrate Small Group Communication Principles

ERIC Educational Resources Information Center

Fedesco, Heather Noel

2014-01-01

This single class activity described here: (1) illustrates the importance of interdependence in groups; (2) can be used to measure group productivity and performance; (3) can encourage groups to engage in group learning; and (4) can facilitate group cohesion for newly formed groups. Students will be working in groups for the majority of their…

Motivations for Gang Membership in Lagos, Nigeria: Challenge and Resilience

ERIC Educational Resources Information Center

Salaam, Abeeb Olufemi

2011-01-01

The current study explores the major challenges (in the form of risk factors) that may influence unemployed youths' involvement in gang and criminal activity in Lagos, Nigeria. A combination of techniques (e.g., oral, in-depth interviews, and questionnaires) were used for the data collection. The computed outcomes establish some of the major…

The Activity of Meaning Making: A Holistic Perspective on College Student Development

ERIC Educational Resources Information Center

Baxter Magolda, Marcia B.

2009-01-01

In this article, the author briefly traces the academic traditions that have formed the major body of student development literature, highlighting the evolution of separate rather than integrated constructs. She then summarizes Robert Kegan's conception of a metapsychology that integrates many of these separate lines of research. Next, she offers…

Landscapes of Literacy: An Ethnographic Study of Functional Literacy in Marginal Philippine Communities.

ERIC Educational Resources Information Center

Canieso-Doronila, Maria Luisa

Thirteen marginal Philippine communities were examined in an ethnographic study of the meaning of functional literacy and whether literacy invariably promotes development. The 13 sites were purposely selected to provide a broad sampling from three standpoints: (1) major livelihood and form of economic activity (farming, fishing, urban poor,…

Brain Activity Associated with Logical Inferences in Geometry: Focusing on Students with Different Levels of Ability

ERIC Educational Resources Information Center

Waisman, Ilana; Leikin, Mark; Leikin, Roza

2016-01-01

Mathematical processing associated with solving short geometry problems requiring logical inference was examined among students who differ in their levels of general giftedness (G) and excellence in mathematics (EM) using ERP research methodology. Sixty-seven male adolescents formed four major research groups designed according to various…

Antileishmanial activity of the hydroalcoholic extract of Miconia langsdorffii, isolated compounds, and semi-synthetic derivatives.

PubMed

Peixoto, Juliana A; Andrade E Silva, Márcio Luis; Crotti, Antônio E M; Cassio Sola Veneziani, Rodrigo; Gimenez, Valéria M M; Januário, Ana H; Groppo, Milton; Magalhães, Lizandra G; Dos Santos, Fransérgio F; Albuquerque, Sérgio; da Silva Filho, Ademar A; Cunha, Wilson R

2011-02-22

The in vitro activity of the crude hydroalcoholic extract of the aerial parts of Miconia langsdorffii Cogn. was evaluated against the promastigote forms of L. amazonensis, the causative agent of cutaneous leishmaniasis in humans. The bioassay-guided fractionation of this extract led to identification of the triterpenes ursolic acid and oleanolic acid as the major compounds in the fraction that displayed the highest activity. Several ursolic acid semi-synthetic derivatives were prepared, to find out whether more active compounds could be obtained. Among these ursolic acid-derived substances, the C-28 methyl ester derivative exhibited the best antileishmanial activity.

Isolation of a latent polyphenol oxidase from loquat fruit (Eriobotrya japonica Lindl.): kinetic characterization and comparison with the active form.

PubMed

Sellés-Marchart, Susana; Casado-Vela, Juan; Bru-Martínez, Roque

2006-02-15

Polyphenol oxidase (PPO) has been extracted from both soluble and particulate fractions of loquat fruit (Eriobotrya japonica Lindl. cv. Algerie). The soluble PPO (20% of total activity) was partially purified 3.3-fold after ammonium sulfate fractionation being in its active state. The particulate PPO fraction (80% of total activity) was purified to homogeneity in a latent form being activable by sodium dodecyl sulfate (SDS). The enzyme was purified 40.0-fold with a total yield of 15.3% after extraction by phase partitioning in Triton X-114 followed by three chromatographic steps. The molecular weight was estimated to be about 59.2 and 61.2 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration chromatography, respectively, indicating that latent PPO is a monomer. Latent PPO catalyzed the oxidation of chlorogenic acid (CA) at a rate 50-fold faster than that of 4-tert-butylcatechol (TBC) but the soluble active counterpart only twice. Both PPOs exhibited similar Km values for TBC but Km for CA was 5-fold higher for the latent than for the active soluble PPO. Other kinetic characteristics, including sensitivity to inhibitors, substrate specificity, thermal stability, temperature, and pH profiles, were quite different between both PPOs. These results provide strong evidences that the soluble active and the particulate latent are different forms of PPO in loquat fruit flesh. The results suggest that the major PPO form for the oxidation of CA, leading to enzymatic browning under physiological conditions, is the latent one.

The acylation state of mycobacterial lipomannans modulates innate immunity response through toll-like receptor 2.

PubMed

Gilleron, Martine; Nigou, Jérôme; Nicolle, Delphine; Quesniaux, Valérie; Puzo, Germain

2006-01-01

Detection of Mycobacterium tuberculosis antigens by professional phagocytes via toll-like receptors (TLR) contributes to controlling chronic M. tuberculosis infection. Lipomannans (LM), which are major lipoglycans of the mycobacterial envelope, were recently described as agonists of TLR2 with potent activity on proinflammatory cytokine regulation. LM correspond to a heterogeneous population of acyl- and glyco-forms. We report here the purification and the complete structural characterization of four LM acyl-forms from Mycobacterium bovis BCG using MALDI MS and 2D (1)H-(31)P NMR analyses. All this biochemical work provided the tools to investigate the implication of LM acylation degree on its proinflammatory activity. The latter was ascribed to the triacylated LM form, essentially an agonist of TLR2, using TLR2/TLR1 heterodimers for signaling. Altogether, these findings shed more light on the molecular basis of LM recognition by TLR.

An Exploratory Study of a New Kink Activity: "Pup Play".

PubMed

Wignall, Liam; McCormack, Mark

2017-04-01

This study presents the narratives and experiences of 30 gay and bisexual men who participate in a behavior known as "pup play." Never empirically studied before, we use in-depth interviews and a modified form of grounded theory to describe the dynamics of pup play and develop a conceptual framework with which to understand it. We discuss the dynamics of pup play, demonstrating that it primarily consists of mimicking the behaviors and adopting the role of a dog. We show that the majority of participants use pup play for sexual satisfaction. It is also a form of relaxation, demonstrated primarily through the existence of a "headspace." We classify pup play as a kink, and find no evidence for the framing of it as a form of zoophilia. We call for further research on pup play as a sexual kink and leisure activity from both qualitative and quantitative perspectives.

Rediscovering the wound haematoma as a site of haemostasis during major arterial haemorrhage

PubMed Central

White, N.J.; Mehic, E.; Wang, X.; Chien, D.; Lim, E.; St. John, A.E.; Stern, S.A.; Mourad, P.D.; Rieger, M.; Fries, D.; Martinowitz, U.

2015-01-01

Background Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical haemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial haemostasis, or how these commonly-used treatments might influence haemostasis. Objectives (1) Use a swine model of femoral artery bleeding to understand the perivascular haemostatic response to contained arterial haemorrhage. (2) Directly confirm the association between hemodynamics and bleeding velocity. (3) Observe the feasibility of delivering an activated clotting factor directly to internal sites of bleeding using a simplified angiographic approach. Methods Ultrasound was used to measure bleeding velocity and in vivo clot formation by elastography in a swine model of contained femoral artery bleeding with fluid resuscitation. A swine model of internal pelvic and axillary artery haemorrhage was also used to demonstrate feasibility of local delivery of an activated clotting factor. Results In this model, clots formed slowly within the peri-wound hematoma , but eventually containing the bleeding. Central hemodynamics correlated positively with bleeding velocity. Infusion of recombinant human activated Factor VII into the injured artery nearby the site of major internal haemorrhage in the pelvis and axillae was feasible. Conclusions We rediscover that clot formation within the peri-wound haematoma is an integral component of haemostasis and a feasible target for treatment of major internal bleeding using activated clotting factors delivered using a simplified angiographic approach. PMID:26414624

Plasma protein hydroperoxides during aging in humans: correlation with paraoxonase 1 (PON1) arylesterase activity and plasma total thiols.

PubMed

Mehdi, Mohammad Murtaza; Rizvi, Syed Ibrahim

2013-02-01

Oxidative stress is thought to play a major role in the development of several age-dependent diseases. Proteins are major targets for oxidative attack. Protein hydroperoxides are formed by hydroxyl and singlet oxygen attack on protein, forming relatively stable hydroperoxides on histidine, tyrosine and tryptophan residues. This study investigated the levels of plasma protein hydroperoxides and antioxidant potential of plasma during aging in humans. We correlated the protein hydroperoxide formation with plasma antioxidant potential, paraoxonase 1 (PON1) arylesterase activity and plasma total thiols. The protein hydroperoxides and antioxidant potential were measured in plasma of human subjects aged between 20 and 81 years of both genders. Increase in plasma protein hydroperoxides and decrease in plasma antioxidant potential were observed as function of human age. This study provides strong correlation between plasma protein hydroperoxides formation and decrease in plasma antioxidant potential during aging. PON1 arylesterase activity and plasma total thiols levels were also found to show significant correlation with increasing levels of plasma protein hydroperoxides during aging. The plasma protein hydroperoxides provide a reliable marker of long-term redox balance and degree of oxidative stress during aging process. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

[The newborn infant of a mother with tuberculosis].

PubMed

Pedicino, R; Bressan, K; Bedetta, M

2010-06-01

TBC is a major infectious emergency in the world. OMS suggest that there are 8 millions of affected every year and 2 millions of deaths. Italy is considered a country with low prevalence, but the increase of the immigration from Africa Asia and Est Europa (country with high risk) imposes attention to the problem. The delivery is a critical moment to investigate people at risk of disease. The infection of the newborn can happen intrauterine or in the expulsive period, but is possible also at home, from somebody affected by an active pulmonary disease. Diagnosis in the newborn is not easy for the aspecificity of clinical signs and for the frequent initial negativeness of Mantoux test. Culture of placenta, gastric aspirate, tracheal secretions, urine would be requested, cerebrospinal fluid if necessary. Neonatal disease needs therapy with isoniazide, rifampicine, pirazinamide and, or ethambutol, or streptomycin. Profilaxis of a newborn from a woman affected by an active form of tuberculosis or living with people affected by an active pulmonary form consists in giving isoniazide until diagnostic tests are negative and in removing the sicks (only with pulmonary disease). New dangerous kinds of pharmacological multiresistent tuberculosis are appeared in the last years in the world and, with the coinfection HIV-TBC and the reorganization of the surveillance system, represents the major obligation for the next years.

Water Mass Classification on a Highly Variable Arctic Shelf Region: Origin of Laptev Sea Water Masses and Implications for the Nutrient Budget

NASA Astrophysics Data System (ADS)

Bauch, D.; Cherniavskaia, E.

2018-03-01

Large gradients and inter annual variations on the Laptev Sea shelf prevent the use of uniform property ranges for a classification of major water masses. The central Laptev Sea is dominated by predominantly marine waters, locally formed polynya waters and riverine summer surface waters. Marine waters enter the central Laptev Sea from the northwestern Laptev Sea shelf and originate from the Kara Sea or the Arctic Ocean halocline. Local polynya waters are formed in the Laptev Sea coastal polynyas. Riverine summer surface waters are formed from Lena river discharge and local melt. We use a principal component analysis (PCA) in order to assess the distribution and importance of water masses within the Laptev Sea. This mathematical method is applied to hydro-chemical summer data sets from the Laptev Sea from five years and allows to define water types based on objective and statistically significant criteria. We argue that the PCA-derived water types are consistent with the Laptev Sea hydrography and indeed represent the major water masses on the central Laptev Sea shelf. Budgets estimated for the thus defined major Laptev Sea water masses indicate that freshwater inflow from the western Laptev Sea is about half or in the same order of magnitude as freshwater stored in locally formed polynya waters. Imported water dominates the nutrient budget in the central Laptev Sea; and only in years with enhanced local polynya activity is the nutrient budget of the locally formed water in the same order as imported nutrients.

Multiple-generator errors are unavoidable under model misspecification.

PubMed

Jewett, D L; Zhang, Z

1995-08-01

Model misspecification poses a major problem for dipole source localization (DSL) because it causes insidious multiple-generator errors (MulGenErrs) to occur in the fitted dipole parameters. This paper describes how and why this occurs, based upon simple algebraic considerations. MulGenErrs must occur, to some degree, in any DSL analysis of real data because there is model misspecification and mathematically the equations used for the simultaneously active generators must be of a different form than the equations for each generator active alone.

Blocking Blood Supply to Breast Carcinoma With a DNA Vaccine Encoding VEGF Receptor-2

DTIC Science & Technology

2006-03-01

recognize antigens in the form of 8 to 10 amino acid long peptides, presented to T- cell receptors (TCRs) on the cell surface as complexes with major... receptor , and providing tumor- associated antigens , our DNA vaccine can efficiently activate DCs, NK cells , and CTLs, presumably in Peyer’s patches. The... immunoreceptor in immune cell activation and natural killing. Immunity. 2002;17:19-29. (5) Snyder MR, Weyand CM, Goronzy JJ. The double life of NK receptors

Nili Fossae

NASA Image and Video Library

2016-07-20

Nili Fossae is a large band of parallel graben located to the northeast of Syrtis Major. The graben in this image from NASA 2001 Mars Odyssey spacecraft were formed by tectonic activity, with faulting that creates the linear depression. Orbit Number: 64105 Latitude: 23.3115 Longitude: 78.6126 Instrument: VIS Captured: 2016-05-27 05:24 http://photojournal.jpl.nasa.gov/catalog/PIA20785

Dang An: A Brief History of the Chinese Imperial Archives and Its Administration

ERIC Educational Resources Information Center

Zhang, Wenxian

2004-01-01

Archives are preserved records of human activities. An account of Chinese archival development is as long as the written records of the Chinese history. Oracle bones, bronze ware, and wood and bamboo strips are the three most important recording forms of the early Chinese civilization, as they represented three major stages of archival development…

Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biswas, Arunima; Pasquel, Danielle; Tyagi, Rakesh Kumar

2011-03-18

Research highlights: {yields} Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. {yields} PXR undergoes dynamic deacetylation upon ligand-mediated activation. {yields} SIRT1 partially mediates PXR deacetylation. {yields} PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependentmore » functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.« less

In vitro screening of major neurotransmitter systems possibly involved in the mechanism of action of antibodies to S100 protein in released-active form

PubMed Central

Gorbunov, Evgeniy A; Ertuzun, Irina A; Kachaeva, Evgeniya V; Tarasov, Sergey A; Epstein, Oleg I

2015-01-01

Experimentally and clinically, it was shown that released-active form of antibodies to S100 protein (RAF of Abs to S100) exerts a wide range of pharmacological activities: anxiolytic, antiasthenic, antiaggressive, stress-protective, antihypoxic, antiischemic, neuroprotective, and nootropic. The purpose of this study was to determine the influence of RAF of Abs to S100 on major neurotransmitter systems (serotoninergic, GABAergic, dopaminergic, and on sigma receptors as well) which are possibly involved in its mechanism of pharmacological activity. Radioligand binding assays were used for assessment of the drug influence on ligand–receptor interaction. [35S]GTPγS binding assay, cyclic adenosine monophosphate HTRF™, cellular dielectric spectroscopy assays, and assays based on measurement of intracellular concentration of Ca2+ ions were used for assessment of agonist or antagonist properties of the drug toward receptors. RAF of Abs to S100 increased radioligand binding to 5-HT1F, 5-HT2B, 5-HT2Cedited, 5-HT3, and to D3 receptors by 142.0%, 131.9%, 149.3%, 120.7%, and 126.3%, respectively. Also, the drug significantly inhibited specific binding of radioligands to GABAB1A/B2 receptors by 25.8%, and to both native and recombinant human sigma1 receptors by 75.3% and 40.32%, respectively. In the functional assays, it was shown that the drug exerted antagonism at 5-HT1B, D3, and GABAB1A/B2 receptors inhibiting agonist-induced responses by 23.24%, 32.76%, and 30.2%, respectively. On the contrary, the drug exerted an agonist effect at 5-HT1A receptors enhancing receptor functional activity by 28.0%. The pharmacological profiling of RAF of Abs to S100 among 27 receptor provides evidence for drug-related modification of major neurotransmitter systems. PMID:26604768

Models for the action of barley alpha-amylase isozymes on linear substrates.

PubMed

MacGregor, E A; MacGregor, A W; Macri, L J; Morgan, J E

1994-05-05

The formation of maltodextrins, G1 to G12, during the hydrolysis of amylose by alpha-amylases 1 and 2 from barley malt was followed by HPLC. Similar, but not identical, distributions of products were obtained with the two alpha-amylase components. Maltose, G6, and G7 were major products, but G7 was degraded as hydrolysis proceeded. alpha-Amylase 1 produced more G1 and G3 than did alpha-amylase 2 at all stages of hydrolysis. Products formed during the hydrolysis of G9, G10, G11, and G12 by the two alpha-amylases were also determined. A different spectrum of products was observed with each substrate and small differences were observed in the action pattern of the two alpha-amylases, e.g., G3 and G7 were the major products formed during the hydrolysis of G10 by alpha-amylase 1, whereas G2 and G8 were the major products formed by alpha-amylase 2 on the same substrate. These results were used to develop a model of the active site of barley malt alpha-amylases. This site contains ten contiguous subsites with the catalytic site situated between subsites 7 and 8. The model can be used to predict hydrolysis patterns of amylose and maltodextrins by cereal alpha-amylases.

Peroxidases from root exudates of Medicago sativa and Sorghum bicolor: Catalytic properties and involvement in PAH degradation.

PubMed

Dubrovskaya, Ekaterina; Pozdnyakova, Natalia; Golubev, Sergey; Muratova, Anna; Grinev, Vyacheslav; Bondarenkova, Anastasiya; Turkovskaya, Olga

2017-02-01

Peroxidases from root exudates of sorghum (Sorghum bicolor L. Moench) and alfalfa (Medicago sativa L.) were purified and characterized, and their ability to oxidize native PAHs and PAH-derivatives was evaluated. The obtained data confirm that peroxidases are involved in the rhizosphere degradation of PAHs. Nondenaturing PAGE showed that the peroxidases of both plants were represented by a range of isoforms/isoenzymes (five to eight). Minor forms were lost during further purification, and as a result, the major anionic form from alfalfa root exudates and the major cationic form from those of sorghum were obtained. Both electrophoretically homogeneous peroxidases were monomeric proteins with a molecular weight of about 46-48 kDa. The pH optima and the main catalytic constants for the test substrates were determined. On the basis of their molecular and catalytic properties, the obtained enzymes were found to be typical plant peroxidases. Derivatives of PAHs and potential products of their microbial degradation (9-phenanthrol and 9,10-phenanthrenequinone), unlike the parent PAH (phenanthrene), inhibited the catalytic activity of the peroxidases, possibly indicating greater availability of the enzymes' active centers to these substances. Peroxidase-catalyzed decreases in the concentrations of a number of PAHs and their derivatives were observed. Sorghum peroxidase oxidized anthracene and phenanthrene, while alfalfa peroxidase oxidized only phenanthrene. 1-Hydroxy-2-naphthoic acid was best oxidized by peroxidase of alfalfa. However, quinone derivatives of PAHs were unavailable to sorghum peroxidase, but were oxidized by alfalfa peroxidase. These results indicate that the major peroxidases from root exudates of alfalfa and sorghum can have a role in the rhizosphere degradation of PAHs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Connecting the Bird's Head to the Bird's Body - Cenozoic arc magmatism extends along the length of New Guinea.

NASA Astrophysics Data System (ADS)

Webb, Max; White, Lloyd; Jost, Benjamin

2017-04-01

New Guinea has a long, complicated history of arc magmatism. The present day shape of the island (resembling that of a bird in flight) formed as a result of oblique convergence of the Pacific and Caroline/Philippine plates with the northward moving Australian plate. This convergence resulted in multiple collisions of island arcs with continental crust, representing a modern day analogue to ancient accretionary orogens. This complex geological history has formed four major tectonic belts; accreted Palaeogene island arcs, the New Guinea Mobile Belt, the New Guinea Fold Belt and a stable platform. These tectonic belts are drawn across most of New Guinea in major review papers. However, these tectonic belts are not generally considered to extend through to New Guinea's western most peninsula (the Bird's Head). We present new field evidence, together with new U-Pb zircon geochronology and geochemical analyses from rocks collected within the Bird's Head. These document Middle to Late Miocene intermediate to felsic volcanic rocks and associated granitoid intrusives that formed along an active continental margin. These are effectively the equivalent of the Maramuni arc and Freida River Complex in eastern New Guinea. Several, broadly Eocene island arcs composed of dominantly mafic volcanic rocks are also found in the Bird's Head. These island arcs accreted along the Bird's Head sometime after their initial formation, possibly coinciding with Middle to Late Miocene active continental margin magmatism and we consider them to be equivalents of the Cyclops Mountains arc in Central New Guinea. This work demonstrates that New Guinea's east-west terranes are more extensive than previously thought. This potentially has implications for locating future ore deposits and understanding the relative position of the Bird's Head with respect to the rest of New Guinea in major plate reconstructions.

Molecular dynamics simulations suggest changes in electrostatic interactions as a potential mechanism through which serine phosphorylation inhibits DNA Polymerase β's activity.

PubMed

Homouz, Dirar; Joyce-Tan, Kwee Hong; Shahir Shamsir, Mohd; Moustafa, Ibrahim M; Idriss, Haitham

2018-01-01

DNA polymerase β is a 39kDa enzyme that is a major component of Base Excision Repair in human cells. The enzyme comprises two major domains, a 31kDa domain responsible for the polymerase activity and an 8kDa domain, which bind ssDNA and has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase β was shown to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55 (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its ability to bind ssDNA. In this study, we investigate the potential phosphorylation-induced structural changes for DNA polymerase β using molecular dynamics. The simulations show drastic conformational changes of the polymerase structure as a result of S44 phosphorylation. Phosphorylation-induced conformational changes transform the closed (active) enzyme structure into an open one. Further analysis of the results points to a key hydrogen bond and newly formed salt bridges as potential drivers of these structural fluctuations. The changes observed with S44/55 and S55 phosphorylation were less dramatic than S44 and the integrity of the H-bond was not compromised. Thus the phosphorylation of S44 is likely the major contributor to structural fluctuations that lead to loss of enzymatic activity. Copyright © 2017. Published by Elsevier Inc.

The Spectrum of Epstein-Barr Virus-Associated Lymphoproliferative Disease in Korea: Incidence of Disease Entities by Age Groups

PubMed Central

Cho, Eun-Yoon; Kim, Ki-Hyun; Kim, Won-Seog; Yoo, Keon Hee; Koo, Hong-Hoe

2008-01-01

This study is to identify the spectrum of Epstein-Barr virus (EBV)-positive lymphoproliferative diseases (LPD) and relationships between these diseases in Korea. The EBV status and clinicopathology of 764 patients, including acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV (CAEBV) infections, B-LPD arising in chronic latent EBV infection, T & natural killer (NK) cell non-Hodgkin's lymphomas (NHL), B-NHLs, and Hodgkin's lymphomas (HD), were analyzed. T or NK cell NHLs were the most common forms of EBV-positive NHLs (107/167, 64%); among these, nasal-type NK/T cell lymphomas were the most common (89/107, 83%). According to the age, Burkitt's lymphoma was the most common in early childhood; in teenagers, chronic (active) EBV infection-associated LPD was the most common type. The incidence of NK/T cell lymphoma began to increase from the twenties and formed the major type of EBV-associated tumor throughout life. Diffuse large B cell lymphoma formed the major type in the sixties and seventies. In conclusion, primary infections in early childhood are complicated by the development of CAEBV infections that are main predisposing factors for EBV-associated T or NK cell malignancies in young adults. In old patients, decreased immunity associated with old age and environmental cofactors may provoke the development of peripheral T cell lymphoma, unspecified, and diffuse large B cell lymphoma. PMID:18436998

The spectrum of Epstein-Barr virus-associated lymphoproliferative disease in Korea: incidence of disease entities by age groups.

PubMed

Cho, Eun-Yoon; Kim, Ki-Hyun; Kim, Won-Seog; Yoo, Keon Hee; Koo, Hong-Hoe; Ko, Young-Hyeh

2008-04-01

This study is to identify the spectrum of Epstein-Barr virus (EBV)-positive lymphoproliferative diseases (LPD) and relationships between these diseases in Korea. The EBV status and clinicopathology of 764 patients, including acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV (CAEBV) infections, B-LPD arising in chronic latent EBV infection, T & natural killer (NK) cell non-Hodgkin's lymphomas (NHL), B-NHLs, and Hodgkin's lymphomas (HD), were analyzed. T or NK cell NHLs were the most common forms of EBV-positive NHLs (107/167, 64%); among these, nasal-type NK/T cell lymphomas were the most common (89/107, 83%). According to the age, Burkitt's lymphoma was the most common in early childhood; in teenagers, chronic (active) EBV infection-associated LPD was the most common type. The incidence of NK/T cell lymphoma began to increase from the twenties and formed the major type of EBV-associated tumor throughout life. Diffuse large B cell lymphoma formed the major type in the sixties and seventies. In conclusion, primary infections in early childhood are complicated by the development of CAEBV infections that are main predisposing factors for EBV-associated T or NK cell malignancies in young adults. In old patients, decreased immunity associated with old age and environmental cofactors may provoke the development of peripheral T cell lymphoma, unspecified, and diffuse large B cell lymphoma.

Hierarchical Modeling of Activation Mechanisms in the ABL and EGFR Kinase Domains: Thermodynamic and Mechanistic Catalysts of Kinase Activation by Cancer Mutations

PubMed Central

Dixit, Anshuman; Verkhivker, Gennady M.

2009-01-01

Structural and functional studies of the ABL and EGFR kinase domains have recently suggested a common mechanism of activation by cancer-causing mutations. However, dynamics and mechanistic aspects of kinase activation by cancer mutations that stimulate conformational transitions and thermodynamic stabilization of the constitutively active kinase form remain elusive. We present a large-scale computational investigation of activation mechanisms in the ABL and EGFR kinase domains by a panel of clinically important cancer mutants ABL-T315I, ABL-L387M, EGFR-T790M, and EGFR-L858R. We have also simulated the activating effect of the gatekeeper mutation on conformational dynamics and allosteric interactions in functional states of the ABL-SH2-SH3 regulatory complexes. A comprehensive analysis was conducted using a hierarchy of computational approaches that included homology modeling, molecular dynamics simulations, protein stability analysis, targeted molecular dynamics, and molecular docking. Collectively, the results of this study have revealed thermodynamic and mechanistic catalysts of kinase activation by major cancer-causing mutations in the ABL and EGFR kinase domains. By using multiple crystallographic states of ABL and EGFR, computer simulations have allowed one to map dynamics of conformational fluctuations and transitions in the normal (wild-type) and oncogenic kinase forms. A proposed multi-stage mechanistic model of activation involves a series of cooperative transitions between different conformational states, including assembly of the hydrophobic spine, the formation of the Src-like intermediate structure, and a cooperative breakage and formation of characteristic salt bridges, which signify transition to the active kinase form. We suggest that molecular mechanisms of activation by cancer mutations could mimic the activation process of the normal kinase, yet exploiting conserved structural catalysts to accelerate a conformational transition and the enhanced stabilization of the active kinase form. The results of this study reconcile current experimental data with insights from theoretical approaches, pointing to general mechanistic aspects of activating transitions in protein kinases. PMID:19714203

Biotransformation potential of 6:2 fluorotelomer sulfonate (6:2 FTSA) in aerobic and anaerobic sediment.

PubMed

Zhang, Shu; Lu, Xiaoxia; Wang, Ning; Buck, Robert C

2016-07-01

Aqueous film-forming foam (AFFF) products are used in industrial and military firefighting around the globe. These products contain fluoroalkylthioamido sulfonates, fluoroalkylthiobetaine, and other related substances as the major ingredients, which can be biotransformed in the environment to form 6:2 fluorotelomer sulfonate (6:2 FTSA, F(CF2)6CH2CH2SO3-) as one of the major initial biotransformation products. Limited information is available on 6:2 FTSA aerobic biotransformation in activated sludge and pure microbial culture. This is the first study to report 6:2 FTSA biotransformation in aerobic and anaerobic sediment. 6:2 FTSA was rapidly biotransformed in aerobic river sediment with a half-life less than 5 d. Major stable transformation products observed after 90 d included 5:3 Acid [F(CF2)5CH2CH2COOH), 16 mol%), PFPeA [F(CF2)4COOH, 21 mol%] and PFHxA (F(CF2)5COOH, 20 mol%). 6:2 fluorotelomer alcohol [6:2 FTOH, F(CF2)6CH2CH2OH] was readily biotransfomed whereas 6:2 FTSA biotransformation did not occur in anaerobic sediment over 100 d, indicating that the enzymatic desulfonation step limited 6:2 FTSA biotransformation in anaerobic sediment. These results suggest that 6:2 FTSA related products, after release to the aerobic environment, is likely to biodegrade forming 5:3 Acid, PFPeA and PFHxA. This study also indicates that 6:2 FTSA formed from its aforementioned precursors may be persistent in the anaerobic environment after their potential release. This work provides insight to understanding the fate and environmental loading of AFFF-related products and their major transformation products in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolic potential of lithifying cyanobacteria-dominated thrombolitic mats.

PubMed

Mobberley, Jennifer M; Khodadad, Christina L M; Foster, Jamie S

2013-11-01

Thrombolites are unlaminated carbonate deposits formed by the metabolic activities of microbial mats and can serve as potential models for understanding the molecular mechanisms underlying the formation of lithifying communities. To assess the metabolic complexity of these ecosystems, high throughput DNA sequencing of a thrombolitic mat metagenome was coupled with phenotypic microarray analysis. Functional protein analysis of the thrombolite community metagenome delineated several of the major metabolic pathways that influence carbonate mineralization including cyanobacterial photosynthesis, sulfate reduction, sulfide oxidation, and aerobic heterotrophy. Spatial profiling of metabolite utilization within the thrombolite-forming microbial mats suggested that the top 5 mm contained a more metabolically diverse and active community than the deeper within the mat. This study provides evidence that despite the lack of mineral layering within the clotted thrombolite structure there is a vertical gradient of metabolic activity within the thrombolitic mat community. This metagenomic profiling also serves as a foundation for examining the active role individual functional groups of microbes play in coordinating metabolisms that lead to mineralization.

Meanings teachers make of teaching science outdoors as they explore citizen science

NASA Astrophysics Data System (ADS)

Benavides, Aerin Benavides

This descriptive case study examined the meanings public elementary school teachers (N = 13) made of learning to enact citizen science projects in their schoolyards in partnership with a local Arboretum. Utilizing Engestrom's (2001) framework of cultural-historical activity theory (CHAT), the Arboretum's outreach program for area Title 1 schools was viewed as an activity system composed of and acting in partnership with the teachers. The major finding was that teachers designed and mastered new ways of teaching (expansive learning) and transformed their citizen science activity to facilitate student engagement and learning. I highlight four important themes in teachers' expansive learning: (a) discussion, (b) inclusion, (c) integration, and (d) collaboration. Teacher learning communities formed when colleagues shared responsibilities, formed mentor/mentee relationships, and included student teachers and interns in the activity. This program could serve as a model for elementary school citizen science education, as well as a model for professional development for teachers to learn to teach science and Environmental Education outdoors.

[The characteristics of medical technologies in emergency medical care hospital].

PubMed

Murakhovskiĭ, A G; Babenko, A I; Bravve, Iu I; Tataurova, E A

2013-01-01

The article analyzes the implementation of major 12 diagnostic and 17 treatment technologies applied during medical care of patients with 12 key nosology forms of diseases in departments of the emergency medical care hospital No 2 of Omsk. It is established that key groups of technologies in the implementation of diagnostic process are the laboratory clinical diagnostic analyses and common diagnostic activities at reception into hospital and corresponding departments. The percentage of this kind of activities is about 78.3% of all diagnostic technologies. During the realization of treatment process the priority technologies are common curative and rehabilitation activities, intensive therapy activities and clinical diagnostic monitoring activities. All of them consist 80.1% of all curative technologies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joseph, J.S.; Saikatendu, K.S.; Subramanian, V.

Mature nonstructural protein-15 (nsp15) from the severe acute respiratory syndrome coronavirus (SARS-CoV) contains a novel uridylate-specific Mn{sup 2+}-dependent endoribonuclease (NendoU). Structure studies of the full-length form of the obligate hexameric enzyme from two CoVs, SARS-CoV and murine hepatitis virus, and its monomeric homologue, XendoU from Xenopus laevis, combined with mutagenesis studies have implicated several residues in enzymatic activity and the N-terminal domain as the major determinant of hexamerization. However, the tight link between hexamerization and enzyme activity in NendoUs has remained an enigma. Here, we report the structure of a trimmed, monomeric form of SARS-CoV nsp15 (residues 28 to 335)more » determined to a resolution of 2.9 Angstroms. The catalytic loop (residues 234 to 249) with its two reactive histidines (His 234 and His 249) is dramatically flipped by {approx}120 degrees into the active site cleft. Furthermore, the catalytic nucleophile Lys 289 points in a diametrically opposite direction, a consequence of an outward displacement of the supporting loop (residues 276 to 295). In the full-length hexameric forms, these two loops are packed against each other and are stabilized by intimate intersubunit interactions. Our results support the hypothesis that absence of an adjacent monomer due to deletion of the hexamerization domain is the most likely cause for disruption of the active site, offering a structural basis for why only the hexameric form of this enzyme is active.« less

A Distal Disulfide Bridge in OXA-1 β-Lactamase Stabilizes the Catalytic Center and Alters the Dynamics of the Specificity Determining Ω Loop

DOE PAGES

Simakov, Nikolay; Leonard, David A.; Smith, Jeremy C.; ...

2016-09-26

Widespread antibiotic resistance, particularly when mediated by broad-spectrum β-lactamases, has major implications for public health. Substitutions in the active site often allow broad-spectrum enzymes to accommodate diverse types of β-lactams. Substitutions observed outside the active site are thought to compensate for the loss of thermal stability. The OXA-1 clade of class D β-lactamases contains a pair of conserved cysteines located outside the active site that forms a disulfide bond in the periplasm. In this paper, the effect of the distal disulfide bond on the structure and dynamics of OXA-1 was investigated via 4 μs molecular dynamics simulations. The results revealmore » that the disulfide promotes the preorganized orientation of the catalytic residues and affects the conformation of the functionally important Ω loop. Furthermore, principal component analysis reveals differences in the global dynamics between the oxidized and reduced forms, especially in the motions involving the Ω loop. A dynamical network analysis indicates that, in the oxidized form, in addition to its role in ligand binding, the KTG family motif is a central hub of the global dynamics. Finally, as activity of OXA-1 has been measured only in the reduced form, we suggest that accurate assessment of its functional profile would require oxidative conditions mimicking periplasm.« less

Geology and geochemistry of the Arctic prospect, Ambler District, Alaska

NASA Astrophysics Data System (ADS)

Schmidt, J. M.

The Arctic volcanogenic massive sulfide prospect is the largest known (40 million ton) deposit hosted by the low greenschist grade, latest Devonian Ambler Sequence of bimodal, basaltic and rhyolitic volcanic and volcanoclastic rocks, pelitic, graphitic and calcareous metasediments. Detailed field mapping, core logging, petrography, X-ray diffractometry, electron microprobe analyses and whole-rock major element analyses of hydrothermally altered rocks were used to determine the emplacement history and setting of sulfide deposition. Low greenschist grade metamorphism was essentially isochemical on a macroscopic scale, and preserved volcanic compositions, the major element chemistry of alteration and the compositions of individual metamorphic, alteration and relict igneous minerals. Mineralization at Arctic was formed along a synvolcanic fault in a tectonically and volcanically active basin within a rifted continental margin, possibly related to an actively spreading oceanic rift.

Conformations of 1,3,3,5,7,7-Hexamethyl-1,5-diazacyclooctane and Its Bis-BH(3) Adduct. Mono- and Bis-BH(3) Adducts of Di-Tertiary Amines.

PubMed

Livant, P.; Majors, A. W.; Webb, T. R.

1996-05-03

A variable-temperature (1)H- and (13)C-NMR study revealed a conformational equilibrium for 1,3,3,5,7,7-hexamethyl-1,5-diazacyclooctane (4) having DeltaG() = 8.8 +/- 0.6 kcal/mol at 184 K. This activation barrier connects a major and a minor form of 4. Molecular mechanics calculations on 4 led to the conclusion that the major form is a set of twist-chair-chairs interconverting rapidly via the chair-chair and that the minor form is most likely a set of twist-boat-boats interconverting rapidly via the boat-boat. The proximity of the two nitrogen lone pairs in the major form of 4 made plausible the expectation that 4, as well as a related diamine with apposed nitrogens, 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (3), might bind a Lewis acid, namely BH(3), using both lone pairs simultaneously and equally. This proved not to be the case: for 3 only the bis-BH(3) adduct was found and for 4 the mono-BH(3) adduct utilized only one nitrogen lone pair. The structure of the bis-BH(3) adduct of 4 (12) was determined by X-ray crystallography to be a twist-boat-boat with BH(3)s cis. Molecular mechanics calculations on 12 were consistent with the solid state conformation found.

Rediscovering the wound hematoma as a site of hemostasis during major arterial hemorrhage.

PubMed

White, N J; Mehic, E; Wang, X; Chien, D; Lim, E; St John, A E; Stern, S A; Mourad, P D; Rieger, M; Fries, D; Martinowitz, U

2015-12-01

Treatments for major internal bleeding after injury include permissive hypotension to decrease the rate of blood loss, intravenous infusion of plasma or clotting factors to improve clot formation, and rapid surgical hemostasis or arterial embolization to control bleeding vessels. Yet, little is known regarding major internal arterial hemostasis, or how these commonly used treatments might influence hemostasis. (i) To use a swine model of femoral artery bleeding to understand the perivascular hemostatic response to contained arterial hemorrhage. (ii) To directly confirm the association between hemodynamics and bleeding velocity. (iii) To observe the feasibility of delivering an activated clotting factor directly to internal sites of bleeding using a simplified angiographic approach. Ultrasound was used to measure bleeding velocity and in vivo clot formation by elastography in a swine model of contained femoral artery bleeding with fluid resuscitation. A swine model of internal pelvic and axillary artery hemorrhage was also used to demonstrate the feasibility of local delivery of an activated clotting factor. In this model, clots formed slowly within the peri-wound hematoma, but eventually contained the bleeding. Central hemodynamics correlated positively with bleeding velocity. Infusion of recombinant human activated factor VII into the injured artery near the site of major internal hemorrhage in the pelvis and axillae was feasible. We rediscovered that clot formation within the peri-wound hematoma is an integral component of hemostasis and a feasible target for the treatment of major internal bleeding using activated clotting factors delivered using a simplified angiographic approach. © 2015 International Society on Thrombosis and Haemostasis.

Bifurcation theory and cardiac arrhythmias

PubMed Central

Karagueuzian, Hrayr S; Stepanyan, Hayk; Mandel, William J

2013-01-01

In this paper we review two types of dynamic behaviors defined by the bifurcation theory that are found to be particularly useful in describing two forms of cardiac electrical instabilities that are of considerable importance in cardiac arrhythmogenesis. The first is action potential duration (APD) alternans with an underlying dynamics consistent with the period doubling bifurcation theory. This form of electrical instability could lead to spatially discordant APD alternans leading to wavebreak and reentrant form of tachyarrhythmias. Factors that modulate the APD alternans are discussed. The second form of bifurcation of importance to cardiac arrhythmogenesis is the Hopf-homoclinic bifurcation that adequately describes the dynamics of the onset of early afterdepolarization (EAD)-mediated triggered activity (Hopf) that may cause ventricular tachycardia and ventricular fibrillation (VT/VF respectively). The self-termination of the triggered activity is compatible with the homoclinic bifurcation. Ionic and intracellular calcium dynamics underlying these dynamics are discussed using available experimental and simulation data. The dynamic analysis provides novel insights into the mechanisms of VT/VF, a major cause of sudden cardiac death in the US. PMID:23459417

Heterologous Quaternary Structure of CXCL12 and its Relationship to the CC Chemokine Family

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murphy, J.; Yuan, H; Kong, Y

2010-01-01

X-ray crystallographic studies reveal that CXCL12 is able to form multiple dimer types, a traditional CXC dimer and a 'CC-like' form. Phylogenetic analysis of all known human chemokines demonstrates CXCL12 is more closely related to the CC chemokine class than other CXC chemokines. These observations indicate that CXCL12 contains genomic and structural elements characteristic of both CXC and CC chemokines.Chemokines are members of a superfamily of proteins involved in the migration of cells to the proper anatomical position during embryonic development or in response to infection or stress during an immune response. There are two major (CC and CXC) andmore » two minor (CX3C and XC) families based on the sequence around the first conserved cysteine. The topology of all structures is essentially identical with a flexible N-terminal region of 3-8 amino acids, a 10-20 residue N-terminal loop, a short 3{sub 10}-helix, three {beta}-strands, and a {alpha}-helix. The major consequence of the subtle difference between the families occurs at the oligomeric level. Monomers of the CC, CXC, and CX3C families form dimers in a family-specific manner. The XCL1 chemokine is a monomer that can interconvert between two folded states. All chemokines activate GPCRs according to family-specificity, however there are a few examples of chemokines crossing the family boundary to function as antagonists. A two-stage mechanism for chemokine activation of GPCRs has been proposed. The N-terminal region of the receptor interacts with the chemokine, followed by receptor activation by the chemokine N-terminal region. Monomeric chemokines have been demonstrated to be the active form for receptor function. There are numerous examples of both chemokines and their receptors forming dimers. While family-specific dimerization may be an attractive explanation for why specific chemokines only activate GPCRs within their own family, the role of dimers in the function of chemokines has not been resolved. Given that CXCL12 is in the CXC family, the CXC dimer is considered the physiologic dimer in all previous studies based on crystallographic evidence. NMR and mutational studies agree with the CXC dimer form in solution. The CXC form of the dimer is seen in recent structures of CXCL12 bound to a heparin disaccharide and several CXCR4 peptides. In one case, crystals of the CXC-type dimer were soaked in a heparin disaccharide solution to determine the interactions between this dimer and bound disaccharide. In another case, in order to overcome NMR chemical shift line broadening when CXCR4 peptides are added, a 'locked' dimer was constructed by introducing a cysteine mutant that linked subunits as a CXC dimer through an inter-subunit disulfide bond. The solution structures of the locked CXC dimer with CXCR4 peptides were determined. The locked CXC dimer retained Ca{sup 2+} mobilization yet lost chemotaxis activity, presumably because the monomer is the active form. In addition to existing as a monomer and CXC dimer, CXCL12 is now demonstrated to have the capacity to form CC type dimers in the presence of a CXCR4 peptide.« less

Structure and Function of Thermostable Direct Hemolysin (TDH) from Vibrio Parahaemolyticus

NASA Astrophysics Data System (ADS)

Hashimoto, Hiroshi; Yamane, Tsutomu; Ikeguchi, Mitsunori; Nakahira, Kumiko; Yanagihara, Itaru

Thermostable direct hemolysin (TDH) is a major virulence factor of Vibrio parahaemolyticus that causes pandemic food-borne enterocolitis mediated by seafood. TDH exists as a tetramer in solution, and it possesses extreme hemolytic activity. Here, we present the crystal structure of the TDH tetramer at 1.5 Å resolution. The TDH tetramer forms a central pore with dimensions of 23 Å in diameter and ∼50 Å in depth. π-cation interactions between protomers comprising the tetramer were indispensable for hemolytic activity of TDH. The N-terminal region was intrinsically disordered outside the pore. Molecular dynamics (MD) simulations suggested that water molecules permeate freely through the central and side channel pores. These findings imply a novel membrane attachment mechanism by a soluble tetrameric pore-forming toxin.

Inorganic Corrosion-Inhibitive Pigments for High-Temperature Alkali-activated Well Casing Foam Cement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugama, T.; Pyatina, T.

2014-11-01

This study evaluates inorganic pigments for improving carbon steel (CS) brine-corrosion protection by the sodium metasilicate-activated calcium aluminate cement/Fly Ash blend at 300°C. Calcium borosilicate (CBS) and zinc phosphate, significantly improved CS corrosion-protection by decreasing cement’s permeability for corrosive ions and inhibiting anodic corrosion. An amorphous Na 2O-Al 2O 3-SiO 2-H 2O phase tightly attached to CS surface formed at 300oC in CBS-modified cement pore solution. The corrosion rate of the CS covered with this phase was nearly 4-fold lower than in the case of nonmodified cement pore solution where the major phase formed on the surface of CS wasmore » crystalline analcime.« less

Inorganic Corrosion-Inhibitive Pigments for High-Temperature Alkali-activated Well Casing Foam Cement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugama, T.; Pyatina, T.

2014-11-14

This study evaluates inorganic pigments for improving carbon steel (CS) brine-corrosion protection by the sodium metasilicate-activated calcium aluminate cement/Fly Ash blend at 300°C. Calcium borosilicate (CBS) and zinc phosphate, significantly improved CS corrosion-protection by decreasing cement’s permeability for corrosive ions and inhibiting anodic corrosion. An amorphous Na 2O-Al 2O 3-SiO 2-H 2O phase tightly attached to CS surface formed at 300oC in CBS-modified cement pore solution. The corrosion rate of the CS covered with this phase was nearly 4-fold lower than in the case of nonmodified cement pore solution where the major phase formed on the surface of CS wasmore » crystalline analcime.« less

Physical activity in the prevention and treatment of anxiety and depression.

PubMed

Martinsen, Egil W

2008-01-01

Anxiety and depressive disorders are major public health problems, and desirable changes in lifestyle, such as physical exercise, can have great potential in prevention and treatment. There is growing evidence that physically active people are at a reduced risk of developing depression, and that exercise interventions are associated with significant benefits for patients with mild to moderate forms of depression as well as in reducing anxiety. These findings have led to the proposal that exercise may serve as an alternative or a supplement to traditional forms of therapy. This paper will present a broad overview of research involving the efficacy of exercise as means to prevent and treat depression and anxiety, and related issues regarding dosage and compliance. Finally, exercise will be discussed in the frame of cognitive-behavioural theory.

The development of synthetic biology: a patent analysis.

PubMed

van Doren, Davy; Koenigstein, Stefan; Reiss, Thomas

2013-12-01

In the past decades, synthetic biology has gained interest regarding research and development efforts within the biotechnology domain. However, it is unclear to what extent synthetic biology has matured already into being commercially exploitable. By means of a patent analysis, this study shows that there is an increasing trend regarding synthetic biology related patent applications. The majority of retrieved patents relates to innovations facilitating the realisation of synthetic biology through improved understanding of biological systems. In addition, there is increased activity concerning the development of synthetic biology based applications. When looking at potential application areas, the majority of synthetic biology patents seems most relevant for the medical, energy and industrial sector. Furthermore, the analysis shows that most activity has been carried out by the USA, with Japan and a number of European countries considerably trailing behind. In addition, both universities and companies are major patent applicant actor types. The results presented here form a starting point for follow-up studies concerning the identification of drivers explaining the observed patent application trends in synthetic biology.

S-acylation dependent post-translational cross-talk regulates large conductance calcium- and voltage- activated potassium (BK) channels

PubMed Central

Shipston, Michael J.

2014-01-01

Mechanisms that control surface expression and/or activity of large conductance calcium-activated potassium (BK) channels are important determinants of their (patho)physiological function. Indeed, BK channel dysfunction is associated with major human disorders ranging from epilepsy to hypertension and obesity. S-acylation (S-palmitoylation) represents a major reversible, post-translational modification controlling the properties and function of many proteins including ion channels. Recent evidence reveals that both pore-forming and regulatory subunits of BK channels are S-acylated and control channel trafficking and regulation by AGC-family protein kinases. The pore-forming α-subunit is S-acylated at two distinct sites within the N- and C-terminus, each site being regulated by different palmitoyl acyl transferases (zDHHCs) and acyl thioesterases (APTs). S-acylation of the N-terminus controls channel trafficking and surface expression whereas S-acylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. S-acylation of the regulatory β4-subunit controls ER exit and surface expression of BK channels but does not affect ion channel kinetics at the plasma membrane. Furthermore, a significant number of previously identified BK-channel interacting proteins have been shown, or are predicted to be, S-acylated. Thus, the BK channel multi-molecular signaling complex may be dynamically regulated by this fundamental post-translational modification and thus S-acylation likely represents an important determinant of BK channel physiology in health and disease. PMID:25140154

MAJOR MERGERS WITH SMALL GALAXIES: THE DISCOVERY OF A MAGELLANIC-TYPE GALAXY AT z = 0.12

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koch, Andreas; Frank, Matthias J.; Pasquali, Anna

We report on the serendipitous discovery of a star-forming galaxy at redshift z = 0.116 with morphological features that indicate an ongoing merger. This object exhibits two clearly separated components with significantly different colors, plus a possible tidal stream. Follow-up spectroscopy of the bluer component revealed a low star-forming activity of 0.09 M{sub ⊙} yr{sup −1} and a high metallicity of 12 + log(O/H) = 8.6. Based on comparison with mass–star formation-rate and mass–metallicity relations, and on fitting of spectral energy distributions, we obtain a stellar mass of 3 × 10{sup 9} M{sub ⊙}, which renders this object comparable to the Largemore » Magellanic Cloud. Thus our finding provides a further piece of evidence of a major merger already acting on small, dwarf-galaxy-like scales.« less

Global transport of atmospheric smoke following a major nuclear exchange

NASA Technical Reports Server (NTRS)

Haberle, R. M.; Ackerman, T. P.; Toon, O. B.; Hollingsworth, J. L.

1985-01-01

A fully interactive zonally symmetric general circulation model is used to simulate the transport and evolution of a massive smoke cloud that is likely to form in the atmosphere following a major nuclear war. The presence of such a cloud significantly alters the simulated circulation and the subsequent transport of the smoke particles themselves. While the model indicates a tendency for interhemispheric exchange, the most immediate effect is that the radiatively active particles are carried into the stratosphere by the generation of strong vertical motions and intense convection regardless of their initial injection altitudes.

Global transport of atmospheric smoke following a major nuclear exchange

NASA Astrophysics Data System (ADS)

Haberle, Robert M.; Ackerman, Thomas P.; Toon, Owen B.; Hollingsworth, Jeffery L.

A fully interactive zonally symmetric general circulation model is used to simulate the transport and evolution of a massive smoke cloud that is likely to form in the atmosphere following a major nuclear war. The presence of such a cloud significantly alters the simulated circulation and the subsequent transport of the smoke particles themselves. While the model indicates a tendency for interhemispheric exchange, the most immediate effect is that the radiatively active particles are carried into the stratosphere by the generation of strong vertical motions and intense convection regardless of their initial injection altitudes.

Control of synaptic function by endocannabinoid-mediated retrograde signaling.

PubMed

Kano, Masanobu

2014-01-01

Since the first reports in 2001, great advances have been made towards the understanding of endocannabinoid-mediated synaptic modulation. Electrophysiological studies have revealed that one of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), is produced from membrane lipids upon postsynaptic Ca(2+) elevation and/or activation of Gq/11-coupled receptors, and released from postsynaptic neurons. The released 2-AG then acts retrogradely onto presynaptic cannabinoid CB1 receptors and induces suppression of neurotransmitter release either transiently or persistently. These forms of 2-AG-mediated retrograde synaptic modulation are functional throughout the brain. The other major endocannabinoid, anandamide, mediates a certain form of endocannabinoid-mediated long-term depression (LTD). Anandamide also functions as an agonist for transient receptor potential vanilloid receptor type 1 (TRPV1) and mediates endocannabinoid-independent and TRPV1-dependent forms of LTD. It has also been demonstrated that the endocannabinoid system itself is plastic, which can be either up- or down-regulated by experimental or environmental conditions. In this review, I will make an overview of the mechanisms underlying endocannabinoid-mediated synaptic modulation.

Control of synaptic function by endocannabinoid-mediated retrograde signaling

PubMed Central

KANO, Masanobu

2014-01-01

Since the first reports in 2001, great advances have been made towards the understanding of endocannabinoid-mediated synaptic modulation. Electrophysiological studies have revealed that one of the two major endocannabinoids, 2-arachidonoylglycerol (2-AG), is produced from membrane lipids upon postsynaptic Ca2+ elevation and/or activation of Gq/11-coupled receptors, and released from postsynaptic neurons. The released 2-AG then acts retrogradely onto presynaptic cannabinoid CB1 receptors and induces suppression of neurotransmitter release either transiently or persistently. These forms of 2-AG-mediated retrograde synaptic modulation are functional throughout the brain. The other major endocannabinoid, anandamide, mediates a certain form of endocannabinoid-mediated long-term depression (LTD). Anandamide also functions as an agonist for transient receptor potential vanilloid receptor type 1 (TRPV1) and mediates endocannabinoid-independent and TRPV1-dependent forms of LTD. It has also been demonstrated that the endocannabinoid system itself is plastic, which can be either up- or down-regulated by experimental or environmental conditions. In this review, I will make an overview of the mechanisms underlying endocannabinoid-mediated synaptic modulation. PMID:25169670

[Alternative sources for a history of sciences].

PubMed

Edler, F

In this study we call attention to the importance of Manguinhos' scientific collections, which preserve a major portion of the memory of scientific practice as developed by Brazilian researchers in the field of biomedical sciences. We make use of these collections to approach some little-known aspects of scientific activity: the historical evaluation of forms of zoological classification and efforts as legitimating scientific practice.

The 1983 ARI Survey of Army Recruits: Tabular Description of 1983 (Active) Army Accessions. Volume 1

DTIC Science & Technology

1984-04-01

games D - Major league baseball-regular season games E - NFL playoffs and Super Bowl F - College football G - Baseball playoffs and World Series H - NBA ... basketball I - College basketball J - NHL hockey Survey forms (position): A155 C125 TOTAL surveyed is 5,741 T138 BY GENDER MALE FEMALE TOTAL 2 n 4810

Pore-forming toxin-mediated ion dysregulation leads to death receptor-independent necroptosis of lung epithelial cells during bacterial pneumonia

PubMed Central

González-Juarbe, Norberto; Bradley, Kelley Margaret; Shenoy, Anukul Taranath; Gilley, Ryan Paul; Reyes, Luis Felipe; Hinojosa, Cecilia Anahí; Restrepo, Marcos Ignacio; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier

2017-01-01

We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling. PMID:28387756

Pore-forming toxin-mediated ion dysregulation leads to death receptor-independent necroptosis of lung epithelial cells during bacterial pneumonia.

PubMed

González-Juarbe, Norberto; Bradley, Kelley Margaret; Shenoy, Anukul Taranath; Gilley, Ryan Paul; Reyes, Luis Felipe; Hinojosa, Cecilia Anahí; Restrepo, Marcos Ignacio; Dube, Peter Herman; Bergman, Molly Ann; Orihuela, Carlos Javier

2017-05-01

We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling.

Flavor precursors and sensory-active sulfur compounds in alliaceae species native to South Africa and South America.

PubMed

Kubec, Roman; Krejčová, Petra; Mansur, Leví; García, Nicolás

2013-02-13

Profiles of S-substituted cysteine flavor precursors were determined in 42 Alliaceae species native to South Africa and South America. It was found that the pool of cysteine derivatives present in these plants is remarkably very simple, with S-((methylthio)methyl)cysteine 4-oxide (marasmin) being the principal flavor precursor, typically accounting for 93-100% of the pool. Out of the other cysteine derivatives, only minor quantities of methiin were present in some species. The marasmin-derived thiosulfinate marasmicin (2,4,5,7-tetrathiaoctane 4-oxide), a major sensory-active compound of the freshly disrupted plants, was isolated, and its organoleptic properties were evaluated. Furthermore, sulfur-containing volatiles formed upon boiling of these alliaceous species were studied by GC-MS. The profile of the volatiles formed was relatively simple, with 2,3,5-trithiahexane and 2,4,5,7-tetrathiaoctane being the major components. Despite the traditional belief, ingestion of the marasmin-rich plants was always accompanied by development of a strong "garlic breath". We believe that especially several Tulbaghia species deserve to attract much greater attention from the food industry thanks to their pungent garlicky taste and unusual yet pleasant alliaceous smell.

Geochemistry and petrology of selected coal samples from Sumatra, Kalimantan, Sulawesi, and Papua, Indonesia

USGS Publications Warehouse

Belkin, H.E.; Tewalt, S.J.; Hower, J.C.; Stucker, J.D.; O'Keefe, J.M.K.

2009-01-01

Indonesia has become the world's largest exporter of thermal coal and is a major supplier to the Asian coal market, particularly as the People's Republic of China is now (2007) and perhaps may remain a net importer of coal. Indonesia has had a long history of coal production, mainly in Sumatra and Kalimantan, but only in the last two decades have government and commercial forces resulted in a remarkable coal boom. A recent assessment of Indonesian coal-bed methane (CBM) potential has motivated active CBM exploration. Most of the coal is Paleogene and Neogene, low to moderate rank and has low ash yield and sulfur (generally < 10 and < 1??wt.%, respectively). Active tectonic and igneous activity has resulted in significant rank increase in some coal basins. Eight coal samples are described that represent the major export and/or resource potential of Sumatra, Kalimantan, Sulawesi, and Papua. Detailed geochemistry, including proximate and ultimate analysis, sulfur forms, and major, minor, and trace element determinations are presented. Organic petrology and vitrinite reflectance data reflect various precursor flora assemblages and rank variations, including sample composites from active igneous and tectonic areas. A comparison of Hazardous Air Pollutants (HAPs) elements abundance with world and US averages show that the Indonesian coals have low combustion pollution potential.

Structural Evidence of a Major Conformational Change Triggered by Substrate Binding in DapE Enzymes: Impact on the Catalytic Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nocek, Boguslaw; Reidl, Cory; Starus, Anna

In this paper, the X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ~50° and shifts ~10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to the dinuclearmore » Zn(II) active site with the succinate carboxylate moiety bridging the dinculear Zn(II) cluster in a μ-1,3 fashion forming a bis(μ-carboxylato)dizinc(II) core with a Zn–Zn distance of 3.8 Å. Surprisingly, His194.B, which is located on the dimerization domain of the opposing chain ~10.1 Å from the dinuclear Zn(II) active site, forms a hydrogen bond (2.9 Å) with the oxygen atom of succinic acid bound to Zn2, forming an oxyanion hole. As the closed structure forms upon substrate binding, the movement of His194.B by more than ~10 Å is critical, based on site-directed mutagenesis data, for activation of the scissile carbonyl carbon of the substrate for nucleophilic attack by a hydroxide nucleophile. Employing the HiDapE product-bound structure as the starting point, a reverse engineering approach called product-based transition-state modeling provided structural models for each major catalytic step. Finally, these data provide insight into the catalytic reaction mechanism and also the future design of new, potent inhibitors of DapE enzymes.« less

Structural Evidence of a Major Conformational Change Triggered by Substrate Binding in DapE Enzymes: Impact on the Catalytic Mechanism

DOE PAGES

Nocek, Boguslaw; Reidl, Cory; Starus, Anna; ...

2017-12-22

In this paper, the X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ~50° and shifts ~10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to the dinuclearmore » Zn(II) active site with the succinate carboxylate moiety bridging the dinculear Zn(II) cluster in a μ-1,3 fashion forming a bis(μ-carboxylato)dizinc(II) core with a Zn–Zn distance of 3.8 Å. Surprisingly, His194.B, which is located on the dimerization domain of the opposing chain ~10.1 Å from the dinuclear Zn(II) active site, forms a hydrogen bond (2.9 Å) with the oxygen atom of succinic acid bound to Zn2, forming an oxyanion hole. As the closed structure forms upon substrate binding, the movement of His194.B by more than ~10 Å is critical, based on site-directed mutagenesis data, for activation of the scissile carbonyl carbon of the substrate for nucleophilic attack by a hydroxide nucleophile. Employing the HiDapE product-bound structure as the starting point, a reverse engineering approach called product-based transition-state modeling provided structural models for each major catalytic step. Finally, these data provide insight into the catalytic reaction mechanism and also the future design of new, potent inhibitors of DapE enzymes.« less

Structural Evidence of a Major Conformational Change Triggered by Substrate Binding in DapE Enzymes: Impact on the Catalytic Mechanism.

PubMed

Nocek, Boguslaw; Reidl, Cory; Starus, Anna; Heath, Tahirah; Bienvenue, David; Osipiuk, Jerzy; Jedrzejczak, Robert; Joachimiak, Andrzej; Becker, Daniel P; Holz, Richard C

2018-02-06

The X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ∼50° and shifts ∼10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to the dinuclear Zn(II) active site with the succinate carboxylate moiety bridging the dinculear Zn(II) cluster in a μ-1,3 fashion forming a bis(μ-carboxylato)dizinc(II) core with a Zn-Zn distance of 3.8 Å. Surprisingly, His194.B, which is located on the dimerization domain of the opposing chain ∼10.1 Å from the dinuclear Zn(II) active site, forms a hydrogen bond (2.9 Å) with the oxygen atom of succinic acid bound to Zn2, forming an oxyanion hole. As the closed structure forms upon substrate binding, the movement of His194.B by more than ∼10 Å is critical, based on site-directed mutagenesis data, for activation of the scissile carbonyl carbon of the substrate for nucleophilic attack by a hydroxide nucleophile. Employing the HiDapE product-bound structure as the starting point, a reverse engineering approach called product-based transition-state modeling provided structural models for each major catalytic step. These data provide insight into the catalytic reaction mechanism and also the future design of new, potent inhibitors of DapE enzymes.

Extension of helix II of an HIV-1-directed hammerhead ribozyme with long antisense flanks does not alter kinetic parameters in vitro but causes loss of the inhibitory potential in living cells.

PubMed Central

Homann, M; Tabler, M; Tzortzakaki, S; Sczakiel, G

1994-01-01

When designed to cleave a target RNA in trans, the hammerhead ribozyme contains two antisense flanks which form helix I and helix III by pairing with the complementary target RNA. The sequences forming helix II are contained on the ribozyme strand and represent a major structural component of the hammerhead structure. In the case of an inhibitory 429 nucleotides long trans-ribozyme (2as-Rz12) which was directed against the 5'-leader/gag region of the human immunodeficiency virus type 1 (HIV-1), helix II was not pre-formed in the single-stranded molecule. Thus, major structural changes are necessary before cleavage can occur. To study whether pre-formation of helix II in the non-paired 2as-Rz12 RNA could influence the observed cleavage rate in vitro and its inhibitory activity on HIV-1 replication, we extended the 4 base pair helix II of 2as-Rz12 to 6, 10, 21, and 22 base pairs respectively. Limited RNase cleavage reactions performed in vitro at 37 degrees C and at physiological ion strength indicated that a helix II of the hammerhead domain was pre-formed when its length was at least six base pairs. This modification neither affected the association rate with target RNA nor the cleavage rate in vitro. In contrast to this, extension of helix II led to a significantly decreased inhibition of HIV-1 replication in human cells. Together with the finding of others that shortening of helix II to less than two base pairs reduces the catalytic activity in vitro, this observation indicates that the length of helix II in the naturally occurring RNAs with a hammerhead domain is already close or identical to the optimal length for catalytic activity in vitro and in vivo. Images PMID:7524030

Oxidative damage to DNA: counterion-assisted addition of water to ionized DNA.

PubMed

Barnett, Robert N; Bongiorno, Angelo; Cleveland, Charles L; Joy, Abraham; Landman, Uzi; Schuster, Gary B

2006-08-23

Oxidative damage to DNA, implicated in mutagenesis, aging, and cancer, follows electron loss that generates a radical cation that migrates to a guanine, where it may react with water to form 8-oxo-7,8-dihydroguanine (8-OxoG). Molecular dynamics and ab initio quantum simulations on a B-DNA tetradecamer reveal activated reaction pathways that depend on the local counterion arrangement. The lowest activation barrier, 0.73 eV, is found for a reaction that starts from a configuration where a Na(+) resides in the major groove near the N7 atoms of adjacent guanines, and evolves through a transition state where a bond between a water oxygen atom and a carbon atom forms concurrently with displacement of a proton toward a neighboring water molecule. Subsequently, a bonded complex of a hydronium ion and the nearest backbone phosphate group forms. This counterion-assisted proton shuttle mechanism is supported by experiments exploiting selective substitution of backbone phosphates by methylphosphonates.

Orogenesis, high-T thermal events, and gold vein formation within metamorphic rocks of the Alaskan Cordillera

USGS Publications Warehouse

Goldfarb, R.J.; Snee, L.W.; Pickthorn, W.J.

1993-01-01

Mesothermal, gold-bearing quartz veins are widespread within allochthonous terranes of Alaska that are composed dominantly of greenschist-facies metasedimentary rocks. The most productive lode deposits are concentrated in south-central and southeastern Alaska; small and generally nonproductive gold-bearing veins occur upstream from major placer deposits in interior and northern Alaska. Ore-forming fluids in all areas are consistent with derivation from metamorphic devolatilisation reactions, and a close temporal relationship exists between high-T tectonic deformation, igneous activity, and gold mineralization. Ore fluids were of consistently low salinity, CO2-rich, and had ??18O values of 7 ???-12??? and ??D values between -15??? and -35???. Upper-crustal temperatures within the metamorphosed terranes reached at least 450-500??C before onset of significant gold-forming hydrothermal activity. In southern Alaska, gold deposits formed during latter stages of Tertiary, subduction-related, collisional orogenesis and were often temporally coeval with calc-alkaline magmatism. -from Authors

Leishmanicidal activity of Nystatin (mycostatin): a potent polyene compound.

PubMed

Ali, S A; Iqbal, J; Nabeel; Khalil, Y; Manzoor, A; Bukhari, I; Ahmad, B; Yasinzai, M M

1997-10-01

The susceptibility of promastigote of Leishmania major to Nystatin in vitro was examined. L. major (MHOM/PK/88/DESTO) promastigote were cultured in medium 199 supplemented with 10% heat inactivated foetal bovine serum and 2% urine. The growth of the promastigote was monitored in the absence and presence of the experimental compound (Nystatin) for upto 5 days post-inoculation. The EC50 value (the concentration of drug necessary to inhibit the growth rate of cells to 50% of the control value) obtained for Nystatin against the promastigote of L. major was less than 9.76 iu ml. Certain polyene compounds like Amphotericin-B and Nystatin (mycostatin) are familiar for their fungicidal activity. Amphotericin-B is used since long as antileishmanial drug as well. Results obtained suggest that Nystatin has a very good anti leishmanial activity in vitro. The mode of action proposed for this drug is same as for Amphotericin-B as both of these polyene compounds interact with the various sterols present on the surface of the parasite, thus unusual gaps and pores are formed on the surface that results in the leakage of the ions. This leakage finally leads to the destruction of the parasite.

Extensive Basal Level Activation of Complement Mannose-Binding Lectin-Associated Serine Protease-3: Kinetic Modeling of Lectin Pathway Activation Provides Possible Mechanism.

PubMed

Oroszlán, Gábor; Dani, Ráhel; Szilágyi, András; Závodszky, Péter; Thiel, Steffen; Gál, Péter; Dobó, József

2017-01-01

Serine proteases (SPs) are typically synthesized as precursors, termed proenzymes or zymogens, and the fully active form is produced via limited proteolysis by another protease or by autoactivation. The lectin pathway of the complement system is initiated by mannose-binding lectin (MBL)-associated SPs (MASP)-1, and MASP-2, which are known to be present as proenzymes in blood. The third SP of the lectin pathway, MASP-3, was recently shown to be the major activator, and the exclusive "resting blood" activator of profactor D, producing factor D, the initiator protease of the alternative pathway. Because only activated MASP-3 is capable of carrying out this cleavage, it was presumed that a significant fraction of MASP-3 must be present in the active form in resting blood. Here, we aimed to detect active MASP-3 in the blood by a more direct technique and to quantitate the active to zymogen ratio. First, MASPs were partially purified (enriched) from human plasma samples by affinity chromatography using immobilized MBL in the presence of inhibitors. Using this MASP pool, only the zymogen form of MASP-1 was detected by Western blot, whereas over 70% MASP-3 was in an activated form in the same samples. Furthermore, the active to zymogen ratio of MASP-3 showed little individual variation. It is enigmatic how MASP-3, which is not able to autoactivate, is present mostly as an active enzyme, whereas MASP-1, which has a potent autoactivation capability, is predominantly proenzymic in resting blood. In an attempt to explain this phenomenon, we modeled the basal level fluid-phase activation of lectin pathway proteases and their subsequent inactivation by C1 inhibitor and antithrombin using available and newly determined kinetic constants. The model can explain extensive MASP-3 activation only if we assume efficient intracomplex activation of MASP-3 by zymogen MASP-1. On the other hand, the model is in good agreement with the fact that MASP-1 and -2 are predominantly proenzymic and some of them is present in the form of inactive serpin-protease complexes. As an alternative hypothesis, MASP-3 activation by proprotein convertases is also discussed.

Fibrin/fibrinogen degradation products in children with renal disease

PubMed Central

Uttley, W. S.; Maxwell, Heather; Cash, J. D.

1974-01-01

Fibrin/fibrinogen degradation products (FDP) were measured in the serum and urine of children with various forms of renal disease. Serum FDP was raised both with nephrosis and with active proliferative nephritis. Urine FDP was rarely present in nephrosis but was significantly increased during the active phase of proliferative nephritis and also in urinary tract infection with frank haematuria. Urinary FDP correlated with total urinary protein in proliferative nephritis but not in nephrosis, nor did it correlate with serum FDP in either condition. The major application of urinary FDP determination in clinical practice is as an indicator of activity and possible response to treatment in the management of active proliferative nephritis. PMID:4817446

Two distinct forms of Factor VIII coagulant protein in human plasma. Cleavage by thrombin, and differences in coagulant activity and association with von Willebrand factor.

PubMed Central

Weinstein, M J; Chute, L E

1984-01-01

We have characterized Factor VIII coagulant protein, present in normal human plasma, that reacts with a specific human 125I-labeled anti-human VIII:C antigen Fab antibody fragment. Two major Factor VIII coagulant antigen populations were present. The first, approximately 85% of the total antigen, was bound to von Willebrand factor and when tested in a standard one-stage assay had Factor VIII coagulant activity. The second antigenic population, eluting near fibrinogen when plasma was gel filtered, was not bound to von Willebrand protein, did not have Factor VIII coagulant activity unless activated, but did block anti-VIII:C Fab neutralization of clotting activity. The two antigenic populations were separable by cryoprecipitation and agarose gel electrophoresis. Although the two antigenic populations differed in their Factor VIII coagulant activity and in their binding to von Willebrand factor, the principal member of both populations is of mol wt 2.4 X 10(5). Both antigens, when proteolyzed by thrombin, were quickly converted to a 1 X 10(5)-mol wt form in association with the appearance of VIII:C activity. The 1 X 10(5)-mol wt antigen was further slowly degraded to an 8 X 10(4)-mol wt form while Factor VIII coagulant activity declined. These results demonstrate the presence of an inactive Factor VIII coagulant protein in plasma, not associated with von Willebrand factor, that can react with thrombin to yield Factor VIII coagulant activity. Images PMID:6421875

[Methuosis: a novel type of cell death].

PubMed

Cai, Hongbing; Liu, Jinkun; Fan, Qin; Li, Xin

2013-12-01

Cell death is a major physiological or pathological phenomenon in life activities. The classic forms of cell death include apoptosis, necrosis, and autophagy. Recently, a novel type of cell death has been observed and termed as methuosis, in which excessive stimuli can induce cytoplasmic uptake and accumulation of small bubbles that gradually merge into giant vacuoles, eventually leading to decreased cellular metabolic activity, cell membrane rupture and cell death. In this article, we describe the nomenclature, morphological characteristics and underlying mechanisms of methuosis, compare methuosis with autophagy, oncosis and paraptosis, and review the related researches.

Evaluation and treatment of biking and running injuries.

PubMed

Oser, Sean M; Oser, Tamara K; Silvis, Matthew L

2013-12-01

Exercise is universally recognized as a key feature for maintaining good health. Likewise, lack of physical activity is a major risk factor for chronic disease and disability, an especially important fact considering our rapidly aging population. Biking and running are frequently recommended as forms of exercise. As more individuals participate in running-related and cycling-related activities, physicians must be increasingly aware of the common injuries encountered in these pursuits. This review focuses on the evaluation and management of common running-related and cycling-related injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

Medicinal Plants Used by a Mbyá-Guarani Tribe Against Infections: Activity on KPC-Producing Isolates and Biofilm-Forming Bacteria.

PubMed

Brandelli, Clara Lia Costa; Ribeiro, Vanessa Bley; Zimmer, Karine Rigon; Barth, Afonso Luís; Tasca, Tiana; Macedo, Alexandre José

2015-11-01

The traditional use of medicinal plants for treatment of infectious diseases by an indigenous Mbyá-Guarani tribe from South Brazil was assessed by evaluating the antibiotic and antibiofilm activities against relevant bacterial pathogens. Aqueous extracts from 10 medicinal plants were prepared according to indigenous Mbyá-Guarani traditional uses. To evaluate antibiotic (OD600) and antibiofilm (crystal violet method) activities, Pseudomonas aeruginosa ATCC 27853, Staphylococcus epidermidis ATCC 35984 and seven multi-drug resistant Klebsiella pneumoniae carbapenemase (KPC)-producing bacterial clinical isolates were challenged with the extracts. Furthermore, the susceptibility profile of KPC-producing bacteria and the ability of these isolates to form biofilm were evaluated. The plants Campomanesia xanthocarpa, Maytenus ilicifolia, Bidens pilosa and Verbena sp. showed the best activity against bacterial growth and biofilm formation. The majority of KPC-producing isolates, which showed strong ability to form biofilm and a multidrug resistance profile, was inhibited by more than 50% by some extracts. The Enterobacter cloacae (KPC 05) clinical isolate was the only one resistant to all extracts. This study confirms the importance of indigenous traditional medicinal knowledge and describes for the first time the ability of these plants to inhibit biofilm formation and/or bacterial growth of multi-drug resistant KPC-producing isolates.

PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release

PubMed Central

Singh, Ramandeep; Manjunatha, Ujjini; Boshoff, Helena I. M.; Ha, Young Hwan; Niyomrattanakit, Pornwaratt; Ledwidge, Richard; Dowd, Cynthia S.; Lee, Ill Young; Kim, Pilho; Zhang, Liang; Kang, Sunhee; Keller, Thomas H.; Jiricek, Jan; Barry, Clifton E.

2009-01-01

Bicyclic nitroimidazoles, including PA-824, are exciting candidates for the treatment of tuberculosis. These prodrugs require intracellular activation for their biological function. We found that Rv3547 is a deazaflavin-dependent nitroreductase (Ddn) that converts PA-824 into three primary metabolites; the major one is the corresponding des-nitroimidazole (des-nitro). When derivatives of PA-824 were used, the amount of des-nitro metabolite formed was highly correlated with anaerobic killing of Mycobacterium tuberculosis (Mtb). Des-nitro metabolite formation generated reactive nitrogen species, including nitric oxide (NO), which are the major effectors of the anaerobic activity of these compounds. Furthermore, NO scavengers protected the bacilli from the lethal effects of the drug. Thus, these compounds may act as intracellular NO donors and could augment a killing mechanism intrinsic to the innate immune system. PMID:19039139

Synaptic Plasticity in Cardiac Innervation and Its Potential Role in Atrial Fibrillation

PubMed Central

Ashton, Jesse L.; Burton, Rebecca A. B.; Bub, Gil; Smaill, Bruce H.; Montgomery, Johanna M.

2018-01-01

Synaptic plasticity is defined as the ability of synapses to change their strength of transmission. Plasticity of synaptic connections in the brain is a major focus of neuroscience research, as it is the primary mechanism underpinning learning and memory. Beyond the brain however, plasticity in peripheral neurons is less well understood, particularly in the neurons innervating the heart. The atria receive rich innervation from the autonomic branch of the peripheral nervous system. Sympathetic neurons are clustered in stellate and cervical ganglia alongside the spinal cord and extend fibers to the heart directly innervating the myocardium. These neurons are major drivers of hyperactive sympathetic activity observed in heart disease, ventricular arrhythmias, and sudden cardiac death. Both pre- and postsynaptic changes have been observed to occur at synapses formed by sympathetic ganglion neurons, suggesting that plasticity at sympathetic neuro-cardiac synapses is a major contributor to arrhythmias. Less is known about the plasticity in parasympathetic neurons located in clusters on the heart surface. These neuronal clusters, termed ganglionated plexi, or “little brains,” can independently modulate neural control of the heart and stimulation that enhances their excitability can induce arrhythmia such as atrial fibrillation. The ability of these neurons to alter parasympathetic activity suggests that plasticity may indeed occur at the synapses formed on and by ganglionated plexi neurons. Such changes may not only fine-tune autonomic innervation of the heart, but could also be a source of maladaptive plasticity during atrial fibrillation. PMID:29615932

Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1

PubMed Central

Xiao, Qian; Jiang, Yan; Liu, Qingbo; Yue, Jiao; Liu, Chunying; Zhao, Xiaotong; Qiao, Yuemei; Ji, Hongbin; Chen, Jianfeng; Ge, Gaoxiang

2015-01-01

Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV α chains form α1α1α2, α3α4α5 and α5α5α6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (α1α1α2), little is known whether minor Col IV (α3α4α5 and α5α5α6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV α5 chain is indispensable in cancer development by using α5(IV)-deficient mouse model. Ablation of α5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial α5(IV) supports cancer cell proliferation, while endothelial α5(IV) is essential for efficient tumor angiogenesis. α5(IV), but not α1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of α5(IV). Constitutively active DDR1 or MEK1 rescued the defects of α5(IV)-ablated cells. Thus, minor Col IV α5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV. PMID:25992553

Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

PubMed Central

Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

2014-01-01

Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

Ferredoxin and ferredoxin-NADP reductase from photosynthetic and nonphotosynthetic tissues of tomato

NASA Technical Reports Server (NTRS)

Green, L. S.; Yee, B. C.; Buchanan, B. B.; Kamide, K.; Sanada, Y.; Wada, K.

1991-01-01

Ferredoxin and ferredoxin-NADP+ oxidoreductase (FNR) were purified from leaves, roots, and red and green pericarp of tomato (Lycopersicon esculentum, cv VFNT and cv Momotaro). Four different ferredoxins were identified on the basis of N-terminal amino acid sequence and charge. Ferredoxins I and II were the most prevalent forms in leaves and green pericarp, and ferredoxin III was the most prevalent in roots. Red pericarp of the VFNT cv yielded variable amounts of ferredoxins II and III plus a unique form, ferredoxin IV. Red pericarp of the Momotaro cv contained ferredoxins I, II, and IV. This represents the first demonstration of ferredoxin in a chromoplast-containing tissue. There were no major differences among the tomato ferredoxins in absorption spectrum or cytochrome c reduction activity. Two forms of FNR were present in tomato as judged by anion exchange chromatography and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. FNR II had a lower apparent relative molecular weight, a slightly altered absorption spectrum, and a lower specific activity for cytochrome c reduction than FNR I. FNR II could be a partially degraded form of FNR I. The FNRs from the different tissues of tomato plants all showed diaphorase activity, with FNR II being more active than FNR I. The presence of ferredoxin and FNR in heterotrophic tissues of tomato is consistent with the existence of a nonphotosynthetic ferredoxin/FNR redox pathway to support the function of ferredoxin-dependent enzymes.

Evidence for involvement of multiple forms of cytochrome P-450 in aflatoxin B sup 1 metabolism in human liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forrester, L.M.; Wolf, C.R.; Neal, G.E.

Liver cancer is a major cause of premature death in many areas of Africa and Asia and its incidence is strongly correlated with exposure to aflatoxin B{sub 1} (AFB{sub 1}). Because AFB{sub 1} requires metabolic activation to achieve a biological response, there is a need for detailed knowledge of the mechanism of activation to assess individual risk. The authors carried out an extensive study using a total of 19 human liver samples to determine the individual variability in the metabolism of the toxin to mutagenic or detoxification products and to identify the specific cytochrome P-450 forms involved in these processes.more » Metabolism to the toxic 8,9-epoxide or to products mutagenic in the Ames test was found to exhibit very large individual variation. These data demonstrate that, although P450IIIA probably plays an important role in AFB{sub 1} activation, several other cytochrome P-450 forms have the capacity to activate the toxin. Similar considerations apply to detoxifying metabolism to aflatoxin Q{sub 1} and aflatoxin M{sub 1}. The levels of expression of many of the forms of cytochrome P-450 involved in AFB{sub 1} metabolism are known to be highly sensitive to environmental factors. This indicates that such factors will be an important determinant in individual susceptibility to the tumorigenic action of AFB{sub 1}.« less

Amplification and oscillations in the FAK/Src kinase system during integrin signaling.

PubMed

Caron-Lormier, G; Berry, H

2005-01-21

Integrin signaling is a major pathway of cell adhesion to extracellular matrices that regulates many physiological cell behaviors such as cell proliferation, migration or differentiation and is implied in pathologies such as tumor invasion. In this paper, we focused on the molecular system formed by the two kinases FAK (focal adhesion kinase) and Src, which undergo auto- and co-activation during early steps of integrin signaling. The system is modelled using classical kinetic equations and yields a set of three nonlinear ordinary differential equations describing the dynamics of the different phosphorylation forms of FAK. Analytical and numerical analysis of these equations show that this system may in certain cases amplify incoming signals from the integrins. A quantitative condition is obtained, which indicates that the total FAK charge in the system acts as a critical mass that must be exceeded for amplification to be effective. Furthermore, we show that when FAK activity is lower than Src activity, spontaneous oscillations of FAK phosphorylation forms may appear. The oscillatory behavior is studied using bifurcation and stability diagrams. We finally discuss the significance of this behavior with respect to recent experimental results evidencing FAK dynamics.

Active Learning and Student-centered Pedagogy Improve Student Attitudes and Performance in Introductory Biology

PubMed Central

Patel, Maya; Johnson, Erika; Weiss, Martha

2009-01-01

We describe the development and implementation of an instructional design that focused on bringing multiple forms of active learning and student-centered pedagogies to a one-semester, undergraduate introductory biology course for both majors and nonmajors. Our course redesign consisted of three major elements: 1) reordering the presentation of the course content in an attempt to teach specific content within the context of broad conceptual themes, 2) incorporating active and problem-based learning into every lecture, and 3) adopting strategies to create a more student-centered learning environment. Assessment of our instructional design consisted of a student survey and comparison of final exam performance across 3 years—1 year before our course redesign was implemented (2006) and during two successive years of implementation (2007 and 2008). The course restructuring led to significant improvement of self-reported student engagement and satisfaction and increased academic performance. We discuss the successes and ongoing challenges of our course restructuring and consider issues relevant to institutional change. PMID:19723815

Homogenization versus homogenization-free method to measure muscle glycogen fractions.

PubMed

Mojibi, N; Rasouli, M

2016-12-01

The glycogen is extracted from animal tissues with or without homogenization using cold perchloric acid. Three methods were compared for determination of glycogen in rat muscle at different physiological states. Two groups of five rats were kept at rest or 45 minutes muscular activity. The glycogen fractions were extracted and measured by using three methods. The data of homogenization method shows that total glycogen decreased following 45 min physical activity and the change occurred entirely in acid soluble glycogen (ASG), while AIG did not change significantly. Similar results were obtained by using "total-glycogen-fractionation methods". The findings of "homogenization-free method" indicate that the acid insoluble fraction (AIG) was the main portion of muscle glycogen and the majority of changes occurred in AIG fraction. The results of "homogenization method" are identical with "total glycogen fractionation", but differ with "homogenization-free" protocol. The ASG fraction is the major portion of muscle glycogen and is more metabolically active form.

18 CFR 260.1 - FERC Form No. 2, Annual report for Major natural gas companies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... report for Major natural gas companies. 260.1 Section 260.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY APPROVED FORMS, NATURAL GAS ACT STATEMENTS AND REPORTS (SCHEDULES) § 260.1 FERC Form No. 2, Annual report for Major natural gas companies. (a...

18 CFR 260.1 - FERC Form No. 2, Annual report for Major natural gas companies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... report for Major natural gas companies. 260.1 Section 260.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY APPROVED FORMS, NATURAL GAS ACT STATEMENTS AND REPORTS (SCHEDULES) § 260.1 FERC Form No. 2, Annual report for Major natural gas companies. (a...

The Relationship of Sub-Components of Manifold Dimensions of Vocabulary Depth Knowledge and Academic Reading Comprehension among English as a Foreign Language Learners at Tertiary Level

ERIC Educational Resources Information Center

Hasan, Md. Kamrul; Shabdin, Ahmad Affendi

2017-01-01

This study makes an attempt to investigate the correlations between manifold aspects, namely both syntagmatic and paradigmatic relations, the four major derivative word forms, which represented morphological knowledge, six dimensions of analytic relations (i.e. component-integral, member-collection, portion-mass, stuff-object, feature-activity,…

Electronic Measurement of Rock Stress

DTIC Science & Technology

atomic resonances that are pressure-sensitive. Nuclear quadrupole resonance ( NQR ) appeared clearly applicable, since no magnetic aligning field is needed...there are several common NQR -active nuclear species in major rock-forming minerals, and rf magnetic fields between 0.3 and 3 megahertz (the resonant...comprehensive literature search has been completed on NQR in minerals, which shows that aluminum-27 and a few other elements in feldspars are promising

Composite battery separator

NASA Technical Reports Server (NTRS)

Edwards, Dean B. (Inventor); Rippel, Wally E. (Inventor)

1987-01-01

A composite battery separator comprises a support element (10) having an open pore structure such as a ribbed lattice and at least one liquid permeable sheet (20,22) to distribute the compressive force evenly onto the surfaces of the layers (24, 26) of negative active material and positive active material. In a non-flooded battery cell the compressible, porous material (18), such as a glass mat which absorbs the electrolyte, is compressed into a major portion of the pores or openings (16) in the support element. The unfilled pores in the material (18) form a gas diffusion path as the channels (41) formed between adjacent ribs in the lattice element (30,36). Facing two lattice elements (30, 31) with acute angled cross-ribs (34, 38) facing each other prevents the elements from interlocking and distorting a porous, separator (42) disposed between the lattice elements.

[The head of the medical service must be the person...(To the 70th anniversary of N.G. Ryzhman)].

PubMed

Val'skiĭ, V V; Butikov, V P; Rybakov, S M; Chernikov, O G

2014-09-01

The article is devoted to contribution of major general (rear Admiral. - navy) of medical service Nikolay Grigoryevich Ryzhman (1944-2005), the chief of the medical service of the Northern fleet (1991-1999), to development of naval medicine, who would have turn 70 years this September. The constant analysis, and experience generalization of the medical services of the fleet connections and associations and aspiration to provide fighting capacity for the fleet crew - were a keynote of Ryzhman's activity concerned development and deployment of the new forms and methods of medical support and searching of ways to increase crew efficiency. The implemented methods and forms of organization of the medical support and scientific development of the medical support are used even now in the practical activities of the medical service of the Northern fleet.

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with Primary Hyperoxaluria Type I☆

PubMed Central

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5′-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. PMID:22018727

Biochemical analyses are instrumental in identifying the impact of mutations on holo and/or apo-forms and on the region(s) of alanine:glyoxylate aminotransferase variants associated with primary hyperoxaluria type I.

PubMed

Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara

2012-01-01

Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. Copyright © 2011 Elsevier Inc. All rights reserved.

Factor XII (Hageman factor) is a missing link between stress and hypercoagulability and plays an important role in the pathophysiology of ischemic stroke.

PubMed

Eggers, Arnold E

2006-01-01

A new hypothesis is presented on the function of factor XII, which is postulated to be a "missing link" between acute stress and transient hypercoagulability. The implications of this idea are developed to show how chronic stress, which involves activation of hypertension and migraine as well as hypercoagulability, can cause of cerebrovascular disease. "Acute stress" is defined as "the normal short-term physiological response to the perception of major threats or demands". "Chronic stress" is "the abnormal ongoing physiological response to the continuing perception of unresolvable major threats or demands". The factor XII hypothesis is as follows: Acute stress includes release of epinephrine by the adrenal medulla. Epinephrine activates platelets by binding to alpha-2A adrenergic receptors. Activated platelets convert pre-bound factor XII to its active form, which then initiates the intrinsic coagulation cascade. This can be called the "activated platelet initiation pathway" for coagulation. Neither tissue factor nor pre-formed thrombin is required. Thrombosis proceeds to completion, but only a minute amount of thrombin is formed, and the process normally stops at this point. In people who lapse into a state of chronic stress, essential hypertension, which is also a manifestation of stress, synergizes with hypercoagulability: there is both a baseline rise in blood pressure and systemic platelet activation as well as superimposed labile rises of both. Upregulation of these two stress parameters is atherogenic: epinephrine-activated platelets stimulating thrombin formation interact with endothelial cells activated by angiotensin II to cause, first, smooth muscle cell proliferation, which is a histological hallmark of atherosclerosis, and, lastly, a symptomatic thrombotic occlusion-the stroke. The migraine symptoms which often accompany this process are a marker of chronic stress and ongoing pathophysiologic damage. Therapeutic predictions are made regarding novel ways of blocking stress-induced hypercoagulability and hypertension. Hypercoagulability could be targeted by monoclonal antibodies directed against the platelet-specific alpha-2 adrenergic receptor or the (putative) platelet receptor for Factor XII; hypertension could be treated with monoclonal antibodies directed against the beta-adrenergic receptor in the juxtaglomerular apparatus or by surgical denervation of the kidneys, either of which would decrease the renin release which helps drive the hypertension.

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major

PubMed Central

Ricci-Azevedo, Rafael; Oliveira, Aline Ferreira; Conrado, Marina C. A. V.; Carvalho, Fernanda Caroline; Roque-Barreira, Maria Cristina

2016-01-01

ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an appropriate molecular template for the construction of an efficient anti-infective agent. PMID:27058234

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major.

PubMed

Ricci-Azevedo, Rafael; Oliveira, Aline Ferreira; Conrado, Marina C A V; Carvalho, Fernanda Caroline; Roque-Barreira, Maria Cristina

2016-04-01

ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an appropriate molecular template for the construction of an efficient anti-infective agent.

Anticoagulant Activity of a Unique Sulfated Pyranosic (1→3)-β-l-Arabinan through Direct Interaction with Thrombin*

PubMed Central

Fernández, Paula V.; Quintana, Irene; Cerezo, Alberto S.; Caramelo, Julio J.; Pol-Fachin, Laercio; Verli, Hugo; Estevez, José M.; Ciancia, Marina

2013-01-01

A highly sulfated 3-linked β-arabinan (Ab1) with arabinose in the pyranose form was obtained from green seaweed Codium vermilara (Bryopsidales). It comprised major amounts of units sulfated on C-2 and C-4 and constitutes the first polysaccharide of this type isolated in the pure form and fully characterized. Ab1 showed anticoagulant activity by global coagulation tests. Less sulfated arabinans obtained from the same seaweed have less or no activity. Ab1 exerts its activity through direct and indirect (antithrombin- and heparin cofactor II-mediated) inhibition of thrombin. Direct thrombin inhibition was studied in detail. By native PAGE, it was possible to detect formation of a complex between Ab1 and human thrombin (HT). Ab1 binding to HT was measured by fluorescence spectroscopy. CD spectra of the Ab1 complex suggested that ligand binding induced a small conformational change on HT. Ab1-thrombin interactions were studied by molecular dynamic simulations using the persulfated octasaccharide as model compound. Most carbohydrate-protein contacts would occur by interaction of sulfate groups with basic amino acid residues on the surface of the enzyme, more than 60% of them being performed by the exosite 2-composing residues. In these interactions, the sulfate groups on C-2 were shown to interact more intensely with the thrombin structure. In contrast, the disulfated oligosaccharide does not promote major conformational modifications at the catalytic site when complexed to exosite 1. These results show that this novel pyranosic sulfated arabinan Ab1 exerts its anticoagulant activity by a mechanism different from those found previously for other sulfated polysaccharides and glycosaminoglycans. PMID:23161548

Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011.

PubMed

Izumi, Kiyohiko; Ohkado, Akihiro; Uchimura, Kazuhiro; Murase, Yoshiro; Tatsumi, Yuriko; Kayebeta, Aya; Watanabe, Yu; Ishikawa, Nobukatsu

2015-01-01

Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots. Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics) identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed. Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2%) were general inhabitants, 42 (6.5%) were foreign-born people, and 184 were homeless people (28.6%). The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households. Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission dynamics in an urban setting in Japan.

[The hyperiricosuria as an indicator of derangement of biologic functions of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension].

PubMed

Titov, V N; Oshchepkova, E V; Dmitriev, V A; Gushchina, O V; Shiriaeva, Iu K; Iashin, A Ia

2012-04-01

During millions years in all animals allantoine (oxidized by uricase uric acid) was catabolite of purines and ascorbic acid was an acceptor of active forms of oxygen. The proximal tubules of nephron reabsorbed the trace amounts of uric acid Then during phylogenesis the primates had a mutation of ascorbic acid gen minus. Later on occurred a second spontaneous mutation and uricase gen minus and uric acid became catabolites of purines. In absence of ascorbic acid synthesis ions of urates became a major capturers of active forms of oxygen and all uric acid as before underwent the reabsorption. Later the carriers were formed which began in epithelium of proximal tubules to secrete all uric acid into urine. At every incident of "littering" of intercellular medium with endogenic flogogens (impairment of biologic function of endoecology) under compensatory development of biologic reaction of inflammation the need in inactivation of active forms of oxygen increases. Hence later on in phylogenesis one more stage was formed--post secretory reabsorption of uric acid In the biologic reaction of inflammation epithelium of proximal tubules initiates retentional hyperiricosuria. The general antioxidant activity of human blood plasma in 60% is presented by urates' ions. The excretion of uric acid includes 4 stages: filtration, full reabsorption, secretion and post secretory reabsorption. In phylogenesis these stages formed in sequence. The mild hyperiricosuria is most frequently considered as a non-specific indicator of activation of biologic reaction of inflammation. The productive hyperiricosuria develops more infrequently under surplus of meat food and cytolysis syndrome (intensification of cell loss in vivo). Under concentration of uric acid more than 400 mkmol/l part of urates circulates in intercellular medium in the form of crystals. The microcrystals of uric acid (biologic "litter") initiate the syndrome of systemic inflammatory response as an endogenic flogogen--initiator of inflammation. The uric acid in the form of ion-capturers of active forms of oxygen is involved into in the formation of syndrome of compensatory anti-inflammatory defense. It may be assumed that simultaneously with post-secretory reabsorption of ions of urates in proximal tubules of nephron occurs intensification of philogenetically late post-secretory reabsorption of ions of sodium and activation of of biologic reaction of hydrodynamic and hydraulic pressure in local pool of intravascular medium i.e. arterial tension. The uric acid simultaneously participates in realization of biologic function of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension.

Complex enzyme hydrolysis releases antioxidative phenolics from rice bran.

PubMed

Liu, Lei; Wen, Wei; Zhang, Ruifen; Wei, Zhencheng; Deng, Yuanyuan; Xiao, Juan; Zhang, Mingwei

2017-01-01

In this study, phenolic profiles and antioxidant activity of rice bran were analyzed following successive treatment by gelatinization, liquefaction and complex enzyme hydrolysis. Compared with gelatinization alone, liquefaction slightly increased the total amount of phenolics and antioxidant activity as measured by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Complex enzyme hydrolysis significantly increased the total phenolics, flavonoids, FRAP and ORAC by 46.24%, 79.13%, 159.14% and 41.98%, respectively, compared to gelatinization alone. Furthermore, ten individual phenolics present in free or soluble conjugate forms were also analyzed following enzymatic processing. Ferulic acid experienced the largest release, followed by protocatechuic acid and then quercetin. Interestingly, a major proportion of phenolics existed as soluble conjugates, rather than free form. Overall, complex enzyme hydrolysis releases phenolics, thus increasing the antioxidant activity of rice bran extract. This study provides useful information for processing rice bran into functional beverage rich in phenolics. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Biochemical basis of the single theory of aging. Part II. The cell aerobic status, the hypoxia resistance and proliferation].

PubMed

Kirova, Iu I; Borodulin, V B

2009-01-01

Cells of an organism have different parameters of morphology, metabolism, isoenzyme composition, proliferation and respiration. These differences are derivatives of the cell aerobic status. The primary oxygen acceptors are the "macroscopic" cells (neurons, cardiocytes). In these obligatory aerobic cells oxygen is converted into metabolic water directly by the cytochrome oxidase activity. The secondary oxygen acceptors are the "microscopic" cells (other single-nucleus cells). In these facultative aerobic cells oxygen is converted into hydrogen peroxide. The intracellular labile peroxide pool of oxygen is formed by the oxidase, cytochrome P450, superoxide dismutase, and the mitochondrial cyan-resistance oxidase. The mitochondrial isoenzymes of catalase, glutation peroxidase, and thioredoxin reductase convert hydrogen peroxide into molecular oxygen and form high local oxygen concentration as the major factor for the cytochrome oxidase activity. The hypoxia resistance is increased by the growth of the functional activity of the peroxide-generative and peroxide-mobilizative enzyme systems.

Characterisation of phenolics, betanins and antioxidant activities in seeds of three Chenopodium quinoa Willd. genotypes.

PubMed

Tang, Yao; Li, Xihong; Zhang, Bing; Chen, Peter X; Liu, Ronghua; Tsao, Rong

2015-01-01

Quinoa (Chenopodium quinoa Willd.) is known for its exceptional nutritional value and potential health benefits. The present study identified the composition of different forms of extractable phenolics and betacyanins of quinoa cultivars in white, red and black, and how they contribute to antioxidant activities. Results showed that at least 23 phenolic compounds were found in either free or conjugated forms (liberated by alkaline and/or acid hydrolysis); the majority of which were phenolic acids, mainly vanillic acid, ferulic acid and their derivatives as well as main flavonoids quercetin, kaempferol and their glycosides. Betacyanins, mainly betanin and isobetanin, were confirmed for the first time to be the pigments of the red and black quinoa seeds, instead of anthocyanins. Darker quinoa seeds had higher phenolic concentration and antioxidant activity. Findings of these phenolics, along with betacyanins in this study add new knowledge to the functional components of quinoa seeds of different cultivar background. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Intelligent command and control systems for satellite ground operations

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1994-01-01

The Georgia Tech portion of the Intelligent Control Center project includes several complementary activities. Two major activities entail thesis level research; the other activities are either support activities or preliminary explorations (e.g., task analyses) to support the research. The first research activity is the development of principles for the design of active interfaces to support monitoring during real-time supports. It is well known that as the operator's task becomes less active, i.e., more monitoring and less active control, there is concern that the operator will be less involved and less able to rapidly identify anomalous or failure situations. The research project to design active monitoring interfaces is an attempt to remediate this undesirable side-effect of increasingly automated control systems that still depend ultimately on operator supervision. The second research activity is the exploration of the use of case-based reasoning as a way to accumulate operator experience and make it available in computational form.

A study of Quaternary structures in the Qom region, West Central Iran

NASA Astrophysics Data System (ADS)

Babaahmadi, A.; Safaei, H.; Yassaghi, A.; Vafa, H.; Naeimi, A.; Madanipour, S.; Ahmadi, M.

2010-12-01

West Central Iran comprises numerous Quaternary faults. Having either strike-slip or thrust mechanisms, these faults are potentially active and therefore capable of creating destructive earthquakes. In this paper, we use satellite images as well as field trips to identify these active faults in the Qom region. The Qom and Indes faults are the main NW-trending faults along which a Quaternary restraining step-over zone has formed. Kamarkuh, Mohsen Abad, and Ferdows anticlines are potentially active structures that formed in this restraining step-over zone. There are some thrusts and anticlines, such as the Alborz anticline and Alborz fault, which are parallel to strike-slip faults such as the Qom fault, indicating deformation partitioning in the area. In addition to NW-trending structures, there is an important NE-trending fault known as the Qomrud fault that has deformed Quaternary deposits and affected Kushk-e-Nosrat fault, Alborz anticline, and Qomrud River. The results of this study imply that the major Quaternary faults of West Central Iran and their restraining step-over zones are potentially active.

Red Misfits in the Sloan Digital Sky Survey: properties of star-forming red galaxies

NASA Astrophysics Data System (ADS)

Evans, Fraser A.; Parker, Laura C.; Roberts, Ian D.

2018-06-01

We study Red Misfits, a population of red, star-forming galaxies in the local Universe. We classify galaxies based on inclination-corrected optical colours and specific star formation rates derived from the Sloan Digital Sky Survey Data Release 7. Although the majority of blue galaxies are star-forming and most red galaxies exhibit little to no ongoing star formation, a small but significant population of galaxies (˜11 per cent at all stellar masses) are classified as red in colour yet actively star-forming. We explore a number of properties of these galaxies and demonstrate that Red Misfits are not simply dusty or highly inclined blue cloud galaxies or quiescent red galaxies with poorly constrained star formation. The proportion of Red Misfits is nearly independent of environment, and this population exhibits both intermediate morphologies and an enhanced likelihood of hosting an active galactic nucleus. We conclude that Red Misfits are a transition population, gradually quenching on their way to the red sequence and this quenching is dominated by internal processes rather than environmentally driven processes. We discuss the connection between Red Misfits and other transition galaxy populations, namely S0s, red spirals, and green valley galaxies.

Earth Observations taken by the Expedition 17 Crew

NASA Image and Video Library

2008-04-20

ISS017-E-005037 (19 April 2008) --- Santorini Volcano, Greece is featured in this image photographed by an Expedition 17 crewmember on the International Space Station. According to scientists, one of the largest volcanic eruptions in the past 10,000 years occurred approximately 1620 BC on the volcanic island of Santorini in the Aegean Sea. This view illustrates the center of Santorini Volcano, located approximately 118 kilometers to the north of Crete (not shown). Prior to 1620 BC, the island of Santorini -- now known as Thera -- had been built up by layers of lava created by overlapping shield volcanoes, and had experienced three significant eruptions that formed overlapping calderas, or collapsed magma chambers. Around 1620 BC, the fourth (and latest) major eruption created the present-day islands and caldera bay of Santorini Volcano. The caldera rim is clearly visible in this image as a steep cliff forming the western shoreline of the island of Thera. Following the 1620 BC eruption, much of the previous island of Santorini was destroyed or submerged. The white rooftops of cities and towns trace the caldera rim on the island of Thera, and overlook the young central islands of Nea Kameni and Palaea Kameni -- both, according to scientists, formed from lava domes and flows that started erupting approximately 1400 years after the last major caldera-forming event. Several of these flows are visible in the image as brown to dark-brown irregular masses forming Nea Kameni (left). The most recent volcanic activity in the Kameni islands occurred in 1950, and included some small explosions and production of lava. The extent of development and location of an airport (upper right) on Thera illustrate the popularity of Santorini Volcano as a tourist destination. Today, volcanic activity is closely monitored by the Institute for the Study and Monitoring of the Santorini Volcano, or ISMOSAV.

Pediatric scleroderma: systemic or localized forms.

PubMed

Torok, Kathryn S

2012-04-01

Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, with up to a quarter of patients showing extracutaneous disease manifestations such as arthritis and uveitis. Vascular, cutaneous, gastrointestinal, pulmonary, and musculoskeletal involvement are most commonly seen in children with SSc. Treatment of both forms targets the active inflammatory stage and halts disease progression; however, progress needs to be made toward the development of more effective antifibrotic therapy to help reverse disease damage. Copyright © 2012 Elsevier Inc. All rights reserved.

Leishmanicidal activity of the crude extract, fractions and major piperidine alkaloids from the flowers of Senna spectabilis.

PubMed

de Albuquerque Melo, Gabriela Muniz; Silva, Marcela Campelo Rodrigues; Guimarães, Thaís Pereira; Pinheiro, Kátia Mantovani; da Matta, Carolina Barbosa Brito; de Queiroz, Aline Cavalcanti; Pivatto, Marcos; Bolzani, Vanderlan da Silva; Alexandre-Moreira, Magna Suzana; Viegas, Claudio

2014-02-15

Senna spectabilis (sin. Cassia excelsa, C. spectabilis) is an endemic tree of South America and Africa, very common in Brazil, where it is known as "canafistula-de-besouro" and "cassia-do-nordeste". In folk medicine, this plant is indicated for the treatment of constipation, insomnia, anxiety, epilepsy, malaria, dysentery and headache. Phytopharmacological studies have also confirmed anticonvulsive, sedative, anti-malarial, antimicrobial and cytotoxic properties of many parts of S. spectabilis. In this communication, we present a comparative study of the leishmanicidal activity of the crude ethanolic extract, its fractions and also the two major alkaloidal metabolites (-)-cassine/(-)-spectaline, trying to establish a relationship between the presence of piperidine alkaloidal constituents and leishmanicidal activity. The growth inhibitory effect of promastigote forms of Leishmania major was determined for the crude extract, fractions of the flowers of S. spectabilis and a mixture of (-)-cassine/(-)-spectaline in comparison to pentamidine used as standard drug. The cytotoxic effects were assessed on macrophage strain J774 by lactate dehydrogenase assay. Fractions dichloromethane (FL-DCM) and n-butanol (FL-Bu) and a mixture of (-)-cassine/(-)-spectaline (∼7:3) exhibited significant activity against the parasite Leishmania major (IC50 values of 0.6±0.1 μg/ml, 1.6±0.9 μg/ml and 24.9±1.4 μg/ml, respectively), without toxic effects on murine macrophages. Due to the promising results elicited, further studies in vivo need to be performed to confirm the therapeutic potential of Senna spectabilis. Copyright © 2013 Elsevier GmbH. All rights reserved.

Anti-cancer and other bioactivities of Korean Angelica gigas Nakai (AGN) and its major pyranocoumarin compounds.

PubMed

Zhang, Jinhui; Li, Li; Jiang, Cheng; Xing, Chengguo; Kim, Sung-Hoon; Lü, Junxuan

2012-12-01

Korean Angelica gigas Nakai (AGN) is a major medicinal herb used in Asian countries such as Korea and China. Traditionally, its dried root has been used to treat anemia, pain, infection and articular rheumatism in Korea, most often through boiling in water to prepare the dosage forms. The pyranocoumarin compound decursin and its isomer decursinol angelate (DA) are the major chemical components in the alcoholic extracts of the root of AGN. The in vitro anti-tumor activities of decursin and/or DA against prostate cancer, lung cancer, breast cancer, colon cancer, bladder cancer, sarcoma, myeloma and leukemia have been increasingly reported in the past decade whereas the in vivo efficacy in mouse models was established only for a few organ sites. Preliminary pharmacokinetic studies by us and others in rodent models indicated that decursinol (DOH), which has much less in vitro direct anticancer activities by itself, is the major and rapid in vivo hydrolysis metabolite of both decursin and DA. Besides decursin, DA and DOH, other chemical components in AGN such as polysaccharides and polyacetylenes have been reported to exert anti-cancer and anti-inflammation activities as well. We systematically reviewed the published literature on the anti-cancer and other bio-activities effects of AGN extract and decursin, DA and DOH, as well as other chemicals identified from AGN. Although a number of areas are identified that merit further investigation, one critical need is first-in-human studies of the pharmacokinetics of decursin/DA to determine whether humans differ from rodents in absorption and metabolism of these compounds.

Structural Maturation of HIV-1 Reverse Transcriptase—A Metamorphic Solution to Genomic Instability

PubMed Central

London, Robert E.

2016-01-01

Human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT)—a critical enzyme of the viral life cycle—undergoes a complex maturation process, required so that a pair of p66 precursor proteins can develop conformationally along different pathways, one evolving to form active polymerase and ribonuclease H (RH) domains, while the second forms a non-functional polymerase and a proteolyzed RH domain. These parallel maturation pathways rely on the structural ambiguity of a metamorphic polymerase domain, for which the sequence–structure relationship is not unique. Recent nuclear magnetic resonance (NMR) studies utilizing selective labeling techniques, and structural characterization of the p66 monomer precursor have provided important insights into the details of this maturation pathway, revealing many aspects of the three major steps involved: (1) domain rearrangement; (2) dimerization; and (3) subunit-selective RH domain proteolysis. This review summarizes the major structural changes that occur during the maturation process. We also highlight how mutations, often viewed within the context of the mature RT heterodimer, can exert a major influence on maturation and dimerization. It is further suggested that several steps in the RT maturation pathway may provide attractive targets for drug development. PMID:27690082

Potent and Selective Peptide-based Inhibition of the G Protein Gαq*

PubMed Central

Charpentier, Thomas H.; Waldo, Gary L.; Lowery-Gionta, Emily G.; Krajewski, Krzysztof; Strahl, Brian D.; Kash, Thomas L.; Harden, T. Kendall; Sondek, John

2016-01-01

In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gαq binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gαq within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gαq in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gαq. A representative peptide was specific for active Gαq because it did not bind inactive Gαq or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ1γ2. In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gαq; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gαq in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gαq-dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gαq in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gαq in cells. PMID:27742837

Potent and Selective Peptide-based Inhibition of the G Protein Gαq.

PubMed

Charpentier, Thomas H; Waldo, Gary L; Lowery-Gionta, Emily G; Krajewski, Krzysztof; Strahl, Brian D; Kash, Thomas L; Harden, T Kendall; Sondek, John

2016-12-02

In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gα q binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gα q within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gα q in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gα q A representative peptide was specific for active Gα q because it did not bind inactive Gα q or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ 1 γ 2 In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gα q ; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gα q in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gα q -dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gα q in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gα q in cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Candida albicans orf19.3727 encodes phytase activity and is essential for human tissue damage

PubMed Central

Fong, Wing-Ping; Samaranayake, Lakshman Perera

2017-01-01

Candida albicans is a clinically important human fungal pathogen. We previously identified the presence of cell-associated phytase activity in C. albicans. Here, we reveal for the first time, that orf19.3727 contributes to phytase activity in C. albicans and ultimately to its virulence potency. Compared with its wild type counterpart, disruption of C. albicans orf19.3727 led to decreased phytase activity, reduced ability to form hyphae, attenuated in vitro adhesion, and reduced ability to penetrate human epithelium, which are the major virulence attributes of this yeast. Thus, orf19.3727 of C. albicans plays a key role in fungal pathogenesis. Further, our data uncover a putative novel strategy for anti-Candidal drug design through inhibition of phytase activity of this common pathogen. PMID:29216308

Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania.

PubMed

Chan, Marion Man-Ying; Adapala, Naga Suresh; Fong, Dunne

2005-04-01

Upon Leishmania infection, macrophages are activated to produce nitrogen and oxygen radicals simultaneously. It is well established that the infected host cells rely on nitric oxide (NO) as the major weapon against the intracellular parasite. In India where leishmaniasis is endemic, the spice turmeric is used prolifically in food and for insect bites. Curcumin, the active principle of turmeric, is a scavenger of NO. This report shows that curcumin protects promastigotes and amastigotes of the visceral species, Leishmania donovani, and promastigotes of the cutaneous species, L. major, against the actions of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and DETANONOate, which release NO, 3-morpholino-sydnonimine hydrochloride (SIN-1), which releases NO and superoxide, and peroxynitrite, which is formed from the reaction of NO with superoxide. Thus, curcumin, as an antioxidant, is capable of blocking the action of both NO and NO congeners on the Leishmania parasite.

Whiskerless Schottky diode

NASA Technical Reports Server (NTRS)

Bishop, William L. (Inventor); Mcleod, Kathleen A. (Inventor); Mattauch, Robert J. (Inventor)

1991-01-01

A Schottky diode for millimeter and submillimeter wave applications is comprised of a multi-layered structure including active layers of gallium arsenide on a semi-insulating gallium arsenide substrate with first and second insulating layers of silicon dioxide on the active layers of gallium arsenide. An ohmic contact pad lays on the silicon dioxide layers. An anode is formed in a window which is in and through the silicon dioxide layers. An elongated contact finger extends from the pad to the anode and a trench, preferably a transverse channel or trench of predetermined width, is formed in the active layers of the diode structure under the contact finger. The channel extends through the active layers to or substantially to the interface of the semi-insulating gallium arsenide substrate and the adjacent gallium arsenide layer which constitutes a buffer layer. Such a structure minimizes the effect of the major source of shunt capacitance by interrupting the current path between the conductive layers beneath the anode contact pad and the ohmic contact. Other embodiments of the diode may substitute various insulating or semi-insulating materials for the silicon dioxide, various semi-conductors for the active layers of gallium arsenide, and other materials for the substrate, which may be insulating or semi-insulating.

Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration-Resistant Prostate Cancers

DTIC Science & Technology

2015-10-01

Prostate Cancers PRINCIPAL INVESTIGATORS: Scott Dehm CONTRACTING ORGANIZATION: University of Minnesota Minneapolis, MN 55455 REPORT DATE: October...7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Regents of the University of Minnesota Office of...for pharmacological development b. Accomplishments under these goals: Major Activities for University of Minnesota Site (Dehm, PI) In the

Chimeric antigen receptor T-cell therapy in AML: How close are we?

PubMed Central

Gill, Saar

2016-01-01

The majority of patients presenting with acute myeloid leukemia (AML) initially respond to chemotherapy but post-remission therapy is required to consolidate this response and achieve long-term disease-free survival. The most effective form of post-remission therapy relies on T-cell immunotherapy in the form of allogeneic hematopoietic cell transplantation (HCT). However, patients with active disease cannot usually expect to be cured with HCT. This inherent dichotomy implies that traditional T cell-based immunotherapy in the form of allogeneic HCT stops being efficacious somewhere between the measurable residual disease (MRD) and the morphologically obvious range. This is in part because the full power of T cells must be restrained in order to avoid lethal graft-versus-host disease (GVHD) and partly because only a sub-population of donor T cells are expected to be able to recognize AML cells via their T cell receptor. Chimeric antigen receptor (CAR) T cell therapy, most advanced in the treatment of patients with B-cell malignancies, may circumvent some of these limitations. However, major challenges remain to be overcome before CAR T cell therapy can be safely applied to AML. PMID:27890255

The magnitude of growth hormone elevation is related with the proportion of monomeric form in acromegaly.

PubMed

Ochoa, R; Fonseca, E; Mercado, M; Galván, R E; Hernández, M; Zárate, A

1995-01-01

In acromegalic patients monomeric GH form constitutes the larger proportion of circulating GH; however, no data are available concerning the relation between total GH elevation and the predominance of GH forms. Therefore, we studied the relationship between the degree of GH elevation and the proportion of GH isoforms. Sera from 11 patients with active acromegaly were subjected to gel chromatography on Sephadex G-100 column and fractions were collected for RIA to measure GH. The monomeric form of GH was predominant and exhibited a lineal correlation (r = 0.76, p < 0.01) with the circulating GH, thus the higher elevation of GH, the major proportion of monomeric GH. IGF-1 changes correlate with changes in monomeric GH but no better than for total GH. There was a correlation observed (r = 0.65) between the proportion of low GH forms and the presence of hyperglycemia, although the physiological role of the lower molecular GH forms is still unknown. In conclusion, it was demonstrated that the relative proportion of GH molecular forms changes according to the magnitude of the elevation of total GH.

The role of major rift faults in the evolution of deformation bands in the Rio do Peixe Basin, Brazil

NASA Astrophysics Data System (ADS)

Hilario Bezerra, Francisco; Araujo, Renata; Maciel, Ingrid; Cezar Nogueira, Francisco; Balsamo, Fabrizio; Storti, Fabrizio; Souza, Jorge Andre; Carvalho, Bruno

2017-04-01

Many studies have investigated on the evolution and properties of deformation bands, but their occurrence and relationships with basin-boundary faults remain elusive when the latter form by brittle reactivation of structural inheritance in crystalline basements. The main objective of our study was to systematically record the location, kinematics, geometry, and density of deformation bands in the early Cretaceous Rio do Peixe basin, NE Brazil, and analyze their relationship with major syn-rift fault zones. Reactivation in early Cretaceous times of continental-scale ductile shear zones led to the development of rift basins in NE Brazil. These shear zones form a network of NE- and E-W-trending structures hundreds of kilometers long and 3-10 km wide. They were active in the Brasiliano orogeny at 540-740 Ma. Brittle reactivation of these structures occurred in Neocomian times ( 140-120 Ma) prior the breakup between the South American and African plates in the late Cretaceous. The Rio do Peixe basin formed at the intersection between the NE-SW-striking Portalegre shear zone and the E-W-striking Patos shear zone. The brittle fault systems developed by the shear zone reactivation are the Portalegre Fault and the Malta Fault, respectively. In this research we used field structural investigations and drone imagery with centimetric resolution. Our results indicate that deformation bands occur in poorly sorted, medium to coarse grain size sandstones and localize in 3-4 km wide belts in the hanging wall of the two main syn-rifts fault systems. Deformation bands formed when sandstones were not completely lithified. They strike NE along the Portalegre Fault and E-W along the Malta Fault and have slip lineations with rake values ranging from 40 to 90. The kinematics recorded in deformation bands is consistent with that characterizing major rift fault systems, i.e. major extension with a strike-slip component. Since deformations bands are typical sub-seismic features, our findings can have implications for the prediction of deformation band occurrence in sedimentary basins and their geometric and kinematic relations with major basin-boundary fault systems.

Decadal Survey: Planetary Rings Panel

NASA Astrophysics Data System (ADS)

Gordon, M. K.; Cuzzi, J. N.; Lissauer, J. J.; Poulet, F.; Brahic, A.; Charnoz, S.; Ferrari, C.; Burns, J. A.; Nicholson, P. D.; Durisen, R. H.; Rappaport, N. J.; Spilker, L. J.; Yanamandra-Fisher, P.; Bosh, A. S.; Olkin, C.; Larson, S. M.; Graps, A. L.; Krueger, H.; Black, G. J.; Festou, M.; Karjalainen, R.; Salo, H. J.; Murray, C. D.; Showalter, M. R.; Dones, L.; Levison, H. F.; Namouni, F.; Araki, S.; Lewis, M. C.; Brooks, S.; Colwell, J. E.; Esposito, L. W.; Horanyi, M.; Stewart, G. R.; Krivov, A.; Schmidt, J.; Spahn, F.; Hamilton, D. P.; Giuliatti-Winter, S.; French, R. G.

2001-11-01

The National Research Council's Committee on Planetary and Lunar Exploration(COMPLEX) met earlier this year to begin the organization of a major activity, "A New Strategy for Solar System Exploration." Several members of the planetary rings community formed an ad hoc panel to discuss the current state and future prospects for the study of planetary rings. In this paper we summarize fundamental questions of ring science, list the key science questions expected to occupy the planetary rings community for the decade 2003-2013, outline the initiatives, missions, and other supporting activities needed to address those questions, and recommend priorities.

Regulation of Auxin Homeostasis and Gradients in Arabidopsis Roots through the Formation of the Indole-3-Acetic Acid Catabolite 2-Oxindole-3-Acetic Acid[C][W][OPEN

PubMed Central

Pěnčík, Aleš; Simonovik, Biljana; Petersson, Sara V.; Henyková, Eva; Simon, Sibu; Greenham, Kathleen; Zhang, Yi; Kowalczyk, Mariusz; Estelle, Mark; Zažímalová, Eva; Novák, Ondřej; Sandberg, Göran; Ljung, Karin

2013-01-01

The native auxin, indole-3-acetic acid (IAA), is a major regulator of plant growth and development. Its nonuniform distribution between cells and tissues underlies the spatiotemporal coordination of many developmental events and responses to environmental stimuli. The regulation of auxin gradients and the formation of auxin maxima/minima most likely involve the regulation of both metabolic and transport processes. In this article, we have demonstrated that 2-oxindole-3-acetic acid (oxIAA) is a major primary IAA catabolite formed in Arabidopsis thaliana root tissues. OxIAA had little biological activity and was formed rapidly and irreversibly in response to increases in auxin levels. We further showed that there is cell type–specific regulation of oxIAA levels in the Arabidopsis root apex. We propose that oxIAA is an important element in the regulation of output from auxin gradients and, therefore, in the regulation of auxin homeostasis and response mechanisms. PMID:24163311

Of channels and pumps: different ways to boost the aldosterone?

PubMed

Bandulik, S

2017-07-01

The mineralocorticoid aldosterone is a major factor controlling the salt and water balance and thereby also the arterial blood pressure. Accordingly, primary aldosteronism (PA) characterized by an inappropriately high aldosterone secretion is the most common form of secondary hypertension. The physiological stimulation of aldosterone synthesis in adrenocortical glomerulosa cells by angiotensin II and an increased plasma K + concentration depends on a membrane depolarization and an increase in the cytosolic Ca 2+ activity. Recurrent gain-of-function mutations of ion channels and transporters have been identified in a majority of cases of aldosterone-producing adenomas and in familial forms of PA. In this review, the physiological role of these genes in the regulation of aldosterone synthesis and the altered function of the mutant proteins as well are described. The specific changes of the membrane potential and the cellular ion homoeostasis in adrenal cells expressing the different mutants are compared, and their impact on autonomous aldosterone production and proliferation is discussed. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

C-fos induction in forebrain areas of two different visual pathways during consolidation of sexual imprinting in the zebra finch (Taeniopygia guttata).

PubMed

Sadananda, Monika; Bischof, Hans-Joachim

2006-10-16

Two forebrain areas in the hyperpallium apicale and in the lateral nidopallium of isolated male zebra finches are highly active (2-deoxyglucose technique) on exposure to females for the first time, that is first courtship. These areas also demonstrate enhanced neuronal plasticity when screened with c-fos immunocytochemistry. Both are areas involved in the processing of visual information conveyed by the two major visual pathways in birds, strengthening our hypothesis that courtship in the zebra finch is a visually guided behaviour. First courtship and chased birds show enhanced c-fos induction in the hyperpallial area, which could represent neuronal activity reflecting changes in the immediate environment. The enhanced expression of fos in first courtship birds in lateral nidopallial neurons indicates imminent long-lasting changes at the synaptic level that form the substrate for imprinting, a stable form of learning in birds.

Thermogravimetric study on pyrolysis kinetics of Chlorella pyrenoidosa and bloom-forming cyanobacteria.

PubMed

Hu, Mian; Chen, Zhihua; Guo, Dabin; Liu, Cuixia; Xiao, Bo; Hu, Zhiquan; Liu, Shiming

2015-02-01

The pyrolysis process of two microalgae, Chlorella pyrenoidosa (CP) and bloom-forming cyanobacteria (CB) was examined by thermo-gravimetry to investigate their thermal decomposition behavior under non-isothermal conditions. It has found that the pyrolysis of both microalgae consists of three stages and stage II is the major mass reduction stage with mass loss of 70.69% for CP and 64.43% for CB, respectively. The pyrolysis kinetics of both microalgae was further studied using single-step global model (SSGM) and distributed activation energy model (DAEM). The mean apparent activation energy of CP and CB in SSGM was calculated as 143.71 and 173.46 kJ/mol, respectively. However, SSGM was not suitable for modeling pyrolysis kinetic of both microalgae due to the mechanism change during conversion. The DAEM with 200 first-order reactions showed an excellent fit between simulated data and experimental results. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure and Functional Characterization of Vibrio parahaemolyticus Thermostable Direct Hemolysin*

PubMed Central

Yanagihara, Itaru; Nakahira, Kumiko; Yamane, Tsutomu; Kaieda, Shuji; Mayanagi, Kouta; Hamada, Daizo; Fukui, Takashi; Ohnishi, Kiyouhisa; Kajiyama, Shin'ichiro; Shimizu, Toshiyuki; Sato, Mamoru; Ikegami, Takahisa; Ikeguchi, Mitsunori; Honda, Takeshi; Hashimoto, Hiroshi

2010-01-01

Thermostable direct hemolysin (TDH) is a major virulence factor of Vibrio parahaemolyticus that causes pandemic foodborne enterocolitis mediated by seafood. TDH exists as a tetramer in solution, and it possesses extreme hemolytic activity. Here, we present the crystal structure of the TDH tetramer at 1.5 Å resolution. The TDH tetramer forms a central pore with dimensions of 23 Å in diameter and ∼50 Å in depth. π-Cation interactions between protomers comprising the tetramer were indispensable for hemolytic activity of TDH. The N-terminal region was intrinsically disordered outside of the pore. Molecular dynamic simulations suggested that water molecules permeate freely through the central and side channel pores. Electron micrographs showed that tetrameric TDH attached to liposomes, and some of the tetramer associated with liposome via one protomer. These findings imply a novel membrane attachment mechanism by a soluble tetrameric pore-forming toxin. PMID:20335168

Stereoselective potencies and relative toxicities of coniine enantiomers.

PubMed

Lee, Stephen T; Green, Benedict T; Welch, Kevin D; Pfister, James A; Panter, Kip E

2008-10-01

Coniine, one of the major toxic alkaloids present in poison hemlock ( Conium maculatum), occurs in two optically active forms. A comparison of the relative potencies of (+)- and (-)-coniine enantiomers has not been previously reported. In this study, we separated the enantiomers of coniine and determined the biological activity of each enantiomer in vitro and in vivo. The relative potencies of these enantiomers on TE-671 cells expressing human fetal nicotinic neuromuscular receptors had the rank order of (-)-coniine > (+/-)-coniine > (+)-coniine. A mouse bioassay was used to determine the relative lethalities of (-)-, (+/-)-, and (+)-coniine in vivo. The LD 50 values of the coniine enantiomers were 7.0, 7.7, and 12.1 mg/kg for the (-)-, (+/-)-, and (+)- forms of coniine, respectively. The results from this study demonstrate that there is a stereoselective difference in the in vitro potencies of the enantiomers of coniine that directly correlates with the relative toxicities of the enantiomers in vivo.

Genetically Engineered Materials for Biofuels Production

NASA Astrophysics Data System (ADS)

Raab, Michael

2012-02-01

Agrivida, Inc., is an agricultural biotechnology company developing industrial crop feedstocks for the fuel and chemical industries. Agrivida's crops have improved processing traits that enable efficient, low cost conversion of the crops' cellulosic components into fermentable sugars. Currently, pretreatment and enzymatic conversion of the major cell wall components, cellulose and hemicellulose, into fermentable sugars is the most expensive processing step that prevents widespread adoption of biomass in biofuels processes. To lower production costs we are consolidating pretreatment and enzyme production within the crop. In this strategy, transgenic plants express engineered cell wall degrading enzymes in an inactive form, which can be reactivated after harvest. We have engineered protein elements that disrupt enzyme activity during normal plant growth. Upon exposure to specific processing conditions, the engineered enzymes are converted into their active forms. This mechanism significantly lowers pretreatment costs and enzyme loadings (>75% reduction) below those currently available to the industry.

Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation.

PubMed

Nieminen, Mikko T; Listyarifah, Dyah; Hagström, Jaana; Haglund, Caj; Grenier, Daniel; Nordström, Dan; Uitto, Veli-Jukka; Hernandez, Marcela; Yucel-Lindberg, Tülay; Tervahartiala, Taina; Ainola, Mari; Sorsa, Timo

2018-02-06

Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis. The presence of Td-CTLP within orodigestive tumour tissues was examined using immunohistochemistry. Oral, tonsillar, and oesophageal squamous cell carcinomas, alongside gastric, pancreatic, and colon adenocarcinomas were stained with a Td-CTLP-specific antibody. Gingival tissue from periodontitis patients served as positive controls. SDS-PAGE and immunoblot were used to analyse the immumodulatory activity of Td-CTLP in vitro. Td-CTLP was present in majority of orodigestive tumour samples. Td-CTLP was found to convert pro MMP-8 and -9 into their active forms. In addition, Td-CTLP was able to degrade the proteinase inhibitors TIMP-1, TIMP-2, and α-1-antichymotrypsin, as well as complement C1q. Because of its presence within tumours and regulatory activity on proteins critical for the regulation of tumour microenvironment and inflammation, the Td-CTLP may contribute to orodigestive carcinogenesis.

Identifying the Factors That Facilitate or Hinder Advance Planning by Persons With Dementia

PubMed Central

Hirschman, Karen B.; Kapo, Jennifer M.; Karlawish, Jason H. T.

2009-01-01

We performed semistructured interviews with 30 family members of patients with advanced dementia to identify the factors that facilitate or hinder advance planning by persons with dementia. All interviews were analyzed using qualitative data analysis techniques. The majority (77%) of family members reported that their relative had some form of written advance directive, and at least half reported previous discussions about health care preferences (57%), living situation or placement issues (50%), and finances or estate planning (60%) with the patient. Family members reported some themes that prompted planning and others that were barriers to planning. Events that most often triggered planning were medical, living situation, or financial issues associated with a friend or family member of the patient (57%). Barriers to planning included both passive and active avoidance. The most common form of passive avoidance was not realizing the importance of planning until it was too late to have the discussion (63%). The most common form of active avoidance was avoiding the discussion (53%). These data suggest potentially remediable strategies to address barriers to advance planning discussions. PMID:18580595

ATP-sulfurylase, sulfur-compounds, and plant stress tolerance

PubMed Central

Anjum, Naser A.; Gill, Ritu; Kaushik, Manjeri; Hasanuzzaman, Mirza; Pereira, Eduarda; Ahmad, Iqbal; Tuteja, Narendra; Gill, Sarvajeet S.

2015-01-01

Sulfur (S) stands fourth in the list of major plant nutrients after N, P, and K. Sulfate (SO42-), a form of soil-S taken up by plant roots is metabolically inert. As the first committed step of S-assimilation, ATP-sulfurylase (ATP-S) catalyzes SO42--activation and yields activated high-energy compound adenosine-5′-phosphosulfate that is reduced to sulfide (S2-) and incorporated into cysteine (Cys). In turn, Cys acts as a precursor or donor of reduced S for a range of S-compounds such as methionine (Met), glutathione (GSH), homo-GSH (h-GSH), and phytochelatins (PCs). Among S-compounds, GSH, h-GSH, and PCs are known for their involvement in plant tolerance to varied abiotic stresses, Cys is a major component of GSH, h-GSH, and PCs; whereas, several key stress-metabolites such as ethylene, are controlled by Met through its first metabolite S-adenosylmethionine. With the major aim of briefly highlighting S-compound-mediated role of ATP-S in plant stress tolerance, this paper: (a) overviews ATP-S structure/chemistry and occurrence, (b) appraises recent literature available on ATP-S roles and regulations, and underlying mechanisms in plant abiotic and biotic stress tolerance, (c) summarizes ATP-S-intrinsic regulation by major S-compounds, and (d) highlights major open-questions in the present context. Future research in the current direction can be devised based on the discussion outcomes. PMID:25904923

Active Oxidation of SiC

NASA Technical Reports Server (NTRS)

Jacobson, Nathan S.; Myers,Dwight L.; Harder, Bryan J.

2011-01-01

The high temperature oxidation of silicon carbide occurs in either a passive or active mode, depending on temperature and oxygen potential. Passive oxidation forms a protective oxide film which limits attack of the SiC:SiC(s) + 3/2 O2(g) = SiO2(s) + CO(g.) Active oxidation forms a volatile oxide and leads to extensive attack of the SiC: SiC(s) + O2(g) = SiO(g) + CO(g). The transition points and rates of active oxidation are a major issue. Previous studies are reviewed and the leading theories of passive/active transitions summarized. Comparisons are made to the active/passive transitions in pure Si, which are relatively well-understood. Critical questions remain about the difference between the active-to-passive transition and passive-to-active transition. For Si, Wagner [2] points out that the active-to-passive transition is governed by the criterion for a stable Si/SiO2 equilibria and the passive-to-active transition is governed by the decomposition of the SiO2 film. This suggests a significant oxygen potential difference between these two transitions and our experiments confirm this. For Si, the initial stages of active oxidation are characterized by the formation of SiO(g) and further oxidation to SiO2(s) as micron-sized rods, with a distinctive morphology. SiC shows significant differences. The active-to-passive and the passive-to-active transitions are close. The SiO2 rods only appear as the passive film breaks down. These differences are explained in terms of the reactions at the SiC/SiO2 interface. In order to understand the breakdown of the passive film, pre-oxidation experiments are conducted. These involve forming dense protective scales of 0.5, 1, and 2 microns and then subjecting the samples with these scales to a known active oxidation environment. Microstructural studies show that SiC/SiO2 interfacial reactions lead to a breakdown of the scale with a distinct morphology.

Chitosan Composites for Bone Tissue Engineering—An Overview

PubMed Central

Venkatesan, Jayachandran; Kim, Se-Kwon

2010-01-01

Bone contains considerable amounts of minerals and proteins. Hydroxyapatite [Ca10(PO4)6(OH)2] is one of the most stable forms of calcium phosphate and it occurs in bones as major component (60 to 65%), along with other materials including collagen, chondroitin sulfate, keratin sulfate and lipids. In recent years, significant progress has been made in organ transplantation, surgical reconstruction and the use of artificial protheses to treat the loss or failure of an organ or bone tissue. Chitosan has played a major role in bone tissue engineering over the last two decades, being a natural polymer obtained from chitin, which forms a major component of crustacean exoskeleton. In recent years, considerable attention has been given to chitosan composite materials and their applications in the field of bone tissue engineering due to its minimal foreign body reactions, an intrinsic antibacterial nature, biocompatibility, biodegradability, and the ability to be molded into various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. The composite of chitosan including hydroxyapatite is very popular because of the biodegradability and biocompatibility in nature. Recently, grafted chitosan natural polymer with carbon nanotubes has been incorporated to increase the mechanical strength of these composites. Chitosan composites are thus emerging as potential materials for artificial bone and bone regeneration in tissue engineering. Herein, the preparation, mechanical properties, chemical interactions and in vitro activity of chitosan composites for bone tissue engineering will be discussed. PMID:20948907

Biological activities of xanthatin from Xanthium strumarium leaves.

PubMed

Nibret, Endalkachew; Youns, Mahamoud; Krauth-Siegel, R Luise; Wink, Michael

2011-12-01

The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis. Copyright © 2011 John Wiley & Sons, Ltd.

Crystallization and preliminary crystallographic characterization of LmACR2, an arsenate/antimonate reductase from Leishmania major

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bisacchi, Davide; Zhou, Yao; Rosen, Barry P.

2006-10-01

LmACR2 from L. major is the first rhodanese-like enzyme directly involved in the reduction of arsenate and antimonate to be crystallized. Diffraction data have been collected to 1.99 Å resolution using synchrotron X-rays. Arsenic is present in the biosphere owing either to the presence of pesticides and herbicides used in agricultural and industrial activities or to leaching from geological formations. The health effects of prolonged exposure to arsenic can be devastating and may lead to various forms of cancer. Antimony(V), which is chemically very similar to arsenic, is used instead in the treatment of leishmaniasis, an infection caused by themore » protozoan parasite Leishmania sp.; the reduction of pentavalent antimony contained in the drug Pentostam to the active trivalent form arises from the presence in the Leishmania genome of a gene, LmACR2, coding for the protein LmACR2 (14.5 kDa, 127 amino acids) that displays weak but significant sequence similarity to the catalytic domain of Cdc25 phosphatase and to rhodanese enzymes. For structural characterization, LmACR2 was overexpressed, purified to homogeneity and crystallized in a trigonal space group (P321 or P3{sub 1}21/P3{sub 2}21). The protein crystallized in two distinct trigonal crystal forms, with unit-cell parameters a = b = 111.0, c = 86.1 Å and a = b = 111.0, c = 175.6 Å, respectively. At a synchrotron beamline, the diffraction pattern extended to a resolution limit of 1.99 Å.« less

Structural modeling and docking studies of ribose 5-phosphate isomerase from Leishmania major and Homo sapiens: a comparative analysis for Leishmaniasis treatment.

PubMed

Capriles, Priscila V S Z; Baptista, Luiz Phillippe R; Guedes, Isabella A; Guimarães, Ana Carolina R; Custódio, Fabio L; Alves-Ferreira, Marcelo; Dardenne, Laurent E

2015-02-01

Leishmaniases are caused by protozoa of the genus Leishmania and are considered the second-highest cause of death worldwide by parasitic infection. The drugs available for treatment in humans are becoming ineffective mainly due to parasite resistance; therefore, it is extremely important to develop a new chemotherapy against these parasites. A crucial aspect of drug design development is the identification and characterization of novel molecular targets. In this work, through an in silico comparative analysis between the genomes of Leishmania major and Homo sapiens, the enzyme ribose 5-phosphate isomerase (R5PI) was indicated as a promising molecular target. R5PI is an important enzyme that acts in the pentose phosphate pathway and catalyzes the interconversion of d-ribose-5-phosphate (R5P) and d-ribulose-5-phosphate (5RP). R5PI activity is found in two analogous groups of enzymes called RpiA (found in H. sapiens) and RpiB (found in L. major). Here, we present the first report of the three-dimensional (3D) structures and active sites of RpiB from L. major (LmRpiB) and RpiA from H. sapiens (HsRpiA). Three-dimensional models were constructed by applying a hybrid methodology that combines comparative and ab initio modeling techniques, and the active site was characterized based on docking studies of the substrates R5P (furanose and ring-opened forms) and 5RP. Our comparative analyses show that these proteins are structural analogs and that distinct residues participate in the interconversion of R5P and 5RP. We propose two distinct reaction mechanisms for the reversible isomerization of R5P to 5RP, which is catalyzed by LmRpiB and HsRpiA. We expect that the present results will be important in guiding future molecular modeling studies to develop new drugs that are specially designed to inhibit the parasitic form of the enzyme without significant effects on the human analog. Copyright © 2014 Elsevier Inc. All rights reserved.

Cryptic antifungal compounds active by synergism with polyene antibiotics.

PubMed

Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

2016-04-01

The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Extraction of information from major element chemical analyses of lunar basalts

NASA Technical Reports Server (NTRS)

Butler, J. C.

1985-01-01

Major element chemical analyses often form the framework within which similarities and differences of analyzed specimens are noted and used to propose or devise models. When percentages are formed the ratios of pairs of components are preserved whereas many familiar statistical and geometrical descriptors are likely to exhibit major changes. This ratio preserving aspect forms the basis for a proposed framework. An analysis of compositional variability within the data set of 42 major element analyses of lunar reference samples was selected to investigate this proposal.

GDF3 is a BMP inhibitor that can activate Nodal signaling only at very high doses

PubMed Central

Levine, Ariel J.; Levine, Zachary J.; Brivanlou, Ali H.

2013-01-01

Within the TGF-β superfamily, there are approximately forty ligands divided into two major branches: the TGF-β/Activin/Nodal ligands and the BMP/GDF ligands. We studied the ligand GDF3 and found that it inhibits signaling by its co-family members, the BMPs; however, GDF3 has been described by others to have Nodal-like activity. Here, we show that GDF3 can activate Nodal signaling, but only at very high doses and only upon mRNA over-expression. In contrast, GDF3 inhibits BMP signaling upon over-expression of GDF3 mRNA, as recombinant protein, and regardless of its dose. We therefore further characterized the mechanism through which GDF3 protein acts as a specific BMP inhibitor and found that the BMP inhibitory activity of GDF3 resides redundantly in the unprocessed, predominant form and in the mature form of the protein. These results confirm and extend the activity that we described for GDF3 and illuminate the experimental basis for the different observations of others. We suggest that GDF3 is either a bi-functional TGF-β ligand, or, more likely, that it is a BMP inhibitor that can artificially activate Nodal signaling under non-physiological conditions. PMID:18823971

Productive engagement among older Americans: prevalence, patterns, and implications for public policy.

PubMed

Hinterlong, James E

2008-01-01

This study estimates the prevalence of productive engagement among adults aged 60 and over residing in the United States over a nine-year period. We analyze three waves of data from the Americans' Changing Lives Study, which allows the findings to describe the non-institutionalized older American population. Focusing upon five activities--formal paid employment, irregular paid work, unpaid volunteerism, caregiving, and informal assistance to others--we identify changes in the engagement rates, examine the extent to which engagement occurs through single or multiple concurrent activities, and document intra-individual patterns of engagement within and across forms of productive activity, including the continuity, initiation, and cessation of involvement. The findings reveal that late-life productive engagement is widespread, with the majority of older individuals involved in multiple forms of activity concurrently. Non-market-based activities such as caregiving, informal assistance, and volunteering are most prevalent. Initiation and cessation of activities are common and yield more complex patterns and lower rates of non-participation than are revealed in cross-sectional analyses. Time spent in productive engagement is highly variable and exhibits an overall decline across time. We conclude by highlighting policy strategies to increase the availability and quality of opportunities for productive engagement and promote planning for engagement in late life.

Plant Nitrogen Acquisition Under Low Availability: Regulation of Uptake and Root Architecture

PubMed Central

Kiba, Takatoshi; Krapp, Anne

2016-01-01

Nitrogen availability is a major factor determining plant growth and productivity. Plants acquire nitrogen nutrients from the soil through their roots mostly in the form of ammonium and nitrate. Since these nutrients are scarce in natural soils, plants have evolved adaptive responses to cope with the environment. One of the most important responses is the regulation of nitrogen acquisition efficiency. This review provides an update on the molecular determinants of two major drivers of the nitrogen acquisition efficiency: (i) uptake activity (e.g. high-affinity nitrogen transporters) and (ii) root architecture (e.g. low-nitrogen-availability-specific regulators of primary and lateral root growth). Major emphasis is laid on the regulation of these determinants by nitrogen supply at the transcriptional and post-transcriptional levels, which enables plants to optimize nitrogen acquisition efficiency under low nitrogen availability. PMID:27025887

Purification and ATPase activity of human ABCA1.

PubMed

Takahashi, Kei; Kimura, Yasuhisa; Kioka, Noriyuki; Matsuo, Michinori; Ueda, Kazumitsu

2006-04-21

ATP-binding cassette protein A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein metabolism. Apolipoprotein A-I binds to ABCA1 and cellular cholesterol and phospholipids, mainly phosphatidylcholine, are loaded onto apoA-I to form pre-beta high density lipoprotein (HDL). It is proposed that ABCA1 translocates phospholipids and cholesterol directly or indirectly to form pre-beta HDL. To explore the mechanism of ABCA1-mediated pre-beta HDL formation, we expressed human ABCA1 in insect Sf9 cells and purified it. Trypsin limited-digestion of purified ABCA1 in the detergent-soluble form suggested that it retained conformation similar to ABCA1 expressed in the membranes of human fibroblast WI-38 cells. Purified ABCA1 showed robust ATPase activity when reconstituted in liposomes made of synthetic phosphatidylcholine. ABCA1 showed lower ATPase activity when reconstituted in liposomes containing phosphatidylserine, phosphatidylethanolamine, or phosphatidylglycerol and also showed weak specificity in acyl chain species. ATPase activity was reduced by the addition of cholesterol and decreased by 25% in the presence of 20% cholesterol. Beta-sitosterol and campesterol showed similar inhibitory effects but stigmasterol did not, suggesting structure-specific interaction between ABCA1 and sterols. Glibenclamide suppressed ABCA1 ATPase, suggesting that it inhibits apoA-I-dependent cellular cholesterol efflux by suppressing ABCA1 ATPase activity. These results suggest that the ATPase activity of ABCA1 is stimulated preferentially by phospholipids with choline head groups, phosphatidylcholine and sphingomyelin. This study with purified human ABCA1 provides the first biochemical basis of the mechanism for HDL formation mediated by ABCA1.

A Natural Chimeric Pseudomonas Bacteriocin with Novel Pore-Forming Activity Parasitizes the Ferrichrome Transporter

PubMed Central

Kemland, Lieselore; Anoz-Carbonell, Ernesto; Buchanan, Susan K.; De Mot, René

2017-01-01

ABSTRACT Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin’s activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, a Pseudomonas bacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain in Pseudomonas aeruginosa pyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that of Pseudomonas colicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities. PMID:28223456

Direct comparison of XAFS spectroscopy and sequential extraction for arsenic speciation in coal

USGS Publications Warehouse

Huggins, Frank E.; Huffman, G.P.; Kolker, A.; Mroczkowski, S.; Palmer, C.A.; Finkelman, R.B.

2000-01-01

The speciation of arsenic in an Ohio bituminous coal and a North Dakota lignite has been examined by the complementary methods of arsenic XAFS spectroscopy and sequential extraction by aqueous solutions of ammonium acetate, HCl, HF, and HNO3. In order to facilitate a more direct comparison of the two methods, the arsenic XAFS spectra were obtained from aliquots of the coal prepared after each stage of the leaching procedure. For the aliquots, approximately linear correlations (r2 > 0.98 for the Ohio coal, > 0.90 for the ND lignite) were observed between the height of the edge-step in the XAFS analysis and the concentration of arsenic measured by instrumental neutron activation analysis. Results from the leaching sequence indicate that there are two major arsenic forms present in both coals; one is removed by leaching with HCl and the other by HNO3. Whereas the XAFS spectral signatures of the arsenic leached by HCl are compatible with arsenate for both coals, the arsenic leached by HNO3 is identified as arsenic associated with pyrite for the Ohio coal and as an As3+ species for the North Dakota lignite. Minor arsenate forms persist in both coals after the final leaching with nitric acid. The arsenate forms extracted in HCl are believed to be oxidation products derived from the other major arsenic forms upon exposure of the pulverized coals to air.

Pentachlorophenol: Uptake/elimination kinetics and metabolism in an aquatic plant, Eichhornia crassipes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy, S.; Haenninen, O.

1994-05-01

Eichhornia crassipes [(Mart) Solms], an aquatic plant widely used for the treatment of wastewaters, was used to study uptake/elimination kinetics and metabolism of pentachlorophenol (PCP). PCP is a well-known industrial by-product and a major pollutant of the aquatic environment. The initial phase of PCP uptake by the plant was rapid and reached a nearly steady state between 24 and 48 h of exposure to PCP. The major by-products of PCP metabolisms in Eichhornia crassipes were identified as ortho- and para- substituted chlorohydroxyphenols (chlorocatechols and -hydroquiones), -anisoles, and -veratroles. Partially dechlorinated products of PCP were also detected. A major portion ofmore » the absorbed PCP and metabolites was found in bound/conjugated form. The response of the enzyme systems involved in the xenobiotic metabolism and antioxidative system were also studied following PCP exposure. A significant increase was observed in the activity of glutathione S-transferase (GST), a major conjugating enzyme, and in the activities of superoxide dismutase and ascorbate peroxidase of PCP exposed plants. Such responses of plant enzymes may be implemented as useful markers of aquatic pollution. The result related to the uptake and metabolism of PCP obtained from the present study suggests a crucial role of aquatic plants in determining the fate of environmental chemicals.« less

Identification, cloning, and characterization of a major cat flea salivary allergen (Cte f 1).

PubMed

McDermott, M J; Weber, E; Hunter, S; Stedman, K E; Best, E; Frank, G R; Wang, R; Escudero, J; Kuner, J; McCall, C

2000-05-01

An 18 kDa protein isolated from saliva of the cat flea, Ctenocephalides felis, elicits a positive intradermal skin test (IDST) in 100 and 80% of experimental and clinical flea allergic dogs, respectively. Using solid-phase enzyme-linked immuno assay (ELISA), this protein detected IgE in 100 and 80% of experimental and clinical flea allergic dogs, respectively. A cDNA (pFSI) encoding a full-length Cte f 1 protein was isolated from a C. felis salivary gland cDNA library, using a combination of PCR and hybridization screening. This cDNA is 658 bp in length, and contains an open reading frame of 528 bp. The open reading frame encodes a protein of 176 amino acids, consisting of an 18 amino acid signal sequence and a 158 amino acid mature protein. The calculated molecular weight and pI of the mature protein are 18106 Da and 9.3, respectively. The protein, named Cte f 1, is the first novel major allergen described for canine flea allergy. Recombinant Cte f 1 (rCte f 1) was expressed in Escherichia coli, Pichia pastoris and baculovirus infected Trichoplusia ni cells. Approximately, 90% of the rCte f 1 expressed in E. coli accumulated in insoluble inclusion bodies, which could be refolded to a soluble mixture of disulfide isomers with partial IgE binding activity. Small quantities of an apparently correctly refolded form of rCte f 1, which had IgE binding activity equal to the native antigen, was isolated from the soluble fraction of E. coli cells. However, P. pastoris and baculovirus infected insect cells expressed and secreted a fully processed, correctly refolded and fully active form of rCte f 1. Mass spectrometry analysis of the active forms of rCte f 1confirmed that eight intact disulfide bonds were present, matching the number observed in the native allergen. The relative ability of rCte f 1 to bind IgE in the serum of flea allergic animals, produced in these three expression systems, matched that of the native allergen. Competition ELISA demonstrated that approximately 90% of the specific IgE binding to native Cte f 1 could be blocked by the different forms of rCte f 1.

Optimization of Delayed Tolerance Induction in Swine: A Clinically-Relevant Protocol for Immunosuppression-Free Vascularized Composite Allotransplantation

DTIC Science & Technology

2017-10-01

information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October...been achieved in nonhuman primates (NHPs) using a the delayed period protocol, i.e combination of post- transplant non -myeloablative conditioning and...seminars, study groups , and individual study. Include participation in conferences, workshops, and seminars not listed under major activities

Mission description. [major mission events and data collection periods during Apollo 17 lunar exploration

NASA Technical Reports Server (NTRS)

Baldwin, R. R.

1973-01-01

The accomplishments of the Apollo 17 flight are discussed. The scientific objectives included geological surveying and sampling of materials and surface features in a preselected area of the Taurus-Littrow region, deploying and activating surface experiments, and conducting inflight experiments and photographic tasks during lunar orbit and transearth coast. The individual Apollo 17 experiments and photographic tasks are presented in outline form. Charts are developed to show the major mission events and data collection periods correlated to Greenwich Mean Time and ground elapsed time. Maps of the lunar surface ground track envelope for the Apollo 17 orbiting spacecraft for revolutions one to seventy-five is shown.

The Metabolism of Clopidogrel: CYP2C19 Is a Minor Pathway.

PubMed

Ford, Neville F

2016-12-01

The major metabolic pathway of clopidogrel is conversion to carboxylic acid by an esterase (CES1), forming clopidogrelic acid (SR26334) that is inactive. There is agreement on the structure of the active metabolite; however, there are differing views about the mechanism of its formation. Sanofi studied the conversion of clopidogrel to the active metabolite using human liver microsomes. It was concluded that 2-oxo-clopidogrel was formed via CYP3A oxidation. From a subsequent in vitro study by Sankyo of the metabolism of clopidogrel using recombinant DNA CYPs, it was concluded that CYP2C19 was the major oxidative pathway. Such CYPs can give false-negative results particularly with drugs such as clopidogrel that have high first-pass metabolism in the enterocyte. CYP3A is present in the enterocyte but not CYP2C19. However, the view that clopidogrel is a CYP2C19 substrate was reinforced by a finding that omeprazole, a CYP2C19 inhibitor, reduced the ability of clopidogrel to inhibit platelet aggregation. The drug-drug interaction study of clopidogrel with omeprazole had the effect of reducing the area under the curve (AUC) of the clopidogrel active metabolite by 45%. However, a drug interaction study with a CYP3A inhibitor, grapefruit juice, caused a 6-fold reduction in the AUC of the active metabolite. Clopidogrel is therefore now considered to be primarily a CYP3A4/5 substrate. CYP2C19 has a minor role whose effect can be detected using a sensitive methodology such as platelet aggregometry. © 2016, The American College of Clinical Pharmacology.

Functional roles of the major chloroplast lipids in the violaxanthin cycle.

PubMed

Yamamoto, Harry Y

2006-08-01

Monogalactosyldiacylglyceride (MGDG) and digalactosyldiacylglyceride (DGDG) are the major membrane lipids of chloroplasts. The question of the specialized functions of these unique lipids has received limited attention. One function is to support violaxanthin de-epoxidase (VDE) activity, an enzyme of the violaxanthin cycle. To understand better the properties of this system, the effects of galactolipids and phosphatidylcholines on VDE activity were examined by two independent methods. The results show that the micelle-forming lipid (MGDG) and bilayer forming lipids (DGDG and phosphatidylcholines) support VDE activity differently. MGDG supported rapid and complete de-epoxidation starting at a threshold lipid concentration (10 microM) coincident with complete solubilization of violaxanthin. In contrast, DGDG supported slow but nevertheless complete to nearly complete de-epoxidation at a lower lipid concentration (6.7 microM) that did not completely solubilize violaxanthin. Phosphotidylcholines showed similar effects as DGDG except that de-epoxidation was incomplete. Since VDE requires solubilized violaxanthin, aggregated violaxanthin in DGDG at low concentration must become solubilized as de-epoxidation proceeds. High lipid concentrations had lower activity possibly due to formation of multilayered structures (liposomes) that restrict accessibility of violaxanthin to VDE. MGDG micelles do not present such restrictions. The results indicate VDE operates throughout the lipid phase of the single bilayer thylakoid membrane and is not limited to putative MGDG micelle domains. Additionally, the results also explain the differential partitioning of violaxanthin between the envelope and thylakoid as due to the relative solubilities of violaxanthin and zeaxanthin in MGDG, DGDG and phospholipids. The violaxanthin cycle is hypothesized to be a linked system of the thylakoid and envelope for signal transduction of light stress.

Plantago major in Traditional Persian Medicine and modern phytotherapy: a narrative review.

PubMed

Najafian, Younes; Hamedi, Shokouh Sadat; Farshchi, Masoumeh Kaboli; Feyzabadi, Zohre

2018-02-01

Plantago major has been used widely since ancient times, to manage a wide range of diseases including constipation, coughs and wounds. The aim of this study is to review the traditional application, botanical characterization, pharmacological activities, phytochemistry effects and toxicity of Plantago major. In this review study, medicinal properties of Plantago major are collected from credible pharmacopeias, textbooks of traditional Persian medicine (TPM) belonging to the 10-18th century AD, such as "The Canon of Medicine", "Makhzan-Al- Advia" and so on. Moreover, electronic databases including Scopus, Medline and Web of science were explored for this purpose. Plantago major has been prescribed in various forms such as roasted seeds, decoction, syrup, liniment, gargle, rectal enema, vaginal suppository, eye and nasal drop for each illness by TPM scholars. Some of its traditional properties including wound healing, antipyretic, antitussive, anti-infective, anti-hemorrhagic, anti-inflammatory, diuretic, laxative, astringent and hemostatic have been confirmed in recent researches. Phytochemical investigations showed that Plantago major contains volatile compounds, triterpenoids, phenolic acids and flavonoids. Modern pharmacological studies have proven some of the traditional applications of Plantago major. Nevertheless, more investigations are required on this plant, because it has the potential to be used to produce various natural medications.

Impact of Intraseasonal Oscillations on the Tropical Cyclone Activity Over the Gulf of Mexico and Western Caribbean Sea in GFDL HiRAM

NASA Astrophysics Data System (ADS)

Gao, Kun; Chen, Jan-Huey; Harris, Lucas M.; Lin, Shian-Jiann; Xiang, Baoqiang; Zhao, Ming

2017-12-01

The tropical cyclones (TCs) that form over the warm waters in the Gulf of Mexico region pose a major threat to the surrounding coastal communities. Skillful subseasonal prediction of TC activity is important for early preparedness and reducing the TC damage in this region. In this study, we evaluate the performance of a 25 km resolution Geophysical Fluid Dynamics Laboratory (GFDL) High Resolution Atmospheric Model (HiRAM) in simulating the modulation of the TC activity in the Gulf of Mexico and western Caribbean Sea by the intraseasonal oscillation (ISO) based on multiyear retrospective seasonal predictions. We demonstrate that the HiRAM faithfully captures the observed influence of ISO on TC activity over the region of interest, including the formation of tropical storms and (major) hurricanes, as well as the landfalling storms. This is likely because of the realistic representation of the large-scale anomalies associated with boreal summer ISO over Northeast Pacific in HiRAM, especially the enhanced (reduced) moisture throughout the troposphere during the convectively enhanced (suppressed) phase of ISO. The reasonable performance of HiRAM suggests its potential for the subseasonal prediction of regional TC risk.

Metabolism of Flavonoids in Novel Banana Germplasm during Fruit Development

PubMed Central

Dong, Chen; Hu, Huigang; Hu, Yulin; Xie, Jianghui

2016-01-01

Banana is a commercially important fruit, but its flavonoid composition and characteristics has not been well studied in detail. In the present study, the metabolism of flavonoids was investigated in banana pulp during the entire developmental period of fruit. ‘Xiangfen 1,’ a novel flavonoid-rich banana germplasm, was studied with ‘Brazil’ serving as a control. In both varieties, flavonoids were found to exist mainly in free soluble form and quercetin was the predominant flavonoid. The most abundant free soluble flavonoid was cyanidin-3-O-glucoside chloride, and quercetin was the major conjugated soluble and bound flavonoid. Higher content of soluble flavonoids was associated with stronger antioxidant activity compared with the bound flavonoids. Strong correlation was observed between antioxidant activity and cyanidin-3-O-glucoside chloride content, suggesting that cyanidin-3-O-glucoside chloride is one of the major antioxidants in banana. In addition, compared with ‘Brazil,’ ‘Xiangfen 1’ fruit exhibited higher antioxidant activity and had more total flavonoids. These results indicate that soluble flavonoids play a key role in the antioxidant activity of banana, and ‘Xiangfen 1’ banana can be a rich source of natural antioxidants in human diets. PMID:27625665

Oxidative Addition and Reductive Elimination at Main-Group Element Centers.

PubMed

Chu, Terry; Nikonov, Georgii I

2018-04-11

Oxidative addition and reductive elimination are key steps in a wide variety of catalytic reactions mediated by transition-metal complexes. Historically, this reactivity has been considered to be the exclusive domain of d-block elements. However, this paradigm has changed in recent years with the demonstration of transition-metal-like reactivity by main-group compounds. This Review highlights the substantial progress achieved in the past decade for the activation of robust single bonds by main-group compounds and the more recently realized activation of multiple bonds by these elements. We also discuss the significant discovery of reversible activation of single bonds and distinct examples of reductive elimination at main-group element centers. The review consists of three major parts, starting with oxidative addition of single bonds, proceeding to cleavage of multiple bonds, and culminated by the discussion of reversible bond activation and reductive elimination. Within each subsection, the discussion is arranged according to the type of bond being cleaved or formed and considers elements from the left to the right of each period and down each group of the periodic table. The majority of results discussed in this Review come from the past decade; however, earlier reports are also included to ensure completeness.

Neuroinflammation in hepatic encephalopathy: mechanistic aspects.

PubMed

Jayakumar, Arumugam R; Rama Rao, Kakulavarapu V; Norenberg, Michael D

2015-03-01

Hepatic encephalopathy (HE) is a major neurological complication of severe liver disease that presents in acute and chronic forms. While elevated brain ammonia level is known to be a major etiological factor in this disorder, recent studies have shown a significant role of neuroinflammation in the pathogenesis of both acute and chronic HE. This review summarizes the involvement of ammonia in the activation of microglia, as well as the means by which ammonia triggers inflammatory responses in these cells. Additionally, the role of ammonia in stimulating inflammatory events in brain endothelial cells (ECs), likely through the activation of the toll-like receptor-4 and the associated production of cytokines, as well as the stimulation of various inflammatory factors in ECs and in astrocytes, are discussed. This review also summarizes the inflammatory mechanisms by which activation of ECs and microglia impact on astrocytes leading to their dysfunction, ultimately contributing to astrocyte swelling/brain edema in acute HE. The role of microglial activation and its contribution to the progression of neurobehavioral abnormalities in chronic HE are also briefly presented. We posit that a better understanding of the inflammatory events associated with acute and chronic HE will uncover novel therapeutic targets useful in the treatment of patients afflicted with HE.

Active CryoCubeSat

NASA Technical Reports Server (NTRS)

Swenson, Charles

2016-01-01

The Active CryoCubeSat project will demonstrate an advanced thermal control system for a 6-Unit (6U) CubeSat platform. A miniature, active thermal control system, in which a fluid is circulated in a closed loop from thermal loads to radiators, will be developed. A miniature cryogenic cooler will be integrated with this system to form a two-stage thermal control system. Key components will be miniaturized by using advanced additive manufacturing techniques resulting in a thermal testbed for proving out these technologies. Previous CubeSat missions have not tackled the problem of active thermal control systems nor have any past or current CubeSat missions included cryogenic instrumentation. This Active CryoCubeSat development effort will provide completely new capacities for CubeSats and constitutes a major advancement over the state-of-the-art in CubeSat thermal control.

Anti-inflammatory properties of α- and γ-tocopherol

PubMed Central

Reiter, Elke; Jiang, Qing; Christen, Stephan

2007-01-01

Natural vitamin E consists of four different tocopherol and four different tocotrienol homologues (α, β, γ, δ) that all have antioxidant activity. However, recent data indicate that the different vitamin E homologues also have biological activity unrelated to their antioxidant activity. In this review, we discuss the anti-inflammatory properties of the two major forms of vitamin E, α-tocopherol (αT) and γ-tocopherol (γT), and discuss the potential molecular mechanisms involved in these effects. While both tocopherols exhibit anti-inflammatory activity in vitro and in vivo, supplementation with mixed (γT-enriched) tocopherols seems to be more potent than supplementation with αT alone. This may explain the mostly negative outcomes of the recent large-scale interventional chronic disease prevention trials with αT and thus warrants further investigation. PMID:17316780

The effect of functional forms of nitrogen on fuel-NOx emissions.

PubMed

Zhang, Linghui; Su, Dagen; Zhong, Mingfeng

2015-01-01

This work explores the effects of different nitrogen functional forms on fuel-NOx emissions at 900 °C. The majority of tests are performed with an excess air coefficient of 1.4. Fuel-NOx is detected by measuring N-(1-naphthyl) ethylenediamine dihydrochloride (C₁₂H₁₆Cl₂N₂) via spectrophotometry. The different functional forms of nitrogen in the raw materials are identified by using X-ray photoelectron spectroscopy (XPS). A reliable density functional theory (DFT) method at the B3LYP/6-311++G** level is employed to investigate the reaction pathways of all functional forms of nitrogen during combustion. The results indicate that the functional forms of nitrogen influence the formation of nitrogen oxides. While under the same experimental conditions, fuel-NOx emissions increase by using less activation energy and nitrogen-containing groups with poor thermal stability. It is determined that fuel-NOx emissions vary in the following order: glycine > pyrrole > pyridine > methylenedi-p-phenylene diisocyanate (MDI). Glycine is the chain structure of amino acids in waste-leather and has low activation energy and poor thermal stability. With these properties, it is noted that glycine produces the most fuel-NOx in all of the raw materials studied. More pyrrole than pyridine in coal lead to high yields of fuel-NOx. The lowest yields of fuel-NO x are obtained using polyurethanes in waste-PU.

Association between physical activity and major depressive disorder among current or former smokers with pulmonary disease.

PubMed

Loprinzi, Paul D; Kane, Christy; Walker, Jerome F

2013-11-01

To examine the association between physical activity and major depressive disorder (MDD) in a nationally representative sample of current or former smokers with pulmonary impairments. The analyzed sample from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 included 536 adults who indicated that they were current or former smokers, had at least mild pulmonary impairment (FEV1/FVC<0.70), and provided depression and physical activity data. After controlling for asthma status, pulmonary impairment, age, poverty-to-income ratio (PIR), education, gender, marital status, body mass index (BMI), cotinine, comorbidity index, race-ethnicity, and smoking status, those who met physical activity guidelines had a 59% (odds ratio (OR)=0.41; 95% confidence interval (CI): 0.18-0.94) lower odds of having MDD. Using multivariate linear regression with depression symptoms as the outcome variable, and after adjustments, physical activity was inversely associated with depression symptoms in a dose-response manner; lowest tertile was the referent group, middle tertile coefficient: -1.06 (95% CI: -1.98 to -0.14), and highest tertile coefficient: -1.10 (95% CI: -1.84 to -0.34). Physical activity inversely associates with MDD in adults with pulmonary impairments, and does so in a dose-response manner. This suggests that individuals with pulmonary impairments should be encouraged to engage in enjoyable, safe forms of physical activity in a progressive manner. © 2013.

Metabolic flexibility: the key to long-term evolutionary success in Bryozoa?

PubMed

Peck, Lloyd S; Barnes, David K A

2004-02-07

Oxygen consumption (MO2) and activity were evaluated in Antarctic Bryozoa. Three species representing two different morphologies, flat sheet, laminar forms, Isoseculiflustra tenuis and Kymella polaris, and the bush form Camptoplites bicornis were used. In Bryozoa, activity is measured as the proportion of colony zooids with their lophophores extended. In I. tenuis and K. polaris, residual analysis showed that the percentage of zooids with extended lophophores was not correlated with colony MO2. Lophophore extension is, therefore, a poor measure of activity, and other costs (e.g. growth, reproduction, storage) probably form the major metabolic costs. MO2 per unit of ash-free dry mass (AFDM) in the laminar forms was low compared with other Antarctic marine invertebrates, but not lower than brachiopods and echinoderms. However, the lowest rate here, 16.8 microg O2 g AFDM(-1) h(-1) for a K. polaris colony, is (to our knowledge) the lowest for any animal so far reported. MO2 per unit of AFDM for C. bicornis, however, is among the highest reported for sessile or slow moving Antarctic marine ectotherms, with values similar to those for bivalve and gastropod molluscs. The highest rate, 527 microg O2 g AFDM(-1) h(-1) for one colony is (to our knowledge) the highest reported for polar animals of this type. Extreme diversity in metabolic strategy may explain the bryozoan long evolutionary record and great success in shallow marine environments worldwide.

Crystal structure of low-molecular-weight protein tyrosine phosphatase from Mycobacterium tuberculosis at 1.9-A resolution.

PubMed

Madhurantakam, Chaithanya; Rajakumara, Eerappa; Mazumdar, Pooja Anjali; Saha, Baisakhee; Mitra, Devrani; Wiker, Harald G; Sankaranarayanan, Rajan; Das, Amit Kumar

2005-03-01

The low-molecular-weight protein tyrosine phosphatase (LMWPTPase) belongs to a distinctive class of phosphotyrosine phosphatases widely distributed among prokaryotes and eukaryotes. We report here the crystal structure of LMWPTPase of microbial origin, the first of its kind from Mycobacterium tuberculosis. The structure was determined to be two crystal forms at 1.9- and 2.5-A resolutions. These structural forms are compared with those of the LMWPTPases of eukaryotes. Though the overall structure resembles that of the eukaryotic LMWPTPases, there are significant changes around the active site and the protein tyrosine phosphatase (PTP) loop. The variable loop forming the wall of the crevice leading to the active site is conformationally unchanged from that of mammalian LMWPTPase; however, differences are observed in the residues involved, suggesting that they have a role in influencing different substrate specificities. The single amino acid substitution (Leu12Thr [underlined below]) in the consensus sequence of the PTP loop, CTGNICRS, has a major role in the stabilization of the PTP loop, unlike what occurs in mammalian LMWPTPases. A chloride ion and a glycerol molecule were modeled in the active site where the chloride ion interacts in a manner similar to that of phosphate with the main chain nitrogens of the PTP loop. This structural study, in addition to identifying specific mycobacterial features, may also form the basis for exploring the mechanism of the substrate specificities of bacterial LMWPTPases.

Interests and needs for participation in tourism among disabled from eastern regions of Poland.

PubMed

Bergier, Barbara; Kubińska, Zofia; Bergier, Józef

2013-01-01

The scope of problems concerning the disabled still remains a constantly up-to-date social issue, which requires current scientific analysis. In concern for the disabled, the problem of physical activity through their participation in tourism occupies an important position. The studies concern the disabled from three regions: Lublin, Białystok and Rzeszów, where there occurs the highest intensity of the phenomenon of disability. The recognition of interests and needs manifested by the disabled from the eastern regions of Poland concerning the use of forms of tourism during leisure time. The method of a diagnostic survey and questionnaire technique were applied. A total number of 750 disabled were examined. The study showed that the majority of the disabled spend their free time devoted to tourist activity according to their needs. The main forms of participation in tourism are sightseeing tours and package holidays, and the respondents would like most to participate in rehabilitation camps and sightseeing tours. A considerable variation was observed in the participation in forms of tourism among the disabled from individual regions. The disabled who do not wish to participate in sports-recreation and tourist activities, and for whom their state of health is the main barrier, require special interest. A relatively large variation of tourism forms used by the disabled in individual regions indicate the need for an exchange of experiences between specialist facilities taking care of the disabled.

Living with cracks: Damage and repair in human bone

NASA Astrophysics Data System (ADS)

Taylor, David; Hazenberg, Jan G.; Lee, T. Clive

2007-04-01

Our bones are full of cracks, which form and grow as a result of daily loading activities. Bone is the major structural material in our bodies. Although weaker than many engineering materials, it has one trick that keeps it ahead - it can repair itself. Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous. This article reviews the work that has been done to understand how cracks form and grow in bone, and how they can be detected and repaired in a timely manner. This is truly an interdisciplinary research field, requiring the close cooperation of materials scientists, biologists and engineers.

Human violence: a treatable epidemic.

PubMed

De Zulueta, F I

1998-01-01

Domestic violence is common, afflicting at least one in 15 of the population. The victims are usually women and children and the perpetrators often the traditional male head of the family. It commonly leads to a form of post-traumatic stress disorder manifested as psychiatric illness in women and violent crime in men. It is proposed that a major underlying factor is a failure of attachment in infancy. This form of violence can be prevented by better health care before and after birth, particularly in the inner cities and with reduction of inequality; education for parenting; free nursery education; and diminishing 'legitimate' violence, in the media, by government (capital or corporal punishment) and as violent sporting activities.

SQ109, a New Drug Lead for Chagas Disease

PubMed Central

Veiga-Santos, Phercyles; Li, Kai; Lameira, Lilianne; de Carvalho, Tecia Maria Ulisses; Huang, Guozhong; Galizzi, Melina; Shang, Na; Li, Qian; Gonzalez-Pacanowska, Dolores; Hernandez-Rodriguez, Vanessa; Benaim, Gustavo; Guo, Rey-Ting; Urbina, Julio A.; Docampo, Roberto; de Souza, Wanderley

2015-01-01

We tested the antituberculosis drug SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, for its in vitro activity against the trypanosomatid parasite Trypanosoma cruzi, the causative agent of Chagas disease. SQ109 was found to be a potent inhibitor of the trypomastigote form of the parasite, with a 50% inhibitory concentration (IC50) for cell killing of 50 ± 8 nM, but it had little effect (50% effective concentration [EC50], ∼80 μM) in a red blood cell hemolysis assay. It also inhibited extracellular epimastigotes (IC50, 4.6 ± 1 μM) and the clinically relevant intracellular amastigotes (IC50, ∼0.5 to 1 μM), with a selectivity index of ∼10 to 20. SQ109 caused major ultrastructural changes in all three life cycle forms, as observed by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). It rapidly collapsed the inner mitochondrial membrane potential (Δψm) in succinate-energized mitochondria, acting in the same manner as the uncoupler FCCP [carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone], and it caused the alkalinization of internal acidic compartments, effects that are likely to make major contributions to its mechanism of action. The compound also had activity against squalene synthase, binding to its active site; it inhibited sterol side-chain reduction and, in the amastigote assay, acted synergistically with the antifungal drug posaconazole, with a fractional inhibitory concentration index (FICI) of 0.48, but these effects are unlikely to account for the rapid effects seen on cell morphology and cell killing. SQ109 thus most likely acts, at least in part, by collapsing Δψ/ΔpH, one of the major mechanisms demonstrated previously for its action against Mycobacterium tuberculosis. Overall, the results suggest that SQ109, which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, may also have potential as a drug lead against Chagas disease. PMID:25583723

Evaluating the B-cell density with various activation functions using White Noise Path Integral Approach

NASA Astrophysics Data System (ADS)

Aban, C. J. G.; Bacolod, R. O.; Confesor, M. N. P.

2015-06-01

A The White Noise Path Integral Approach is used in evaluating the B-cell density or the number of B-cell per unit volume for a basic type of immune system response based on the modeling done by Perelson and Wiegel. From the scaling principles of Perelson [1], the B- cell density is obtained where antigens and antibodies mutates and activation function f(|S-SA|) is defined describing the interaction between a specific antigen and a B-cell. If the activation function f(|S-SA|) is held constant, the major form of the B-cell density evaluated using white noise analysis is similar to the form of the B-cell density obtained by Perelson and Wiegel using a differential approach.A piecewise linear functionis also used to describe the activation f(|S-SA|). If f(|S-SA|) is zero, the density decreases exponentially. If f(|S-SA|) = S-SA-SB, the B- cell density increases exponentially until it reaches a certain maximum value. For f(|S-SA|) = 2SA-SB-S, the behavior of B-cell density is oscillating and remains to be in small values.

Digestion in adult females of the leaf-footed bug Leptoglossus zonatus (Hemiptera: Coreidae) with emphasis on the glycoside hydrolases α-amylase, α-galactosidase, and α-glucosidase.

PubMed

Rocha, Ariane A; Pinto, Carlos J C; Samuels, Richard I; Alexandre, Daniel; Silva, Carlos P

2014-03-01

The leaffooted bug, Leptoglossus zonatus (Hemiptera: Coreidae) is an emerging pest of several crops around the World and up to now very little is known of its digestive system. In this article, glycoside hydrolase (carbohydrase) activities in the adult midgut cells and in the luminal contents of L. zonatus adult females were studied. The results showed the distribution of digestive carbohydrases in adults of this heteropteran species in the different intestinal compartments. Determination of the spatial distribution of α-glucosidase activity in L. zonatus midgut showed only one major molecular form, which was not equally distributed between soluble and membrane-bound isoforms, being more abundant as a membrane-bound enzyme. The majority of digestive carbohydrases were found in the soluble fractions. Activities against starch, maltose and the synthetic substrate NPαGlu were found to show the highest levels of activity, followed by enzymes active against galactosyl oligosaccharides. Based on ion-exchange chromatography elution profiles and banding patterns in mildly denaturing electrophoresis, both midgut α-amylases and α-galactosidases showed at least two isoforms. The data suggested that the majority of carbohydrases involved in initial digestion were present in the midgut lumen, whereas final digestion of starch and of galactosyl oligosaccharides takes place partially within the lumen and partially at the cell surface. The complex of carbohydrases here described was qualitatively appropriate for the digestion of free oligosaccharides and oligomaltodextrins released by α-amylases acting on maize seed starch granules. © 2014 Wiley Periodicals, Inc.

Qualitative Analysis of Collaborative Learning Groups in Large Enrollment Introductory Astronomy

NASA Astrophysics Data System (ADS)

Skala, Chija; Slater, Timothy F.; Adams, Jeffrey P.

2000-08-01

Large-lecture introductory astronomy courses for undergraduate, non-science majors present numerous problems for faculty. As part of a systematic effort to improve the course learning environment, a series of small-group, collaborative learning activities were implemented in an otherwise conventional lecture astronomy survey course. These activities were used once each week during the regularly scheduled lecture period. After eight weeks, ten focus group interviews were conducted to qualitatively assess the impact and dynamics of these small group learning activities. Overall, the data strongly suggest that students enjoy participating in the in-class learning activities in learning teams of three to four students. These students firmly believe that they are learning more than they would from lectures alone. Inductive analysis of the transcripts revealed five major themes prevalent among the students' perspectives: (1) self-formed, cooperative group composition and formation should be more regulated by the instructor; (2) team members' assigned rolls should be less formally structured by the instructors; (3) cooperative groups helped in learning the course content; (4) time constraints on lectures and activities need to be more carefully aligned; and (5) gender issues can exist within the groups. These themes serve as a guide for instructors who are developing instructional interventions for large lecture courses.

Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells.

PubMed Central

Cuenda, A; Alonso, G; Morrice, N; Jones, M; Meier, R; Cohen, P; Nebreda, A R

1996-01-01

Two chromatographically distinct stress-activated protein kinase kinases (SAPKKs) have been identified in several mammalian cells, termed SAPKK2 and SAPKK3, which activate the MAP kinase family member RK/p38 but not JNK/SAPK in vitro. Here we demonstrate that SAPKK2 is identical or very closely related to the MAP kinase kinase family member MKK3. However, under our assay conditions, SAPKK3 was the major activator of RK/p38 detected in extracts prepared from stress- or interleukin-1-stimulated epithelial (KB) cells, from bacterial lipopolysaccharide and tumour necrosis factor alpha-stimulated THP1 monocytes or from rabbit skeletal muscle. The activated form of SAPKK3 was purified from muscle to near homogeneity, and tryptic peptide sequences were used to clone human and murine cDNAs encoding this enzyme. Human SAPKK3 comprised 334 amino acids and was 78% identical to MKK3. The murine and human SAPKK3 were 97% identical in their amino acid sequences. We also cloned a different murine cDNA that appears to encode a SAPKK3 protein truncated at the N-terminus. SAPKK3 is identical to the recently cloned MKK6. Images PMID:8861944

Necrotic platelets provide a procoagulant surface during thrombosis

PubMed Central

Hua, Vu Minh; Abeynaike, Latasha; Glaros, Elias; Campbell, Heather; Pasalic, Leonardo; Chen, Vivien M. Y.

2015-01-01

A subpopulation of platelets fulfills a procoagulant role in hemostasis and thrombosis by enabling the thrombin burst required for fibrin formation and clot stability at the site of vascular injury. Excess procoagulant activity is linked with pathological thrombosis. The identity of the procoagulant platelet has been elusive. The cell death marker 4-[N-(S-glutathionylacetyl)amino]phenylarsonous acid (GSAO) rapidly enters a subpopulation of agonist-stimulated platelets via an organic anion-transporting polypeptide and is retained in the cytosol through covalent reaction with protein dithiols. Labeling with GSAO, together with exposure of P-selectin, distinguishes necrotic from apoptotic platelets and correlates with procoagulant potential. GSAO+ platelets form in occluding murine thrombi after ferric chloride injury and are attenuated with megakaryocyte-directed deletion of the cyclophilin D gene. These platelets form a procoagulant surface, supporting fibrin formation, and reduction in GSAO+ platelets is associated with reduction in platelet thrombus size and fibrin formation. Analysis of platelets from human subjects receiving aspirin therapy indicates that these procoagulant platelets form despite aspirin therapy, but are attenuated by inhibition of the necrosis pathway. These findings indicate that the major subpopulation of platelets involved in fibrin formation are formed via regulated necrosis involving cyclophilin D, and that they may be targeted independent of platelet activation. PMID:26474813

Specialised sympathetic neuroeffector associations in immature rat iris arterioles

PubMed Central

SANDOW, SHAUN L.; HILL, CARYL E.

1999-01-01

Sympathetic nerve-mediated vasoconstriction in iris arterioles of mature rats occurs via the activation of α1B-adrenoceptors alone, while in immature rat iris arterioles, vasoconstriction occurs via activation of both α1- and α2-adrenoceptors. In mature rats the vast majority of sympathetic varicosities form close neuroeffector junctions. Serial section electron microscopy of 14 d iris arterioles has been used to determine whether restriction in physiological receptor types with age may result from the establishment of these close neuroeffector junctions. Ninety varicosities which lay within 4 μm of arteriolar smooth muscle were followed for their entire length. Varicosities rarely contained dense cored vesicles even after treatment with 5-hydroxydopamine. 47% of varicosities formed close associations with muscle cells and 88% formed close associations with muscle cells or melanocytes. Varicosities in bundles were as likely as single varicosities to form close associations with vascular smooth muscle cells, although the distribution of synaptic vesicles in single varicosities did not show the asymmetric accumulation towards the smooth muscle cells seen in the varicosities in bundles which were frequently clustered together. We conclude that restriction of physiological receptor types during development does not appear to correlate with the establishment of close neuroeffector junctions, although changes in presynaptic structures may contribute to the refinement of postsynaptic responses. PMID:10529061

Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase

PubMed Central

Levitas, Aviva; Muhammad, Emad; Harel, Gali; Saada, Ann; Caspi, Vered Chalifa; Manor, Esther; Beck, John C; Sheffield, Val; Parvari, Ruti

2010-01-01

Cardiomyopathies are common disorders resulting in heart failure; the most frequent form is dilated cardiomyopathy (DCM), which is characterized by dilatation of the left or both ventricles and impaired systolic function. DCM causes considerable morbidity and mortality, and is one of the major causes of sudden cardiac death. Although about one-third of patients are reported to have a genetic form of DCM, reported mutations explain only a minority of familial DCM. Moreover, the recessive neonatal isolated form of DCM has rarely been associated with a mutation. In this study, we present the association of a mutation in the SDHA gene with recessive neonatal isolated DCM in 15 patients of two large consanguineous Bedouin families. The cardiomyopathy is presumably caused by the significant tissue-specific reduction in SDH enzymatic activity in the heart muscle, whereas substantial activity is retained in the skeletal muscle and lymphoblastoid cells. Notably, the same mutation was previously reported to cause a multisystemic failure leading to neonatal death and Leigh's syndrome. This study contributes to the molecular characterization of a severe form of neonatal cardiomyopathy and highlights extreme phenotypic variability resulting from a specific missense mutation in a nuclear gene encoding a protein of the mitochondrial respiratory chain. PMID:20551992

Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase.

PubMed

Levitas, Aviva; Muhammad, Emad; Harel, Gali; Saada, Ann; Caspi, Vered Chalifa; Manor, Esther; Beck, John C; Sheffield, Val; Parvari, Ruti

2010-10-01

Cardiomyopathies are common disorders resulting in heart failure; the most frequent form is dilated cardiomyopathy (DCM), which is characterized by dilatation of the left or both ventricles and impaired systolic function. DCM causes considerable morbidity and mortality, and is one of the major causes of sudden cardiac death. Although about one-third of patients are reported to have a genetic form of DCM, reported mutations explain only a minority of familial DCM. Moreover, the recessive neonatal isolated form of DCM has rarely been associated with a mutation. In this study, we present the association of a mutation in the SDHA gene with recessive neonatal isolated DCM in 15 patients of two large consanguineous Bedouin families. The cardiomyopathy is presumably caused by the significant tissue-specific reduction in SDH enzymatic activity in the heart muscle, whereas substantial activity is retained in the skeletal muscle and lymphoblastoid cells. Notably, the same mutation was previously reported to cause a multisystemic failure leading to neonatal death and Leigh's syndrome. This study contributes to the molecular characterization of a severe form of neonatal cardiomyopathy and highlights extreme phenotypic variability resulting from a specific missense mutation in a nuclear gene encoding a protein of the mitochondrial respiratory chain.

Protein–Protein Interactions between Sucrose Transporters of Different Affinities Colocalized in the Same Enucleate Sieve Element

PubMed Central

Reinders, Anke; Schulze, Waltraud; Kühn, Christina; Barker, Laurence; Schulz, Alexander; Ward, John M.; Frommer, Wolf B.

2002-01-01

Suc represents the major transport form for carbohydrates in plants. Suc is loaded actively against a concentration gradient into sieve elements, which constitute the conduit for assimilate export out of leaves. Three members of the Suc transporter family with different properties were identified: SUT1, a high-affinity Suc proton cotransporter; SUT4, a low-affinity transporter; and SUT2, which in yeast is only weakly active and shows features similar to those of the yeast sugar sensors RGT2 and SNF3. Immunolocalization demonstrated that all three SUT proteins are localized in the same enucleate sieve element. Thus, the potential of Suc transporters to form homooligomers was tested by the yeast-based split-ubiquitin system. The results show that both SUT1 and SUT2 have the potential to form homooligomers. Moreover, all three Suc transporters have the potential to interact with each other. As controls, a potassium channel and a monosaccharide transporter, expressed in the plasma membrane, did not interact with the SUTs. The in vivo interaction between the functionally different Suc transporters indicates that the membrane proteins are capable of forming oligomeric structures that, like mammalian Glc transporter complexes, might be of functional significance for the regulation of transport. PMID:12119375

Crystal structure of arrestin-3 reveals the basis of the difference in receptor binding between two non-visual subtypes

PubMed Central

Zhan, Xuanzhi; Gimenez, Luis E.; Gurevich, Vsevolod V.; Spiller, Benjamin W.

2011-01-01

Arrestins are multi-functional proteins that regulate signaling and trafficking of the majority of G protein-coupled receptors (GPCRs), as well as sub-cellular localization and activity of many other signaling proteins. Here we report the first crystal structure of arrestin-3, solved at 3.0Å. Arrestin-3 is an elongated two-domain molecule with the overall fold and key inter-domain interactions that hold free protein in the basal conformation similar to the other subtypes. Arrestin-3 is the least selective member of the family, binding wide variety of GPCRs with high affinity and demonstrating lower preference for active phosphorylated forms of the receptors. In contrast to the other three arrestins, part of the receptor-binding surface in the arrestin-3 C-domain does not form a contiguous β-sheet, consistent with increased flexibility. By swapping the corresponding elements between arrestin-2 and -3 we show that the presence of this loose structure correlates with reduced arrestin selectivity for activated receptor, consistent with a conformational change in this β-sheet upon receptor binding. PMID:21215759

Neuroprotective effect of resveratrol against brain ischemia reperfusion injury in rats entails reduction of DJ-1 protein expression and activation of PI3K/Akt/GSK3b survival pathway.

PubMed

Abdel-Aleem, Ghada A; Khaleel, Eman F; Mostafa, Dalia G; Elberier, Lydia K

2016-10-01

In the current study, we aimed to investigate the mechanistic role of DJ-1/PI3K/Akt survival pathway in ischemia/reperfusion (I/R) induced cerebral damage and to investigate if the resveratrol (RES) mediates its ischemic neuroptotection through this pathway. RES administration to Sham rats boosted glutathione level and superoxide dismutase activity and downregulated inducible nitric oxide synthase expression without affecting redox levels of DJ-1 forms or components of PI3K/Akt pathway including PTEN, p-Akt or p/p-GSK3b. However, RES pre-administration to I/R rats reduced infarction area, oxidative stress, inflammation and apoptosis. Concomitantly, RES ameliorated the decreased levels of oxidized forms of DJ-1 and enhancing its reduction, increased the nuclear protein expression of Nfr-2 and led to activation of PI3K/Akt survival pathway. In conclusion, overoxidation of DJ-1 is a major factor that contributes to post-I/R cerebral damage and its reduction by RES could explain the neuroprotection offered by RES.

Fermentation and complex enzyme hydrolysis for improving the total soluble phenolic contents, flavonoid aglycones contents and bio-activities of guava leaves tea.

PubMed

Wang, Lu; Luo, You; Wu, Yanan; Liu, Yan; Wu, Zhenqiang

2018-10-30

There are both soluble and insoluble-bound forms of phenolics in tea-leaf products. In order to increase total soluble phenolics contents, guava leaves tea (GLT) was first fermented with Monascus anka and Saccharomyces cerevisiae, and then hydrolyzed with complex enzymes. The changes in phenolics profiles, antioxidant activities and inhibitory effect on α-glucosidase in processed GLT were investigated. Compared with the un-fermented GLT, fermentation and complex enzymatic processing (FE) significantly increased the total phenolics, total flavonoids, quercetin and kaempferol contents by 2.1, 2.0, 13.0 and 6.8 times, respectively. After the FE, a major proportion of phenolics existed in the soluble form. Quercetin was released in the highest amount among different phenolics. In addition, soluble phenolic extracts from GLT following FE exhibited a highest antioxidant activity and inhibitory effect on α-glucosidase. The paper suggested an improved method for processing GLT into high-value products rich in phenolics and flavonoids aglycones with enhanced health benefits. Copyright © 2018 Elsevier Ltd. All rights reserved.

The neural basis of conditional reasoning with arbitrary content.

PubMed

Noveck, Ira A; Goel, Vinod; Smith, Kathleen W

2004-01-01

Behavioral predictions about reasoning have usually contrasted two accounts, Mental Logic and Mental Models. Neuroimaging techniques have been providing new measures that transcend this debate. We tested a hypothesis from Goel and Dolan (2003) that predicts neural activity predominantly in a left parietal-frontal system when participants reason with arbitrary (non-meaningful) materials. In an event-related fMRI investigation, we employed propositional syllogisms, the majority of which involved conditional reasoning. While investigating conditional reasoning generally, we ultimately focused on the neural activity linked to the two valid conditional forms--Modus Ponens (If p then q; p//q) and Modus Tollens (If p then q; not-q//not-p). Consistent with Goel and Dolan (2003), we found a left lateralized parietal frontal network for both inference forms with increasing activation when reasoning becomes more challenging by way of Modus Tollens. These findings show that the previous findings with more complex Aristotlean syllogisms are robust and cast doubt upon accounts of reasoning that accord primary inferential processes uniquely to either the right hemisphere or to language areas.

The neural basis of audiomotor entrainment: an ALE meta-analysis

PubMed Central

Chauvigné, Léa A. S.; Gitau, Kevin M.; Brown, Steven

2014-01-01

Synchronization of body movement to an acoustic rhythm is a major form of entrainment, such as occurs in dance. This is exemplified in experimental studies of finger tapping. Entrainment to a beat is contrasted with movement that is internally driven and is therefore self-paced. In order to examine brain areas important for entrainment to an acoustic beat, we meta-analyzed the functional neuroimaging literature on finger tapping (43 studies) using activation likelihood estimation (ALE) meta-analysis with a focus on the contrast between externally-paced and self-paced tapping. The results demonstrated a dissociation between two subcortical systems involved in timing, namely the cerebellum and the basal ganglia. Externally-paced tapping highlighted the importance of the spinocerebellum, most especially the vermis, which was not activated at all by self-paced tapping. In contrast, the basal ganglia, including the putamen and globus pallidus, were active during both types of tapping, but preferentially during self-paced tapping. These results suggest a central role for the spinocerebellum in audiomotor entrainment. We conclude with a theoretical discussion about the various forms of entrainment in humans and other animals. PMID:25324765

The Shallow Plumbing System of Piton de la Fournaise Volcano (La Réunion island, Indian Ocean) Revealed by the Major 2007 Caldera Forming Eruption (Invited)

NASA Astrophysics Data System (ADS)

Di Muro, A.; Metrich, N.; Daniele, V.; Rosi, M.; Armienti, P.; Fougeroux, T.; Deloule, E.; Arienzo, I.; Civetta, L.

2013-12-01

The 2007 eruption represents a major event in the recent history of Piton de la Fournaise volcano because it produced: i) the most voluminous lava field (at least 0.21 km3), ii) the most intense lava fountaining activity (>200 m high), iii) the largest SO2 plume (>230 kt), iv) the largest summit collapse (1 km wide x 0.34 km deep) and v) the main flank slip event (up to 1.4 m eastwards) ever documented at PdF. The bulk magma volume extruded during the 2007 eruptive sequence is similar to that emitted during the entire 1998-2006 period. As a whole, the volume of magma emitted during the whole 1998-2007 activity cycle is remarkably close to that estimated (~0.35 km3) for the shallow plumbing system of Piton de la Fournaise. The 2007 eruptive sequence consisted of three successive phases (February, March and April). The main caldera forming phase of April ended a 9 years long period (1998-2007) of continuous edifice inflation and frequent eruptive activity (3 eruptions per year on average). On the contrary, post-2007 activity punctuates a trend of continuous deflation and consists of small-volume summit eruptions of moderate/low MgO magmas and frequent shallow magma intrusions. The 2007 lavas and pyroclasts cover the complete range of textures and crystal content an composition typically found in PdF products. The broad range of textures and the large volumes of pyroclasts, lava and gas emitted in 2007 provide an unique and exceptional record of the time-integrated evolution of PdF magma, and represent an unique opportunity to image the volcano plumbing system and bring new constraints on the processes controlling its magmatic and volatile budget. We here address these issues by using an unprecedented geochemical dataset (major, volatile and trace elements, Sr-Nd isotopes) on bulk rocks, minerals, glass inclusions and glass matrices from a very detailed sample set, representative of the time evolution of extruded magma during the entire 2007 eruptive sequence.

Assembly and activation of neurotrophic factor receptor complexes.

PubMed

Simi, Anastasia; Ibáñez, Carlos F

2010-04-01

Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

Suicidal ideation among patients with Behçet's syndrome.

PubMed

Saygin, Caner; Uzunaslan, Didem; Hatemi, Gulen; Hamuryudan, Vedat

2015-01-01

To evaluate the frequency of suicidal ideation among Behçet's syndrome (BS) patients compared to healthy and diseased controls and to delineate possible factors predicting an increase in suicidal ideation. We included consecutive BS patients attending our outpatient clinic, patients with ankylosing spondylitis (AS) and healthy hospital staff as controls. Suicidal ideation was assessed by a standard questionnaire. Linear regression was used to identify the factors associated with suicidal ideation, such as demographic and clinical features, drugs, disease activity assessed using the Behçet's disease current activity form (BDCAF) for BS patients and BASDAI for AS patients, Behçet's disease quality of life (BDQoL) and Beck depression inventory (BDI) score. We surveyed 303 BS patients, 52 AS patients and 106 healthy controls. Suicidal thoughts, as reflected by a positive response to the first three items of the questionnaire, were higher among BS patients with major organ involvement (42%) than those with mucocutaneous involvement (35%) and the control groups. There were significantly more BS patients with active major organ involvement who had thought to terminate their lives without plans within the last year (25.5%) compared to those with active mucocutaneous involvement (8.7%) and active AS patients (10%) (p=0.012). Patient-reported joint pain (β=-0.155, p=0.046), BDQoL (β=0.176, p=0.032), and BDI (β=0.017, p<0.0001) scores, suicidal thoughts before the onset of BS (β=-0.124, p=0.043), neurologic involvement (β=0.119, p=0.047) and past prednisone use (β=0.212, p=0.005) were independent predictors of suicidal thoughts. BS patients with major organ involvement have increased thoughts of suicide during the active stages of their disease. A number of risk factors could help physicians to identify patients with increased suicidal thoughts.

Exercise is medicine for patients with major depressive disorders: but only if the “pill” is taken!

PubMed Central

Gerber, Markus; Holsboer-Trachsler, Edith; Pühse, Uwe; Brand, Serge

2016-01-01

Major depressive disorders (MDDs) are a widespread and burdensome mental illness associated with a high comorbidity with other conditions and a significantly reduced life expectancy compared to the general population. Therefore, targeted actions are needed to improve physical health in people with MDDs, in addition to ongoing efforts to enhance psychological well-being. Meanwhile, the positive effects of exercise training on the treatment of MDDs are well documented, while compelling evidence exists that exercise interventions can improve cardiorespiratory fitness in clinically meaningful ways. On the flipside, the long-term effects of exercise therapy are still not well documented, and recent studies suggest that initial improvements in MDDs dissipate if regular exercise participation is discontinued after the end of interventions. A recent survey among Swiss psychiatric hospitals further shows that all institutions provide some form of physical activity and exercise program. However, only a limited number of patients participate in these programs, mainly because participation is voluntary and no particular efforts are undertaken to engage patients with the lowest physical activity levels. We argue that more systematic efforts are needed to fully exploit the potential of physical activity and exercise programs in psychiatric care. We also emphasize that initiating and maintaining regular physical activity among psychiatric patients is a major challenge because specific dysfunctional cognitive–emotional processes might interfere with their capacity to self-regulate health-related behaviors. Specifically, we claim that behavioral skill training should be used to support patients with MDDs in overcoming barriers to initiating and maintaining physical activity. Moreover, we suggest that the assessment of physical activity and cardiorespiratory fitness should become routine in psychiatric practice. PMID:27540294

[Bioavailability of antiglaucoma drugs].

PubMed

Demailly, P

2000-05-01

The biodisponibility of antiglaucoma drugs, generally delivered in an aqueous eye-drop solution depends on their capacity to cross the cornea. The structure of the cornea forms a barrier to strongly lipophilic substances and the continuous renewal of the lacrimal film creates a major obstacle, preventing active substances from penetrating the eye. Active substances must thus be delivered in highly concentrated solutions. The systemic bioavailability of antiglaucoma drugs taken orally, for example beta-blockers, is well known, their behavior after eye-drop administration remains poorly elucidated and highly dependent on individual susceptibility. We reviewed the literature on pilocarpine, beta-blockers, adrenergic drugs (dipivalyl-epinephrine, apraclonidine, brimonidine), carbon anhydrase inhibitors (acetazolamide, dorzolamide).

Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species

PubMed Central

Andrade, Juvana M.; Baba, Elio H.; Machado-de-Avila, Ricardo A.; Chavez-Olortegui, Carlos; Demicheli, Cynthia P.; Frézard, Frédéric

2016-01-01

Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in Leishmania, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing Leishmania guyanensis and L. braziliensis mutants and investigated their susceptibility to the trivalent form of Sb (SbIII) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased SbIII susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to SbIII exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, SbIII-sodium nitrate or SbIII-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of SbIII alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to SbIII and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated SbIII susceptibility modulation by silver in Leishmania and suggests the potential antileishmanial activity of the combination of nitrate salts and SbIII. PMID:27161624

Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species.

PubMed

Andrade, Juvana M; Baba, Elio H; Machado-de-Avila, Ricardo A; Chavez-Olortegui, Carlos; Demicheli, Cynthia P; Frézard, Frédéric; Monte-Neto, Rubens L; Murta, Silvane M F

2016-08-01

Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in Leishmania, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing Leishmania guyanensis and L. braziliensis mutants and investigated their susceptibility to the trivalent form of Sb (Sb(III)) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased Sb(III) susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to Sb(III) exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, Sb(III)-sodium nitrate or Sb(III)-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of Sb(III) alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to Sb(III) and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated Sb(III) susceptibility modulation by silver in Leishmania and suggests the potential antileishmanial activity of the combination of nitrate salts and Sb(III). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Wasatch fault zone, Utah - segmentation and history of Holocene earthquakes

USGS Publications Warehouse

Machette, Michael N.; Personius, Stephen F.; Nelson, Alan R.; Schwartz, David P.; Lund, William R.

1991-01-01

The Wasatch fault zone (WFZ) forms the eastern boundary of the Basin and Range province and is the longest continuous, active normal fault (343 km) in the United States. It underlies an urban corridor of 1.6 million people (80% of Utah's population) representing the largest earthquake risk in the interior of the western United States. The authors have used paleoseismological data to identify 10 discrete segments of the WFZ. Five are active, medial segments with Holocene slip rates of 1-2 mm a-1, recurrence intervals of 2000-4000 years and average lengths of about 50 km. Five are less active, distal segments with mostly pre-Holocene surface ruptures, late Quaternary slip rates of <0.5 mm a-1, recurrence intervals of ???10,000 years and average lengths of about 20 km. Surface-faulting events on each of the medial segments of the WFZ formed 2-4-m-high scarps repeatedly during the Holocene. Paleoseismological records for the past 6000 years indicate that a major surface-rupturing earthquake has occurred along one of the medial segments about every 395 ?? 60 years. However, between about 400 and 1500 years ago, the WFZ experienced six major surface-rupturing events, an average of one event every 220 years, or about twice as often as expected from the 6000-year record. Evidence has been found that surface-rupturing events occurred on the WFZ during the past 400 years, a time period which is twice the average intracluster recurrence interval and equal to the average Holocene recurrence interval.

Real Life Active Gaming Practices of 7-11-Year-Old Children.

PubMed

Allsop, Susan; Rumbold, Penny Louise Sheena; Debuse, Dorothée; Dodd-Reynolds, Caroline

2013-12-01

In the laboratory, active gaming has been shown to increase physical activity levels in children compared with seated media activities. The information is sparse, however, about children's real life active gaming practices, and the laboratory protocols used thus far might not be representative. The purpose of the present study was to establish the sociodemographic characteristics, real life active gaming practices, and reasons for gameplay, to later inform intervention studies. An "Active Gaming Questionnaire" was purposely developed and distributed to 44 7-11-year-old children and their parents. Forty questionnaires were completed and returned. Analysis found 95 percent of the children had access to active gaming consoles "at home." The favorite console was the Nintendo (Kyoto, Japan) Wii™, and the favorite game was Nintendo "Wii Sports." The majority of children frequently played active games against other people. The average reported gameplay time was 81 minutes on 1-2 days per week, usually on a Saturday. More than half of the children (52.5 percent) consumed foods and/or drinks during play, which was significantly associated (P=0.000) with an extended average gameplay time (increased by 25 minutes). The majority of participants (65 percent) considered active gaming to be an alternative form of exercise, and main reasons for active videogame play included for entertainment, health benefits, and the environment. In conclusion, children 9.3±1.4 years old typically play Nintendo "Wii Sports," once or twice per week for 81 minutes. Reported active gameplay time is extended by 25 minutes when food and/or drinks are consumed.

Rice phytochrome-interacting factor protein OsPIFff14 represses OsDREB1B gene expression through an extended N-box and interacts preferentially with the active form of phytochrome B

USDA-ARS?s Scientific Manuscript database

DREB1/CBF genes, known as major regulators of plant stress responses, are rapidly and transiently induced by low temperatures. Using a Yeast one Hybrid screening, we identified a putative Phytochrome-Interacting bHLH Factor (OsPIF14), as binding to the OsDREB1B promoter. bHLH proteins are able to bi...

Space Commercialization Trends and Consequences for the Workforce

NASA Astrophysics Data System (ADS)

Peeters, W.

2002-01-01

The major trend we are currently witnessing in space activities is an increasing level of commercialization. This trend is emphasized by: consolidation, mergers and forming strategic alliances. In USA, from the 20 major space companies in the 80's only 3 `prime' ones were left by 1997. A similar effect took place in Europe in the 90's, where at present only primarily 2 major space conglomerates are operating at prime contractor level. Such strategic alliances in the first place result in the creation of end-to-end capabilities, with larger internal R&D and broader access to technologies. Due to the bigger financial volume of such conglomerates there is also better access to new capital and sharing of risks. In a second step, we can at present observe the creation of transatlantic alliances to enter the worldwide market. These trends have a considerable effect on the workforce requirements in industry:

Plant Nitrogen Acquisition Under Low Availability: Regulation of Uptake and Root Architecture.

PubMed

Kiba, Takatoshi; Krapp, Anne

2016-04-01

Nitrogen availability is a major factor determining plant growth and productivity. Plants acquire nitrogen nutrients from the soil through their roots mostly in the form of ammonium and nitrate. Since these nutrients are scarce in natural soils, plants have evolved adaptive responses to cope with the environment. One of the most important responses is the regulation of nitrogen acquisition efficiency. This review provides an update on the molecular determinants of two major drivers of the nitrogen acquisition efficiency: (i) uptake activity (e.g. high-affinity nitrogen transporters) and (ii) root architecture (e.g. low-nitrogen-availability-specific regulators of primary and lateral root growth). Major emphasis is laid on the regulation of these determinants by nitrogen supply at the transcriptional and post-transcriptional levels, which enables plants to optimize nitrogen acquisition efficiency under low nitrogen availability. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

Serum Vitamin E Concentrations and Recovery of Physical Function During the Year After Hip Fracture

PubMed Central

Miller, Ram R.; Hicks, Gregory E.; Orwig, Denise L.; Hochberg, Marc C.; Semba, Richard D.; Yu-Yahiro, Janet A.; Ferrucci, Luigi; Magaziner, Jay; Shardell, Michelle D.

2011-01-01

Background. Poor nutritional status after hip fracture is common and may contribute to physical function decline. Low serum concentrations of vitamin E have been associated with decline in physical function among older adults, but the role of vitamin E in physical recovery from hip fracture has never been explored. Methods. Serum concentrations of α- and γ-tocopherol, the two major forms of vitamin E, were measured in female hip fracture patients from the Baltimore Hip Studies cohort 4 at baseline and at 2-, 6-, and 12-month postfracture follow-up visits. Four physical function measures—Six-Minute Walk Distance, Lower Extremity Gain Scale, Short Form-36 Physical Functioning Domain, and Yale Physical Activity Survey—were assessed at 2, 6, and 12 months postfracture. Generalized estimating equations modeled the relationship between baseline and time-varying serum tocopherol concentrations and physical function after hip fracture. Results. A total of 148 women aged 65 years and older were studied. After adjusting for covariates, baseline vitamin E concentrations were positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, and Yale Physical Activity Survey scores (p < .1) and faster improvement in Lower Extremity Gain Scale and Yale Physical Activity Survey scores (p < .008). Time-varying vitamin E was also positively associated with Six-Minute Walk Distance, Lower Extremity Gain Scale, Yale Physical Activity Survey, and Short Form-36 Physical Functioning Domain (p < .03) and faster improvement in Six-Minute Walk Distance and Short Form-36 Physical Functioning Domain (p < .07). Conclusions. Serum concentrations of both α- and γ-tocopherol were associated with better physical function after hip fracture. Vitamin E may represent a potentially modifiable factor related to recovery of postfracture physical function. PMID:21486921

Kinetic study on the catalytic performance of Rh/TiO/sub 2/ reduced at different temperatures in the CO-H/sub 2/ reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujitsu, H.; Ikeyama, N.; Mochida, I.

1986-08-01

Catalytic CO-H/sub 2/ reaction on Rh/TiO/sub 2/ reduced at 200, 400, and 500/sup 0/C (Cat-200, -400, -500) for 2 h was kinetically studied at 250/sup 0/C using a circulating reactor and Fourier transform-infrared (FT-IR) spectroscopy to determine how Cat-400 exhibited the highest activity. The rate equation distinguished the best catalyst with zero and first orders in CO and H/sub 2/, respectively, from other catalysts with negative order in CO. The adsorption ability of the catalyst at 200/sup 0/C was comparable to that of Cat-200, and two to three times larger than that of Cat-500, although the ability of Cat-200 wasmore » much larger at room temperature. Carbon monoxide adsorbed on the catalysts reversibly as well as irreversibly. IR spectroscopy revealed that the major form of irreversibly adsorbed CO was linear on Cat-200, whereas similar amounts of linear and bridge forms were observed on Cat-400 and Cat-500. These latter forms were highly reactive against hydrogen molecules when no carbon monoxide was present in the gas phase. Based on these results, the highest activity of Cat-400 is ascribed to rhodium metal modified by properly reduced TiO/sub 2/ to show the appropriate adsorption ability of carbon monoxide which least retards the activation of hydrogen according to first-order kinetics. Typical strong metal-support interaction decreases the catalytic activity by decreasing the active sites and strengthening the CO adsorption too much.« less

Trypanosoma cruzi. Surface antigens of blood and culture forms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nogueira, N.; Chaplan, S.; Tydings, J.D.

1981-03-01

The surface polypeptides of both cultured and blood forms of Trypanosoma cruzi were iodinated by the glucose oxidase-lactoperoxidase technique. Blood-form trypomastigotes (BFT) isolated form infected mice displayed a major 90,000-Mr component. In contrast, both epimastigotes and trypomastigotes obtained form acellular cultures expressed a smaller 75,000-Mr peptide. Both major surface components were presumably glycoproteins in terms of their binding to concanavalin A-Sepharose 4B. Within a 3-h period, both blood and culture forms synthesized their respective surface glycoproteins (90,000 Mr and 75,000 Mr, respectively in vitro. (/sub 35/S)methionine-labeled surface peptides were immunoprecipitated with immune sera of both human and murine origin. Amore » panel of sera form patients with chronic Chagas' disease and hyperimmunized mice recognized similar surface peptides. These immunogens were the same components as the major iodinated species. The major BFT surface peptide was readily removed by trypsin treatment of the parasites, although the procedure did not affect the 75,000-Mr peptide from the culture forms. Two-dimensional polyacrylamide gel electrophoresis revealed that the 90,000-Mr peptide found on BFT was an acidic protein of isoelectric point (pI) 5.0, whereas, the 75,000-Mr peptide form culture-form trypomastigotes has a pI of 7.2. The 90,000-Mr component is thought to be responsible for the anti-phagocytic properties of the BFT (1).« less

The Journalists Initiatives on Immunisation Against Polio and Improved Acceptance of the Polio Vaccine in Northern Nigeria 2007-2015.

PubMed

Warigon, Charity; Mkanda, Pascal; Banda, Richard; Zakari, Furera; Damisa, Eunice; Idowu, Audu; Bawa, Samuel; Gali, Emmanuel; Tegegne, Sisay G; Hammanyero, Kulchumi; Nsubuga, Peter; Korir, Charles; Vaz, Rui G

2016-05-01

The polio eradication initiative had major setbacks in 2003 and 2007 due to media campaigns in which renowned scholars and Islamic clerics criticized polio vaccines. The World Health Organization (WHO) partnered with journalists in 2007 to form the Journalists Initiatives on Immunisation Against Polio (JAP), to develop communication initiatives aimed at highlighting polio eradication activities and the importance of immunization in northern Nigeria. We evaluated the impact of JAP activities in Kaduna State by determining the total number of media materials produced and the number of newspaper clips and bulletins published in support of polio eradication. We also determined the number of households in noncompliant communities that became compliant with vaccination during 2015 supplementary immunization activities (SIAs) after JAP interventions and compared caregivers' sources of information about SIAs in 2007 before and after the JAP was formed. Since creation of the JAP, >500 reports have been published and aired, with most portraying polio vaccine positively. During June 2015 SIAs in high-risk wards of Kaduna STATE, JAP interventions resulted in vaccination of 5122 of 5991 children (85.5%) from noncompliant households. During early 2007, the number of caregivers who had heard about SIA rounds from the media increased from 26% in January, before the JAP was formed, to 33% in March, after the initiation of JAP activities. The formation of the JAP resulted in measurable improvement in the acceptance of polio vaccine in northern Nigeria. © 2016 World Health Organization; licensee Oxford Journals.

NMR and computational studies of stereoisomeric equine estrogen-derived DNA cytidine adducts in oligonucleotide duplexes: opposite orientations of diastereomeric forms.

PubMed

Zhang, Na; Ding, Shuang; Kolbanovskiy, Alexander; Shastry, Anant; Kuzmin, Vladimir A; Bolton, Judy L; Patel, Dinshaw J; Broyde, Suse; Geacintov, Nicholas E

2009-08-04

The equine estrogens equilin (EQ) and equilenin (EN) are the active components in the widely prescribed hormone replacement therapy formulation Premarin. Metabolic activation of EQ and EN generates the catechol 4-hydroxyequilenin (4-OHEN) that autoxidizes to the reactive o-quinone form in aerated aqueous solutions. The o-quinones react predominantly with C, and to a lesser extent with A and G, to form premutagenic cyclic covalent DNA adducts in vitro and in vivo. To obtain insights into the structural properties of these biologically important DNA lesions, we have synthesized site-specifically modified oligonucleotides containing the stereoisomeric 1'S,2'R,3'R-4-OHEN-C3 and 1'R,2'S,3'S-4-OHEN-C4 adducts derived from the reaction of 4-OHEN with the C in the oligonucleotide 5'-GGTAGCGATGG in aqueous solution. A combined NMR and computational approach was utilized to determine the conformational characteristics of the two major 4-OHEN-C3 and 4-OHEN-C4 stereoisomeric adducts formed in this oligonucleotide hybridized with its complementary strand. In both cases, the modified C adopts an anti glycosidic bond conformation; the equilenin distal ring protrudes into the minor groove while its two proximal hydroxyl groups are exposed on the major groove side of the DNA duplex. The bulky 4-OHEN-C adduct distorts the duplex within the central GC*G portion, but Watson-Crick pairing is maintained adjacent to C* in both stereoisomeric adducts. For the 4-OHEN-C3 adduct, the equilenin rings are oriented toward the 5'-end of the modified strand, while in 4-OHEN-C4 the equilenin is 3'-directed. Correspondingly, the distortions of the double-helical structures are more pronounced on the 5'- or the 3'-side of the lesion, respectively. These differences in stereoisomeric adduct conformations may play a role in the processing of these lesions in cellular environments.

In situ Studies of Phase Evolution in (Pr 1-x Nd x) 2 NiO 4 Electrodes with Various Interlayer Chemistries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dogdibegovic, Emir; Alabri, Nawf Saif; Wright, Christopher J.

The interest in Pr2NiO4 (PNO) electrode stems from the necessity to develop active and stable oxygen electrodes (1-6) for solid oxide fuel cells (SOFCs) (7-9). PNO is known for its highly active nature (7,8,10), originating from its superior oxygen ion diffusion, surface exchange coefficient (2,7,9-11) and structural flexibility over a wide temperature region (from 500 to 900oC) (3,12). PNO electrode, however, does undergo structural evolution to form a higher order phase (Pr3Ni2O7) and Pr6O11 (PrOx) (8). The structural change has been a major concern because it possibly links with the performance degradation over long-term operation (7,8) Conventional x-ray diffraction (XRD)more » has been extensively used to investigate the structural evolution in nickelates in the form of powders or planar electrodes (8,10). This method has two major limitations due to its low flux and low resolution: (1) it might overlook the presence of additional phases in the system, which is especially true for praseodymium nickelates where XRD diffraction patterns of higher order phase(s) (e.g. Pr3Ni2O7) may overlap with the parent PNO phase, making quantification challenging (8); and (2) the quantification of phase evolution in electrochemically operated PNO electrode may show major structural change with almost 100% of the parent phase transition from the conventional XRD analysis, while the transmission electron microscopy (TEM) studies clearly show the regions of preserved PNO phase (7).« less

In situ Studies of Phase Evolution in (Pr1-xNdx)2NiO4 Electrodes with Various Interlayer Chemistries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dogdibegovic, Emir; Alabri, Nawf S.; Wright, Christopher J.

2017-07-24

The interest in Pr2NiO4 (PNO) electrode stems from the necessity to develop active and stable oxygen electrodes (1-6) for solid oxide fuel cells (SOFCs) (7-9). PNO is known for its highly active nature (7,8,10), originating from its superior oxygen ion diffusion, surface exchange coefficient (2,7,9-11) and structural flexibility over a wide temperature region (from 500 to 900oC) (3,12). PNO electrode, however, does undergo structural evolution to form a higher order phase (Pr3Ni2O7) and Pr6O11 (PrOx) (8). The structural change has been a major concern because it possibly links with the performance degradation over long-term operation (7,8) Conventional x-ray diffraction (XRD)more » has been extensively used to investigate the structural evolution in nickelates in the form of powders or planar electrodes (8,10). This method has two major limitations due to its low flux and low resolution: (1) it might overlook the presence of additional phases in the system, which is especially true for praseodymium nickelates where XRD diffraction patterns of higher order phase(s) (e.g. Pr3Ni2O7) may overlap with the parent PNO phase, making quantification challenging (8); and (2) the quantification of phase evolution in electrochemically operated PNO electrode may show major structural change with almost 100% of the parent phase transition from the conventional XRD analysis, while the transmission electron microscopy (TEM) studies clearly show the regions of preserved PNO phase (7).« less

Corrosion resistant solar mirror

DOEpatents

Medwick, Paul A.; Abbott, Edward E.

2016-07-19

A reflective article includes a transparent substrate having a first major surface and a second major surface. A base coat is formed over at least a portion of the second major surface. A primary reflective coating having at least one metallic layer is formed over at least a portion of the base coat. A protective coating is formed over at least a portion of the primary reflective coating. The article further includes a solar cell and an anode, with the solar cell connected to the metallic layer and the anode.

[Effect of β-cyclodextrin inclusion complex on transport of major components of Xiangfu Siwu decoction essential oil in Caco-2 cell monolayer model].

PubMed

Xi, Jun-zuan; Qian, Da-wei; Duan, Jin-ao; Liu, Pei; Zhu, Yue; Zhu, Zhen-hua; Zhang, Li

2015-08-01

Although the essential oil of Xiangfu Siwu decoction (XFSWD) has strong pharmacological activity, its special physical and chemical properties restrict the clinical application and curative effect. In this paper, Xiangfu Siwu decoction essential oil (XFS-WO) was prepared by forming inclusion complex with β-cyclodextrin (β-CD). The present study is to investigate the effect of β-CD inclusion complex on the transport of major components of XFSWO using Caco-2 cell monolayer model, thus to research the effect of this formation on the absorption of drugs with low solubility and high permeability, which belong to class 2 in biopharmaceutics classification system. A sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of senkyunolide A, 3-n-butylphthalide, Z-ligustilide, dehydrocostus lactone and α-cyperone, which are active compounds in XFSWO. The transport parameters were analyzed and compared in free oil and its β-CD inclusion complex. The result revealed that the formation of XFSWO/β-CD inclusion complex has significantly increased the transportation and absorption of major active ingredients than free oil. Accordingly, it can be speculated that cyclodextrin inclusion complex can improve bioavailability of poorly water-soluble drugs. Above all these mentioned researches, it provided foundation and basis for physiological disposition and pharmaceutical study of XFSWD.

Identification of the gene encoding the major NAD(P)H-flavin oxidoreductase of the bioluminescent bacterium Vibrio fischeri ATCC 7744.

PubMed Central

Zenno, S; Saigo, K; Kanoh, H; Inouye, S

1994-01-01

The gene encoding the major NAD(P)H-flavin oxidoreductase (flavin reductase) of the luminous bacterium Vibrio fischeri ATCC 7744 was isolated by using synthetic oligonucleotide probes corresponding to the N-terminal amino acid sequence of the enzyme. Nucleotide sequence analysis suggested that the major flavin reductase of V. fischeri consisted of 218 amino acids and had a calculated molecular weight of 24,562. Cloned flavin reductase expressed in Escherichia coli was purified virtually to homogeneity, and its basic biochemical properties were examined. As in the major flavin reductase in crude extracts of V. fischeri, cloned flavin reductase showed broad substrate specificity and served well as a catalyst to supply reduced flavin mononucleotide (FMNH2) to the bioluminescence reaction. The major flavin reductase of V. fischeri not only showed significant similarity in amino acid sequence to oxygen-insensitive NAD(P)H nitroreductases of Salmonella typhimurium, Enterobacter cloacae, and E. coli but also was associated with a low level of nitroreductase activity. The major flavin reductase of V. fischeri and the nitroreductases of members of the family Enterobacteriaceae would thus appear closely related in evolution and form a novel protein family. Images PMID:8206830

Orbitofrontal cortex function and structure in depression.

PubMed

Drevets, Wayne C

2007-12-01

The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

Antitrypanosomal compounds from the essential oil and extracts of Keetia leucantha leaves with inhibitor activity on Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase.

PubMed

Bero, J; Beaufay, C; Hannaert, V; Hérent, M-F; Michels, P A; Quetin-Leclercq, J

2013-02-15

Keetia leucantha is a West African tree used in traditional medicine to treat several diseases among which parasitic infections. The dichloromethane extract of leaves was previously shown to possess growth-inhibitory activities on Plasmodium falciparum, Trypanosoma brucei brucei and Leishmania mexicana mexicana with low or no cytotoxicity (>100 μg/ml on human normal fibroblasts) (Bero et al. 2009, 2011). In continuation of our investigations on the antitrypanosomal compounds from this dichloromethane extract, we analyzed by GC-FID and GC-MS the essential oil of its leaves obtained by hydrodistillation and the major triterpenic acids in this extract by LC-MS. Twenty-seven compounds were identified in the oil whose percentages were calculated using the normalization method. The essential oil, seven of its constituents and the three triterpenic acids were evaluated for their antitrypanosomal activity on Trypanosoma brucei brucei bloodstream forms (Tbb BSF) and procyclic forms (Tbb PF) to identify an activity on the glycolytic process of trypanosomes. The oil showed an IC(50) of 20.9 μg/ml on Tbb BSF and no activity was observed on Tbb PF. The best antitrypanosomal activity was observed for ursolic acid with IC(50) of 2.5 and 6.5 μg/ml respectively on Tbb BSF and Tbb PF. The inhibitory activity on a glycolytic enzyme of T. brucei, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was also evaluated for betulinic acid, olenaolic acid, ursolic acid, phytol, α-ionone and β-ionone. The three triterpenic acids and β-ionone showed inhibitory activities on GAPDH with oleanolic acid being the most active with an inhibition of 72.63% at 20 μg/ml. This paper reports for the first time the composition and antitrypanosomal activity of the essential oil of Keetia leucantha. Several of its constituents and three triterpenic acids present in the dichloromethane leaves extract showed a higher antitrypanosomal activity on bloodstream forms of Tbb as compared to procyclic forms, namely geranyl acetone, phytol, α-ionone, β-ionone, ursolic acid, oleanolic acid and betulinic acid. The four last compounds were proven to be inhibitors of trypanosomal GAPDH, which may in part explain these antitrypanosomal activities. Copyright © 2012 Elsevier GmbH. All rights reserved.

Antimicrobial activity of synthetic cationic peptides and lipopeptides derived from human lactoferricin against Pseudomonas aeruginosa planktonic cultures and biofilms.

PubMed

Sánchez-Gómez, Susana; Ferrer-Espada, Raquel; Stewart, Philip S; Pitts, Betsey; Lohner, Karl; Martínez de Tejada, Guillermo

2015-07-07

Infections by Pseudomonas aeruginosa constitute a serious health threat because this pathogen -particularly when it forms biofilms - can acquire resistance to the majority of conventional antibiotics. This study evaluated the antimicrobial activity of synthetic peptides based on LF11, an 11-mer peptide derived from human lactoferricin against P. aeruginosa planktonic and biofilm-forming cells. We included in this analysis selected N-acylated derivatives of the peptides to analyze the effect of acylation in antimicrobial activity. To assess the efficacy of compounds against planktonic bacteria, microdilution assays to determine the minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill studies were conducted. The anti-biofilm activity of the agents was assessed on biofilms grown under static (on microplates) and dynamic (in a CDC-reactor) flow regimes. The antimicrobial activity of lipopeptides differed from that of non-acylated peptides in their killing mechanisms on planktonic and biofilm-forming cells. Thus, acylation enhanced the bactericidal activity of the parental peptides and resulted in lipopeptides that were uniformly bactericidal at their MIC. In contrast, acylation of the most potent anti-biofilm peptides resulted in compounds with lower anti-biofilm activity. Both peptides and lipopeptides displayed very rapid killing kinetics and all of them required less than 21 min to reduce 1,000 times the viability of planktonic cells when tested at 2 times their MBC. The peptides, LF11-215 (FWRIRIRR) and LF11-227 (FWRRFWRR), displayed the most potent anti-biofilm activity causing a 10,000 fold reduction in cell viability after 1 h of treatment at 10 times their MIC. At that concentration, these two compounds exhibited low citotoxicity on human cells. In addition to its bactericidal activity, LF11-227 removed more that 50 % of the biofilm mass in independent assays. Peptide LF11-215 and two of the shortest and least hydrophobic lipopeptides, DI-MB-LF11-322 (2,2-dimethylbutanoyl-PFWRIRIRR) and DI-MB-LF11-215, penetrated deep into the biofilm structure and homogenously killed biofilm-forming bacteria. We identified peptides derived from human lactoferricin with potent antimicrobial activity against P. aeruginosa growing either in planktonic or in biofilm mode. Although further structure-activity relationship analyses are necessary to optimize the anti-biofilm activity of these compounds, the results indicate that lactoferricin derived peptides are promising anti-biofilm agents.

Athletic activity after spine surgery in children and adolescents: results of a survey.

PubMed

Rubery, Paul T; Bradford, David S

2002-02-15

Questionnaire-based survey. To poll the members of the Scoliosis Research Society regarding their opinions and experience with athletic activity after spine surgery performed on children and adolescents. Athletic activity is increasingly important in society. Patients are very concerned about returning to sports and exercise after spinal surgery. There are no generally accepted guidelines for surgeons regarding either appropriate sports or the appropriate time to resume sports after spinal surgery. A survey was designed by the authors and reviewed by a statistical consultant. The form was mailed to the 721 individuals on the Scoliosis Research Society mailing list. Returned surveys were hand scored and entered into an Excel spreadsheet. Of the 316 forms returned, 278 indicated that the respondent performed spinal fusion on children and adolescents. Two hundred sixty-one completed forms, representing approximately 45% of the society's estimated active clinicians, were reviewed. Formal physical therapy was unlikely to be recommended by members of the society regardless of procedure, although postoperative home exercise was used by many after spondylolisthesis fusion. The majority of patients were returned to gym class between 6 months and 1 year (range, immediate to never) after surgery. Most respondents returned patients to noncontact sports between 6 months and 1 year postoperatively. Contact sports were generally withheld until 1 year after surgery. Close to 20% of respondents required, and 35% suggested, that patients never return to collision sports. Twenty percent of respondents for scoliosis and 5% for spondylolisthesis reported having notable adverse outcomes attributed to athletic activity. These survey results show the varying approaches taken by members of the Scoliosis Research Society to postoperative athletic activity, and they provide a starting point for investigations regarding alternative approaches.

Quantitative accuracy of the closed-form least-squares solution for targeted SPECT.

PubMed

Shcherbinin, S; Celler, A

2010-10-07

The aim of this study is to investigate the quantitative accuracy of the closed-form least-squares solution (LSS) for single photon emission computed tomography (SPECT). The main limitation for employing this method in actual clinical reconstructions is the computational cost related to operations with a large-sized system matrix. However, in some clinical situations, the size of the system matrix can be decreased using targeted reconstruction. For example, some oncology SPECT studies are characterized by intense tracer uptakes that are localized in relatively small areas, while the remaining parts of the patient body have only a low activity background. Conventional procedures reconstruct the activity distribution in the whole object, which leads to relatively poor image accuracy/resolution for tumors while computer resources are wasted, trying to rebuild diagnostically useless background. In this study, we apply a concept of targeted reconstruction to SPECT phantom experiments imitating such oncology scans. Our approach includes two major components: (i) disconnection of the entire imaging system of equations and extraction of only those parts that correspond to the targets, i.e., regions of interest (ROI) encompassing active containers/tumors and (ii) generation of the closed-form LSS for each target ROI. We compared these ROI-based LSS with those reconstructed by the conventional MLEM approach. The analysis of the five processed cases from two phantom experiments demonstrated that the LSS approach outperformed MLEM in terms of the noise level inside ROI. On the other hand, MLEM better recovered total activity if the number of iterations was large enough. For the experiment without background activity, the ROI-based LSS led to noticeably better spatial activity distribution inside ROI. However, the distributions pertaining to both approaches were practically identical for the experiment with the concentration ratio 7:1 between the containers and the background.

Fingerprinting of near-homogeneous DNA ligase I and II from human cells. Similarity of their AMP-binding domains.

PubMed

Yang, S W; Becker, F F; Chan, J Y

1990-10-25

DNA ligases play obligatory roles during replication, repair, and recombination. Multiple forms of DNA ligase have been reported in mammalian cells including DNA ligase I, the high molecular mass species which functions during replication, and DNA ligase II, the low molecular mass species which is associated with repair. In addition, alterations in DNA ligase activities have been reported in acute lymphocytic leukemia cells, Bloom's syndrome cells, and cells undergoing differentiation and development. To better distinguish the biochemical and molecular properties of the various DNA ligases from human cells, we have developed a method of purifying multiple species of DNA ligase from HeLa cells by chromatography through DEAE-Bio-Gel, CM-Bio-Gel, hydroxylapatite, Sephacryl S-300, Mono P, and DNA-cellulose. DNA-cellulose chromatography of the partially purified enzymes resolved multiple species of DNA ligase after labeling the enzyme with [alpha-32P]ATP to form the ligase-[32P]AMP adduct. The early eluting enzyme activity (0.25 M NaCl) contained a major 67-kDa-labeled protein, while the late eluting activity (0.48 M NaCl) contained two major labeled proteins of 90 and 78 kDa. Neutralization experiments with antiligase I antibodies indicated that the early and late eluting activity peaks were DNA ligase II and I, respectively. The three major ligase-[32P]AMP polypeptides (90, 78, and 67 kDa) were subsequently purified to near homogeneity by elution from preparative sodium dodecyl sulfate-polyacrylamide gels. All three polypeptides retained DNA ligase activities after gel elution and renaturation. To further reveal the relationship between these enzymes, partial digestion by V8-protease was performed. All three purified polypeptides gave rise to a common 22-kDa-labeled fragment for their AMP-binding domains, indicating that the catalytic sites of ligase I and II are quite similar, if not identical. Similar findings were obtained from the two-dimensional gel electrophoresis of their AMP-binding domains in the trypsin-digested protein fragments. The results also suggested that these isozymes have been derived from the same primordial DNA sequence or from the same precursor protein. The purification scheme and the data obtained will be instrumental for the further elucidation of the biological roles of various DNA ligases from human cells.

Akt/PKB Controls the Activity-Dependent Bulk Endocytosis of Synaptic Vesicles

PubMed Central

Smillie, Karen J; Cousin, Michael A

2012-01-01

Activity-dependent bulk endocytosis (ADBE) is the dominant SV endocytosis mode during intense neuronal activity. The dephosphorylation of Ser774 on dynamin I is essential for triggering of ADBE, as is its subsequent rephosphorylation by glycogen synthase kinase 3 (GSK3). We show that in primary cultures of cerebellar granule neurons the protein kinase Akt phosphorylates GSK3 during intense neuronal activity, ensuring that GSK3 is inactive during intense stimulation to aid dynamin I dephosphorylation. Furthermore, when a constitutively active form of Akt was overexpressed in primary neuronal cultures, ADBE was inhibited with no effect on clathrin-mediated endocytosis. Thus Akt has two major regulatory roles (i) to ensure efficient dynamin I dephosphorylation via acute activity-dependent inhibition of GSK3 and (ii) to negatively regulate ADBE when activated in the longer term. This is the first demonstration of a role for Akt in SV recycling and suggests a key role for this protein kinase in modulating synaptic strength during elevated neuronal activity. PMID:22487004

K2P TASK-2 and KCNQ1-KCNE3 K+ channels are major players contributing to intestinal anion and fluid secretion.

PubMed

Julio-Kalajzić, Francisca; Villanueva, Sandra; Burgos, Johanna; Ojeda, Margarita; Cid, L Pablo; Jentsch, Thomas J; Sepúlveda, Francisco V

2018-02-01

K + channels are important in intestinal epithelium as they ensure the ionic homeostasis and electrical potential of epithelial cells during anion and fluid secretion. Intestinal epithelium cAMP-activated anion secretion depends on the activity of the (also cAMP dependent) KCNQ1-KCNE3 K + channel, but the secretory process survives after genetic inactivation of the K + channel in the mouse. Here we use double mutant mice to investigate which alternative K + channels come into action to compensate for the absence of KCNQ1-KCNE3 K + channels. Our data establish that whilst Ca 2+ -activated K Ca 3.1 channels are not involved, K 2P two-pore domain TASK-2 K + channels are major players providing an alternative conductance to sustain the intestinal secretory process. Work with double mutant mice lacking both TASK-2 and KCNQ1-KCNE3 channels nevertheless points to yet-unidentified K + channels that contribute to the robustness of the cAMP-activated anion secretion process. Anion and fluid secretion across the intestinal epithelium, a process altered in cystic fibrosis and secretory diarrhoea, is mediated by cAMP-activated CFTR Cl - channels and requires the simultaneous activity of basolateral K + channels to maintain cellular ionic homeostasis and membrane potential. This function is fulfilled by the cAMP-activated K + channel formed by the association of pore-forming KCNQ1 with its obligatory KCNE3 β-subunit. Studies using mice show sizeable cAMP-activated intestinal anion secretion in the absence of either KCNQ1 or KCNE3 suggesting that an alternative K + conductance must compensate for the loss of KCNQ1-KCNE3 activity. We used double mutant mouse and pharmacological approaches to identify such a conductance. Ca 2+ -dependent anion secretion can also be supported by Ca 2+ -dependent K Ca 3.1 channels after independent CFTR activation, but cAMP-dependent anion secretion is not further decreased in the combined absence of K Ca 3.1 and KCNQ1-KCNE3 K + channel activity. We show that the K 2P K + channel TASK-2 is expressed in the epithelium of the small and large intestine. Tetrapentylammonium, a TASK-2 inhibitor, abolishes anion secretory current remaining in the absence of KCNQ1-KCNE3 activity. A double mutant mouse lacking both KCNQ1-KCNE3 and TASK-2 showed a much reduced cAMP-mediated anion secretion compared to that observed in the single KCNQ1-KCNE3 deficient mouse. We conclude that KCNQ1-KCNE3 and TASK-2 play major roles in the intestinal anion and fluid secretory phenotype. The persistence of an, admittedly reduced, secretory activity in the absence of these two conductances suggests that further additional K + channel(s) as yet unidentified contribute to the robustness of the intestinal anion secretory process. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Active touch and self-motion encoding by Merkel cell-associated afferents

PubMed Central

Severson, Kyle S.; Xu, Duo; Van de Loo, Margaret; Bai, Ling; Ginty, David D.; O’Connor, Daniel H.

2017-01-01

Summary Touch perception depends on integrating signals from multiple types of peripheral mechanoreceptors. Merkel-cell associated afferents are thought to play a major role in form perception by encoding surface features of touched objects. However, activity of Merkel afferents during active touch has not been directly measured. Here, we show that Merkel and unidentified slowly adapting afferents in the whisker system of behaving mice respond to both self-motion and active touch. Touch responses were dominated by sensitivity to bending moment (torque) at the base of the whisker and its rate of change, and largely explained by a simple mechanical model. Self-motion responses encoded whisker position within a whisk cycle (phase), not absolute whisker angle, and arose from stresses reflecting whisker inertia and activity of specific muscles. Thus, Merkel afferents send to the brain multiplexed information about whisker position and surface features, suggesting that proprioception and touch converge at the earliest neural level. PMID:28434802

Plants’ Natural Products as Alternative Promising Anti-Candida Drugs

PubMed Central

Soliman, Sameh; Alnajdy, Dina; El-Keblawy, Ali A.; Mosa, Kareem A.; Khoder, Ghalia; Noreddin, Ayman M.

2017-01-01

Candida is a serious life-threatening pathogen, particularly with immunocompromised patients. Candida infections are considered as a major cause of morbidity and mortality in a broad range of immunocompromised patients. Candida infections are common in hospitalized patients and elderly people. The difficulty to eradicate Candida infections is owing to its unique switch between yeast and hyphae forms and more likely to biofilm formations that render resistance to antifungal therapy. Plants are known sources of natural medicines. Several plants show significant anti-Candida activities and some of them have lower minimum inhibitory concentration, making them promising candidates for anti-Candida therapy. However, none of these plant products is marketed for anti-Candida therapy because of lack of sufficient information about their efficacy, toxicity, and kinetics. This review revises major plants that have been tested for anti-Candida activities with recommendations for further use of some of these plants for more investigation and in vivo testing including the use of nanostructure lipid system. PMID:28989245

Summary Document: Restoration Plan for Major Airports after a Bioterrorist Attack

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raber, E

2007-01-11

This document provides general guidelines for developing a Restoration Plan for a major airport following release of a biological warfare agent. San Francisco International Airport was selected as the example airport during development of the Plan to illustrate specific details. The spore forming bacterium Bacillus anthracis was selected as the biological agent of primary concern because it is the most difficult of known bioterrorism agents to inactivate and is considered to be one of the agents most likely to be used as a biological weapon. The focus of the Plan is on activities associated with the Characterization, Remediation, and Clearancemore » Phases that are defined herein. Activities associated with the Notification and First-Response Phases are briefly discussed in Appendixes A and B, respectively. In addition to the main text of this Plan and associated appendixes, a data supplement was developed specifically for San Francisco International Airport. Requests for the data supplement must be made directly to the Emergency Planning Operations Division of San Francisco International Airport.« less

Identification of katG Mutations Associated with High-Level Isoniazid Resistance in Mycobacterium tuberculosis▿ †

PubMed Central

Ando, Hiroki; Kondo, Yuji; Suetake, Toshinori; Toyota, Emiko; Kato, Seiya; Mori, Toru; Kirikae, Teruo

2010-01-01

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates. PMID:20211896

Geologic map of the Lassen region, Cascade Range, USA

USGS Publications Warehouse

Clynne, Michael; Muffler, L.J.

1990-01-01

A preliminary geologic map at 1:50,000 of the Lassen region encompasses 1400 km2. The map displays many small, monogenetic volcanoes of basalt to andesite as well as three major late Pliocene and Quaternary volcanic centers that have erupted products ranging from basaltic andesite to rhyolite. The youngest of these volcanic centers is the Lassen volcanic center, active from 600,000 years B.P. to the present. A major caldera formed at 400,000 years B.P. and has subsequently been filled with silicic lavas. The Lassen geothermal system, which consists of a central vapor-dominated reservoir at a temperature of 235??C underlain by a reservoir of hot water, is centered at Bumpass Hell within Lassen Volcanic National Park.

Comments on filament-disintegration and its relation to other aspects of solar activity.

NASA Technical Reports Server (NTRS)

Dodson, H. W.; Hedeman, E. R.; Rovira De Miceli, M.

1972-01-01

Studies of sudden disintegrations of filaments in solar cycles 19 and 20 (to 1969) indicate that such events occur frequently. Approximately 30% of all large filaments in these cycles disintegrated in the course of their transit across the solar disk. 'Major' flares occurred with above average frequency on the last day on which 141 large disappearing filaments were observed. Relationships between a disintegrating filament on July 10-11, 1959, a prior major flare, a newly formed spot, and concomitant growth of H-alpha plage are presented. Observation of prior descending prominence material apparently directed towards the location of the flare of July 15, 1959 is reported. The development of the filament-associated flare of Feb. 13, 1967 is described.

Major and trace element chemistry of Boulder 1 at Station 2, Apollo 17

NASA Technical Reports Server (NTRS)

Blanchard, D. P.; Haskin, L. A.; Jacobs, J. W.; Brannon, J. C.; Korotev, R. L.

1975-01-01

Twenty-seven samples from Boulder 1 at Station 2 are analyzed for major and trace elements by atomic absorption spectrophotometry and neutron activation analysis. Two types of matrix and several types of clast materials are characterized on the basis of their chemistry. It is shown that one matrix type is a common material at the Apollo 17 site, while the other is probably exotic to that site. The most unusual clast materials found are coarse norite (an old rock no longer found in millimeter fragments at the site) and pigeonite basalt (possibly a highland volcanic rock). It is concluded that the boulder-forming process combined materials from at least two different localities or vertical strata.

Generation of thromboxane A2 and aorta-contracting activity from platelets stimulated with modified C-reactive protein.

PubMed Central

Simpson, R M; Prancan, A; Izzi, J M; Fiedel, B A

1982-01-01

The classical acute phase reactant, C-reactive protein (CRP), appears in markedly elevated concentration in the sera of individuals undergoing reactions of acute inflammation and tissue degradation. We previously demonstrated that like IgG, appropriately purified CRP could be thermally modified (H-CRP) such that it enhanced platelet activation in plasma and initiated platelet responses in isolated systems. We now report that this direct platelet activation by modified CRP results in the secretion of both platelet dense body and alpha-granule constituents, and is sensitive to non-steroidal anti-inflammatory drugs as well as the adenosine diphosphate (ADP)-removing enzyme system creatine phosphate/creatine phosphokinase. Thin-layer chromatographic (TLC) analysis of prostanoate endproducts following platelet activation with H-CRP revealed the formation of thromboxane B2 (the hydrated endproduct of thromboxane A2), an important endogenous platelet activator and contractor of vascular tissue; bioassay on rabbit aorta strips of supernatants obtained from platelets undergoing challenge with H-CRP supported the TLC analysis. Complexes formed between CRP and one major ligand, the polycation, were found to share certain platelet activating properties with H-CRP, as does latex-aggregated CRP. These data imply a potential agonist role for this acute phase reactant in platelet physiology and suggest that the interaction of modified forms of CRP with the platelet at sites of vascular damage could have pathological significance. PMID:7118160

[Cellular and intracellular transport of vitamin C. The physiologic aspects].

PubMed

Szarka, András; Lőrincz, Tamás

2013-10-20

Vitamin C requirement is satisfied by natural sources and vitamin C supplements in the ordinary human diet. The two major forms of vitamin C in the diet are L-ascorbic acid and L-dehydroascorbic acid. Both ascorbate and dehydroascorbate are absorbed along the entire length of the human intestine. The reduced form, L-ascorbic acid is imported by an active mechanism, requiring two sodium-dependent vitamin C transporters (SVCT1 and SVCT2). The transport of the oxidized form, dehydroascorbate is mediated by glucose transporters GLUT1, GLUT3 and possibly GLUT4. Initial rate of uptake of both ascorbate and dehydroascorbate is saturable with increasing external substrate concentration. Vitamin C plasma concentrations are tightly controlled when the vitamin is taken orally. It has two simple reasons, on the one hand, the capacity of the transporters is limited, on the other hand the two Na+-dependent transporters can be down-regulated by an elevated level of ascorbate.

Complex Enzyme-Assisted Extraction Releases Antioxidative Phenolic Compositions from Guava Leaves.

PubMed

Wang, Lu; Wu, Yanan; Liu, Yan; Wu, Zhenqiang

2017-09-30

Phenolics in food and fruit tree leaves exist in free, soluble-conjugate, and insoluble-bound forms. In this study, in order to enhance the bioavailability of insoluble-bound phenolics from guava leaves (GL), the ability of enzyme-assisted extraction in improving the release of insoluble-bound phenolics was investigated. Compared to untreated GL, single xylanase-assisted extraction did not change the composition and yield of soluble phenolics, whereas single cellulase or β -glucosidase-assisted extraction significantly enhanced the soluble phenolics content of PGL. However, complex enzyme-assisted extraction (CEAE) greatly improved the soluble phenolics content, flavonoids content, ABTS, DPPH, and FRAP by 103.2%, 81.6%, 104.4%, 126.5%, and 90.3%, respectively. Interestingly, after CEAE, a major proportion of phenolics existed in the soluble form, and rarely in the insoluble-bound form. Especially, the contents of quercetin and kaempferol with higher bio-activity were enhanced by 3.5- and 2.2-fold, respectively. More importantly, total soluble phenolics extracts of GL following CEAE exhibited the highest antioxidant activity and protective effect against supercoiled DNA damage. This enzyme-assisted extraction technology can be useful for extracting biochemical components from plant matrix, and has good potential for use in the food and pharmaceutical industries.

From synapses to behavior: development of a sensory-motor circuit in the leech.

PubMed

Marin-Burgin, Antonia; Kristan, William B; French, Kathleen A

2008-05-01

The development of neuronal circuits has been advanced greatly by the use of imaging techniques that reveal the activity of neurons during the period when they are constructing synapses and forming circuits. This review focuses on experiments performed in leech embryos to characterize the development of a neuronal circuit that produces a simple segmental behavior called "local bending." The experiments combined electrophysiology, anatomy, and FRET-based voltage-sensitive dyes (VSDs). The VSDs offered two major advantages in these experiments: they allowed us to record simultaneously the activity of many neurons, and unlike other imaging techniques, they revealed inhibition as well as excitation. The results indicated that connections within the circuit are formed in a predictable sequence: initially neurons in the circuit are connected by electrical synapses, forming a network that itself generates an embryonic behavior and prefigures the adult circuit; later chemical synapses, including inhibitory connections, appear, "sculpting" the circuit to generate a different, mature behavior. In this developmental process, some of the electrical connections are completely replaced by chemical synapses, others are maintained into adulthood, and still others persist and share their targets with chemical synaptic connections.

Antigenic peptides containing large PEG loops designed to extend out of the HLA-A2 binding site form stable complexes with class I major histocompatibility complex molecules.

PubMed Central

Bouvier, M; Wiley, D C

1996-01-01

Recognition of peptides bound to class I major histocompatibility complex (MHC) molecules by specific receptors on T cells regulates the development and activity of the cellular immune system. We have designed and synthesized de novo cyclic peptides that incorporate PEG in the ring structure for binding to class I MHC molecules. The large PEG loops are positioned to extend out of the peptide binding site, thus creating steric effects aimed at preventing the recognition of class I MHC complexes by T-cell receptors. Peptides were synthesized and cyclized on polymer support using high molecular weight symmetrical PEG dicarboxylic acids to link the side chains of lysine residues substituted at positions 4 and 8 in the sequence of the HLA-A2-restricted human T-lymphotrophic virus type I Tax peptide. Cyclic peptides promoted the in vitro folding and assembly of HLA-A2 complexes. Thermal denaturation studies using circular dichroism spectroscopy showed that these complexes are as stable as complexes formed with antigenic peptides. Images Fig. 2 Fig. 4 PMID:8643447

Synthesis of structurally diverse major groove DNA interstrand crosslinks using three different aldehyde precursors

PubMed Central

Mukherjee, Shivam; Guainazzi, Angelo; Schärer, Orlando D.

2014-01-01

DNA interstrand crosslinks (ICLs) are extremely cytotoxic lesions that block essential cellular processes, such as replication and transcription. Crosslinking agents are widely used in cancer chemotherapy and form an array of structurally diverse ICLs. Despite the clinical success of these agents, resistance of tumors to crosslinking agents, for example, through repair of these lesions by the cellular machinery remains a problem. We have previously reported the synthesis of site-specific ICLs mimicking those formed by nitrogen mustards to facilitate the studies of cellular responses to ICL formation. Here we extend these efforts and report the synthesis of structurally diverse major groove ICLs that induce severe, little or no distortion in the DNA. Our approach employs the incorporation of aldehyde precursors of different lengths into complementary strands and ICL formation using a double reductive amination with a variety of amines. Our studies provide insight into the structure and reactivity parameters of ICL formation by double reductive amination and yield a set of diverse ICLs that will be invaluable for exploring structure–activity relationships in ICL repair. PMID:24782532

Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance.

PubMed

Vale, Nuno; Gouveia, Maria João; Rinaldi, Gabriel; Brindley, Paul J; Gärtner, Fátima; Correia da Costa, José M

2017-05-01

Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes. Copyright © 2017 American Society for Microbiology.

Spatiotemporal psychopathology I: No rest for the brain's resting state activity in depression? Spatiotemporal psychopathology of depressive symptoms.

PubMed

Northoff, Georg

2016-01-15

Despite intense neurobiological investigation in psychiatric disorders like major depressive disorder (MDD), the basic disturbance that underlies the psychopathological symptoms of MDD remains, nevertheless, unclear. Neuroimaging has focused mainly on the brain's extrinsic activity, specifically task-evoked or stimulus-induced activity, as related to the various sensorimotor, affective, cognitive, and social functions. Recently, the focus has shifted to the brain's intrinsic activity, otherwise known as its resting state activity. While various abnormalities have been observed during this activity, their meaning and significance for depression, along with its various psychopathological symptoms, are yet to be defined. Based on findings in healthy brain resting state activity and its particular spatial and temporal structure - defined in a functional and physiological sense rather than anatomical and structural - I claim that the various depressive symptoms are spatiotemporal disturbances of the resting state activity and its spatiotemporal structure. This is supported by recent findings that link ruminations and increased self-focus in depression to abnormal spatial organization of resting state activity. Analogously, affective and cognitive symptoms like anhedonia, suicidal ideation, and thought disorder can be traced to an increased focus on the past, increased past-focus as basic temporal disturbance o the resting state. Based on these findings, I conclude that the various depressive symptoms must be conceived as spatiotemporal disturbances of the brain's resting state's activity and its spatiotemporal structure. Importantly, this entails a new form of psychopathology, "Spatiotemporal Psychopathology" that directly links the brain and psyche, therefore having major diagnostic and therapeutic implications for clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

NO-Synthase Activity in Patients with Coronary Heart Disease Associated with Hypertension of Different Age Groups.

PubMed

Besedina, Anna

2016-01-01

Coronary heart disease is the leading cause of death and disability worldwide. Hypertension is a major independent risk factor for the development of CHD. Abnormalities in NO generation or activity have been proposed as a major mechanism of CHD. The purpose of this article is to determine the activity of eNOS and iNOS in patients with isolated CHD and CHD associated with HT of different age groups. Fifty patients with isolated CHD and 42 patients with CHD associated with HT were enrolled in this study. NOS activity was determined by nitrite anion formed in the reaction. A statistically significant increase in iNOS activity is observed in elderly donors. In patients with isolated coronary heart disease cNOS activity is statistically significantly reduced with respect to the control group. The reduction of enzymatic activity of cNOS is more expressed in elderly patients than in middle-aged patients with coronary heart disease. Alterations in eNOS activity are more expressed in patients with coronary heart disease associated with hypertension than in patients with isolated coronary heart disease. Against the background of cNOS inhibition in the patients, a sharp increase in iNOS activity is observed. It has been shown that disturbance of endothelial function in patients with coronary heart disease associated with hypertension is characterized by reduced endothelial NO synthesis by cNOS and increased systemic NO synthesis due to increased iNOS activity. It has been found that the lack of endothelial NO and hyperproduction of »harmful« NO by iNOS are more expressed in elderly patients.

The assessment and management of third party risk around a major airport.

PubMed

Ale, B J; Piers, M

2000-01-07

Schiphol, the main airport of the Netherlands, is growing rapidly. The aircraft movements, also growing in number, place a considerable environmental burden on the surrounding population, notably, noise and odour nuisance and risks. In the process of deciding on how to extend the capacity of the airport to accommodate the anticipated twofold growth in the number of movements with respect to 1990, environmental problems form a major concern. The concern about risks for the surrounding population was enhanced after the crash on 4 October 1992, in which a Boeing 747 cargo carrier bored into a block of flats in a suburb of Amsterdam near Schiphol. In this accident, the four crew members were killed, together with 39 inhabitants of the flats/apartment building. These risks were studied as part of the Environmental Impact Assessment (EIA). To make these studies useful for decision making necessitated a major improvement in the available techniques for risk quantification. The results of the quantitative analyses, using several different methods, have all indicated that the activities of Schiphol pose a considerable risk compared to other major industrial activities in the Netherlands. This paper describes the development of the methodology from 1990 in the light of the policy context in which it took place. Use of the methods in the decision-making process is illustrated by describing the current status of this process.

In Vitro and In Vivo Antileishmanial Effects of Pistacia khinjuk against Leishmania tropica and Leishmania major

PubMed Central

Saedi Dezaki, Ebrahim; Mahmoudvand, Hossein; Azadpour, Mojgan; Ezzatkhah, Fatemeh

2015-01-01

The present study aims to evaluate the in vitro and in vivo antileishmanial activities of Pistacia khinjuk Stocks (Anacardiaceae) alcoholic extract and to compare its efficacy with a reference drug, meglumine antimoniate (MA, Glucantime), against Leishmania tropica and Leishmania major. This extract (0–100 µg/mL) was evaluated in vitro against promastigote and intracellular amastigote forms of L. tropica (MRHO/IR/75/ER) and then tested on cutaneous leishmaniasis (CL) in male BALB/c mice with L. major to reproduce the antileishmanial activity topically. In vitro, P. khinjuk extract significantly (P < 0.05) inhibited the growth rate of promastigote (IC50 58.6 ± 3.2 µg/mL) and intramacrophage amastigotes (37.3 ± 2.5 µg/mL) of L. tropica as a dose-dependent response. In the in vivo assay, after 30 days of treatment, 75% recovery was observed in the infected mice treated with 30% extract. After treatment of the subgroups with the concentration of 20 and 30% of P. khinjuk extract, mean diameter of lesions was significantly (P < 0.05) reduced. To conclude, the present investigation demonstrated that P. vera extract had in vitro and in vivo effectiveness against L. major. Obtained findings also provide the scientific evidences that natural plants could be used in the traditional medicine for the prevention and treatment of CL. PMID:25815025

Natural Docosahexaenoic Acid in the Triglyceride Form Attenuates In Vitro Microglial Activation and Ameliorates Autoimmune Encephalomyelitis in Mice.

PubMed

Mancera, Pilar; Wappenhans, Blanca; Cordobilla, Begoña; Virgili, Noemí; Pugliese, Marco; Rueda, Fèlix; Espinosa-Parrilla, Juan F; Domingo, Joan C

2017-06-30

Many neurodegenerative diseases are associated, at least in part, to an inflammatory process in which microglia plays a major role. The effect of the triglyceride form of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (TG-DHA) was assayed in vitro and in vivo to assess the protective and anti-inflammatory activity of this compound. In the in vitro study, BV-2 microglia cells were previously treated with TG-DHA and then activated with Lipopolysaccharide (LPS) and Interferon-gamma (IFN-γ). TG-DHA treatment protected BV-2 microglia cells from oxidative stress toxicity attenuating NO production and suppressing the induction of inflammatory cytokines. When compared with DHA in the ethyl-ester form, a significant difference in the ability to inhibit NO production in favor of TG-DHA was observed. TG-DHA inhibited significantly splenocyte proliferation but isolated CD4+ lymphocyte proliferation was unaffected. In a mice model of autoimmune encephalomyelitis (EAE), 250 mg/kg/day oral TG-DHA treatment was associated with a significant amelioration of the course and severity of the disease as compared to untreated animals. TG-DHA-treated EAE mice showed a better weight profile, which is a symptom related to a better course of encephalomyelitis. TG-DHA may be a promising therapeutic agent in neuroinflammatory processes and merit to be more extensively studied in human neurodegenerative disorders.

Earth Observations taken by the Expedition 14 crew

NASA Image and Video Library

2007-01-11

ISS014-E-11872 (11 Jan. 2007) --- Pagan Island, Northern Mariana Islands, is featured in this image photographed by an Expedition 14 crewmember on the International Space Station. According to scientists, the Mariana Islands are part a volcanic island arc -- surface volcanoes formed from magma generation as one tectonic plate is overridden (or subducted) beneath another. In the case of the Mariana Islands, the Pacific Plate is being subducted beneath the Philippine Plate along the famously deep Mariana Trench (more than 11 kilometers below sea level). Pagan Island (right) is comprised of two stratovolcanoes (tall, typically cone-shaped structures formed by layers of dense crystallized lava and less-dense ash and pumice) connected by a narrow isthmus of land. Mount Pagan, the larger of the two volcanoes, forms the northeastern portion of the island and has been the most active historically. The most recent major eruption took place in 1981, but since then numerous steam- and ash-producing events have been observed at the volcano -- the latest reported one occurring between Dec. 5-8, 2006. This image records volcanic activity on Jan. 11, 2007 that produced a thin plume (most probably steam, say NASA scientists, possibly with minor ash content) that extended westwards away from Mount Pagan. The island is sparsely populated, and monitored for volcanic activity by the United States Geological Survey and the Commonwealth of the Mariana Islands.

Abundance and Speciation of Water and Sulfate at Gusev Crater and Meridiani Planum

NASA Technical Reports Server (NTRS)

Ming, D. W.; Clark, B. C.; Klingelhoefer, G.; Gellert, R.; Rodionov, D.; Schroeder, C.; deSouza, P.; Yen, A.

2005-01-01

A major science goal of the Mars Exploration Rover (MER) mission is to search for evidence of water activity, and direct mineralogical evidence for aqueous activity has been reported for Meridiani Planum in the form of the iron sulfate hydroxide mineral jarosite and at Gusev crater in the form of goethite. The Spirit and Opportunity rovers have each collected 110+ Moessbauer (MB) and 75+ Alpha Particle X-Ray Spectrometer (APXS) spectra from Gusev crater and Meridiani Planum [1 - 4]. In this abstract, we use mineralogical and elemental data, primarily from the Moessbauer and APXS instruments, to infer the speciation and estimate the abundance of sulfate and water (as either the H2O molecule or the hydroxyl anion) at Gusev crater and Meridiani Planum. Throughout the abstract, we adopt a format for mineral formulas that shows water explicitly rather than the usual practice of structure-based formulas (e.g., for goethite we write Fe2O3xH2O instead of FeOOH).

Pediatric Scleroderma –Systemic and Localized Forms

PubMed Central

Torok, Kathryn S.

2012-01-01

Synopsis statement Pediatric scleroderma includes two major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, with an initial inflammatory phase associated with endothelial activation, and a later fibrotic phase evidenced by collagenization of tissue and appreciable skin thickness, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, and though not fatal like SSc, up to a quarter of the patients may have extracutaneous disease manifestations, such as arthritis and uveitis. While any organ may be affected in SSc, vascular (Raynaud’s phenomenon), cutaneous (skin thickening), GI, pulmonary and musculoskeletal involvement are most commonly seen in children. Auto-antibody profiles in childhood onset SSc can assist in predicting internal organ involvement. Treatment for both forms of scleroderma targets the active inflammatory stage and halts disease progression; however, progress still needs to be made towards the development of a more effective anti-fibrotic therapy to help reverse disease damage. PMID:22560576

Necroptosis: Fifty shades of RIPKs.

PubMed

Ichim, Gabriel; Tait, Stephen Wg

2015-01-01

Apoptosis and necroptosis are 2 major, yet distinct, forms of regulated cell death. Whereas apoptosis requires caspase protease function, necroptosis requires activation of the receptor interacting protein kinases 1 (RIPK1) and RIPK3. Following activation, RIPK3 phosphorylates mixed-lineage kinase domain-like (MLKL), leading to cell death. Apoptosis and necroptosis are deeply intertwined such that a given death stimulus can often engage either form of cell death. Recent studies published in Cell Death and Differentiation by the Han, Oberst, and Vaux laboratories provide exciting new insights into necroptosis and how it interconnects with apoptosis. As we will discuss, their findings address key questions including: How does a cell choose between apoptosis or necroptosis? How can RIPK3 also induce apoptosis? What is the nature of the RIPK1-3 signaling cascade leading to necroptosis? Finally, data from the Oberst and Han groups strongly argue that RIPK1 is not only involved in executing necroptosis, but also protects against this process in some settings.

HIV-1 Tat protein promotes formation of more-processive elongation complexes.

PubMed Central

Marciniak, R A; Sharp, P A

1991-01-01

The Tat protein of HIV-1 trans-activates transcription in vitro in a cell-free extract of HeLa nuclei. Quantitative analysis of the efficiency of elongation revealed that a majority of the elongation complexes generated by the HIV-1 promoter were not highly processive and terminated within the first 500 nucleotides. Tat trans-activation of transcription from the HIV-1 promoter resulted from an increase in processive character of the elongation complexes. More specifically, the analysis suggests that there exist two classes of elongation complexes initiating from the HIV promoter: a less-processive form and a more-processive form. Addition of purified Tat protein was found to increase the abundance of the more-processive class of elongation complex. The purine nucleoside analog, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) inhibits transcription in this reaction by decreasing the efficiency of elongation. Surprisingly, stimulation of transcription elongation by Tat was preferentially inhibited by the addition of DRB. Images PMID:1756726

The search for a hippocampal engram.

PubMed

Mayford, Mark

2014-01-05

Understanding the molecular and cellular changes that underlie memory, the engram, requires the identification, isolation and manipulation of the neurons involved. This presents a major difficulty for complex forms of memory, for example hippocampus-dependent declarative memory, where the participating neurons are likely to be sparse, anatomically distributed and unique to each individual brain and learning event. In this paper, I discuss several new approaches to this problem. In vivo calcium imaging techniques provide a means of assessing the activity patterns of large numbers of neurons over long periods of time with precise anatomical identification. This provides important insight into how the brain represents complex information and how this is altered with learning. The development of techniques for the genetic modification of neural ensembles based on their natural, sensory-evoked, activity along with optogenetics allows direct tests of the coding function of these ensembles. These approaches provide a new methodological framework in which to examine the mechanisms of complex forms of learning at the level of the neurons involved in a specific memory.

The search for a hippocampal engram

PubMed Central

Mayford, Mark

2014-01-01

Understanding the molecular and cellular changes that underlie memory, the engram, requires the identification, isolation and manipulation of the neurons involved. This presents a major difficulty for complex forms of memory, for example hippocampus-dependent declarative memory, where the participating neurons are likely to be sparse, anatomically distributed and unique to each individual brain and learning event. In this paper, I discuss several new approaches to this problem. In vivo calcium imaging techniques provide a means of assessing the activity patterns of large numbers of neurons over long periods of time with precise anatomical identification. This provides important insight into how the brain represents complex information and how this is altered with learning. The development of techniques for the genetic modification of neural ensembles based on their natural, sensory-evoked, activity along with optogenetics allows direct tests of the coding function of these ensembles. These approaches provide a new methodological framework in which to examine the mechanisms of complex forms of learning at the level of the neurons involved in a specific memory. PMID:24298162

[Generics: essentially similar, bioequivalent but not identical].

PubMed

Even-Adin, D; De Muylder, J A; Sternon, J

2001-12-01

The using of generic forms (GF) is presented as a potential source of budgetary "saving of money" in the field of pharmaceutical expenses. Not frequently prescribed in Belgium, they win a new interest thanks to the recent making use of the "reference repayment". Sale's authorization of GF is controlled by european rules, but some questions about their identity to original medications remain. Do similarities based only upon qualitative and quantitative composition in active molecules, pharmaceutical forms and biodisponibility give us all requested guarantees? Several cases of discordances can appear: the major elements of non conformity are the nature of excipients, notice's contents and the value of biodisponibility studies. However, in term of economy, in the drug market, development of GF appears to constitute an unavoidable phenomenon.

Mid-tertiary ash flow tuff cauldrons, southwestern New Mexico

NASA Technical Reports Server (NTRS)

Elston, W. E.

1984-01-01

Characteristics of 28 known or suspected mid-Tertiary ash-flow tuff cauldrons in New Mexico are described. The largest region is 40 km in diameter, and erosional and block faulting processes have exposed levels as far down as the plutonic roots. The study supports a five-stage process: precursor, caldera collapse, early post-collapse, volcanism, major ring-fracture volcanism, and hydrothermal activity. The stages can repeat or the process can stop at any stage. Post-collapse lavas fell into two categories: cauldron lavas, derived from shallow defluidized residues of caldera-forming ash flow tuff eruption, and framework lavas, evolved from a siliceous pluton below the cauldron complex. The youngest caldera was shallow and formed from asymmetric subsidence and collapse of the caldera walls.

Plantago major in Traditional Persian Medicine and modern phytotherapy: a narrative review

PubMed Central

Najafian, Younes; Hamedi, Shokouh Sadat; Farshchi, Masoumeh Kaboli

2018-01-01

Plantago major has been used widely since ancient times, to manage a wide range of diseases including constipation, coughs and wounds. The aim of this study is to review the traditional application, botanical characterization, pharmacological activities, phytochemistry effects and toxicity of Plantago major. In this review study, medicinal properties of Plantago major are collected from credible pharmacopeias, textbooks of traditional Persian medicine (TPM) belonging to the 10–18th century AD, such as “The Canon of Medicine”, “Makhzan-Al- Advia” and so on. Moreover, electronic databases including Scopus, Medline and Web of science were explored for this purpose. Plantago major has been prescribed in various forms such as roasted seeds, decoction, syrup, liniment, gargle, rectal enema, vaginal suppository, eye and nasal drop for each illness by TPM scholars. Some of its traditional properties including wound healing, antipyretic, antitussive, anti-infective, anti-hemorrhagic, anti-inflammatory, diuretic, laxative, astringent and hemostatic have been confirmed in recent researches. Phytochemical investigations showed that Plantago major contains volatile compounds, triterpenoids, phenolic acids and flavonoids. Modern pharmacological studies have proven some of the traditional applications of Plantago major. Nevertheless, more investigations are required on this plant, because it has the potential to be used to produce various natural medications. PMID:29629064

Characterization of the porins of Campylobacter jejuni and Campylobacter coli and implications for antibiotic susceptibility.

PubMed Central

Page, W J; Huyer, G; Huyer, M; Worobec, E A

1989-01-01

The major outer membrane protein was extracted from Campylobacter coli by Triton X-100/EDTA fractionation of cell envelopes. This heat-modifiable protein was shown to have pore-forming activity in black lipid bilayers. The C. coli porin formed a relatively small cation-selective pore with a mean single-channel conductance of 0.53 +/- 0.16 nS in 1.0 M KCl. There was no evidence of oligomer formation, which suggested that each protein monomer formed a pore. Pore-forming activity of the C. coli porin and similarly prepared Campylobacter jejuni porin was also measured in liposome-swelling assays. These results confirmed the cation selectivity of both pores. The C. coli porin formed a small pore, which hindered the penetration of solutes with a molecular weight of 262, and a larger pore, which hindered the penetration of solutes with a molecular weight of 340, in a protein-concentration-dependent manner. C. jejuni formed one size of pore that was slightly larger than the C. coli pore and just permitted the passage of solutes, with a molecular weight of 340. A review of the literature concerning in vitro screening of antimicrobial agents tended to confirm the low permeability of the C. jejuni outer membrane to hydrophilic antimicrobial agents except when the molecules had molecular weights of less than 360. The porins of C. jejuni and C. coli may contribute to intrinsic resistance to antimicrobial agents, whereas alternative (nonporin) routes of antimicrobial agent uptake may be more important determinants of susceptibility to antimicrobial agents. Images PMID:2543277

Characterization of the porins of Campylobacter jejuni and Campylobacter coli and implications for antibiotic susceptibility.

PubMed

Page, W J; Huyer, G; Huyer, M; Worobec, E A

1989-03-01

The major outer membrane protein was extracted from Campylobacter coli by Triton X-100/EDTA fractionation of cell envelopes. This heat-modifiable protein was shown to have pore-forming activity in black lipid bilayers. The C. coli porin formed a relatively small cation-selective pore with a mean single-channel conductance of 0.53 +/- 0.16 nS in 1.0 M KCl. There was no evidence of oligomer formation, which suggested that each protein monomer formed a pore. Pore-forming activity of the C. coli porin and similarly prepared Campylobacter jejuni porin was also measured in liposome-swelling assays. These results confirmed the cation selectivity of both pores. The C. coli porin formed a small pore, which hindered the penetration of solutes with a molecular weight of 262, and a larger pore, which hindered the penetration of solutes with a molecular weight of 340, in a protein-concentration-dependent manner. C. jejuni formed one size of pore that was slightly larger than the C. coli pore and just permitted the passage of solutes, with a molecular weight of 340. A review of the literature concerning in vitro screening of antimicrobial agents tended to confirm the low permeability of the C. jejuni outer membrane to hydrophilic antimicrobial agents except when the molecules had molecular weights of less than 360. The porins of C. jejuni and C. coli may contribute to intrinsic resistance to antimicrobial agents, whereas alternative (nonporin) routes of antimicrobial agent uptake may be more important determinants of susceptibility to antimicrobial agents.

SAGA: A project to automate the management of software production systems

NASA Technical Reports Server (NTRS)

Campbell, R. H.; Badger, W.; Beckman, C. S.; Beshers, G.; Hammerslag, D.; Kimball, J.; Kirslis, P. A.; Render, H.; Richards, P.; Terwilliger, R.

1984-01-01

The project to automate the management of software production systems is described. The SAGA system is a software environment that is designed to support most of the software development activities that occur in a software lifecycle. The system can be configured to support specific software development applications using given programming languages, tools, and methodologies. Meta-tools are provided to ease configuration. Several major components of the SAGA system are completed to prototype form. The construction methods are described.

Testing the Role of p21-Activated Kinases in Schwannoma Formation Using a Novel Genetically Engineered Murine Model that Closely Phenocopies Human NF2 Disease

DTIC Science & Technology

2016-06-01

control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. The major goal of this research project was to genetically and pharmacologically ...with three different pharmacologic PAK inhibitors to determine if targeted PAK inhibition in a preclinical model of schwannoma genesis rescues tumor...this research project was to genetically and pharmacologically test the requirement of Group A PAK signaling in Nf2 deficient schwannoma genesis. We

Biology Division progress report, October 1, 1983-September 30, 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griesmer, R.A.

1985-01-01

The report provides summaries of the aims, scope and progress from October 1983 through September 1984. Major interest was focused on the health effects of neutron- and heavy-ion radiations on animals with particular attention to the carcinogenic responses to low dose levels and to the RBE of various forms of radiation. Among chemical agents, activities concentrated on evaluating and understanding the toxicological interations when mammals are exposed to complex mixtures, either concurrently or successively. Separate abstracts have been prepared for individual sections. (ACR)

Inhibition of AMPK catabolic action by GSK3

PubMed Central

Suzuki, Tsukasa; Bridges, Dave; Nakada, Daisuke; Skiniotis, Georgios; Morrison, Sean J.; Lin, Jiandie; Saltiel, Alan R.; Inoki, Ken

2013-01-01

SUMMARY AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by inhibiting anabolic and activating catabolic processes. While AMPK activation has been extensively studied, mechanisms that inhibit AMPK remain elusive. Here we report that glycogen synthase kinase 3 (GSK3) inhibits AMPK function. GSK3 forms a stable complex with AMPK through interactions with the AMPK β regulatory subunit and phosphorylates the AMPK α catalytic subunit. This phosphorylation enhances the accessibility of the activation loop of the α subunit to phosphatases, thereby inhibiting AMPK kinase activity. Surprisingly, PI3K-Akt signaling, which is a major anabolic signaling and normally inhibits GSK3 activity, promotes GSK3 phosphorylation and inhibition of AMPK, thus revealing how AMPK senses anabolic environments in addition to cellular energy levels. Consistently, disrupting GSK3 function within the AMPK complex sustains higher AMPK activity and cellular catabolic processes even under anabolic conditions, indicating that GSK3 acts as a critical sensor for anabolic signaling to regulate AMPK. PMID:23623684

PYRIDOXAMINE ANALOGS SCAVENGE LIPID-DERIVED γ-KETOALDEHYDES AND PROTECT AGAINST H2O2-MEDIATED CYTOTOXICITY†

PubMed Central

Davies, Sean S.; Brantley, Eric J.; Voziyan, Paul A.; Amarnath, Venkataraman; Zagol-Ikapitte, Irene; Boutaud, Olivier; Hudson, Billy G.; Oates, John A.; Jackson Roberts, L.

2008-01-01

Isoketals and levuglandins are highly reactive γ-ketoaldehydes formed by oxygenation of arachidonic acid in settings of oxidative injury and cyclooxygenase activation, respectively. These compounds rapidly adduct to proteins via lysyl residues, which can alter protein structure/function. We examined whether pyridoxamine, which has been shown to scavenge α-ketoaldehydes formed by carbohydrate or lipid peroxidation, could also effectively protect proteins from the more reactive γ-ketoaldehydes. Pyridoxamine prevented adduction of ovalbumin and also prevented inhibition of RNase A and glutathione reductase activity by the synthetic γ-ketoaldehyde, 15-E2-isoketal. We identified the major products of the reaction of pyridoxamine with the 15-E2-isoketal, including a stable lactam adduct. Two lipophilic analogs of pyridoxamine, salicylamine and 5’O-pentylpyridoxamine, also formed lactam adducts when reacted with 15-E2-isoketal. When we oxidized arachidonic acid in the presence of pyridoxamine or its analogs, pyridoxamine-isoketal adducts were found in significantly greater abundance than the pyridoxamine-N-acyl adducts formed by α-ketoaldehyde scavenging. Therefore, pyridoxamine and its analogs appear to preferentially scavenge γ-ketoaldehydes. Both pyridoxamine and its lipophilic analogs inhibited the formation of lysyl-levuglandin adducts in platelets activated ex vivo with arachidonic acid. The two lipophilic pyridoxamine analogs provided significant protection against H2O2-mediated cytotoxicity in HepG2 cells. These results demonstrate the utility of pyridoxamine and lipophilic pyridoxamine analogs to assess the potential contributions of isoketals and levuglandins in oxidant injury and inflammation and suggest their potential utility as pharmaceutical agents in these conditions. PMID:17176098

Site-Directed Mutagenesis and Structural Studies Suggest that the Germination Protease, GPR, in Spores of Bacillus Species Is an Atypical Aspartic Acid Protease

PubMed Central

Carroll, Thomas M.; Setlow, Peter

2005-01-01

Germination protease (GPR) initiates the degradation of small, acid-soluble spore proteins (SASP) during germination of spores of Bacillus and Clostridium species. The GPR amino acid sequence is not homologous to members of the major protease families, and previous work has not identified residues involved in GPR catalysis. The current work has focused on identifying catalytically essential amino acids by mutagenesis of Bacillus megaterium gpr. A residue was selected for alteration if it (i) was conserved among spore-forming bacteria, (ii) was a potential nucleophile, and (iii) had not been ruled out as inessential for catalysis. GPR variants were overexpressed in Escherichia coli, and the active form (P41) was assayed for activity against SASP and the zymogen form (P46) was assayed for the ability to autoprocess to P41. Variants inactive against SASP and unable to autoprocess were analyzed by circular dichroism spectroscopy and multiangle laser light scattering to determine whether the variant's inactivity was due to loss of secondary or quaternary structure, respectively. Variation of D127 and D193, but no other residues, resulted in inactive P46 and P41, while variants of each form were well structured and tetrameric, suggesting that D127 and D193 are essential for activity and autoprocessing. Mapping these two aspartate residues and a highly conserved lysine onto the B. megaterium P46 crystal structure revealed a striking similarity to the catalytic residues and propeptide lysine of aspartic acid proteases. These data indicate that GPR is an atypical aspartic acid protease. PMID:16199582

Flood lavas on Earth, Io and Mars

USGS Publications Warehouse

Keszthelyi, L.; Self, S.; Thordarson, T.

2006-01-01

Flood lavas are major geological features on all the major rocky planetary bodies. They provide important insight into the dynamics and chemistry of the interior of these bodies. On the Earth, they appear to be associated with major and mass extinction events. It is therefore not surprising that there has been significant research on flood lavas in recent years. Initial models suggested eruption durations of days and volumetric fluxes of order 107 m3 s-1 with flows moving as turbulent floods. However, our understanding of how lava flows can be emplaced under an insulating crust was revolutionized by the observations of actively inflating pahoehoe flows in Hawaii. These new ideas led to the hypothesis that flood lavas were emplaced over many years with eruption rates of the order of 104 m3 s-1. The field evidence indicates that flood lava flows in the Columbia River Basalts, Deccan Traps, Etendeka lavas, and the Kerguelen Plateau were emplaced as inflated pahoehoe sheet flows. This was reinforced by the observation of active lava flows of ??? 100 km length on Io being formed as tube-fed flow fed by moderate eruption rates (102-103 m3 s-1). More recently it has been found that some flood lavas are also emplaced in a more rapid manner. New high-resolution images from Mars revealed 'platy-ridged' flood lava flows, named after the large rafted plates and ridges formed by compression of the flow top. A search for appropriate terrestrial analogues found an excellent example in Iceland: the 1783-1784 Laki Flow Field. The brecciated Laki flow top consists of pieces of pahoehoe, not aa clinker, leading us to call this 'rubbly pahoehoe'. Similar flows have been found in the Columbia River Basalts and the Kerguelen Plateau. We hypothesize that these flows form with a thick, insulating, but mobile crust, which is disrupted when surges in the erupted flux are too large to maintain the normal pahoehoe mode of emplacement Flood lavas emplaced in this manner could have (intermittently) reached effusion rates of the order of 106 m3 s-1.

Analysis of a delta spot

NASA Astrophysics Data System (ADS)

Liu, Y.; Zhang, H. Q.

2002-05-01

delta -groups generally develop in three different ways: eruption of a single complex active region, eruption of large satellite spots near a large older spot, or collision of spots of opposite polarity from different dipoles. In this paper, we present a rare observational result in which a delta -spot forms from rapid coalescence of two opposite magnetic features in a pre-existing delta -configuration. The white-light (WL) observations of this delta -spot in active region NOAA 9077 were performed by TRACE. The time-lapse movie of the co-aligned WL images shows that the whole active region was undergoing rapid disintegration and reconstruction on 11-17 July 2000. The preceding ({p}) and following ({f}) components of the delta -spot continue to grow in size, while the active region is in the decaying phase. Their proper motions are determined as a function of time using SOHO/MDI full-disk magnetograms. A major flare (3B/X5.7) erupted in the active region on 14 July. Initially, a relative shearing motion is visible between the {p} and {f} spots on this day. About two hours before the major flare, the shearing motion suddenly stops and the velocities change significantly. The ribbons of the flare are located just outside of the delta -configuration. An interesting finding is the sign reversal of the helicity of the {f} spot also just 2 hours before the flare. The delta -spot obviously separates after the flare. Our results clearly demonstrate that helicity reversal in magnetic features of a delta -configuration is likely to destabilize the compact structure, as well as to re-organize the magnetic field configuration, and, hence, is important for the rapid disintegration of a delta -spot during major flares. A model is presented to explain why a spot can change its chirality.

Proteolytic Cascade for the Activation of the Insect Toll Pathway Induced by the Fungal Cell Wall Component

PubMed Central

Roh, Kyung-Baeg; Kim, Chan-Hee; Lee, Hanna; Kwon, Hyun-Mi; Park, Ji-Won; Ryu, Ji-Hwan; Kurokawa, Kenji; Ha, Nam-Chul; Lee, Won-Jae; Lemaitre, Bruno; Söderhäll, Kenneth; Lee, Bok-Luel

2009-01-01

The insect Toll signaling pathway is activated upon recognition of Gram-positive bacteria and fungi, resulting in the expression of antimicrobial peptides via NF-κB-like transcription factor. This activation is mediated by a serine protease cascade leading to the processing of Spätzle, which generates the functional ligand of the Toll receptor. Recently, we identified three serine proteases mediating Toll pathway activation induced by lysine-type peptidoglycan of Gram-positive bacteria. However, the identities of the downstream serine protease components of Gram-negative-binding protein 3 (GNBP3), a receptor for a major cell wall component β-1,3-glucan of fungi, and their order of activation have not been characterized yet. Here, we identified three serine proteases that are required for Toll activation by β-1,3-glucan in the larvae of a large beetle, Tenebrio molitor. The first one is a modular serine protease functioning immediately downstream of GNBP3 that proteolytically activates the second one, a Spätzle-processing enzyme-activating enzyme that in turn activates the third serine protease, a Spätzle-processing enzyme. The active form of Spätzle-processing enzyme then cleaves Spätzle into the processed Spätzle as Toll ligand. In addition, we show that injection of β-1,3-glucan into Tenebrio larvae induces production of two antimicrobial peptides, Tenecin 1 and Tenecin 2, which are also inducible by injection of the active form of Spätzle-processing enzyme-activating enzyme or processed Spätzle. These results demonstrate a three-step proteolytic cascade essential for the Toll pathway activation by fungal β-1,3-glucan in Tenebrio larvae, which is shared with lysine-type peptidoglycan-induced Toll pathway activation. PMID:19473968

Coral Carbonic Anhydrases: Regulation by Ocean Acidification.

PubMed

Zoccola, Didier; Innocenti, Alessio; Bertucci, Anthony; Tambutté, Eric; Supuran, Claudiu T; Tambutté, Sylvie

2016-06-03

Global change is a major threat to the oceans, as it implies temperature increase and acidification. Ocean acidification (OA) involving decreasing pH and changes in seawater carbonate chemistry challenges the capacity of corals to form their skeletons. Despite the large number of studies that have investigated how rates of calcification respond to ocean acidification scenarios, comparatively few studies tackle how ocean acidification impacts the physiological mechanisms that drive calcification itself. The aim of our paper was to determine how the carbonic anhydrases, which play a major role in calcification, are potentially regulated by ocean acidification. For this we measured the effect of pH on enzyme activity of two carbonic anhydrase isoforms that have been previously characterized in the scleractinian coral Stylophora pistillata. In addition we looked at gene expression of these enzymes in vivo. For both isoforms, our results show (1) a change in gene expression under OA (2) an effect of OA and temperature on carbonic anhydrase activity. We suggest that temperature increase could counterbalance the effect of OA on enzyme activity. Finally we point out that caution must, thus, be taken when interpreting transcriptomic data on carbonic anhydrases in ocean acidification and temperature stress experiments, as the effect of these stressors on the physiological function of CA will depend both on gene expression and enzyme activity.

Sulfation of 6-Gingerol by the Human Cytosolic Sulfotransferases: A Systematic Analysis.

PubMed

Luo, Lijun; Mei, Xue; Xi, Yuecheng; Zhou, Chunyang; Hui, Ying; Kurogi, Katsuhisa; Sakakibara, Yoichi; Suiko, Masahito; Liu, Ming-Cheh

2016-02-01

Previous studies have demonstrated the presence of the sulfated form of 6-gingerol, a major pharmacologically active component of ginger, in plasma samples of normal human subjects who were administered 6-gingerol. The current study was designed to systematically identify the major human cytosolic sulfotransferase enzyme(s) capable of mediating the sulfation of 6-gingerol. Of the 13 known human cytosolic sulfotransferases examined, six (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C4, SULT1E1) displayed significant sulfating activity toward 6-gingerol. Kinetic parameters of SULT1A1, SULT1A3, SULT1C4, and SULT1E1 that showed stronger 6-gingerol-sulfating activity were determined. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6-gingerol-sulfating activity than those of the lung and kidney. Moreover, sulfation of 6-gingerol was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under the metabolic setting. Collectively, these results provided useful information relevant to the metabolism of 6-gingerol through sulfation both in vitro and in vivo. Georg Thieme Verlag KG Stuttgart · New York.

Leishmania donovani Argininosuccinate Synthase Is an Active Enzyme Associated with Parasite Pathogenesis

PubMed Central

Lakhal-Naouar, Ines; Jardim, Armando; Strasser, Rona; Luo, Shen; Kozakai, Yukiko; Nakhasi, Hira L.; Duncan, Robert C.

2012-01-01

Background Gene expression analysis in Leishmania donovani (Ld) identified an orthologue of the urea cycle enzyme, argininosuccinate synthase (LdASS), that was more abundantly expressed in amastigotes than in promastigotes. In order to characterize in detail this newly identified protein in Leishmania, we determined its enzymatic activity, subcellular localization in the parasite and affect on virulence in vivo. Methodology/Principal Findings Two parasite cell lines either over expressing wild type LdASS or a mutant form (G128S) associated with severe cases of citrullinemia in humans were developed. In addition we also produced bacterially expressed recombinant forms of the same proteins. Our results demonstrated that LdASS has argininosuccinate synthase enzymatic activity that is abolished using an ASS specific inhibitor (MDLA: methyl-D-L-Aspartic acid). However, the mutant form of the protein is inactive. We demonstrate that though LdASS has a glycosomal targeting signal that binds the targeting apparatus in vitro, only a small proportion of the total cellular ASS is localized in a vesicle, as indicated by protection from protease digestion of the crude organelle fraction. The majority of LdASS was found to be in the cytosolic fraction that may include large cytosolic complexes as indicated by the punctate distribution in IFA. Surprisingly, comparison to known glycosomal proteins by IFA revealed that LdASS was located in a structure different from the known glycosomal vesicles. Significantly, parasites expressing a mutant form of LdASS associated with a loss of in vitro activity had reduced virulence in vivo in BALB/c mice as demonstrated by a significant reduction in the parasite load in spleen and liver. Conclusion/Significance Our study suggests that LdASS is an active enzyme, with unique localization and essential for parasite survival and growth in the mammalian host. Based on these observations LdASS could be further explored as a potential drug target. PMID:23094117

Crisamicin A, a new antibiotic from Micromonospora. I. Taxonomy of the producing strain, fermentation, isolation, physico-chemical characterization and antimicrobial properties.

PubMed

Nelson, R A; Pope, J A; Luedemann, G M; McDaniel, L E; Schaffner, C P

1986-03-01

A microorganism, designated as RV-79-9-101 and now identified as Micromonospora purpureochromogenes subsp. halotolerans, isolated from a mud sample in the Philippines, has been shown to produce a complex of antibiotics called crisamicins. Thin-layer chromatography and bioautography, employing solvent extracts of whole fermentation broths, revealed a minimum of five antimicrobial components. The major biologically-active component of the antibiotic complex, crisamicin A, was obtained in pure form after preparative silica gel column chromatography followed by crystallization. Based on physico-chemical data crisamicin A has been identified as a novel member of the isochromanequinone group of antibiotics. It exhibits excellent in vitro activity against Gram-positive bacteria but little or no activity towards Gram-negative bacteria or fungi.

Enhanced hydrogen evolution reaction on hybrids of cobalt phosphide and molybdenum phosphide

NASA Astrophysics Data System (ADS)

Fang, Si-Ling; Chou, Tsu-Chin; Samireddi, Satyanarayana; Chen, Kuei-Hsien; Chen, Li-Chyong; Chen, Wei-Fu

2017-03-01

Production of hydrogen from water electrolysis has stimulated the search of sustainable electrocatalysts as possible alternatives. Recently, cobalt phosphide (CoP) and molybdenum phosphide (MoP) received great attention owing to their superior catalytic activity and stability towards the hydrogen evolution reaction (HER) which rivals platinum catalysts. In this study, we synthesize and study a series of catalysts based on hybrids of CoP and MoP with different Co/Mo ratio. The HER activity shows a volcano shape and reaches a maximum for Co/Mo = 1. Tafel analysis indicates a change in the dominating step of Volmer-Hyrovský mechanism. Interestingly, X-ray diffraction patterns confirmed a major ternary interstitial hexagonal CoMoP2 crystal phase is formed which enhances the electrochemical activity.

Social media in the promotion of health.

PubMed

Matikainen, Janne; Huovila, Janne

Social media has brought about a major change in communication. Besides ordinary people, the change applies to organizations and public authorities. In the social media, the public becomes an active player and content provider. With social media, communication will become increasingly media-centered. The change in communication scenery has challenged traditional expertise. On the other hand, social media also opens up many possibilities for the establishment of expertise and health communication. Within the social media, communities can become significant sites for the production of knowledge and expertise. They may generate useful activity as regards the combination of health information activities and everyday life, but sometimes they can also become a cradle of false information. In its various forms, social media provides a versatile forum for health communication, where people can be met interactively.

Observation of spatial and temporal variations in X-ray bright point emergence patterns. [at solar surface

NASA Technical Reports Server (NTRS)

Golub, L.; Krieger, A. S.; Vaiana, G. S.

1976-01-01

Observations of X-ray bright points (XBP) over a six-month interval in 1973 show significant variations in both the number density of XBP as a function of heliographic longitude and in the full-sun average number of XBP from one rotation to the next. The observed increases in XBP emergence are estimated to be equivalent to several large active regions emerging per day for several months. The number of XBP emerging at high latitudes varies in phase with the low-latitude variation and reaches a maximum approximately simultaneous with a major outbreak of active regions. The quantity of magnetic flux emerging in the form of XBP at high latitudes alone is estimated to be as large as the contribution from all active regions.

A Natural Chimeric Pseudomonas Bacteriocin with Novel Pore-Forming Activity Parasitizes the Ferrichrome Transporter.

PubMed

Ghequire, Maarten G K; Kemland, Lieselore; Anoz-Carbonell, Ernesto; Buchanan, Susan K; De Mot, René

2017-02-21

Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin's activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, a Pseudomonas bacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain in Pseudomonas aeruginosa pyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that of Pseudomonas colicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities. IMPORTANCE In their continuous struggle for ecological space, bacteria face a huge load of contenders, including phylogenetically related strains that compete for the same niche. One important group of secreted antibacterial proteins assisting in eliminating these rivals are modular bacteriocins of Gram-negative bacteria, comprising a domain for docking onto the cell envelope of a target cell, a translocation domain enabling subsequent cellular entry, and a toxin module that kills target cells via enzymatic or pore-forming activity. We here demonstrate the antagonistic function of a Pseudomonas bacteriocin with unique architecture that combines a putative enzymatic colicin M-like domain and a novel pore-forming toxin module. For target cell recognition and entry, this bacteriocin hybrid takes advantage of the ferrichrome transporter, also parasitized by enzymatic Pseudomonas bacteriocins devoid of the pore-forming module. Bacteriocins with an expanded toxin potential may represent an inventive bacterial strategy to alleviate immunity in target cells. Copyright © 2017 Ghequire et al.

Hungarian travertine: a historic and current stone resource of Central Europe

NASA Astrophysics Data System (ADS)

Török, Ákos

2013-04-01

Travertine is a widespread dimension stone that was used worldwide in monuments. The best known examples are known from the Roman Empire from Italy, where this porous stone belonged to one of the favourite stone types. Ancient quarries of Tivoli provided material to major construction works to Rome. Other occurrences belonging to the Roman Empire outside of Rome were also used by the Romans. Some of the most important European deposits are known from Hungary. Exploitable travertine layers are found at many places in Hungary but at least two major areas were actively quarried by the Romans. One major deposit was not far away from the provincial capital of Roman Pannonia - called Aquincum, which currently forms a part of Budapest, while the other even larger occurrence is at Süttő, at the riverside of Danube some 50 km NE from the past capital. River Danube provided an excellent pathway of transport ting stone to the capital. Evidences indicate that quarrying activity in Süttő area has already begun during the 1st century BC and the travertine has been exploited with some interruptions since then. The present day quarries form the parts of the largest active dimension quarry system of Hungary. The exposed very thick banks (3 to 4m) of travertine were deposited from lukewarm springs during the Pleistocene period. Various types of travertine were used for constructing Roman aqueducts, fortresses, amphitheatre until the 4th century AD and were also transported to other parts of that Roman Province which extended to the present territory of Hungary, Austria, Slovenia and Croatia. Although the use of travertine has significantly decreased after the fall of Roman Empire in Central Europe and in Hungary, the presence of this stone was also documented from numerous Gothic and Baroque buildings from the area. The use of this stone became more popular again in the Carpathian Basin, when major constructions of larger cities such as Bratislava, Vienna or Budapest accelerated in the Austro-Hungarian Monarchy at the second part of the 19th century. The paper also provides information on various lithotypes of travertine and it also presents data on the physical properties and examples of its use in the monuments located in the cities of Central Europe.

Proteasome activity or expression is not altered by activation of the heat shock transcription factor Hsf1 in cultured fibroblasts or myoblasts.

PubMed

Taylor, David M; Kabashi, Edor; Agar, Jeffrey N; Minotti, Sandra; Durham, Heather D

2005-01-01

Heat shock proteins (Hsps) with chaperoning function work together with the ubiquitin-proteasome pathway to prevent the accumulation of misfolded, potentially toxic proteins, as well as to control catabolism of the bulk of cytoplasmic, cellular protein. There is evidence for the involvement of both systems in neurodegenerative disease, and a therapeutic target is the heat shock transcription factor, Hsf1, which mediates upregulation of Hsps in response to cellular stress. The mechanisms regulating expression of proteasomal proteins in mammalian cells are less well defined. To assess any direct effect of Hsf1 on expression of proteasomal subunits and activity in mammalian cells, a plasmid encoding a constitutively active form of Hsf1 (Hsf1act) was expressed in mouse embryonic fibroblasts lacking Hsf1 and in cultured human myoblasts. Plasmid encoding an inactivatible form of Hsf1 (Hsf1inact) served as control. In cultures transfected with plasmid hsf1act, robust expression of the major stress-inducible Hsp, Hsp70, occurred but not in cultures transfected with hsf1inact. No significant changes in the level of expression of representative proteasomal proteins (structural [20Salpha], a nonpeptidase beta subunit [20Sbeta3], or 2 regulatory subunits [19S subunit 6b, 11 Salpha]) or in chymotrypsin-, trypsin-, and caspaselike activities of the proteasome were measured. Thus, stress-induced or pharmacological activation of Hsf1 in mammalian cells would upregulate Hsps but not directly affect expression or activity of proteasomes.

Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome.

PubMed

O'Donoghue, Anthony J; Knudsen, Giselle M; Beekman, Chapman; Perry, Jenna A; Johnson, Alexander D; DeRisi, Joseph L; Craik, Charles S; Bennett, Richard J

2015-06-16

Pseudogymnoascus destructans is the causative agent of white-nose syndrome, a disease that has caused the deaths of millions of bats in North America. This psychrophilic fungus proliferates at low temperatures and targets hibernating bats, resulting in their premature arousal from stupor with catastrophic consequences. Despite the impact of white-nose syndrome, little is known about the fungus itself or how it infects its mammalian host. P. destructans is not amenable to genetic manipulation, and therefore understanding the proteins involved in infection requires alternative approaches. Here, we identify hydrolytic enzymes secreted by P. destructans, and use a novel and unbiased substrate profiling technique to define active peptidases. These experiments revealed that endopeptidases are the major proteolytic activities secreted by P. destructans, and that collagen, the major structural protein in mammals, is actively degraded by the secretome. A serine endopeptidase, hereby-named Destructin-1, was subsequently identified, and a recombinant form overexpressed and purified. Biochemical analysis of Destructin-1 showed that it mediated collagen degradation, and a potent inhibitor of peptidase activity was identified. Treatment of P. destructans-conditioned media with this antagonist blocked collagen degradation and facilitated the detection of additional secreted proteolytic activities, including aminopeptidases and carboxypeptidases. These results provide molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host.

Metabolism of the insecticidally active GABA sub A receptor antagonist 4-sec-(3,4- sup 3 H sub 2 )butyl-1-(4-cyanophenyl)-2,6,7-trioxabicyclo(2. 2. 2)octane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Yanli; Palmer, C.J.; Toia, R.F.

1990-03-01

4-sec-(3,4-{sup 3}H{sub 2})Butyl-1-(4-cyanophenyl)-2,6,7-trioxabicyclo(2.2.2)octane (referred to as ({sup 3}H)COB) was examined as an example of a new class of insecticidally active compounds that block the {gamma}-aminobutyric acid gated chloride channel. Metabolites were identified by thin-layer cochromatography with standards from synthesis and by consideration of their hydrolytic and oxidative degradation products formed in situ on two-dimensional silica gel chromatoplates. Metabolism of ({sup 3}H)COB by mouse liver and housefly abdomen microsomes is dependent on fortification with NADPH. The O-methylene and sec-butyl sites are sensitive to oxidation. Each carbon of the sec-butyl group is individually functionalized with strong preference for the methylene site inmore » the mouse but not the housefly microsomal system. O-Methylene hydroxylation initiates spontaneous cage opening to form an aldehyde that undergoes metabolic reduction, ultimately yielding the same cyanobenzoate ester of 2,2-bis-(hydroxymethyl)-3-methylpentan-1-ol formed by direct hydrolysis. Houseflies injected with ({sup 3}H)COB form many if not all of the same metabolites, with major products being the aforementioned cyanobenzoate, the orthoester oxidized at the sec-butyl methylene site, and polar conjugates.« less

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

PubMed Central

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-01-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel. PMID:24980734

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

NASA Astrophysics Data System (ADS)

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-07-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel.

Effect of aluminum on metabolism of organic acids and chemical forms of aluminum in root tips of Eucalyptus camaldulensis Dehnh.

PubMed

Ikka, Takashi; Ogawa, Tsuyoshi; Li, Donghua; Hiradate, Syuntaro; Morita, Akio

2013-10-01

Eucalyptus (Eucalyptus camaldulensis) has relatively high resistance to aluminum (Al) toxicity than the various herbaceous plants and model plant species. To investigate Al-tolerance mechanism, the metabolism of organic acids and the chemical forms of Al in the target site (root tips) in Eucalyptus was investigated. To do this, 2-year old rooted cuttings of E. camaldulensis were cultivated in half-strength Hoagland solution (pH 4.0) containing Al (0, 0.25, 0.5, 1.0, 2.5 and 5.0mM) salts for 5weeks; growth was not affected at concentrations up to 2.5mM even with Al concentration reaching 6000μgg(-1) DW. In roots, the citrate content also increased with increasing Al application. Concurrently, the activities of aconitase and NADP(+)-isocitrate dehydrogenase, which catalyze the decomposition of citrate, decreased. On the other hand, the activity of citrate synthase was not affected at concentrations up to 2.5mM Al. (27)Al-NMR spectroscopic analyses were carried out where it was found that Al-citrate complexes were a major chemical form present in cell sap of root tips. These findings suggested that E. camaldulensis detoxifies Al by forming Al-citrate complexes, and that this is achieved through Al-induced citrate accumulation in root tips via suppression of the citrate decomposition pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Syzygium cumini (L.) Skeels essential oil and its major constituent α-pinene exhibit anti-Leishmania activity through immunomodulation in vitro.

PubMed

Rodrigues, Klinger Antonio da Franca; Amorim, Layane Valéria; Dias, Clarice Noleto; Moraes, Denise Fernandes Coutinho; Carneiro, Sabrina Maria Portela; Carvalho, Fernando Aécio de Amorim

2015-02-03

Syzygium cumini (L.) Skeels (Myrtaceae), commonly known as "jambolão" in Brazil is widely used in folk medicine against leishmaniasis, inflammation, chronic diarrhea, and ulcers. It is one of the most commonly used plants for the treatment of diabetes worldwide. In previous studies, Syzygium cumini was shown to possess antihyperlipidemic and anti-allergic properties, and to exhibit good performance as an antimicrobial agent against bacteria, fungi, and protozoa parasites of the genus Leishmania and Trypanosoma. This study was aimed at evaluating the effects of S. cumini essential oil (ScEO) and its major component α-pinene on Leishmania (Leishmania) amazonensis, as well as their cytotoxicity and possible mechanisms of action. To evaluate the anti-proliferative effect on Leishmania, effects on promastigote and axenic amastigote forms were assessed using tetrazolium salt (MTT) assay. The intramacrophagic amastigotes were exposed to ScEO and α-pinene to determine the survival index. To gain insight into the mechanism of action involved in the effect on the samples, we evaluated the modulation of macrophage activation state by observing structural (phagocytic and lysosomal activities) and cellular (nitric oxide increase) changes. To assess the safety profile of ScEO and α-pinene, murine macrophages and human red blood cells were treated with ScEO and α-pinene and the selectivity index was calculated for each treatment. α-Pinene was effective against Leishmania amazonensis promastigote forms, with a half-maximal inhibitory concentration (IC50) value of 19.7µg/mL. α-Pinene was more active (IC50 values of 16.1 and 15.6µg/mL against axenic and intracellular amastigotes, respectively) than ScEO (IC50 values of 43.9 and 38.1µg/mL against axenic and intracellular amastigotes, respectively). Our results showed that the anti-Leishmania effects were mediated by immunomodulatory activity, as evidenced by the observed increases in both phagocytic and lysosomal activity, and the elevated NO levels. ScEO and α-pinene exhibited low cytotoxicity against murine macrophages and human erythrocytes. The 50% cytotoxicity concentration (CC50) values for the macrophages in the MTT assay were 614.1 and 425.2µg/mL for ScEO and α-pinene, respectively, while the corresponding half-maximal hemolytic concentration (HC50) values were 874.3 and 233.3µg/mL. Taken together, the results demonstrate that ScEO and its major constituent α-pinene have significant anti-Leishmania activity, modulated by macrophage activation, with acceptable levels of cytotoxicity in murine macrophages and human erythrocytes. Further work is warranted, involving more in-depth mechanistic studies and in vivo investigations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A population of comets in the main asteroid belt.

PubMed

Hsieh, Henry H; Jewitt, David

2006-04-28

Comets are icy bodies that sublimate and become active when close to the Sun. They are believed to originate in two cold reservoirs beyond the orbit of Neptune: the Kuiper Belt (equilibrium temperatures of approximately 40 kelvin) and the Oort Cloud (approximately 10 kelvin). We present optical data showing the existence of a population of comets originating in a third reservoir: the main asteroid belt. The main-belt comets are unlike the Kuiper Belt and Oort Cloud comets in that they likely formed where they currently reside and may be collisionally activated. The existence of the main-belt comets lends new support to the idea that main-belt objects could be a major source of terrestrial water.

Fundamental Characteristics of AAA+ Protein Family Structure and Function.

PubMed

Miller, Justin M; Enemark, Eric J

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

Carbohydrates, volatile and phenolic compounds composition, and antioxidant activity of calabura (Muntingia calabura L.) fruit.

PubMed

Pereira, Gustavo Araujo; Arruda, Henrique Silvano; de Morais, Damila Rodrigues; Eberlin, Marcos Nogueira; Pastore, Glaucia Maria

2018-06-01

Soluble carbohydrates, volatile and phenolic compounds from calabura fruit as well as its antioxidant activity were assessed. The low amount of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) and similar amount of glucose and fructose allow us to classify the calabura berry as low-FODMAPs. The terpenes β-Farnesene and dendrolasin identified by SPME-GC-MS were the major volatile components. UHPLC-MS/MS analysis revelled gallic acid (5325 μg/g dw) and cyanidin-3-O-glucoside (171 μg/g dw) as the main phenolic compounds, followed by gentisic acid, gallocatechin, caffeic acid and protocatechuic acid. In addition, gallic acid was found mainly in esterified (2883 μg/g dw) and insoluble-bound (2272 μg/g dw) forms. Free and glycosylated forms showed however the highest antioxidant activity due to occurrence of flavonoids (0.28-27 μg/g dw) in these fractions, such as catechin, gallocatechin, epigallocatechin, naringenin, and quercetin. These findings clearly suggest that calabura is a berry with low energy value and attractive colour and flavour that may contribute to the intake of several bioactive compounds with antioxidant activity. Furthermore, this berry have great potential for use in the food industry and as functional food. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities.

PubMed

Noël, A; Santavicca, M; Stoll, I; L'Hoir, C; Staub, A; Murphy, G; Rio, M C; Basset, P

1995-09-29

Matrix metalloproteinases (matrixins) constitute a group of extracellular proteinases belonging to the metzincin superfamily. They are involved in both physiological and pathological tissue remodeling processes, including those associated with cancer progression. Stromelysin-3, which is expressed in most invasive human carcinomas, is a matrix metalloproteinase with unusual functional properties. In particular, its mature form does not cleave any of the major extracellular matrix components. To define critical structural determinants involved in controlling stromelysin-3 proteolytic activity, we have used site-directed mutagenesis. We show that the deletion of at least 175 C-terminal amino-acids is sufficient to endow mouse stromelysin-3 with activities against casein, laminin, and type IV collagen. In the case of the human enzyme, however, a further and single Ala-235-->Pro substitution is necessary to observe similar activities. Ala-235, which characterizes human stromelysin-3 among matrixins, is located immediately after the C terminus of the "Met-turn," which forms a hydrophobic basis for the catalytic zinc atom in the metzincin family. We conclude that human stromelysin-3 has gained specific functional properties during evolution by amino acid substitution in the catalytic zinc environment, and that it represents an attractive target for specific inhibitors that may be used to prevent cancer progression.

NFκB is a central regulator of protein quality control in response to protein aggregation stresses via autophagy modulation

PubMed Central

Nivon, Mathieu; Fort, Loïc; Muller, Pascale; Richet, Emma; Simon, Stéphanie; Guey, Baptiste; Fournier, Maëlenn; Arrigo, André-Patrick; Hetz, Claudio; Atkin, Julie D.; Kretz-Remy, Carole

2016-01-01

During cell life, proteins often misfold, depending on particular mutations or environmental changes, which may lead to protein aggregates that are toxic for the cell. Such protein aggregates are the root cause of numerous diseases called “protein conformational diseases,” such as myofibrillar myopathy and familial amyotrophic lateral sclerosis. To fight against aggregates, cells are equipped with protein quality control mechanisms. Here we report that NFκB transcription factor is activated by misincorporation of amino acid analogues into proteins, inhibition of proteasomal activity, expression of the R120G mutated form of HspB5 (associated with myofibrillar myopathy), or expression of the G985R and G93A mutated forms of superoxide dismutase 1 (linked to familial amyotrophic lateral sclerosis). This noncanonical stimulation of NFκB triggers the up-regulation of BAG3 and HspB8 expression, two activators of selective autophagy, which relocalize to protein aggregates. Then NFκB-dependent autophagy allows the clearance of protein aggregates. Thus NFκB appears as a central and major regulator of protein aggregate clearance by modulating autophagic activity. In this context, the pharmacological stimulation of this quality control pathway might represent a valuable strategy for therapies against protein conformational diseases. PMID:27075172

Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats

PubMed Central

Delbosc, Sandrine; Alsac, Jean-Marc; Journe, Clement; Louedec, Liliane; Castier, Yves; Bonnaure-Mallet, Martine; Ruimy, Raymond; Rossignol, Patrick; Bouchard, Philippe; Michel, Jean-Baptiste; Meilhac, Olivier

2011-01-01

Background Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. Methods and Findings Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. Conclusions Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression. PMID:21533243

AMP-activated Protein Kinase Stimulates Warburg-like Glycolysis and Activation of Satellite Cells during Muscle Regeneration*

PubMed Central

Fu, Xing; Zhu, Mei-Jun; Dodson, Mike V.; Du, Min

2015-01-01

Satellite cells are the major myogenic stem cells residing inside skeletal muscle and are indispensable for muscle regeneration. Satellite cells remain largely quiescent but are rapidly activated in response to muscle injury, and the derived myogenic cells then fuse to repair damaged muscle fibers or form new muscle fibers. However, mechanisms eliciting metabolic activation, an inseparable step for satellite cell activation following muscle injury, have not been defined. We found that a noncanonical Sonic Hedgehog (Shh) pathway is rapidly activated in response to muscle injury, which activates AMPK and induces a Warburg-like glycolysis in satellite cells. AMPKα1 is the dominant AMPKα isoform expressed in satellite cells, and AMPKα1 deficiency in satellite cells impairs their activation and myogenic differentiation during muscle regeneration. Drugs activating noncanonical Shh promote proliferation of satellite cells, which is abolished because of satellite cell-specific AMPKα1 knock-out. Taken together, AMPKα1 is a critical mediator linking noncanonical Shh pathway to Warburg-like glycolysis in satellite cells, which is required for satellite activation and muscle regeneration. PMID:26370082

Cool-associated Tyrosine-phosphorylated Protein 1 Is Required for the Anchorage-independent Growth of Cervical Carcinoma Cells by Binding Paxillin and Promoting AKT Activation*

PubMed Central

Yoo, Sungsoo M.; Latifkar, Arash; Cerione, Richard A.; Antonyak, Marc A.

2017-01-01

Cool-associated tyrosine-phosphorylated protein 1 (Cat-1) is a signaling scaffold as well as an ADP-ribosylation factor-GTPase-activating protein. Although best known for its role in cell migration, we recently showed that the ability of Cat-1 to bind paxillin, a major constituent of focal complexes, is also essential for the anchorage-independent growth of HeLa cervical carcinoma cells. Here we set out to learn more about the underlying mechanism by which Cat-paxillin interactions mediate this effect. We show that knocking down paxillin expression in HeLa cells promotes their ability to form colonies in soft agar, whereas ectopically expressing paxillin in these cells inhibits this transformed growth phenotype. Although knocking down Cat-1 prevents HeLa cells from forming colonies in soft agar, when paxillin is knocked down together with Cat-1, the cells are again able to undergo anchorage-independent growth. These results suggest that the requirement of Cat-1 for this hallmark of cellular transformation is coupled to its ability to bind paxillin and abrogate its actions as a negative regulator of anchorage-independent growth. We further show that knocking down Cat-1 expression in HeLa cells leads to a reduction in Akt activation, which can be reversed by knocking down paxillin. Moreover, expression of constitutively active forms of Akt1 and Akt2 restores the anchorage-independent growth capability of HeLa cells depleted of Cat-1 expression. Together, these findings highlight a novel mechanism whereby interactions between Cat-1 and its binding partner paxillin are necessary to ensure sufficient Akt activation so that cancer cells are able to grow under anchorage-independent conditions. PMID:28100775

Cool-associated Tyrosine-phosphorylated Protein 1 Is Required for the Anchorage-independent Growth of Cervical Carcinoma Cells by Binding Paxillin and Promoting AKT Activation.

PubMed

Yoo, Sungsoo M; Latifkar, Arash; Cerione, Richard A; Antonyak, Marc A

2017-03-03

Cool-associated tyrosine-phosphorylated protein 1 (Cat-1) is a signaling scaffold as well as an ADP-ribosylation factor-GTPase-activating protein. Although best known for its role in cell migration, we recently showed that the ability of Cat-1 to bind paxillin, a major constituent of focal complexes, is also essential for the anchorage-independent growth of HeLa cervical carcinoma cells. Here we set out to learn more about the underlying mechanism by which Cat-paxillin interactions mediate this effect. We show that knocking down paxillin expression in HeLa cells promotes their ability to form colonies in soft agar, whereas ectopically expressing paxillin in these cells inhibits this transformed growth phenotype. Although knocking down Cat-1 prevents HeLa cells from forming colonies in soft agar, when paxillin is knocked down together with Cat-1, the cells are again able to undergo anchorage-independent growth. These results suggest that the requirement of Cat-1 for this hallmark of cellular transformation is coupled to its ability to bind paxillin and abrogate its actions as a negative regulator of anchorage-independent growth. We further show that knocking down Cat-1 expression in HeLa cells leads to a reduction in Akt activation, which can be reversed by knocking down paxillin. Moreover, expression of constitutively active forms of Akt1 and Akt2 restores the anchorage-independent growth capability of HeLa cells depleted of Cat-1 expression. Together, these findings highlight a novel mechanism whereby interactions between Cat-1 and its binding partner paxillin are necessary to ensure sufficient Akt activation so that cancer cells are able to grow under anchorage-independent conditions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The Val192Leu mutation in the alpha-subunit of beta-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease.

PubMed Central

Hou, Y.; Vavougios, G.; Hinek, A.; Wu, K. K.; Hechtman, P.; Kaplan, F.; Mahuran, D. J.

1996-01-01

Substitution mutations adversely affecting the alpha-subunit of beta-hexosaminidase A (alphabeta) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-alpha chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an "active-site" residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all alpha-specific activity. This biochemical phenotype is referred to as the "B1-variant form" of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and both subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, alpha-Val192Leu. Chinese hamster ovary cells were permanently cotransfected with an alpha-cDNA-construct encoding the substitution and a mutant beta-cDNA (beta-Arg211Lys), encoding a beta-subunit that is inactive but normal in all other respects. We were surprised to find that the Val192Leu substitution, produced a pro-alpha chain that did not form alpha-beta dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val192Leu substitution does not specifically affect the alpha-active site. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8659543

The Val192Leu mutation in the alpha-subunit of beta-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease.

PubMed

Hou, Y; Vavougios, G; Hinek, A; Wu, K K; Hechtman, P; Kaplan, F; Mahuran, D J

1996-07-01

Substitution mutations adversely affecting the alpha-subunit of beta-hexosaminidase A (alphabeta) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-alpha chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an "active-site" residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all alpha-specific activity. This biochemical phenotype is referred to as the "B1-variant form" of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and both subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, alpha-Val192Leu. Chinese hamster ovary cells were permanently cotransfected with an alpha-cDNA-construct encoding the substitution and a mutant beta-cDNA (beta-Arg211Lys), encoding a beta-subunit that is inactive but normal in all other respects. We were surprised to find that the Val192Leu substitution, produced a pro-alpha chain that did not form alpha-beta dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val192Leu substitution does not specifically affect the alpha-active site.

Replication initiator protein RepE of mini-F plasmid: functional differentiation between monomers (initiator) and dimers (autogenous repressor).

PubMed Central

Ishiai, M; Wada, C; Kawasaki, Y; Yura, T

1994-01-01

Replication of mini-F plasmid requires the plasmid-encoded RepE initiator protein and several host factors including DnaJ, DnaK, and GrpE, heat shock proteins of Escherichia coli. The RepE protein plays a crucial role in replication and exhibits two major functions: initiation of replication from the origin, ori2, and autogenous repression of repE transcription. One of the mini-F plasmid mutants that can replicate in the dnaJ-defective host produces an altered RepE (RepE54) with a markedly enhanced initiator activity but little or no repressor activity. RepE54 has been purified from cell extracts primarily in monomeric form, unlike the wild-type RepE that is recovered in dimeric form. Gel-retardation assays revealed that RepE54 monomers bind to ori2 (direct repeats) with a very high efficiency but hardly bind to the repE operator (inverted repeat), in accordance with the properties of RepE54 in vivo. Furthermore, the treatment of wild-type RepE dimers with protein denaturants enhanced their binding to ori2 but reduced binding to the operator: RepE dimers were partially converted to monomers, and the ori2 binding activity was uniquely associated with monomers. These results strongly suggest that RepE monomers represent an active form by binding to ori2 to initiate replication, whereas dimers act as an autogenous repressor by binding to the operator. We propose that RepE is structurally and functionally differentiated and that monomerization of RepE dimers, presumably mediated by heat shock protein(s), activates the initiator function and participates in regulation of mini-F DNA replication. Images PMID:8170998

Biofilm-forming activity of bacteria isolated from toilet bowl biofilms and the bactericidal activity of disinfectants against the isolates.

PubMed

Mori, Miho; Gomi, Mitsuhiro; Matsumune, Norihiko; Niizeki, Kazuma; Sakagami, Yoshikazu

2013-01-01

To evaluate the sanitary conditions of toilets, the bacterial counts of the toilet bowl biofilms in 5 Kansai area and 11 Kansai and Kanto area homes in Japan were measured in winter and summer seasons, respectively. Isolates (128 strains) were identified by analyzing 16S ribosomal RNA sequences. The number of colonies and bacterial species from biofilms sampled in winter tended to be higher and lower, respectively, than those in summer. Moreover, the composition of bacterial communities in summer and winter samples differed considerably. In summer samples, biofilms in Kansai and Kanto areas were dominated by Blastomonas sp. and Mycobacterium sp., respectively. Methylobacterium sp. was detected in all toilet bowl biofilms except for one sample. Methylobacterium sp. constituted the major presence in biofilms along with Brevundimonas sp., Sphingomonas sp., and/or Pseudomonas sp. The composition ratio of the sum of their genera was 88.0 from 42.9% of the total bacterial flora. The biofilm formation abilities of 128 isolates were investigated, and results suggested that Methylobacterium sp. and Sphingomonas sp. were involved in biofilm formation in toilet bowls. The biofilm formation of a mixed bacteria system that included bacteria with the highest biofilm-forming ability in a winter sample was greater than mixture without such bacteria. This result suggests that isolates possessing a high biofilm-forming activity are involved in the biofilm formation in the actual toilet bowl. A bactericidal test against 25 strains indicated that the bactericidal activities of didecyldimethylammonium chloride (DDAC) tended to be higher than those of polyhexamethylene biguanide (PHMB) and N-benzyl-N,N-dimethyldodecylammonium chloride (ADBAC). In particular, DDAC showed high bactericidal activity against approximately 90% of tested strains under the 5 h treatment.

Hurricane intensification along United States coast suppressed during active hurricane periods

NASA Astrophysics Data System (ADS)

Kossin, James P.

2017-01-01

The North Atlantic ocean/atmosphere environment exhibits pronounced interdecadal variability that is known to strongly modulate Atlantic hurricane activity. Variability in sea surface temperature (SST) is correlated with hurricane variability through its relationship with the genesis and thermodynamic potential intensity of hurricanes. Another key factor that governs the genesis and intensity of hurricanes is ambient environmental vertical wind shear (VWS). Warmer SSTs generally correlate with more frequent genesis and greater potential intensity, while VWS inhibits genesis and prevents any hurricanes that do form from reaching their potential intensity. When averaged over the main hurricane-development region in the Atlantic, SST and VWS co-vary inversely, so that the two factors act in concert to either enhance or inhibit basin-wide hurricane activity. Here I show, however, that conditions conducive to greater basin-wide Atlantic hurricane activity occur together with conditions for more probable weakening of hurricanes near the United States coast. Thus, the VWS and SST form a protective barrier along the United States coast during periods of heightened basin-wide hurricane activity. Conversely, during the most-recent period of basin-wide quiescence, hurricanes (and particularly major hurricanes) near the United States coast, although substantially less frequent, exhibited much greater variability in their rate of intensification, and were much more likely to intensify rapidly. Such heightened variability poses greater challenges to operational forecasting and, consequently, greater coastal risk during hurricane events.

In-silico Leishmania target selectivity of antiparasitic terpenoids.

PubMed

Ogungbe, Ifedayo Victor; Setzer, William N

2013-07-03

Neglected Tropical Diseases (NTDs), like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many antiparasitic plant-derived isoprenoids have been reported, and many of them have good in vitro activity against various forms of Leishmania spp. In this work, potential Leishmania biochemical targets of antiparasitic isoprenoids were studied in silico. Antiparasitic monoterpenoids selectively docked to L. infantum nicotinamidase, L. major uridine diphosphate-glucose pyrophosphorylase and methionyl t-RNA synthetase. The two protein targets selectively targeted by germacranolide sesquiterpenoids were L. major methionyl t-RNA synthetase and dihydroorotate dehydrogenase. Diterpenoids generally favored docking to L. mexicana glycerol-3-phosphate dehydrogenase. Limonoids also showed some selectivity for L. mexicana glycerol-3-phosphate dehydrogenase and L. major dihydroorotate dehydrogenase while withanolides docked more selectively with L. major uridine diphosphate-glucose pyrophosphorylase. The selectivity of the different classes of antiparasitic compounds for the protein targets considered in this work can be explored in fragment- and/or structure-based drug design towards the development of leads for new antileishmanial drugs.

Dynamic DNA Methylation Controls Glutamate Receptor Trafficking and Synaptic Scaling

PubMed Central

Sweatt, J. David

2016-01-01

Hebbian plasticity, including LTP and LTD, has long been regarded as important for local circuit refinement in the context of memory formation and stabilization. However, circuit development and stabilization additionally relies on non-Hebbian, homoeostatic, forms of plasticity such as synaptic scaling. Synaptic scaling is induced by chronic increases or decreases in neuronal activity. Synaptic scaling is associated with cell-wide adjustments in postsynaptic receptor density, and can occur in a multiplicative manner resulting in preservation of relative synaptic strengths across the entire neuron's population of synapses. Both active DNA methylation and de-methylation have been validated as crucial regulators of gene transcription during learning, and synaptic scaling is known to be transcriptionally dependent. However, it has been unclear whether homeostatic forms of plasticity such as synaptic scaling are regulated via epigenetic mechanisms. This review describes exciting recent work that has demonstrated a role for active changes in neuronal DNA methylation and demethylation as a controller of synaptic scaling and glutamate receptor trafficking. These findings bring together three major categories of memory-associated mechanisms that were previously largely considered separately: DNA methylation, homeostatic plasticity, and glutamate receptor trafficking. PMID:26849493

RecQL5 promotes genome stabilization through two parallel mechanisms--interacting with RNA polymerase II and acting as a helicase.

PubMed

Islam, M Nurul; Fox, David; Guo, Rong; Enomoto, Takemi; Wang, Weidong

2010-05-01

The RecQL5 helicase is essential for maintaining genome stability and reducing cancer risk. To elucidate its mechanism of action, we purified a RecQL5-associated complex and identified its major component as RNA polymerase II (Pol II). Bioinformatics and structural modeling-guided mutagenesis revealed two conserved regions in RecQL5 as KIX and SRI domains, already known in transcriptional regulators for Pol II. The RecQL5-KIX domain binds both initiation (Pol IIa) and elongation (Pol IIo) forms of the polymerase, whereas the RecQL5-SRI domain interacts only with the elongation form. Fully functional RecQL5 requires both helicase activity and associations with the initiation polymerase, because mutants lacking either activity are partially defective in the suppression of sister chromatid exchange and resistance to camptothecin-induced DNA damage, and mutants lacking both activities are completely defective. We propose that RecQL5 promotes genome stabilization through two parallel mechanisms: by participation in homologous recombination-dependent DNA repair as a RecQ helicase and by regulating the initiation of Pol II to reduce transcription-associated replication impairment and recombination.

The role of bacteria and mycorrhiza in plant sulfur supply

PubMed Central

Gahan, Jacinta; Schmalenberger, Achim

2014-01-01

Plant growth is highly dependent on bacteria, saprophytic, and mycorrhizal fungi which facilitate the cycling and mobilization of nutrients. Over 95% of the sulfur (S) in soil is present in an organic form. Sulfate-esters and sulfonates, the major forms of organo-S in soils, arise through deposition of biological material and are transformed through subsequent humification. Fungi and bacteria release S from sulfate-esters using sulfatases, however, release of S from sulfonates is catalyzed by a bacterial multi-component mono-oxygenase system. The asfA gene is used as a key marker in this desulfonation process to study sulfonatase activity in soil bacteria identified as Variovorax, Polaromonas, Acidovorax, and Rhodococcus. The rhizosphere is regarded as a hot spot for microbial activity and recent studies indicate that this is also the case for the mycorrhizosphere where bacteria may attach to the fungal hyphae capable of mobilizing organo-S. While current evidence is not showing sulfatase and sulfonatase activity in arbuscular mycorrhiza, their effect on the expression of plant host sulfate transporters is documented. A revision of the role of bacteria, fungi and the interactions between soil bacteria and mycorrhiza in plant S supply was conducted. PMID:25566295

A survey of UK clinical librarianship: February 2004.

PubMed

Ward, Linda

2005-03-01

This article will describe a survey carried out in February 2004, the aim of which was to summarize the form and content of clinical librarian (CL) and other similar outreach information services to UK health professionals in the acute (secondary or tertiary) sector. (i) To survey the activities and views of UK information professionals offering information services involving the librarians' presence in the clinical setting, (ii) to develop a tool to explore critical aspects of this form of information work, (iii) to create a contacts database for UK CLs, to be made available on the Internet. All known information specialists/librarians offering CL or similar services were surveyed. The semi-structured questionnaire was piloted. Respondents were asked to consider their activity over a period of 4 weeks. Twenty-six people responded to the invitation to take part and met the inclusion criteria. A summary of a 'typical' clinical librarian revealed by this survey is given, with a major conclusion that there is a very mixed picture of activity. Opinion on how far CLs should go in fully appraising search results is uncertain. The survey suggests reasons for this and the developments that may influence change are discussed. Recommendations for future research and development are offered.

Cultural patterns in children's learning through keen observation and participation in their communities.

PubMed

Correa-Chávez, Maricela; Roberts, Amy L D; Pérez, Margarita Martínez

2011-01-01

This chapter examines children's learning through careful attention and participation in the ongoing activities of their community. This form of learning, which has been called learning through Intent Community Participation, seems to be especially common in Mesoamerican Indigenous communities. In these communities, children are integrated into the everyday work and lives of adults and their learning may not be the central focus. We contrast this pattern with that of middle-class European American communities where children are segregated from the primary adult functions of the community. In middle-class communities and schools, children are often encouraged to engage in abstract lessons where their attention is explicitly directed to specific events. In contrast, learning through keen attention and observation may rely on learning through attention to instructions not specifically directed to the learner. Studies demonstrate Mesoamerican Indigenous children's ability to learn through simultaneous and open attention to overheard or observed activities. This form of learning is supported through multiple modalities of communication and interaction. Motivation to learn stems from the learner's inclusion into the major activities and goals of the community. Implications of research and future directions for the study of learning through keen observation are discussed.

Purification and Characterization of a Polygalacturonase-Inhibiting Protein from Phaseolus vulgaris L. 1

PubMed Central

Cervone, Felice; De Lorenzo, Giulia; Degrà, Luisa; Salvi, Giovanni; Bergami, Mario

1987-01-01

Homogeneous endo-polygalacturonase (PG) was covalently bound to cyanogen-bromide-activated Sepharose, and the resulting PG-Sepharose conjugate was utilized to purify, by affinity chromatography, a protein from Phaseolus vulgaris hypocotyls that binds to and inhibits PG. Isoelectric focusing of the purified PG-inhibiting protein (PGIP) showed a major protein band that coincided with PG-inhibiting activity. PGIP formed a complex with PG at pH 5.0 and at low salt concentrations. The complex dissociated in 0.5 m Na-acetate and pH values lower than 4.5 or higher than 6.0. Formation of the PG-PGIP complex resulted in complete inhibition of PG activity. PG activity was restored upon dissociation of the complex. The protein exhibited inhibitory activity toward PGs from Colletotrichum lindemuthianum, Fusarium moniliforme and Aspergillus niger. The possible role of PGIP in regulating the activity of fungal PG's and their ability to elicit plant defense reactions are discussed. Images Fig. 3 PMID:16665751

Interindividual Variability in Metabolism of [6]-Shogaol by Gut Microbiota.

PubMed

Wang, Pei; Wang, Ronghui; Zhu, Yingdong; Sang, Shengmin

2017-11-08

[6]-Shogaol (6S), one of the major bioactive components in dry ginger, is attracting considerable attention because of its wide spectrum of biological activities, but its metabolic fate is still not fully understood. In the present study, the microbial metabolism of 6S was examined for the first time in in vitro batch fecal fermentation system and in mice. Two major microbial metabolites were detected and identified as 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9) and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11). Our results indicated that reductions of the double bond and the ketone group are the major metabolic pathways of 6S by the human gut microbiota. We also observed the interindividual variability in the metabolism of M11 to M9 by human gut microbiota. In addition, we demonstrated that the glucuronidated form of 6S and its metabolites could be rapidly deconjugated by human gut microbiota and in mice, which can be regarded as a reactive process taking place in the intestinal tract. To our knowledge, this is the first report involving the identification of the microbial metabolites of 6S in an in vitro fermentation system, and the first demonstration of the critical role of gut microbiota in producing the bioactive free form of 6S and its metabolites in the intestinal tract in mice.

Essential oil from the leaves of Annona vepretorum: chemical composition and bioactivity.

PubMed

Costa, Emmanoel Vilaça; Dutra, Lívia Macedo; Nogueira, Paulo Cesar de Lima; Moraes, Valéria Regina de Souza; Salvador, Marcos José; Ribeiro, Luis Henrique Gonzaga; Gadelha, Fernanda Ramos

2012-02-01

The essential oil from the leaves of Annona vepretorun was obtained by hydrodistillation using a Clevenger-type apparatus and analyzed by GC-MS and GC-FID. Eighteen compounds representing 98.1% of the crude essential oil were identified. The major compounds identified were bicyclogermacrene (43.7%), spathulenol (11.4%), alpha-felandrene (10.0%), alpha-pinene (7.1%), (E)-beta-ocimene (6.8%), germacrene D (5.8%), and p-cymene (4.2%). The trypanocidal activity against Trypanosoma cruzi epimastigote forms, as well as, the antimicrobial and antioxidant proprieties was investigated. The essential oil showed a potent trypanocidal activity with IC50 value of 31.9 +/-1.3 microg x mL(-1). For antimicrobial activity, the best result was observed against Candida tropicalis with a MIC value of 100 microg x mL(-1). For antioxidant capacity the essential oil showed weak activity.

Protein redox regulation in the thylakoid lumen: the importance of disulfide bonds for violaxanthin de-epoxidase.

PubMed

Simionato, Diana; Basso, Stefania; Zaffagnini, Mirko; Lana, Tobia; Marzotto, Francesco; Trost, Paolo; Morosinotto, Tomas

2015-04-02

When exposed to saturating light conditions photosynthetic eukaryotes activate the xanthophyll cycle where the carotenoid violaxanthin is converted into zeaxanthin by the enzyme violaxanthin de-epoxidase (VDE). VDE protein sequence includes 13 cysteine residues, 12 of which are strongly conserved in both land plants and algae. Site directed mutagenesis of Arabidopsis thaliana VDE showed that all these 12 conserved cysteines have a major role in protein function and their mutation leads to a strong reduction of activity. VDE is also shown to be active in its completely oxidized form presenting six disulfide bonds. Redox titration showed that VDE activity is sensitive to variation in redox potential, suggesting the possibility that dithiol/disulfide exchange reactions may represent a mechanism for VDE regulation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The Journalists Initiatives on Immunisation Against Polio and Improved Acceptance of the Polio Vaccine in Northern Nigeria 2007–2015

PubMed Central

Warigon, Charity; Mkanda, Pascal; Banda, Richard; Zakari, Furera; Damisa, Eunice; Idowu, Audu; Bawa, Samuel; Gali, Emmanuel; Tegegne, Sisay G.; Hammanyero, Kulchumi; Nsubuga, Peter; Korir, Charles; Vaz, Rui G.

2016-01-01

Background. The polio eradication initiative had major setbacks in 2003 and 2007 due to media campaigns in which renowned scholars and Islamic clerics criticized polio vaccines. The World Health Organization (WHO) partnered with journalists in 2007 to form the Journalists Initiatives on Immunisation Against Polio (JAP), to develop communication initiatives aimed at highlighting polio eradication activities and the importance of immunization in northern Nigeria. Methods. We evaluated the impact of JAP activities in Kaduna State by determining the total number of media materials produced and the number of newspaper clips and bulletins published in support of polio eradication. We also determined the number of households in noncompliant communities that became compliant with vaccination during 2015 supplementary immunization activities (SIAs) after JAP interventions and compared caregivers’ sources of information about SIAs in 2007 before and after the JAP was formed. Results. Since creation of the JAP, >500 reports have been published and aired, with most portraying polio vaccine positively. During June 2015 SIAs in high-risk wards of Kaduna STATE, JAP interventions resulted in vaccination of 5122 of 5991 children (85.5%) from noncompliant households. During early 2007, the number of caregivers who had heard about SIA rounds from the media increased from 26% in January, before the JAP was formed, to 33% in March, after the initiation of JAP activities. Conclusions. The formation of the JAP resulted in measurable improvement in the acceptance of polio vaccine in northern Nigeria. PMID:26721745

Transcriptional activity of the homopurine-homopyrimidine repeat of the c-Ki-ras promoter is independent of its H-forming potential.

PubMed Central

Raghu, G; Tevosian, S; Anant, S; Subramanian, K N; George, D L; Mirkin, S M

1994-01-01

The mouse c-Ki-ras protooncogene promoter contains an unusual DNA element consisting of a 27 bp-long homopurine-homopyrimidine mirror repeat (H-motif) adjacent to a d(C-G)5 repeat. We have previously shown that in vitro these repeats may adopt H and Z conformations, respectively, causing nuclease and chemical hypersensitivity. Here we have studied the functional role of these DNA stretches using fine deletion analysis of the promoter and a transient transcription assay in vivo. We found that while the H-motif is responsible for approximately half of the promoter activity in both mouse and human cell lines, the Z-forming sequence exhibits little, if any, such activity. Mutational changes introduced within the homopurine-homopyrimidine stretch showed that its sequence integrity, rather than its H-forming potential, is responsible for its effect on transcription. Electrophoretic mobility shift assays revealed that the putative H-motif tightly binds several nuclear proteins, one of which is likely to be transcription factor Sp1, as determined by competition experiments. Southwestern hybridization studies detected two major proteins specifically binding to the H-motif: a 97 kD protein which presumably corresponds to Sp1 and another protein of 60 kD in human and 64 kD in mouse cells. We conclude that the homopurine-homopyrimidine stretch is required for full transcriptional activity of the c-Ki-ras promoter and at least two distinct factors, Sp1 and an unidentified protein, potentially contribute to the positive effect on transcription. Images PMID:8078760

Apple polyphenols, phloretin and phloridzin: new trapping agents of reactive dicarbonyl species.

PubMed

Shao, Xi; Bai, Naisheng; He, Kan; Ho, Chi-Tang; Yang, Chung S; Sang, Shengmin

2008-10-01

Reactive dicarbonyl species, such as methylglyoxal (MGO) and glyoxal (GO), have received extensive attention recently due to their high reactivity and ability to form advanced glycation end products (AGEs) with biological substances such as proteins, phospholipids, and DNA. In the present study, we found that both phloretin and its glucoside, phloridzin, the major bioactive apple polyphenols, could efficiently trap reactive MGO or GO to form mono- and di-MGO or GO adducts under physiological conditions (pH 7.4, 37 degrees C). More than 80% MGO was trapped within 10 min, and 68% GO was trapped within 24 h by phloretin. Phloridzin also had strong trapping efficiency by quenching more than 70% MGO and 60% GO within 24 h. The glucosylation of the hydroxyl group at position 2 could significantly slow down the trapping rate and the formation of MGO or GO adducts. The products formed from phloretin (or phloridzin) and MGO (or GO), combined at different ratios, were analyzed using LC/MS. We successfully purified the major mono-MGO adduct of phloridzin and found that it was a mixture of tautomers based on the one- and two-dimensional NMR spectra. Our LC/MS and NMR data showed that positions 3 and 5 of the phloretin or phloridzin A ring were the major active sites for trapping reactive dicarbonyl species. We also found that phloretin was more reactive than lysine and arginine in terms of trapping reactive dicarbonyl species, MGO or GO. Our results suggest that dietary flavonoids that have the same A ring structure as phloretin may have the potential to trap reactive dicarbonyl species and therefore inhibit the formation of AGEs.

Abundance, distribution and bioavailability of major and trace elements in surface sediments from the Cai River estuary and Nha Trang Bay (South China Sea, Vietnam)

NASA Astrophysics Data System (ADS)

Koukina, S. E.; Lobus, N. V.; Peresypkin, V. I.; Dara, O. M.; Smurov, A. V.

2017-11-01

Major (Si, Al, Fe, Ti, Mg, Ca, Na, K, S, P), minor (Mn) and trace (Li, V, Cr, Co, Ni, Cu, Zn, As, Sr, Zr, Mo, Cd, Ag, Sn, Sb, Cs, Ba, Hg, Pb, Bi and U) elements, their chemical forms and the mineral composition, organic matter (TOC) and carbonates (TIC) in surface sediments from the Cai River estuary and Nha Trang Bay were first determined along the salinity gradient. The abundance and ratio of major and trace elements in surface sediments are discussed in relation to the mineralogy, grain size, depositional conditions, reference background and SQG values. Most trace-element contents are at natural levels and are derived from the composition of rocks and soils in the watershed. A severe enrichment of Ag is most likely derived from metal-rich detrital heavy minerals such as Ag-sulfosalts. Along the salinity gradient, several zones of metal enrichment occur in surface sediments because of the geochemical fractionation of the riverine material. The parts of actually and potentially bioavailable forms (isolated by four single chemical reagent extractions) are most elevated for Mn and Pb (up to 36% and 32% of total content, respectively). The possible anthropogenic input of Pb in the region requires further study. Overall, the most bioavailable parts of trace elements are associated with easily soluble amorphous Fe and Mn oxyhydroxides. The sediments are primarily enriched with bioavailable metal forms in the riverine part of the estuary. Natural (such as turbidities) and human-generated (such as urban and industrial activities) pressures are shown to influence the abundance and speciation of potential contaminants and therefore change their bioavailability in this estuarine system.

Setting Up Shop: The Formation and Function of the Viral Factories of Cauliflower mosaic virus.

PubMed

Schoelz, James E; Leisner, Scott

2017-01-01

Similar to cells, viruses often compartmentalize specific functions such as genome replication or particle assembly. Viral compartments may contain host organelle membranes or they may be mainly composed of viral proteins. These compartments are often termed: inclusion bodies (IBs), viroplasms or viral factories. The same virus may form more than one type of IB, each with different functions, as illustrated by the plant pararetrovirus, Cauliflower mosaic virus (CaMV). CaMV forms two distinct types of IBs in infected plant cells, those composed mainly of the viral proteins P2 (which are responsible for transmission of CaMV by insect vectors) and P6 (required for viral intra-and inter-cellular infection), respectively. P6 IBs are the major focus of this review. Much of our understanding of the formation and function of P6 IBs comes from the analyses of their major protein component, P6. Over time, the interactions and functions of P6 have been gradually elucidated. Coupled with new technologies, such as fluorescence microscopy with fluorophore-tagged viral proteins, these data complement earlier work and provide a clearer picture of P6 IB formation. As the activities and interactions of the viral proteins have gradually been determined, the functions of P6 IBs have become clearer. This review integrates the current state of knowledge on the formation and function of P6 IBs to produce a coherent model for the activities mediated by these sophisticated virus-manufacturing machines.

DOE Office of Scientific and Technical Information (OSTI.GOV)

J. Carmack; L. Braase; F. Goldner

The mission of the Advanced Fuels Campaign (AFC) is to perform Research, Development, and Demonstration (RD&D) activities for advanced fuel forms (including cladding) to enhance the performance and safety of the nation’s current and future reactors, enhance proliferation resistance of nuclear fuel, effectively utilize nuclear energy resources, and address the longer-term waste management challenges. This includes development of a state of the art Research and Development (R&D) infrastructure to support the use of a “goal oriented science based approach.” AFC uses a “goal oriented, science based approach” aimed at a fundamental understanding of fuel and cladding fabrication methods and performancemore » under irradiation, enabling the pursuit of multiple fuel forms for future fuel cycle options. This approach includes fundamental experiments, theory, and advanced modeling and simulation. One of the most challenging aspects of AFC is the management, integration, and coordination of major R&D activities across multiple organizations. AFC interfaces and collaborates with Fuel Cycle Technologies (FCT) campaigns, universities, industry, various DOE programs and laboratories, federal agencies (e.g., Nuclear Regulatory Commission [NRC]), and international organizations. Key challenges are the development of fuel technologies to enable major increases in fuel performance (safety, reliability, power and burnup) beyond current technologies, and development of characterization methods and predictive fuel performance models to enable more efficient development and licensing of advanced fuels. Challenged with the research and development of fuels for two different reactor technology platforms, AFC targeted transmutation fuel development and focused ceramic fuel development for Advanced LWR Fuels.« less

Brain Renin-Angiotensin System and Microglial Polarization: Implications for Aging and Neurodegeneration

PubMed Central

Labandeira-Garcia, Jose L.; Rodríguez-Perez, Ana I.; Garrido-Gil, Pablo; Rodriguez-Pallares, Jannette; Lanciego, Jose L.; Guerra, Maria J.

2017-01-01

Microglia can transform into proinflammatory/classically activated (M1) or anti-inflammatory/alternatively activated (M2) phenotypes following environmental signals related to physiological conditions or brain lesions. An adequate transition from the M1 (proinflammatory) to M2 (immunoregulatory) phenotype is necessary to counteract brain damage. Several factors involved in microglial polarization have already been identified. However, the effects of the brain renin-angiotensin system (RAS) on microglial polarization are less known. It is well known that there is a “classical” circulating RAS; however, a second RAS (local or tissue RAS) has been observed in many tissues, including brain. The locally formed angiotensin is involved in local pathological changes of these tissues and modulates immune cells, which are equipped with all the components of the RAS. There are also recent data showing that brain RAS plays a major role in microglial polarization. Level of microglial NADPH-oxidase (Nox) activation is a major regulator of the shift between M1/proinflammatory and M2/immunoregulatory microglial phenotypes so that Nox activation promotes the proinflammatory and inhibits the immunoregulatory phenotype. Angiotensin II (Ang II), via its type 1 receptor (AT1), is a major activator of the NADPH-oxidase complex, leading to pro-oxidative and pro-inflammatory effects. However, these effects are counteracted by a RAS opposite arm constituted by Angiotensin II/AT2 receptor signaling and Angiotensin 1–7/Mas receptor (MasR) signaling. In addition, activation of prorenin-renin receptors may contribute to activation of the proinflammatory phenotype. Aged brains showed upregulation of AT1 and downregulation of AT2 receptor expression, which may contribute to a pro-oxidative pro-inflammatory state and the increase in neuron vulnerability. Several recent studies have shown interactions between the brain RAS and different factors involved in microglial polarization, such as estrogens, Rho kinase (ROCK), insulin-like growth factor-1 (IGF-1), tumor necrosis factor α (TNF)-α, iron, peroxisome proliferator-activated receptor gamma, and toll-like receptors (TLRs). Metabolic reprogramming has recently been involved in the regulation of the neuroinflammatory response. Interestingly, we have recently observed a mitochondrial RAS, which is altered in aged brains. In conclusion, dysregulation of brain RAS plays a major role in aging-related changes and neurodegeneration by exacerbation of oxidative stress (OS) and neuroinflammation, which may be attenuated by pharmacological manipulation of RAS components. PMID:28515690

Peptidases of the peripheral chemoreceptors: biochemical, immunological, in vitro hydrolytic studies and electron microscopic analysis of neutral endopeptidase-like activity of the carotid body.

PubMed

Kumar, G K

1997-02-14

The purposes of the present study are to identify and characterize the major peptidase(s) that may be involved in the inactivation of neuropeptides in the mammalian carotid body. Measurements of a number of peptidase activities in the cell-free extract of the cat carotid body using specific substrates and inhibitors indicated that the previously identified neutral endopeptidase (NEP)-like activity [Kumar et al., Brain Res., 517 (1990) 341-343] is the major peptidase in the chemoreceptor tissue. The NEP-like activity of the carotid body was further characterized using a monoclonal antibody to human neutral endopeptidase, EC 3.4.24.11. Immune blot analysis indicated strong immunoreactivity toward the cat and calf carotid bodies but a weak cross-reactivity with the rabbit carotid body. Furthermore, western blot analysis of the cat carotid body extract revealed the presence of a major 97-kDa protein and a minor 200-kDa protein. The 97-kDa NEP form of the carotid body was comparable to EC 3.4.24.11 and was consistent with its reported molecular weight suggesting NEP-like activity of the carotid body is structurally similar to the neutral endopeptidase, EC 3.4.24.11. In order to assess whether NEP is the primary peptide degrading activity in the cat carotid body in vitro hydrolysis studies using substance P (SP) as a model peptide were performed. HPLC analysis showed that SP is hydrolyzed maximally at pH 7.0 by carotid body peptidases with the formation of SP(1-7) and SP(1-8) as stable intermediates. Inhibitors specific to NEP also inhibited the SP-hydrolyzing activity of the carotid body. Analyses of the cell-free extracts showed the occurrence of both NEP and SP-hydrolyzing activities in the rabbit and rat carotid bodies although at 2- and 4-fold lower levels respectively than that observed in the cat carotid body. Immunoelectron microscopy showed that NEP-specific immunoreactivity is associated with the intercellular region between the type I cells and cell clusters of the carotid body. Taken together, the results from this investigation demonstrate that neutral endopeptidase (EC 3.4.24.11) is one of the major endopeptidases which mediates the degradation and inactivation of neuropeptides in the carotid body.

Soviet women and the autonomous family.

PubMed

Imbrogno, S; Imbrogno, N I

1989-01-01

"The USSR family is changing in form from that of a social collectivity, a bedrock conception to socialism, to that of an autonomous family. Autonomy discloses a lack of homogeneity, an independence of choices over life-styles and a flexibility toward an interpretation given to the meaning of a socialistic state. Women are exceedingly active in making greater use of their legal rights to divorce and abortion and demanding equal status with men both in the workplace and in the home. Women are initiating major social changes, are readily adapting to changing relations and patterns in a complex society and are serving to spearhead changes in the family unit. These factors have generated major changes in the normative, behavioral and structural dimensions of marriage and family life in the Soviet Union." excerpt

Food and Drug Administration: Helping pharmacists ensure that patients receive high-quality medicines.

PubMed

Kremzner, Mary

2016-01-01

Ensuring that the drugs patients take are safe and effective is critical to the Food and Drug Administration (FDA) mission and a major reason for testing an active pharmaceutical ingredient or currently marketed drug product. To address gaps in the assessment of drug quality, FDA's Center for Drug Evaluation and Research (CDER) has created the Office of Pharmaceutical Quality (OPQ). This newly formed "super-office" within CDER launched a concerted new strategy that enhances the surveillance of drug manufacturing and will bring a comprehensive approach to quality oversight. With OPQ and these new performance measures in place, FDA can sharpen its focus on issues critical to quality and can identify and respond to manufacturing issues before they become major systemic problems. Published by Elsevier Inc.

On the chemistry, toxicology and genetics of the cyanobacterial toxins, microcystin, nodularin, saxitoxin and cylindrospermopsin.

PubMed

Pearson, Leanne; Mihali, Troco; Moffitt, Michelle; Kellmann, Ralf; Neilan, Brett

2010-05-10

The cyanobacteria or "blue-green algae", as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites.

Neonatal Diabetes: An Expanding List of Genes Allows for Improved Diagnosis and Treatment

PubMed Central

Naylor, Rochelle N.; Philipson, Louis H.; Bell, Graeme I.

2011-01-01

There has been major progress in recent years uncovering the genetic causes of diabetes presenting in the first year of life. Twenty genes have been identified to date. The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel (KATP), KCNJ11 and ABCC8, and the insulin gene (INS), as well as abnormalities in chromosome 6q24. Patients with activating mutations in KCNJ11 and ABCC8 can be treated with oral sulfonylureas in lieu of insulin injections. This compelling example of personalized genetic medicine leading to improved glucose regulation and quality of life may—with continued research—be repeated for other forms of neonatal diabetes in the future. PMID:21993633

Advanced Theory of Driven Birdcage Resonator with Losses for Biomedical Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Novikov, Alexander

2010-01-01

A complete time-dependent physics theory of symmetric unperturbed driven Hybrid Birdcage resonator was developed for general application. In particular, the theory can be applied for RF coil engineering, computer simulations of coil-sample interaction, etc. Explicit time dependence is evaluated for different forms of driving voltage. The major steps of the solution development are shown and appropriate explanations are given. Green’s functions and spectral density formula were developed for any form of periodic driving voltage. The concept of distributed power losses based on transmission line theory is developed for evaluation of local losses of a coil. Three major types of power losses are estimated as equivalent series resistances in the circuit of the Birdcage resonator. Values of generated resistances in Legs and End-Rings are estimated. An application of the theory is shown for many practical cases. Experimental curve of B1 field polarization dependence is measured for eight-sections Birdcage coil. It was shown, that the steady-state driven resonance frequencies do not depend on damping factor unlike the free oscillation (transient) frequencies. An equivalent active resistance is generated due to interaction of RF electromagnetic field with a sample. Resistance of the conductor (enhanced by skin effect), Eddy currents and dielectric losses are the major types of losses which contribute to the values of generated resistances. A biomedical sample for magnetic resonance imaging and spectroscopy is the source of the both Eddy current and dielectric losses of a coil. As demonstrated by the theory, Eddy currents losses is the major effect of coil shielding. PMID:20869184

Insights into the Photoprotective Switch of the Major Light-harvesting Complex II (LHCII)

PubMed Central

Sunku, Kiran; de Groot, Huub. J. M.; Pandit, Anjali

2013-01-01

Light-harvesting antennae of the LHC family form transmembrane three-helix bundles of which two helices are interlocked by conserved arginine-glutamate (Arg-Glu) ion pairs that form ligation sites for chlorophylls. The antenna proteins of photosystem II have an intriguing dual function. In excess light, they can switch their conformation from a light-harvesting into a photoprotective state, in which the excess and harmful excitation energies are safely dissipated as heat. Here we applied magic angle spinning NMR and selective Arg isotope enrichment as a noninvasive method to analyze the Arg structures of the major light-harvesting complex II (LHCII). The conformations of the Arg residues that interlock helix A and B appear to be preserved in the light-harvesting and photoprotective state. Several Arg residues have very downfield-shifted proton NMR responses, indicating that they stabilize the complex by strong hydrogen bonds. For the Arg Cα chemical shifts, differences are observed between LHCII in the active, light-harvesting and in the photoprotective, quenched state. These differences are attributed to a conformational change of the Arg residue in the stromal loop region. We conclude that the interlocked helices of LHCII form a rigid core. Consequently, the LHCII conformational switch does not involve changes in A/B helix tilting but likely involves rearrangements of the loops and helical segments close to the stromal and lumenal ends. PMID:23629658

Cancer Chemoprevention with Korean Angelica: Active Compounds, Pharmacokinetics, and Human Translational Considerations

PubMed Central

Lü, Junxuan; Zhang, Jinhui; Li, Li; Jiang, Cheng; Xing, Chengguo

2015-01-01

Angelica gigas Nakai (AGN) is a major medicinal herb used in Korea and several other Asian countries. Traditionally, its dried root has been used to treat anemia, pain, infection and articular rheumatism, most often through boiling in water to prepare the dosage forms. AGN extract or AGN-containing herbal mixtures are sold in the US and globally as dietary supplements for pain killing, memory enhancement and post-menopausal symptom relief. Decursin (D) and its isomer decursinol angelate (DA) are the major chemicals in the alcoholic extracts of the root of AGN. The anti-cancer activity of AGN alcoholic extract has been established in a number of animal cancer models, including a transgenic model of prostate carcinogenesis. Cell culture structure-activity studies have uncovered distinct cellular and molecular effects of D and DA vs. their pyranocoumarin core decursinol (DOH) with respect to cancer cells and those associated with their microenvironment. Pharmacokinetic (PK) study by us and others in rodent models indicated that DOH is the major and rapid in vivo first-pass liver metabolite of D and DA. Cognizant of metabolic differences among rodents and humans, we carried out a first-in-human PK study of D/DA to inform the translational relevance of efficacy and mechanism studies with rodent models. The combined use of vigorous animal tests and human PK studies can provide stronger scientific rationale to inform design and execution of translational studies to move AGN toward evidence-based herbal medicine. PMID:26623248

Cancer Chemoprevention with Korean Angelica: Active Compounds, Pharmacokinetics, and Human Translational Considerations.

PubMed

Lü, Junxuan; Zhang, Jinhui; Li, Li; Jiang, Cheng; Xing, Chengguo

2015-12-01

Angelica gigas Nakai (AGN) is a major medicinal herb used in Korea and several other Asian countries. Traditionally, its dried root has been used to treat anemia, pain, infection and articular rheumatism, most often through boiling in water to prepare the dosage forms. AGN extract or AGN-containing herbal mixtures are sold in the US and globally as dietary supplements for pain killing, memory enhancement and post-menopausal symptom relief. Decursin (D) and its isomer decursinol angelate (DA) are the major chemicals in the alcoholic extracts of the root of AGN. The anti-cancer activity of AGN alcoholic extract has been established in a number of animal cancer models, including a transgenic model of prostate carcinogenesis. Cell culture structure-activity studies have uncovered distinct cellular and molecular effects of D and DA vs. their pyranocoumarin core decursinol (DOH) with respect to cancer cells and those associated with their microenvironment. Pharmacokinetic (PK) study by us and others in rodent models indicated that DOH is the major and rapid in vivo first-pass liver metabolite of D and DA. Cognizant of metabolic differences among rodents and humans, we carried out a first-in-human PK study of D/DA to inform the translational relevance of efficacy and mechanism studies with rodent models. The combined use of vigorous animal tests and human PK studies can provide stronger scientific rationale to inform design and execution of translational studies to move AGN toward evidence-based herbal medicine.

Green tea yogurt: major phenolic compounds and microbial growth.

PubMed

Amirdivani, Shabboo; Baba, Ahmad Salihin Hj

2015-07-01

The purpose of this study was to evaluate fermentation of milk in the presence of green tea (Camellia sinensis) with respect to changes in antioxidant activity, phenolic compounds and the growth of lactic acid bacteria. Pasteurized full fat cow's milk and starter culture were incubated at 41 °C in the presence of two different types of green tea extracts. The yogurts formed were refrigerated (4 °C) for further analysis. The total phenolic content was highest (p < 0.05) in air-dried green tea-yogurt (MGT) followed by steam-treated green tea (JGT) and plain yogurts. Four major compounds in MGTY and JGTY were detected. The highest concentration of major phenolic compounds in both samples was related to quercetin-rhamnosylgalactoside and quercetin-3-O-galactosyl-rhamnosyl-glucoside for MGTY and JGTY respectively during first 7 day of storage. Diphenyl picrylhydrazyl and ferric reducing antioxidant power methods showed highest antioxidant capacity in MGTY, JGTY and PY. Streptococcus thermophillus and Lactobacillus spp. were highest in MGTY followed by JGTY and PY. This paper evaluates the implementation of green tea yogurt as a new product with functional properties and valuable component to promote the growth of beneficial yogurt bacteria and prevention of oxidative stress by enhancing the antioxidant activity of yogurt.

Self-Referential Processing, Rumination, and Cortical Midline Structures in Major Depression

PubMed Central

Nejad, Ayna Baladi; Fossati, Philippe; Lemogne, Cédric

2013-01-01

Major depression is associated with a bias toward negative emotional processing and increased self-focus, i.e., the process by which one engages in self-referential processing. The increased self-focus in depression is suggested to be of a persistent, repetitive and self-critical nature, and is conceptualized as ruminative brooding. The role of the medial prefrontal cortex in self-referential processing has been previously emphasized in acute major depression. There is increasing evidence that self-referential processing as well as the cortical midline structures play a major role in the development, course, and treatment response of major depressive disorder. However, the links between self-referential processing, rumination, and the cortical midline structures in depression are still poorly understood. Here, we reviewed brain imaging studies in depressed patients and healthy subjects that have examined these links. Self-referential processing in major depression seems associated with abnormally increased activity of the anterior cortical midline structures. Abnormal interactions between the lateralized task-positive network, and the midline cortical structures of the default mode network, as well as the emotional response network, may underlie the pervasiveness of ruminative brooding. Furthermore, targeting this maladaptive form of rumination and its underlying neural correlates may be key for effective treatment. PMID:24124416

Longitudinal Physical Activity Patterns Among Older Adults: A Latent Transition Analysis.

PubMed

Mooney, Stephen J; Joshi, Spruha; Cerdá, Magdalena; Kennedy, Gary J; Beard, John R; Rundle, Andrew G

2018-05-14

Most epidemiologic studies of physical activity measure either total energy expenditure or engagement in a single activity type, such as walking. These approaches may gloss over important nuances in activity patterns. We performed a latent transition analysis to identify patterns of activity types as well as neighborhood and individual determinants of changes in those activity patterns over two years in a cohort of 2,023 older adult residents of New York City, NY, surveyed between 2011 and 2013. We identified seven latent classes: 1) Mostly Inactive, 2) Walking, 3) Exercise, 4) Household Activities and Walking, 5) Household Activities and Exercise, 6) Gardening and Household Activities, and 7) Gardening, Household Activities, and Exercise. The majority of subjects retained the same activity patterns between waves (54% unchanged between waves 1 and 2, 66% unchanged between waves 2 and 3).Most latent class transitions were between classes distinguished only by one form of activity, and only neighborhood unemployment was consistently associated with changing between activity latent classes. Future latent transition analyses of physical activity would benefit from larger cohorts and longer follow-up periods to assess predictors of and long-term impacts of changes in activity patterns.

Evolution of specifier proteins in glucosinolate-containing plants

PubMed Central

2012-01-01

Background The glucosinolate-myrosinase system is an activated chemical defense system found in plants of the Brassicales order. Glucosinolates are stored separately from their hydrolytic enzymes, the myrosinases, in plant tissues. Upon tissue damage, e.g. by herbivory, glucosinolates and myrosinases get mixed and glucosinolates are broken down to an array of biologically active compounds of which isothiocyanates are toxic to a wide range of organisms. Specifier proteins occur in some, but not all glucosinolate-containing plants and promote the formation of biologically active non-isothiocyanate products upon myrosinase-catalyzed glucosinolate breakdown. Results Based on a phytochemical screening among representatives of the Brassicales order, we selected candidate species for identification of specifier protein cDNAs. We identified ten specifier proteins from a range of species of the Brassicaceae and assigned each of them to one of the three specifier protein types (NSP, nitrile-specifier protein, ESP, epithiospecifier protein, TFP, thiocyanate-forming protein) after heterologous expression in Escherichia coli. Together with nine known specifier proteins and three putative specifier proteins found in databases, we subjected the newly identified specifier proteins to phylogenetic analyses. Specifier proteins formed three major clusters, named AtNSP5-cluster, AtNSP1-cluster, and ESP/TFP cluster. Within the ESP/TFP cluster, specifier proteins grouped according to the Brassicaceae lineage they were identified from. Non-synonymous vs. synonymous substitution rate ratios suggested purifying selection to act on specifier protein genes. Conclusions Among specifier proteins, NSPs represent the ancestral activity. The data support a monophyletic origin of ESPs from NSPs. The split between NSPs and ESPs/TFPs happened before the radiation of the core Brassicaceae. Future analyses have to show if TFP activity evolved from ESPs at least twice independently in different Brassicaceae lineages as suggested by the phylogeny. The ability to form non-isothiocyanate products by specifier protein activity may provide plants with a selective advantage. The evolution of specifier proteins in the Brassicaceae demonstrates the plasticity of secondary metabolism within an activated plant defense system. PMID:22839361

Characteristics and petrology of the effusive-explosive activity of Colima volcano, in the years 2015-2017

NASA Astrophysics Data System (ADS)

Suarez-Plascencia, C.; Nuñez-Cornu, F. J.; Arreola-Ochoa, L. C.; Suarez, G. B. V.; Carrillo-Gonzalez, D. A.

2017-12-01

The Colima volcano, during the years 2015-2017, presented an important effusive and explosive activity, which began in January 2015 with the growth of a dome that was destroyed by explosions, forming pyroclastic flows reaching distances of up to 2 km by the north and south flanks of the volcano. In May a new dome was extruded, forming three thick lava flows along the northern and southern slopes; the extruded volume was approximately 6 million cubic meters, with a rate in 52 days of 1.3 m3/sec. On July 11 merapi flows were formed it flowed through by the ravines of Montegrande and San Antonio, on the south and southwest flank, reaching distances of 10.4 km. The following days the activity had decreased substantially, leaving a crater of 60 m of depth and 270 m of diameter. In February 2016, a small dome occupied the central part of the main crater, and it was until September that an episode of volcanic tremor began, that was associated with its rapid growth, which in 48 hours filled the crater and formed a lava flow that descended by the south slope. By October 2, 2.3 million m3 of lava were extruded, which caused a deflation of the dome. In October 7, the volcano emitted a great amount of gases and steam of water that formed an acid rain that affected forests and crops of the south and southwest slope, causing losses by 1 million dollars. In November, a series of explosions occurred that destroyed two thirds of the dome. In January 2017, the explosive activity increased and again destroyed the dome. Five events were recorded that reached between 3 km and 4 km of height on the top of the volcano, the dispersion of the ash generally went to the northeast, reaching distances of up to 200 km. Currently the volcano is sustaining reduced seismic and fumarole activity. In 2005, 2015 and 2017, the geochemical analysis of major elements such as SiO2 from the ash emitted by the volcano showed an increase from 54.51% to 60.05% and 60.24%, respectively, which was associated with the increase in volcanic explosions, affecting and causing damages to the economic activities and the localities and settlements in its valleys and piedmont.

HSF1 is activated as a consequence of lymphocyte activation and regulates a major proteostasis network in T cells critical for cell division during stress

PubMed Central

Gandhapudi, Siva K.; Murapa, Patience; Threlkeld, Zachary D.; Ward, Martin; Sarge, Kevin D.; Snow, Charles; Woodward, Jerold G.

2013-01-01

Heat Shock Transcription Factor 1 (HSF1) is a major transcriptional regulator of the heat shock response in eukaryotic cells. HSF1 is also evoked in response to a variety of cellular stressors including elevated temperatures, oxidative stress, and other proteotoxic stressors. Previously, we demonstrated that HSF1 is activated in naive T cells at fever range temperatures (39.5°C) and is critical for in vitro T cell proliferation at fever temperatures. In this study, we demonstrated thatmurine HSF1 became activated to the DNA-binding form and trans-activated a large number of genes in lymphoid cells strictly as a consequence of receptor activation in the absence of apparent cellular stress. Microarray analysis comparing HSF1+/+ and HSF1−/− gene expression in T cells activated at 37°C revealed a diverse set of 323 genes significantly regulated by HSF1 in non-stressed T cells. In vivo proliferation studies revealed a significant impairment of HSF1−/− T cell expansion under conditions mimicking a robust immune response (staphylococcal enterotoxin B induced T cell activation). This proliferation defect due to loss of HSF1 is observed even under non-febrile temperatures. HSF1−/− T cells activated at fever temperatures show a dramatic reduction in cyclin E and cyclin A proteins during the cell cycle, although the transcription of these genes was not affected. Finally, B cell, and hematopoietic stem cell proliferation from HSF1−/− mice, but not HSF1+/+ mice were also attenuated under stressful conditions, indicating that HSF1 is critical for the cell cycle progression of lymphoid cells activated under stressful conditions. PMID:24043900

Candida albicans yeast and hyphae are discriminated by MAPK signaling in vaginal epithelial cells.

PubMed

Moyes, David L; Murciano, Celia; Runglall, Manohursingh; Islam, Ayesha; Thavaraj, Selvam; Naglik, Julian R

2011-01-01

We previously reported that a bi-phasic innate immune MAPK response, constituting activation of the mitogen-activated protein kinase (MAPK) phosphatase MKP1 and c-Fos transcription factor, discriminates between the yeast and hyphal forms of Candida albicans in oral epithelial cells (ECs). Since the vast majority of mucosal Candida infections are vaginal, we sought to determine whether a similar bi-phasic MAPK-based immune response was activated by C. albicans in vaginal ECs. Here, we demonstrate that vaginal ECs orchestrate an innate response to C. albicans via NF-κB and MAPK signaling pathways. However, unlike in oral ECs, the first MAPK response, defined by c-Jun transcription factor activation, is delayed until 2 h in vaginal ECs but is still independent of hypha formation. The 'second' or 'late' MAPK response, constituting MKP1 and c-Fos transcription factor activation, is identical to oral ECs and is dependent upon both hypha formation and fungal burdens. NF-κB activation is immediate but independent of morphology. Furthermore, the proinflammatory response in vaginal ECs is different to oral ECs, with an absence of G-CSF and CCL20 and low level IL-6 production. Therefore, differences exist in how C. albicans activates signaling mechanisms in oral and vaginal ECs; however, the activation of MAPK-based pathways that discriminate between yeast and hyphal forms is retained between these mucosal sites. We conclude that this MAPK-based signaling pathway is a common mechanism enabling different human epithelial tissues to orchestrate innate immune responses specifically against C. albicans hyphae.

Rapid intranasal delivery of chloramphenicol acetyltransferase in the active form to different brain regions as a model for enzyme therapy in the CNS.

PubMed

Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A

2016-02-01

The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.

Active faults in Africa: a review

NASA Astrophysics Data System (ADS)

Skobelev, S. F.; Hanon, M.; Klerkx, J.; Govorova, N. N.; Lukina, N. V.; Kazmin, V. G.

2004-03-01

The active fault database and Map of active faults in Africa, in scale of 1:5,000,000, were compiled according to the ILP Project II-2 "World Map of Major Active Faults". The data were collected in the Royal Museum of Central Africa, Tervuren, Belgium, and in the Geological Institute, Moscow, where the final edition was carried out. Active faults of Africa form three groups. The first group is represented by thrusts and reverse faults associated with compressed folds in the northwest Africa. They belong to the western part of the Alpine-Central Asian collision belt. The faults disturb only the Earth's crust and some of them do not penetrate deeper than the sedimentary cover. The second group comprises the faults of the Great African rift system. The faults form the known Western and Eastern branches, which are rifts with abnormal mantle below. The deep-seated mantle "hot" anomaly probably relates to the eastern volcanic branch. In the north, it joins with the Aden-Red Sea rift zone. Active faults in Egypt, Libya and Tunis may represent a link between the East African rift system and Pantellerian rift zone in the Mediterranean. The third group included rare faults in the west of Equatorial Africa. The data were scarce, so that most of the faults of this group were identified solely by interpretation of space imageries and seismicity. Some longer faults of the group may continue the transverse faults of the Atlantic and thus can penetrate into the mantle. This seems evident for the Cameron fault line.

IGF-1 decreases collagen degradation in diabetic NOD mesangial cells: implications for diabetic nephropathy.

PubMed

Lupia, E; Elliot, S J; Lenz, O; Zheng, F; Hattori, M; Striker, G E; Striker, L J

1999-08-01

Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF-1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ, Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MC. Total collagen degradation was reduced by 58 +/- 18% in diabetic NOD-MCs, which correlated with a constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MC. The addition of recombinant IGF-1 to nondiabetic NOD-MC resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2. In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MC, largely through a reduction of MMP-2 activity. These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis.

Albendazole Microcrystal Formulations Based on Chitosan and Cellulose Derivatives: Physicochemical Characterization and In Vitro Parasiticidal Activity in Trichinella spiralis Adult Worms.

PubMed

Priotti, Josefina; Codina, Ana V; Leonardi, Darío; Vasconi, María D; Hinrichsen, Lucila I; Lamas, María C

2017-05-01

The oral route has notable advantages to administering dosage forms. One of the most important questions to solve is the poor solubility of most drugs which produces low bioavailability and delivery problems, a major challenge for the pharmaceutical industry. Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its extended spectrum activity and low cost. Nevertheless, the main disadvantage is the poor bioavailability due to its very low solubility in water. The main objective of this study was to prepare microcrystal formulations by the bottom-up technology to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. Thus, 20 novel microstructures based on chitosan, cellulose derivatives, and poloxamer as a surfactant were produced and characterized by their physicochemical properties and in vitro biological activity. To determine the significance of type and concentration of polymer, and presence or absence of surfactant in the crystals, the variables area under the curve, albendazole microcrystal solubility, and drug released (%) at 30 min were analyzed with a three-way ANOVA. This analysis indicated that the microcrystals made with hydroxyethylcellulose or chitosan appear to be the best options to optimize oral absorption of the active pharmaceutical ingredient. The in vitro evaluation of anthelmintic activity on adult forms of Trichinella spiralis identified system S10A as the most effective, of choice for testing therapeutic efficacy in vivo.

Development of activity pencil beam algorithm using measured distribution data of positron emitter nuclei generated by proton irradiation of targets containing (12)C, (16)O, and (40)Ca nuclei in preparation of clinical application.

PubMed

Miyatake, Aya; Nishio, Teiji; Ogino, Takashi

2011-10-01

The purpose of this study is to develop a new calculation algorithm that is satisfactory in terms of the requirements for both accuracy and calculation time for a simulation of imaging of the proton-irradiated volume in a patient body in clinical proton therapy. The activity pencil beam algorithm (APB algorithm), which is a new technique to apply the pencil beam algorithm generally used for proton dose calculations in proton therapy to the calculation of activity distributions, was developed as a calculation algorithm of the activity distributions formed by positron emitter nuclei generated from target nuclear fragment reactions. In the APB algorithm, activity distributions are calculated using an activity pencil beam kernel. In addition, the activity pencil beam kernel is constructed using measured activity distributions in the depth direction and calculations in the lateral direction. (12)C, (16)O, and (40)Ca nuclei were determined as the major target nuclei that constitute a human body that are of relevance for calculation of activity distributions. In this study, "virtual positron emitter nuclei" was defined as the integral yield of various positron emitter nuclei generated from each target nucleus by target nuclear fragment reactions with irradiated proton beam. Compounds, namely, polyethylene, water (including some gelatin) and calcium oxide, which contain plenty of the target nuclei, were irradiated using a proton beam. In addition, depth activity distributions of virtual positron emitter nuclei generated in each compound from target nuclear fragment reactions were measured using a beam ON-LINE PET system mounted a rotating gantry port (BOLPs-RGp). The measured activity distributions depend on depth or, in other words, energy. The irradiated proton beam energies were 138, 179, and 223 MeV, and measurement time was about 5 h until the measured activity reached the background level. Furthermore, the activity pencil beam data were made using the activity pencil beam kernel, which was composed of the measured depth data and the lateral data including multiple Coulomb scattering approximated by the Gaussian function, and were used for calculating activity distributions. The data of measured depth activity distributions for every target nucleus by proton beam energy were obtained using BOLPs-RGp. The form of the depth activity distribution was verified, and the data were made in consideration of the time-dependent change of the form. Time dependence of an activity distribution form could be represented by two half-lives. Gaussian form of the lateral distribution of the activity pencil beam kernel was decided by the effect of multiple Coulomb scattering. Thus, the data of activity pencil beam involving time dependence could be obtained in this study. The simulation of imaging of the proton-irradiated volume in a patient body using target nuclear fragment reactions was feasible with the developed APB algorithm taking time dependence into account. With the use of the APB algorithm, it was suggested that a system of simulation of activity distributions that has levels of both accuracy and calculation time appropriate for clinical use can be constructed.

Removal of cadmium from fish sauce using chelate resin.

PubMed

Sasaki, Tetsuya; Araki, Ryohei; Michihata, Toshihide; Kozawa, Miyuki; Tokuda, Koji; Koyanagi, Takashi; Enomoto, Toshiki

2015-04-15

Fish sauce that is prepared from squid organs contains cadmium (Cd), which may be present at hazardous concentrations. Cd molecules are predominantly protein bound in freshly manufactured fish sauce, but are present in a liberated form in air-exposed fish sauce. In the present study, we developed a new method for removing both Cd forms from fish sauce using chelate resin and a previously reported tannin treatment. Sixteen-fold decreases in Cd concentrations were observed (0.78-0.05 mg/100 mL) following the removal of liberated Cd using chelate resin treatment, and the removal of protein-bound Cd using tannin treatment. Major nutritional components of fish sauce were maintained, including free amino acids and peptides, and angiotensin I-converting enzyme inhibitory and antioxidant activities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oxygen electrodes for rechargeable alkaline fuel cells

NASA Technical Reports Server (NTRS)

Swette, Larry; Giner, Jose

1987-01-01

Electrocatalysts and supports for the positive electrode of moderate temperature single unit rechargeable alkaline fuel cells were investigated and developed. The electrocatalysts are defined as the material with a higher activity for the oxygen electrode reaction than the support. Advanced development will require that the materials be prepared in high surface area forms, and may also entail integration of various candidate materials. Eight candidate support materials and seven electrocatalysts were investigated. Of the 8 support, 3 materials meet the preliminary requirements in terms of electrical conductivity and stability. Emphasis is now on preparing in high surface area form and testing under more severe corrosion stress conditions. Of the 7 electrocatalysts prepared and evaluated, at least 5 materials remain as potential candidates. The major emphasis remains on preparation, physical characterization and electrochemical performance testing.

Porphyry-copper ore shells form at stable pressure-temperature fronts within dynamic fluid plumes.

PubMed

Weis, P; Driesner, T; Heinrich, C A

2012-12-21

Porphyry-type ore deposits are major resources of copper and gold, precipitated from fluids expelled by crustal magma chambers. The metals are typically concentrated in confined ore shells within vertically extensive vein networks, formed through hydraulic fracturing of rock by ascending fluids. Numerical modeling shows that dynamic permeability responses to magmatic fluid expulsion can stabilize a front of metal precipitation at the boundary between lithostatically pressured up-flow of hot magmatic fluids and hydrostatically pressured convection of cooler meteoric fluids. The balance between focused heat advection and lateral cooling controls the most important economic characteristics, including size, shape, and ore grade. This self-sustaining process may extend to epithermal gold deposits, venting at active volcanoes, and regions with the potential for geothermal energy production.

Porphyry-Copper Ore Shells Form at Stable Pressure-Temperature Fronts Within Dynamic Fluid Plumes

NASA Astrophysics Data System (ADS)

Weis, P.; Driesner, T.; Heinrich, C. A.

2012-12-01

Porphyry-type ore deposits are major resources of copper and gold, precipitated from fluids expelled by crustal magma chambers. The metals are typically concentrated in confined ore shells within vertically extensive vein networks, formed through hydraulic fracturing of rock by ascending fluids. Numerical modeling shows that dynamic permeability responses to magmatic fluid expulsion can stabilize a front of metal precipitation at the boundary between lithostatically pressured up-flow of hot magmatic fluids and hydrostatically pressured convection of cooler meteoric fluids. The balance between focused heat advection and lateral cooling controls the most important economic characteristics, including size, shape, and ore grade. This self-sustaining process may extend to epithermal gold deposits, venting at active volcanoes, and regions with the potential for geothermal energy production.

The predictive validity of naturally acquired delayed-type hypersensitivity to leishmanin in resistance to Leishmania major-associated cutaneous leishmaniasis.

PubMed

Ben Salah, Afif; Louzir, Hechmi; Chlif, Sadok; Mokni, Mourad; Zaatour, Amor; Raouene, Mohamed; Ismail, Riadh Ben; Dellagi, Koussay

2005-12-01

To accurately quantify the different outcomes of Leishmania major infection and to evaluate the fraction of zoonotic cutaneous leishmaniasis (ZCL) cases prevented by naturally acquired leishmanin skin test (LST) reactivity, a cohort of 470 children was followed up in 2 endemic foci, Remada and Dhiba, in southern Tunisia. During May 1997, before the ZCL emergence season, LST was performed, and results were reassessed 12 months later. Active case detection during the ZCL emergence season showed a high incidence of ZCL: 57.0% in Remada and 13.7% in Dhiba. The preventive fraction of ZCL conferred by LST reactivity increased proportionally with the reaction size before the emergence season, revealing a dose-response effect of approximately 70%. In addition, asymptomatic L. major infection appeared to be a significant form of natural immunization, particularly in the context of relatively low transmission. These findings may help in the design and evaluation of vaccines.

From Allergen Back to Antigen:. a Rational Approach to New Forms of Immunotherapy

NASA Astrophysics Data System (ADS)

Colombo, Paolo; Trapani, Antonino; Geraci, Domenico; Golino, Massimiliano; Gianguzza, Fabrizio; Bonura, Angela

2007-12-01

Mapping an epitope on a protein by gene fragmentation and/or point mutations is often expensive and time consuming. Analysis of a 3D model can be utilized to detect the amino acids residues which are exposed to the solvent surface and thus represent potential epitope residues. Parj1 and Parj2 are the two major allergens of the Parietaria judaica pollen belonging to the Lipid Transfer Protein family. Using their three-dimensional structures as a guide, a head to tail dimer expressing disulphide bond variants of the major allergens was generated by means of DNA recombinant technology. The hybrid was expressed in E.coli and its immunological activity studied in vivo and in vitro. Our results demonstrate that a hybrid polypeptide expressing disulphide bond variants of the major allergens of the Parietaria pollen displayed reduced allergenicity and enhanced T cell reactivity for induction of protective antibodies able to block human IgE induced during the natural course of sensitization against the Parietaria pollen.

Reaction of 3-Amino-1,2,4-Triazole with Diethyl Phosphite and Triethyl Orthoformate: Acid-Base Properties and Antiosteoporotic Activities of the Products.

PubMed

Miszczyk, Patrycja; Wieczorek, Dorota; Gałęzowska, Joanna; Dziuk, Błażej; Wietrzyk, Joanna; Chmielewska, Ewa

2017-02-08

The reaction of diethyl phosphite with triethyl orthoformate and a primary amine followed by hydrolysis is presented, and the reaction was suitable for the preparation of (aminomethylene)bisphosphonates. 3-Amino-1,2,4-triazole was chosen as an interesting substrate for this reaction because it possesses multiple groups that can serve as the amino component in the reaction-namely, the side-chain and triazole amines. This substrate readily forms 1,2,4-triazolyl-3-yl-aminomethylenebisphosphonic acid (compound 1 ) as a major product, along with N -ethylated bisphosphonates as side products. The in vitro antiproliferative effects of the synthesized aminomethylenebisphosphonic acids against J774E macrophages were determined. These compounds exhibit similar activity to zoledronic acid and higher activity than incadronic acid.

A study of microseismicity in northern Baja California, Mexico

NASA Technical Reports Server (NTRS)

Johnson, T. L.; Koczynski, T.; Madrid, J.

1976-01-01

Five microearthquake instruments were operated for 2 months in 1974 in a small mobile array deployed at various sites near the Agua Blanca and San Miguel faults. An 80-km-long section of the San Miguel fault zone is presently active seismically, producing the vast majority of recorded earthquakes. Very low activity was recorded on the Agua Blanca fault. Events were also located near normal faults forming the eastern edge of the Sierra Juarez suggesting that these faults are active. Hypocenters on the San Miguel fault range in depth from 0 to 20 km although two-thirds are in the upper 10 km. A composite focal mechanism showing a mixture of right-lateral and dip slip, east side up, is similar to a solution obtained for the 1956 San Miguel earthquake which proved consistent with observed surface deformation.

An Investigation and Prediction of Springback of Sheet Metals under Cold Forming Condition

NASA Astrophysics Data System (ADS)

Elsayed, A.; Mohamed, M.; Shazly, M.; Hegazy, A.

2017-12-01

Low formability and springback especially at room temperature are known to be major obstacles to advancements in sheet metal forming industries. The integration of numerical simulation within the R&D activities of the automotive industries provides a significant development in overcoming these drawbacks. The aim of the present work is to model and predict the springback of a Galvanized low carbon steel automotive panel part. This part suffers from both positive and negative springback which physically measured using CMM. The objective is to determine the suitable forming process parameters that minimize and compensate the springback through robust FE model. The analysis of the springback was carried out following (Isotropic model and Yoshida - Uemori model) which are calibrated through cyclic stress strain curve. The material data of the Galvanized low carbon steel was implemented via lookup tables in the commercial finite element software Pam-Stamp(TM). Firstly, the FE model was validated using the deformed part which suffers from springback problem at the same forming condition. The FE results were compared with the measured experimental trails providing very good agreement. Secondly, the validated FE model was used to determine the suitable forming parameters which could minimise the springback of the deformed part.

Stratigraphic framework of Holocene volcaniclastic deposits, Akutan Volcano, east-central Aleutian Islands, Alaska

USGS Publications Warehouse

Waythomas, C.F.

1999-01-01

Akutan Volcano is one of the most active volcanoes in the Aleutian arc, but until recently little was known about its history and eruptive character. Following a brief but sustained period of intense seismic activity in March 1996, the Alaska Volcano Observatory began investigating the geology of the volcano and evaluating potential volcanic hazards that could affect residents of Akutan Island. During these studies new information was obtained about the Holocene eruptive history of the volcano on the basis of stratigraphic studies of volcaniclastic deposits and radiocarbon dating of associated buried soils and peat. A black, scoria-bearing, lapilli tephra, informally named the 'Akutan tephra,' is up to 2 m thick and is found over most of the island, primarily east of the volcano summit. Six radiocarbon ages on the humic fraction of soil A-horizons beneath the tephra indicate that the Akutan tephra was erupted approximately 1611 years B.P. At several locations the Akutan tephra is within a conformable stratigraphic sequence of pyroclastic-flow and lahar deposits that are all part of the same eruptive sequence. The thickness, widespread distribution, and conformable stratigraphic association with overlying pyroclastic-flow and lahar deposits indicate that the Akutan tephra likely records a major eruption of Akutan Volcano that may have formed the present summit caldera. Noncohesive lahar and pyroclastic-flow deposits that predate the Akutan tephra occur in the major valleys that head on the volcano and are evidence for six to eight earlier Holocene eruptions. These eruptions were strombolian to subplinian events that generated limited amounts of tephra and small pyroclastic flows that extended only a few kilometers from the vent. The pyroclastic flows melted snow and ice on the volcano flanks and formed lahars that traveled several kilometers down broad, formerly glaciated valleys, reaching the coast as thin, watery, hyperconcentrated flows or water floods. Slightly cohesive lahars in Hot Springs valley and Long valley could have formed from minor flank collapses of hydrothermally altered volcanic bedrock. These lahars may be unrelated to eruptive activity.

SAXS characterization of the interactions among digested food compounds and the anti-oxidant and anti-inflammatory activities of the formed nanocomplexes.

PubMed

Yang, Yingkang; Wang, Xiaoqi; Chen, Guijie; Zhou, Wenhua; Zeng, Xiaoxiong; Hu, Bing; Li, Yunqi; Huang, Qingrong

2018-06-06

In the present study, small angle X-ray scattering (SAXS) is applied to investigate the interaction between caseinophosphopeptides (CPP), the major digested product of milk protein, and chitosan (CS) under simulated gastrointestinal (GI) pH conditions. The change in pH value from the gastric to small intestinal environment induces complexation between CPP and CS, which is mainly driven by electrostatic interactions. The fractal dimension (Df) value of the domains inside the CPP-CS complexes is greater than 3, indicating the formation of dense particles/aggregates at the nanoscale. The Df value generally increases with an increase in the CS/CPP mass ratio. As a representative of polyphenols, (-)-epigallocatechin gallate (EGCG) associates with CS and CPP, forming nanocomplexes with a spherical shape and average particle size of around 208 nm. The formed CS-EGCG-CPP nanocomplexes do not affect the antioxidant activity of EGCG in the in vitro assays. Moreover, in the cellular assay, the nanocomplexes protect the RAW264.7 cells against H2O2-induced oxidative injury. In addition, the nanocomplexes significantly inhibit the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), TNF-α, IL-1β and IL-6. Furthermore, they inhibit the expression of iNOS, phosphorylation and degradation of IκB, as well as the translocation of NF-κB p65; this indicates that the mechanism for their anti-inflammatory activity is via the mediation of the NF-κB signaling pathway.

Cellulose production, activated by cyclic di-GMP through BcsA and BcsZ, is a virulence factor and an essential determinant of the three-dimensional architectures of biofilms formed by Erwinia amylovora Ea1189.

PubMed

Castiblanco, Luisa F; Sundin, George W

2018-01-01

Bacterial biofilms are multicellular aggregates encased in an extracellular matrix mainly composed of exopolysaccharides (EPSs), protein and nucleic acids, which determines the architecture of the biofilm. Erwinia amylovora Ea1189 forms a biofilm inside the xylem of its host, which results in vessel plugging and water transport impairment. The production of the EPSs amylovoran and levan is critical for the formation of a mature biofilm. In addition, cyclic dimeric GMP (c-di-GMP) has been reported to positively regulate amylovoran biosynthesis and biofilm formation in E. amylovora Ea1189. In this study, we demonstrate that cellulose is synthesized by E. amylovora Ea1189 and is a major modulator of the three-dimensional characteristics of biofilms formed by this bacterium, and also contributes to virulence during systemic host invasion. In addition, we demonstrate that the activation of cellulose biosynthesis in E. amylovora is a c-di-GMP-dependent process, through allosteric binding to the cellulose catalytic subunit BcsA. We also report that the endoglucanase BcsZ is a key player in c-di-GMP activation of cellulose biosynthesis. Our results provide evidence of the complex composition of the extracellular matrix produced by E. amylovora and the implications of cellulose biosynthesis in shaping the architecture of the biofilm and in the expression of one of the main virulence phenotypes of this pathogen. © 2016 BSPP AND JOHN WILEY & SONS LTD.

EARLY ONSET OF CRANIOSYNOSTOSIS IN AN APERT MOUSE MODEL REVEALS CRITICAL FEATURES OF THIS PATHOLOGY

PubMed Central

Holmes, Greg; Rothschild, Gerson; Roy, Upal Basu; Deng, Chu-Xia; Mansukhani, Alka; Basilico, Claudio

2009-01-01

Activating mutations of FGFRs1–3 cause craniosynostosis (CS), the premature fusion of cranial bones, in man and mouse. The mechanisms by which such mutations lead to CS have been variously ascribed to increased osteoblast proliferation, differentiation, and apoptosis, but it is not always clear how these disturbances relate to the process of suture fusion. We have reassessed coronal suture fusion in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild increase in osteoprogenitor proliferation precedes but does not accompany this event, and apoptosis is insignificant. On the other hand, the more apical coronal suture initially forms appropriately but then undergoes fusion, albeit at a slower rate, accompanied by a significant decrease in osteoprogenitor proliferation, and increased osteoblast maturation. Apoptosis now accompanies fusion, but is restricted to bone fronts in contact with one another. We correlated these in vivo observations with the intrinsic effects of the activated Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased capacity for both proliferation and differentiation. Our studies suggest that the major determinant of Fgfr2-induced craniosynostosis is the failure to respond to signals that would halt the recruitment or the advancement of osteoprogenitor cells at the sites where sutures should normally form. PMID:19389359

Earth Observation taken by the Expedition 20 crew

NASA Image and Video Library

2009-07-15

ISS020-E-021140 (15 July 2009) --- Teide Volcano on the Canary Islands of Spain is featured in this image photographed by an Expedition 20 crew member on the International Space Station. This detailed photograph features two stratovolcanoes ? Pico de Teide and Pico Viejo ? located on Tenerife Island, part of the Canary Islands of Spain. Stratovolcanoes are steep-sided; typically conical structures formed by interlayered lavas and fragmented rock material from explosive eruptions. Pico de Teide has a relatively sharp peak, whereas an explosion crater forms the summit of Pico Viejo. The two stratovolcanoes formed within an even larger volcanic structure known as the Las Ca?adas caldera ? a large collapse depression typically formed when a major eruption completely empties the underlying magma chamber of a volcano. The last eruption of Teide occurred in 1909. NASA scientists point out sinuous flow levees marking individual lava flows. The scientists consider the flow levees as perhaps the most striking volcanic features visible in the image. Flow levees are formed when the outer edges of a channelized lava flow cool and harden while the still-molten interior continues to flow downhill ? numerous examples radiate outwards from the peaks of both Pico de Teide and Pico Viejo. Brown to tan overlapping lava flows and domes are visible to the east-southeast of the Teide stratovolcano. Increased seismicity, carbon dioxide emissions, and fumarolic activity within the Las Ca?adas caldera and along the northwestern flanks of the volcano were observed in 2004. Monitoring of the volcano to detect renewal of activity is ongoing.

Anti-leishmanial and toxicity activities of some selected Iranian medicinal plants.

PubMed

Kheiri Manjili, Hamidreza; Jafari, Hamidreza; Ramazani, Ali; Davoudi, Noushin

2012-11-01

Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania. Cutaneous leishmaniasis is the most common form of leishmaniasis in Iran. As there is not any vaccine for leishmaniasis, treatment is important to prevent the spreading of parasites. There is, therefore, a need to develop newer drugs from different sources. The aim of this study was to assess anti-leishmanial activity of the ethanolic extracts of 17 different medicinal plants against Leishmania major promastigotes and macrophage cell line J774. The selection of the hereby studied 17 plants was based on the existing information on their local ethnobotanic history. Plants were dried, powdered, and macerated in a hydroalcoholic solution. Resulting extracts have been assessed for in vitro anti-leishmanial and brine shrimp toxicity activities. Four plants, Caesalpinia gilliesii, Satureia hortensis, Carum copticum heirm, and Thymus migricus, displayed high anti-leishmanial activity (IC50, 9.76 ± 1.27, 15.625 ± 3.76, 15.625 ± 5.46, and 31.25 ± 15.44 μM, respectively) and were toxic against the J774 macrophage cell line at higher concentrations than those needed to inhibit the parasite cell growth (IC50, 45.13 ± 3.17, 100.44 ± 17.48, 43.76 ± 0.78, and 39.67 ± 3.29 μM, respectively). Glucantime as positive control inhibited the growth of L. major promastigotes with IC50 = 254 μg/ml on promastigotes (1 × 10(6)/100 μ/well) of a log phase culture, without affecting the growth of J774 macrophages. These data revealed that C. gilliesii, S. hortensis, C. copticum heirm, and T. migricus extracts contain active compounds, which could serve as alternative agents in the control of cutaneous leishmaniasis. The activity of these herbs against L. major promastigotes and macrophage cell line J774 was reported for the first time in our study.

Identification of salivary components that induce transition of hyphae to yeast in Candida albicans.

PubMed

Leito, Jelani T D; Ligtenberg, Antoon J M; Nazmi, Kamran; Veerman, Enno C I

2009-10-01

Candida albicans, the major human fungal pathogen, undergoes a reversible morphological transition from single yeast cells to pseudohyphae and hyphae filaments. The hyphae form is considered the most invasive form of the fungus. The purpose of this study is to investigate the effect of saliva on hyphae growth of C. albicans. Candida albicans hyphae were inoculated in Roswell Park Memorial Institute medium with whole saliva, parotid saliva or buffer mimicking the saliva ion composition, and cultured for 18 h at 37 degrees C under aerobic conditions with 5% CO(2). Whole saliva and parotid saliva induced transition to yeast growth, whereas the culture with buffer remained in the hyphae form. Parotid saliva was fractionated on a reverse-phase C8 column and each fraction was tested for inducing transition to yeast growth. By immunoblotting, the salivary component in the active fraction was identified as statherin, a phosphoprotein of 43 amino acids that has been implicated in remineralization of the teeth. Synthetically made statherin induced transition of hyphae to yeast. By deletion of five amino acids at the negatively charged N-terminal site (DpSpSEE), yeast-inducing activity and binding to C. albicans were increased. In conclusion, statherin induces transition to yeast of C. albicans hyphae and may thus contribute to the oral defense against candidiasis.

CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction.

PubMed

Hesse, Julia; Leberling, Stella; Boden, Elisabeth; Friebe, Daniela; Schmidt, Timo; Ding, Zhaoping; Dieterich, Peter; Deussen, Andreas; Roderigo, Claudia; Rose, Christine R; Floss, Doreen M; Scheller, Jürgen; Schrader, Jürgen

2017-07-01

Epicardium-derived cells (EPDCs) play a fundamental role in embryonic cardiac development and are reactivated in the adult heart in response to myocardial infarction (MI). In this study, EPDCs from post-MI rat hearts highly expressed the ectoenzyme CD73 and secreted the profibrotic matricellular protein tenascin-C (TNC). CD73 on EPDCs extensively generated adenosine from both extracellular ATP and NAD. This in turn stimulated the release of additional nucleotides from a Brefeldin A-sensitive intracellular pool via adenosine-A 2B R signaling, forming a positive-feedback loop. A 2B R activation, in addition, strongly promoted the release of major regulatory cytokines, such as IL-6, IL-11, and VEGF. TNC was found to stimulate EPDC migration and, together with ATP-P2X 7 R signaling, to activate inflammasomes in EPDCs via TLR4. Our results demonstrate that EPDCs are an important source of various proinflammatory factors in the post-MI heart controlled by purinergic and TNC signaling.-Hesse, J., Leberling, S., Boden, E., Friebe, D., Schmidt, T., Ding, Z., Dieterich, P., Deussen, A., Roderigo, C., Rose, C. R., Floss, D. M., Scheller, J., Schrader, J. CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction. © FASEB.

[Public opinion on active euthanasia. The results of a pilot project].

PubMed

Helou, A; Wende, A; Hecke, T; Rohrmann, S; Buser, K; Dierks, M L

2000-03-17

Despite eager public interest there have been few significant studies about the views of the German population on active euthanasia. It was our purpose to investigate, before undertaking a representative enquiry about this controversial and ethically sensitive topic, to what extent public opinion and the underlying norms, values and preferences can be adequately obtained by standardized data collection. COHORT AND METHODS: An interdisciplinary project group established a standardized written form of enquiry for measuring public opinion about active euthanasia. The test was performed on an anonymized convenience [corrected] sample of 110 persons living in North Germany. The questionnaires consisted of ten hypothetical cases, 11 potentially relevant viewpoints on likely decisions and eight frequently expressed arguments used in the debate for and against euthanasia. The reply rate to the questionnaire was 89% (n = 98; 37 men and 59 women, average age 39.5 [21-81] years). Agreement with active euthanasia in the various case examples ranged, according to context, from 85 to 93%. Active euthanasia was accepted by a clear majority, if preconditions of a voluntary decision by a mentally sound person and incurable, terminal disease (cancer) are cumulatively fulfilled. Otherwise it was rejected by most respondents. To a clear majority, active euthanasia implied both the chance that suffering would be shortened, but also the danger of misuse. Among the persons questioned those with professional experience of euthanasia were clearly more sceptical about active euthanasia than those without such experience. The standardized written questionnaire made it possible to obtain a differentiated picture of public opinion on active euthanasia. However, these data represent only a moment in the dynamic process of a norm being established within a society and must on no account be used as legitimizing active euthanasia by plebiscite.

A rational design approach to nanostructured catalysts for the oxidation of carbon monoxide

NASA Astrophysics Data System (ADS)

Karwacki, Christopher

The extraordinary energetic properties of subnanometer (<10 nm) structures consisting of reduced metals, metal oxides, and graphitic carbons are emerging as the principal technologies involving catalytic reactions at ambient temperatures, for such applications as respiratory protection, pollution abatement, chemical synthesis, sensors, and energy conversion. Gold nanoparticles (Au NP) possess unique reactive properties not present in the bulk state and have served in the past decade as a model for the nanosciences, where molecular species are synthesized, scaled, and engineered into functional materials. Gold nanoparticles as isolated structures are not useful as real catalysts and must co-exist with supports that provide enhanced stability and activity. Support oxides such as TiO2, Fe2O 3, CeO2, SiO2, Al2O3, ZrO 2, and graphitic (active) carbons have been shown to increase the active nature of AuNP and have been the subject of several thousand publications in the past decade. Zirconia compared to titania as a support for Au NP catalysis has been studied with limited success. In fact, the majority of observations show that zirconia is one of the lowest performing metal oxide supports involving Au NP oxidation catalysis. The likely reason for these observations is a lack of understanding of the relationship between structure and surface functionality as it pertains to ambient temperature oxidation catalysis (ATOC). Furthermore, virtually all substrate and catalyst preparations in earlier work were performed at high temperatures, typically 400--900°C, thus forming progressively monomorphic structures containing larger crystals with reduced surface functionality and porosity. In this research, I established the hypothesis based on a structural model that surface functional hydroxides are important to sustained hydrolytic reactions, such as those involving Au NP for the oxidation of CO to CO 2. Theoretical calculations by Ignatchenko, Vittadini, et al. show that zirconia readily dissociates adsorbed water on the most active and stable crystal structures (111) compared to other metal oxides, such as the common anatase (101) form of titania. Also, the support must provide a source of activated oxygen as a means to oxidize intermediate carbonates with CO 2 formation. The role of the support is to provide lattice oxygen in an activated state (O2-) for oxidation of adsorbed CO the Au NP:support interface. Furthermore, the primary interest is the energy associated Au NP in proximity to the support surface. Advancing the understanding of this region is believed to be crucial to the future design of active nanostructured materials that function under ambient conditions. The proposed model involves a structure consisting of properly sized and highly dispersed Au NP supported on a hydroxylated form of nanocrystalline zirconia. This type of zirconia is in a highly polymorphic form consisting of aggregates of small crystals less than 10 nm. The structure is highly porous, containing undercoordinated zirconium atoms, and provides an environment for rapid dissociation of molecular water. In this research and in collaboration with Mogilevsky et al., 37 I introduce a novel method for quantifying the surface concentration of two major forms of hydroxide that form on zirconia. Furthermore, in this research I show how both the porosity of the zirconia support and the size of the crystalline aggregates affect the type and surface concentration of hydroxyl groups. This relationship is thus directly related to the oxidation activity of the catalyst consisting of Au NP supported on hydroxylated ZrO 2. These phenomena are exemplified by a reduction in structural porosity and surface hydroxyl groups with increasing temperature treatments of the zirconia support. Gold NP and ZrO2 supports were extended to studies that included interactions with activated carbons. This work was done on the premise that graphitic carbons, based on their tunable porosities and surface chemistries, can enhance or stabilize the catalytic activity of neighboring Au NP. Gold dispersed on active carbon and hybrid structures consisting of Au/ZrO 2/C shows interesting properties, which lend themselves to catalytic particle stabilization and to the advancement of multifunctional material design.

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

PubMed Central

2017-01-01

γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials. PMID:28640622

Dual mode of action of Bt proteins: protoxin efficacy against resistant insects

PubMed Central

Tabashnik, Bruce E.; Zhang, Min; Fabrick, Jeffrey A.; Wu, Yidong; Gao, Meijing; Huang, Fangneng; Wei, Jizhen; Zhang, Jie; Yelich, Alexander; Unnithan, Gopalan C.; Bravo, Alejandra; Soberón, Mario; Carrière, Yves; Li, Xianchun

2015-01-01

Transgenic crops that produce Bacillus thuringiensis (Bt) proteins for pest control are grown extensively, but insect adaptation can reduce their effectiveness. Established mode of action models assert that Bt proteins Cry1Ab and Cry1Ac are produced as inactive protoxins that require conversion to a smaller activated form to exert toxicity. However, contrary to this widely accepted paradigm, we report evidence from seven resistant strains of three major crop pests showing that Cry1Ab and Cry1Ac protoxins were generally more potent than the corresponding activated toxins. Moreover, resistance was higher to activated toxins than protoxins in eight of nine cases evaluated in this study. These data and previously reported results support a new model in which protoxins and activated toxins kill insects via different pathways. Recognizing that protoxins can be more potent than activated toxins against resistant insects may help to enhance and sustain the efficacy of transgenic Bt crops. PMID:26455902

Challenges and complexity of functionality evaluation of flavan-3-ol derivatives.

PubMed

Saito, Akiko

2017-06-01

Flavan-3-ol derivatives are common plant-derived bioactive compounds. In particular, (-)-epigallocatechin-3-O-gallate shows various moderate biological activities without severe toxicity, and its health-promoting effects have been widely studied because it is a main ingredient in green tea and is commercially available at low cost. Although various biologically active flavan-3-ol derivatives are present as minor constituents in plants as well as in green tea, their biological activities have yet to be revealed, mainly due to their relative unavailability. Here, I outline the major factors contributing to the complexity of functionality studies of flavan-3-ol derivatives, including proanthocyanidins and oligomeric flavan-3-ols. I emphasize the importance of conducting structure-activity relationship studies using synthesized flavan-3-ol derivatives that are difficult to obtain from plant extracts in pure form to overcome this challenge. Further discovery of these minor constituents showing strong biological activities is expected to produce useful information for the development of functional health foods.

[Marketing in the world of blood donation].

PubMed

Daigneault, Sylvie

2007-05-01

Public and non-profit organizations have long debated how marketing concepts and management styles apply to their sector of activity as they are largely derived from principles of consumerism and economic decision-making proper to the private sector. The arrival of marketing in the world of blood donation is no exception. The purpose of this article is to illustrate concretely how marketing techniques can contribute in achieving the objectives of a blood donation program: a marketing model that is adapted to the realities of blood donation in Quebec. Although types of marketing are as varied as the fields they are used in, the major marketing activities of this program fall under positioning, operational or relationship marketing. The process is presented in the form of a cycle that includes four major phases containing all marketing functions, that is, raising public awareness, acquiring a clientele, client retention and loyalty building, and establishing the relationship. Finally, the information and effective management of information are at the heart of the marketing process. In fact, research, understanding our customers and their expectations, and measuring our performance are essential for the success of any marketing initiative.

Antimicrobial action and anti-corrosion effect against sulfate reducing bacteria by lemongrass (Cymbopogon citratus) essential oil and its major component, the citral

PubMed Central

2013-01-01

The anti-corrosion effect and the antimicrobial activity of lemongrass essential oil (LEO) against the planktonic and sessile growth of a sulfate reducing bacterium (SRB) were evaluated. Minimum inhibitory concentration (MIC) of LEO and its major component, the citral, was 0.17 mg ml-1. In addition, both LEO and citral showed an immediate killing effect against SRB in liquid medium, suggesting that citral is responsible for the antimicrobial activity of LEO against SRB. Transmission electron microscopy revealed that the MIC of LEO caused discernible cell membrane alterations and formed electron-dense inclusions. Neither biofilm formation nor corrosion was observed on carbon steel coupons after LEO treatment. LEO was effective for the control of the planktonic and sessile SRB growth and for the protection of carbon steel coupons against biocorrosion. The application of LEO as a potential biocide for SRB growth control in petroleum reservoirs and, consequently, for souring prevention, and/or as a coating protection against biocorrosion is of great interest for the petroleum industries. PMID:23938023

Memory T cells: A helpful guard for allogeneic hematopoietic stem cell transplantation without causing graft-versus-host disease.

PubMed

Huang, Wei; Chao, Nelson J

2017-12-01

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (AHSCT) and the major cause of nonrelapse morbidity and mortality of AHSCT. In AHSCT, donor T cells facilitate hematopoietic stem cell (HSC) engraftment, contribute to anti-infection immunity, and mediate graft-versus-leukemia (GVL) responses. However, activated alloreactive T cells also attack recipient cells in vital organs, leading to GVHD. Different T-cell subsets, including naïve T (T N ) cells, memory T (T M ) cells, and regulatory T (T reg ) cells mediate different forms of GVHD and GVL; T N cells mediate severe GVHD, whereas T M cells do not cause GVHD, but preserve T-cell function including GVL. In addition, metabolic reprogramming controls T-cell differentiation and activation in these disease states. This minireview focuses on the role and the related mechanisms of T M cells in AHSCT, and the potential manipulation of T cells in AHSCT. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Titanium surfaces immobilized with the major antimicrobial fragment FK-16 of human cathelicidin LL-37 are potent against multiple antibiotic-resistant bacteria.

PubMed

Mishra, Biswajit; Wang, Guangshun

2017-08-01

Infections on implanted medical devices are a challenging problem, especially when bacteria form difficult-to-treat biofilms. Antimicrobial peptides are considered to be a solution due to their potency against antibiotic-resistant superbugs. Previously, the authors' laboratory demonstrated the prevention of staphylococcal biofilm formation in an animal catheter model by injecting merecidin (formerly known as 17BIPHE2), a peptide engineered based on the only human cathelicidin. This study documents an alternative solution via covalent immobilization of FK-16, amino acid sequence FKRIVQRIKDFLRNLV-amide, which corresponds to the major antimicrobial region (residues 17-32) of LL-37. FK-16 is superior to the longer peptide LL-37 in terms of synthesis cost and the shorter peptide KR-12 in terms of activity spectrum. Indeed, the FK16-coated titanium surface showed a broad-spectrum activity against the ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. It also demonstrated anti-adhesion and biofilm inhibition capabilities against both S. aureus and E. coli.

Antimicrobial action and anti-corrosion effect against sulfate reducing bacteria by lemongrass (Cymbopogon citratus) essential oil and its major component, the citral.

PubMed

Korenblum, Elisa; Regina de Vasconcelos Goulart, Fátima; de Almeida Rodrigues, Igor; Abreu, Fernanda; Lins, Ulysses; Alves, Péricles Barreto; Blank, Arie Fitzgerald; Valoni, Erika; Sebastián, Gina V; Alviano, Daniela Sales; Alviano, Celuta Sales; Seldin, Lucy

2013-08-10

The anti-corrosion effect and the antimicrobial activity of lemongrass essential oil (LEO) against the planktonic and sessile growth of a sulfate reducing bacterium (SRB) were evaluated. Minimum inhibitory concentration (MIC) of LEO and its major component, the citral, was 0.17 mg ml-1. In addition, both LEO and citral showed an immediate killing effect against SRB in liquid medium, suggesting that citral is responsible for the antimicrobial activity of LEO against SRB. Transmission electron microscopy revealed that the MIC of LEO caused discernible cell membrane alterations and formed electron-dense inclusions. Neither biofilm formation nor corrosion was observed on carbon steel coupons after LEO treatment. LEO was effective for the control of the planktonic and sessile SRB growth and for the protection of carbon steel coupons against biocorrosion. The application of LEO as a potential biocide for SRB growth control in petroleum reservoirs and, consequently, for souring prevention, and/or as a coating protection against biocorrosion is of great interest for the petroleum industries.

Histolocalization and physico-chemical characterization of dihydrochalcones: Insight into the role of apple major flavonoids.

PubMed

Gaucher, Matthieu; Dugé de Bernonville, Thomas; Lohou, David; Guyot, Sylvain; Guillemette, Thomas; Brisset, Marie-Noëlle; Dat, James F

2013-06-01

Flavonoids, like other metabolites synthesized via the phenylpropanoid pathway, possess a wide range of biological activities including functions in plant development and its interaction with the environment. Dihydrochalcones (mainly phloridzin, sieboldin, trilobatin, phloretin) represent the major flavonoid subgroup in apple green tissues. Although this class of phenolic compounds is found in very large amounts in some tissues (≈200mg/g of leaf DW), their physiological significance remains unclear. In the present study, we highlight their tissue-specific localization in young growing shoots suggesting a specific role in important physiological processes, most notably in response to biotic stress. Indeed, dihydrochalcones could constitute a basal defense, in particular phloretin which exhibits a strong broad-range bactericidal and fungicidal activity. Our results also indicate that sieboldin forms complexes with iron with strong affinity, reinforcing its antioxidant properties and conferring to this dihydrochalcone a potential for iron seclusion and/or storage. The importance of localization and biochemical properties of dihydrochalcones are discussed in view of the apple tree defense strategy against both biotic and abiotic stresses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multidisciplinary study (CO2 flux, ERT, self-potential, permeability and structural surveys) in Fondi di Baia, Astroni and Agnano volcanoes: insights for the structural architecture of the Campi Flegrei caldera (southern Italy)

NASA Astrophysics Data System (ADS)

Isaia, Roberto; Carapezza, Maria Luisa; Conti, Eric; Giulia Di Giuseppe, Maria; Lucchetti, Carlo; Prinzi, Ernesto; Ranaldi, Massimo; Tarchini, Luca; Tramparulo, Francesco; Troiano, Antonio; Vitale, Stefano; Cascella, Enrico; Castello, Nicola; Cicatiello, Alessandro; Maiolino, Marco; Puzio, Domenico; Tazza, Lucia; Villani, Roberto

2017-04-01

Recent volcanism at Campi Flegrei caldera produced more than 70 eruptions in the last 15 ka formed different volcanic edifices. The vent distribution was related to the main volcano-tectonic structure active in the caldera along which also concentrated part of the present hydrothermal and fumarolic activity, such as in the Solfatara area. In order to define the role of major faults in the Campi Flegrei Caldera, we analyzed some volcanic craters (Fondi di Baia and Astroni) and the Agnano caldera, by means of different geochemical and geophysical technics including CO2 flux, electrical resistivity (ERT), self-potential and permeability surveys. We provided some ERT profiles and different maps of geochemical and geophysical features. Major fault planes were identified comparing ERT imaging with alignments of anomalies in maps. The results can improve the knowledge on the present state of these volcanoes actually not fully monitored though included in the area with high probability of future vent opening within the Campi Flegrei caldera.

Nanosized Drug Delivery Systems in Gastrointestinal Targeting: Interactions with Microbiota

PubMed Central

Karavolos, Michail; Holban, Alina

2016-01-01

The new age of nanotechnology has signaled a stream of entrepreneurial possibilities in various areas, form industry to medicine. Drug delivery has benefited the most by introducing nanostructured systems in the transport and controlled release of therapeutic molecules at targeted sites associated with a particular disease. As many nanosized particles reach the gastrointestinal tract by various means, their interactions with the molecular components of this highly active niche are intensively investigated. The well-characterized antimicrobial activities of numerous nanoparticles are currently being considered as a reliable and efficient alternative to the eminent world crisis in antimicrobial drug discovery. The interactions of nanosystems present in the gastrointestinal route with host microbiota is unavoidable; hence, a major research initiative is needed to explore the mechanisms and effects of these nanomaterials on microbiota and the impact that microbiota may have in the outcome of therapies entailing drug delivery nanosystems through the gastrointestinal route. These coordinated studies will provide novel techniques to replace or act synergistically with current technologies and help develop new treatments for major diseases via the discovery of unique antimicrobial molecules. PMID:27690060

Paleoseismological History of the Acambay Graben (Central Mexico)

NASA Astrophysics Data System (ADS)

Lacan, P.; Zúñiga, R.; Ortuño, M.; Persaud, M.; Aguirre-Diaz, G. J.; Langridge, R. M.; Villamor, P.; Perea, H.; Štěpančíková, P.; Carreon, D.; Cerca, M.; Suñe Puchol, I.; Corominas Calvet, O.; Audin, L.; Baize, S.; Lawton, T. F.; Rendón, A.

2013-12-01

The Acambay graben is part of the Trans-Mexican Volcanic Belt (TMVB) which strikes ESE-WNW across central Mexico, where the major part of the Mexican population is concentrated. The TMVB is an active, calc-alkaline volcanic arc that is related to the subduction of the Rivera and Cocos plates underneath the North American plate. The TMVB contains a series of intra-arc basins that form the Chapala-Tula fault zone (450 km long, 50 km wide). One of these extensive basins, the Acambay graben, is 80 km long and 15 to 30 km wide. It is limited north by the E-W striking Epitacio-Huerta (EHF) and Acambay-Tixmadejé normal faults and south by the Venta de Bravo (VBF) and the Pastores faults (PF) in the south. Other minor active faults are located within the basin, along the axis of the Graben. In the area, the instrumental seismicity is low to moderate, although one major historical earthquake (Ms = 6.9 Acambay event) occurred on November 19, 1912, causing widespread damage. In the last decade, our group has focused on the neotectonic and paleoseismological study of the major faults of the Acambay graben. More than 30 trenches have been dug at 15 sites in order to interpret the paleoseismological history of 7 major faults of the graben. In addition to paleoseismological trench studies, tectonic geomorphology, subsurface geophysics and micro topographic surveys have been used to assess the rupture history. All of the studied faults have to be considered as active faults, with a minimum of 2 to 5 paleoseismic events on each fault during the last 20 ka. Each fault rupture corresponds to a vertical displacement ranging from 1 to 150 centimetres. Considering the size of the observed displacements and the length of active segments, we demonstrate that large earthquakes with magnitude higher than 7 have occurred along some of these faults. Based on paleoseismological results, we calculate a major earthquake recurrence interval ranging from 2,000 to 5,000 years over a time span (~20 ka). These recurrence values overpass the Mexican historical seismicity catalogue that incorporates no more than the last 500 years. This suggests that most of the faults of the TMVB may be active despite the lack of known historical destructive events and could be able to produce earthquakes with serious consequences in the most populated area of Mexico.

Exposure to As(III) and As(V) changes the Ca²⁺-activation properties of the two major fibre types from the chelae of the freshwater crustacean Cherax destructor.

PubMed

Williams, Gemma; Snow, Elizabeth T; West, Jan M

2014-10-01

Arsenic is a known carcinogen found in the soil in gold mining regions at concentrations thousands of times greater than gold. Mining releases arsenic into the environment and surrounding water bodies. The main chemical forms of arsenic found in the environment are inorganic arsenite (As(III)) and arsenate (As(V)). Yabbies (Cherax destructor) accumulate arsenic at levels comparable to those in the sediment of their environment but the effect on their physiological function is not known. The effects of arsenic exposure (10 ppm sodium arsenite, AsNaO2 - 5.7 ppm As(III)) and 10 ppm arsenic acid, Na2HAsO4·7H2O - 2.6 ppm As(V)) for 40 days on the contractile function of the two major fibre types from the chelae were determined. After exposure, individual fibres were isolated from the chela, "skinned" (membrane removed) and attached to the force recording apparatus. Contraction was induced in solutions containing increasing [Ca(2+)] until a maximum Ca(2+)-activation was obtained. Submaximal force responses were plotted as a percentage of the maximum Ca(2+)-activated force. As(V) exposure resulted in lower levels of calcium required for activation than As(III) indicating an increased sensitivity to Ca(2+) after long term exposure to arsenate compared to arsenite. Myosin heavy chain and tropomyosin content in individual fibres was also decreased as a result of arsenic exposure. Single fibres exposed to As(V) produced significantly more force than muscle fibres from control animals. Long-term exposure of yabbies to arsenic alters the contractile function of the two major fibre types in the chelae. Copyright © 2014 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keepin, G.R.

Over the years the Los Alamos safeguards program has developed, tested, and implemented a broad range of passive and active nondestructive analysis (NDA) instruments (based on gamma and x-ray detection and neutron counting) that are now widely employed in safeguarding nuclear materials of all forms. Here very briefly, the major categories of gamma ray and neutron based NDA techniques, give some representative examples of NDA instruments currently in use, and cite a few notable instances of state-of-the-art NDA technique development. Historical aspects and a broad overview of the safeguards program are also presented.

Mission oriented R and D and the advancement of technology: The impact of NASA contributions, volume 2

NASA Technical Reports Server (NTRS)

Robbins, M. D.; Kelley, J. A.; Elliott, L.

1972-01-01

NASA contributions to the advancement of major developments in twelve selected fields of technology are presented. The twelve fields of technology discussed are: (1) cryogenics, (2) electrochemical energy conversion and storage, (3) high-temperature ceramics, (4) high-temperature metals (5) integrated circuits, (6) internal gas dynamics (7) materials machining and forming, (8) materials joining, (9) microwave systems, (10) nondestructive testing, (11) simulation, and (12) telemetry. These field were selected on the basis of both NASA and nonaerospace interest and activity.

Pericytes in kidney fibrosis.

PubMed

Ren, Shuyu; Duffield, Jeremy S

2013-07-01

Pericytes and perivascular fibroblasts have emerged as poorly appreciated yet extensive populations of mesenchymal cells in the kidney that play important roles in homeostasis and responses to injury. This review will update readers on the evolving understanding of the biology of these cells. Fate mapping has identified pericytes and perivascular fibroblasts as the major source of pathological fibrillar matrix-forming cells in interstitial kidney disease. In other organs similar cells have been described and independent fate mapping indicates that pericytes or perivascular cells are myofibroblast progenitors in multiple organs. Over the last year, new insights into the function of pericytes in kidney homeostasis has been uncovered and new molecular pathways that regulate detachment and their transdifferentiation into pathological myofibroblasts, including Wingless/Int, ephrin, transforming growth factor β, platelet derived growth factor, and Hedgehog signaling pathways, have been reported. In addition provocative studies indicate that microRNAs, which regulate posttranscriptional gene expression, may also play important roles in their transdifferentiation. Pericytes and perivascular fibroblasts are the major source of pathological collagen fiber-forming cells in interstitial kidney diseases. New avenues of research into their activation and differentiation has identified new drug candidates for the treatment of interstitial kidney disease.

Tandem phosphorylation of Ser-911 and Thr-912 at the C terminus of yeast plasma membrane H+-ATPase leads to glucose-dependent activation.

PubMed

Lecchi, Silvia; Nelson, Clark J; Allen, Kenneth E; Swaney, Danielle L; Thompson, Katie L; Coon, Joshua J; Sussman, Michael R; Slayman, Carolyn W

2007-12-07

In recent years there has been growing interest in the post-translational regulation of P-type ATPases by protein kinase-mediated phosphorylation. Pma1 H(+)-ATPase, which is responsible for H(+)-dependent nutrient uptake in yeast (Saccharomyces cerevisiae), is one such example, displaying a rapid 5-10-fold increase in activity when carbon-starved cells are exposed to glucose. Activation has been linked to Ser/Thr phosphorylation in the C-terminal tail of the ATPase, but the specific phosphorylation sites have not previously been mapped. The present study has used nanoflow high pressure liquid chromatography coupled with electrospray electron transfer dissociation tandem mass spectrometry to identify Ser-911 and Thr-912 as two major phosphorylation sites that are clearly related to glucose activation. In carbon-starved cells with low Pma1 activity, peptide 896-918, which was derived from the C terminus upon Lys-C proteolysis, was found to be singly phosphorylated at Thr-912, whereas in glucose-metabolizing cells with high ATPase activity, the same peptide was doubly phosphorylated at Ser-911 and Thr-912. Reciprocal (14)N/(15)N metabolic labeling of cells was used to measure the relative phosphorylation levels at the two sites. The addition of glucose to carbon-starved cells led to a 3-fold reduction in the singly phosphorylated form and an 11-fold increase in the doubly phosphorylated form. These results point to a mechanism in which the stepwise phosphorylation of two tandemly positioned residues near the C terminus mediates glucose-dependent activation of the H(+)-ATPase.

Proteasome activity or expression is not altered by activation of the heat shock transcription factor Hsf1 in cultured fibroblasts or myoblasts

PubMed Central

Taylor, David M.; Kabashi, Edor; Agar, Jeffrey N.; Minotti, Sandra; Durham, Heather D.

2005-01-01

Heat shock proteins (Hsps) with chaperoning function work together with the ubiquitin-proteasome pathway to prevent the accumulation of misfolded, potentially toxic proteins, as well as to control catabolism of the bulk of cytoplasmic, cellular protein. There is evidence for the involvement of both systems in neurodegenerative disease, and a therapeutic target is the heat shock transcription factor, Hsf1, which mediates upregulation of Hsps in response to cellular stress. The mechanisms regulating expression of proteasomal proteins in mammalian cells are less well defined. To assess any direct effect of Hsf1 on expression of proteasomal subunits and activity in mammalian cells, a plasmid encoding a constitutively active form of Hsf1 (Hsf1act) was expressed in mouse embryonic fibroblasts lacking Hsf1 and in cultured human myoblasts. Plasmid encoding an inactivatible form of Hsf1 (Hsf1inact) served as control. In cultures transfected with plasmid hsf1act, robust expression of the major stress-inducible Hsp, Hsp70, occurred but not in cultures transfected with hsf1inact. No significant changes in the level of expression of representative proteasomal proteins (structural [20Sα], a nonpeptidase beta subunit [20Sβ3], or 2 regulatory subunits [19S subunit 6b, 11Sα]) or in chymotrypsin-, trypsin-, and caspaselike activities of the proteasome were measured. Thus, stress-induced or pharmacological activation of Hsf1 in mammalian cells would upregulate Hsps but not directly affect expression or activity of proteasomes. PMID:16184768

Coordination and redox state-dependent structural changes of the heme-based oxygen sensor AfGcHK associated with intraprotein signal transduction.

PubMed

Stranava, Martin; Man, Petr; Skálová, Tereza; Kolenko, Petr; Blaha, Jan; Fojtikova, Veronika; Martínek, Václav; Dohnálek, Jan; Lengalova, Alzbeta; Rosůlek, Michal; Shimizu, Toru; Martínková, Markéta

2017-12-22

The heme-based oxygen sensor histidine kinase Af GcHK is part of a two-component signal transduction system in bacteria. O 2 binding to the Fe(II) heme complex of its N-terminal globin domain strongly stimulates autophosphorylation at His 183 in its C-terminal kinase domain. The 6-coordinate heme Fe(III)-OH - and -CN - complexes of Af GcHK are also active, but the 5-coordinate heme Fe(II) complex and the heme-free apo-form are inactive. Here, we determined the crystal structures of the isolated dimeric globin domains of the active Fe(III)-CN - and inactive 5-coordinate Fe(II) forms, revealing striking structural differences on the heme-proximal side of the globin domain. Using hydrogen/deuterium exchange coupled with mass spectrometry to characterize the conformations of the active and inactive forms of full-length Af GcHK in solution, we investigated the intramolecular signal transduction mechanisms. Major differences between the active and inactive forms were observed on the heme-proximal side (helix H5), at the dimerization interface (helices H6 and H7 and loop L7) of the globin domain and in the ATP-binding site (helices H9 and H11) of the kinase domain. Moreover, separation of the sensor and kinase domains, which deactivates catalysis, increased the solvent exposure of the globin domain-dimerization interface (helix H6) as well as the flexibility and solvent exposure of helix H11. Together, these results suggest that structural changes at the heme-proximal side, the globin domain-dimerization interface, and the ATP-binding site are important in the signal transduction mechanism of Af GcHK. We conclude that Af GcHK functions as an ensemble of molecules sampling at least two conformational states. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Metabolism of. cap alpha. -C/sup 14/-histidine in the intact rat. II. Radioactive excretion products in urine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolf, G.; Wu, P.H.L.; Heck, W.W.

1956-09-01

The normal metabolic pathways in the intact rat was investigated via the radioactive urinary excretion products following administration of a physiological dose of a radioactive compound such as ..cap alpha..-C/sup 14/-DL-histidine. The major metabolites, except one, excreted in the urine 5 hours after administration of ..cap alpha..-C/sup 14/-DL-histidine were isolated and identified. Glutamic acid and urocanic acids had simlar and low activities, whereas carboxyl-labeled imidazoacetic acid was found to be the principal metabolite with a high level of activity. It was concluded that the main end-product of the catabolism of DL-histidine is imidazoleacetic acid probably formed through imidazolepyruvic acid.

Evaluation of athletes with complex congenital heart disease.

PubMed

Bates, Benjamin A; Richards, Camille; Hall, Michael; Kerut, Edmund K; Campbell, William; McMullan, Michael R

2017-06-01

As a result of improvements in congenital heart surgery, there are more adults alive today with congenital heart disease (CHD) than children. Individuals with cardiac birth defects may be able to participate in physical activities but require proper cardiovascular evaluation. The American Heart Association and American College of Cardiology released guidelines in 2015 for athletes with cardiovascular abnormalities. The guidelines express that although restriction from competitive athletics may be indicated for some, the majority of individuals with CHD can and should engage in some form of physical activity. This case study demonstrates the importance of combining all aspects of history, physical examination, ECG, and imaging modalities to evaluate cardiac anatomy and function in young athletes with complex CHD. © 2017, Wiley Periodicals, Inc.

Gramicidin D enhances the antibacterial activity of fluoride.

PubMed

Nelson, James W; Zhou, Zhiyuan; Breaker, Ronald R

2014-07-01

Fluoride is a toxic anion found in many natural environments. One of the major bacterial defenses against fluoride is the cell envelope, which limits passage of the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the permeability of bacterial membranes to fluoride should also enhance fluoride toxicity. In this study, we demonstrate that the pore-forming antibiotic gramicidin D increases fluoride uptake in Bacillus subtilis and that the antibacterial activity of this compound is potentiated by fluoride. Polymyxin B, another membrane-targeting antibiotic with a different mechanism of action, shows no such improvement. These results, along with previous findings, indicate that certain compounds that destabilize bacterial cell envelopes can enhance the toxicity of fluoride. Copyright © 2014 Elsevier Ltd. All rights reserved.

The International Space University

NASA Technical Reports Server (NTRS)

Davidian, Kenneth J.

1990-01-01

The International Space University (ISU) was founded on the premise that any major space program in the future would require international cooperation as a necessary first step toward its successful completion. ISU is devoted to being a leading center for educating future authorities in the world space industry. ISU's background, goals, current form, and future plans are described. The results and benefits of the type of education and experience gained from ISU include technical reports describing the design projects undertaken by the students, an exposure to the many different disciplines which are a part of a large space project, an awareness of the existing activities from around the world in the space community, and an international professional network which spans all aspects of space activities and covers the globe.

Prefrontal brain asymmetry and pre-menstrual dysphoric disorder symptomatology.

PubMed

Accortt, Eynav E; Stewart, Jennifer L; Coan, James A; Manber, Rachel; Allen, John J B

2011-01-01

Pre-menstrual dysphoric disorder (PMDD), a dysphoric form of pre-menstrual syndrome, is included as a diagnosis for further study in the DSM-IV-TR (APA, 2000). The present study investigated whether a marker of risk for major depressive disorder (MDD), prefrontal brain asymmetry, also characterizes women with PMDD. In a sample of 25 college women with PMDD symptomatology and 25 matched controls, resting frontal electroencephalographic (EEG) activity was assessed on four occasions within a two-week span. Across several frontal sites women with PMDD had relatively less left than right prefrontal brain activity, consistent with a diathesis-stress model for menstrual-related dysphoria. The findings suggest an overlap in the risk profile for MDD and PMDD. Published by Elsevier B.V.

Fundamental Characteristics of AAA+ Protein Family Structure and Function

PubMed Central

2016-01-01

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

Airport detectors and orthopaedic implants.

PubMed

van der Wal, Bart C H; Grimm, Bernd; Heyligers, Ide C

2005-08-01

As a result of the rising threats of terrorism, airport security has become a major issue. Patients with orthopaedic implants are concerned that they may activate alarms at airport security gates. A literature overview showed that the activation rate of the alarm by hand-held detectors is higher than for arch detectors (100% versus 56%). Arch detection rate has significantly increased from 0% before 1995 up to 83.3% after 1994. Reported factors which influence detection rates are implant mass, implant combinations, implant volume, transfer speed, side of implant, detector model, sensitivity settings, material and tissue masking. Detection rate has been improved by more sensitive devices and improved filter software. Doctors should be able to objectively inform patients. A form is presented which will easily inform the airport security staff.

[Operational costs and control of performance in surgical clinics between marketing and planning economics. Risk or perhaps quadrature of the circle].

PubMed

Kraus, T W; Weber, W; Mieth, M; Funk, H; Klar, E; Herfarth, C

2000-03-01

Surgical hospitals can be seen as operational or even industrial production systems. Doctors have a major impact on both medical performance and costs. For active participation in the management process, knowledge of industrial controlling mechanisms is required. German hospitals currently receive no procedure-related financial revenues, such as prices or tariffs for defined medical treatment activities. Maximum clinical revenues are, furthermore, limited by principles of planned economy and can be increased only slightly by greater medical performance. Costs are the only target that can be autonomously influenced by the management. Operative controlling in hospitals aims at horizontal and vertical coordination of subunits and decentralization of process regulations. Hospital medical performance is not clearly defined, its quantitative measurement very problematic. Process-orientated clinical activities are not taken into account. A high percentage of hospital costs are fixed and can be influenced only by major structural interventions in the long term. Variable costs are primarily dependent on the quantity of clinical activities, but also heavily influenced by patient structure (comorbidity and risk profile). The various forms of industrial cost calculations, such as internal budgeting, internal markets or flexible plan-cost balancing, cannot be directly applied in hospital management. Based on these analyses, current operational concepts and strategic trends are listed to describe cost-management options in hospitals with focus on the German health reforms.

An electromyographic analysis of shoulder muscle activation during push-up variations on stable and labile surfaces.

PubMed

Sandhu, Jaspal S; Mahajan, Shruti; Shenoy, Shweta

2008-04-01

Numerous exercises are used to strengthen muscles around the shoulder joint including the push-up and the push-up plus. An important consideration is the addition of surface instability in the form of swiss ball for rehabilitation and strength. The justification for the use of the swiss ball is based on its potential for increasing muscular demand required to maintain postural stability and for improving joint proprioception. Evidence for this is lacking in literature. To compare the myoelectric amplitude of shoulder muscles during push-ups on labile and stable surface. Same subject experimental study. Thirty healthy male subjects in the age group 20-30 years with a mean height of 173.65 cm (+/- SD 2.56) and a mean weight of 69.9 kg (+/-SD 0.2) were taken. Surface electromyogram was recorded from triceps, pectoralis major, serratus anterior and upper trapezius while performing push-up and push-up plus exercises, both on labile and stable surface. Significant increase in muscle activity was observed in pectoralis major and triceps muscle (only during eccentric phase of elbow pushups), while serratus anterior and upper trapezius showed no change in activation level on swiss ball. The addition of a swiss ball is capable of influencing shoulder muscle activity during push-up variations, although the effect is task and muscle dependent.

Postpartum Perineal Pain in a Low Episiotomy Setting: Association with Severity of Genital Trauma, Labor Care and Birth Variables

PubMed Central

Leeman, Lawrence; Fullilove, Anne M.; Borders, Noelle; Manocchio, Regina; Albers, Leah L.; Rogers, Rebecca G.

2013-01-01

Background Perineal pain is common after childbirth. We studied the effect of genital tract trauma, labor care, and birth variables on the incidence of pain in a population of healthy women exposed to low rates of episiotomy and operative delivery. Methods A prospective study of genital trauma at birth and assessment of postpartum perineal pain and analgesic use was conducted in 565 midwifery patients. Perineal pain was assessed using the Present Pain Intensity (PPI) and Visual Analog Scale (VAS) components of the validated short form McGill pain scale. Multivariate logistic regression examined which patient characteristics or labor care measures were significant determinants of perineal pain and use of analgesic medicines. Results At hospital discharge, women with major trauma reported higher VAS pain scores (2.16 +/− 1.61 vs 1.48 +/− 1.40; P< 0.001) and were more likely to use analgesic medicines (76.3 vs 23.7%, P= 0.002) than women with mild or no trauma. By 3 months average VAS scores were low in each group and not significantly different. Perineal pain at the time of discharge was associated in univariate analysis with higher education level, ethnicity (non-Hispanic white), nulliparity, and longer length of active maternal pushing efforts. In a multivariate model only trauma group and length of active pushing predicted pain at hospital discharge. In women with minor or no trauma, only length of the active part of second stage labor had a positive relationship with pain. In women with major trauma, the length of active second stage labor had no independent effect on level of pain at discharge beyond its effect on the incidence of major trauma. Conclusions Women with spontaneous perineal trauma reported very low rates of postpartum perineal pain. Women with major trauma reported increased perineal pain compared with women who had no or minor trauma; however, by 3 months postpartum this difference was no longer present. In women with minor or no perineal trauma, a longer period of active pushing was associated with increased perineal pain. PMID:20002420

Phospholipid Synthesis in Aging Potato Tuber Tissue 1

PubMed Central

Tang, Wen-Jing; Castelfranco, Paul A.

1968-01-01

The effect of activation (“aging”) of potato tuber slices on their phospholipid metabolism was investigated. Aged slices were incubated with 14C labeled choline, ethanolamine, methionine, serine, and acetate. In all cases, the incorporation of radioactivity into the lipid fraction increased with the length of time the slices were aged. This incorporation was shown to be true synthesis and not exchange between precursors and existing phospholipids. The increased incorporation of labeled choline into lipids was mainly due to an increase in its uptake by the tissue, the presence of actidione during aging prevented this increased uptake. The increase in the incorporation of labeled acetate into lipids resulted from the development of a fatty acid synthetase during aging. In the case of ethanolamine, both its uptake into the tissue and its incorporation into the lipid fraction increased. The phospholipids formed from these precursors were identified by paper and thin-layer chromatography. The major compound formed from choline was lecithin, while phosphatidylethanolamine and a small amount of lecithin were formed from ethanolamine. Images PMID:16656906

Monoclonal antibody form and function: manufacturing the right antibodies for treating drug abuse.

PubMed

Peterson, Eric; Owens, S Michael; Henry, Ralph L

2006-05-26

Drug abuse continues to be a major national and worldwide problem, and effective treatment strategies are badly needed. Antibodies are promising therapies for the treatment of medical problems caused by drug abuse, with several candidates in preclinical and early clinical trials. Monoclonal antibodies can be designed that have customized affinity and specificity against drugs of abuse, and because antibodies can be designed in various forms, in vivo pharmacokinetic characteristics can be tailored to suit specific clinical applications (eg, long-acting for relapse prevention, or short-acting for overdose). Passive immunization with antibodies against drugs of abuse has several advantages over active immunization, but because large doses of monoclonal antibodies may be needed for each patient, efficient antibody production technology is essential. In this minireview we discuss some of the antibody forms that may be effective clinical treatments for drug abuse, as well as several current and emerging production systems that could bridge the gap from discovery to patient use.

A chalcone with potent inhibiting activity against biofilm formation by nontypeable Haemophilus influenzae.

PubMed

Kunthalert, Duangkamol; Baothong, Sudarat; Khetkam, Pichit; Chokchaisiri, Suwadee; Suksamrarn, Apichart

2014-10-01

Nontypeable Haemophilus influenzae (NTHi), an important human respiratory pathogen, frequently causes biofilm infections. Currently, resistance of bacteria within the biofilm to conventional antimicrobials poses a major obstacle to effective medical treatment on a global scale. Novel agents that are effective against NTHi biofilm are therefore urgently required. In this study, a series of natural and synthetic chalcones with various chemical substituents were evaluated in vitro for their antibiofilm activities against strong biofilm-forming strains of NTHi. Of the test chalcones, 3-hydroxychalcone (chalcone 8) exhibited the most potent inhibitory activity, its mean minimum biofilm inhibitory concentration (MBIC50 ) being 16 μg/mL (71.35 μM), or approximately sixfold more active than the reference drug, azithromycin (MBIC50 419.68 μM). The inhibitory activity of chalcone 8, which is a chemically modified chalcone, appeared to be superior to those of the natural chalcones tested. Significantly, chalcone 8 inhibited biofilm formation by all studied NTHi strains, indicating that the antibiofilm activities of this compound occur across multiple strong-biofilm forming NTHi isolates of different clinical origins. According to antimicrobial and growth curve assays, chalcone 8 at concentrations that decreased biofilm formation did not affect growth of NTHi, suggesting the biofilm inhibitory effect of chalcone 8 is non-antimicrobial. In terms of structure-activity relationship, the possible substituent on the chalcone backbone required for antibiofilm activity is discussed. These findings indicate that 3-hydroxychalcone (chalcone 8) has powerful antibiofilm activity and suggest the potential application of chalcone 8 as a new therapeutic agent for control of NTHi biofilm-associated infections. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

An in vitro examination of the antioxidant and anti-inflammatory properties of buckwheat honey.

PubMed

van den Berg, A J J; van den Worm, E; van Ufford, H C Quarles; Halkes, S B A; Hoekstra, M J; Beukelman, C J

2008-04-01

Hydroxyl radical and hypochlorite anion formed at the wound site from superoxide anion produced by activated polymorphonuclear neutrophils (PMNs) are considered important factors in impaired wound healing. Superoxide anion may also react with nitric oxide produced by macrophages to form peroxynitrite, a third strong oxidant that damages surrounding tissue. In order to select honey for use in wound-healing products, different samples were compared for their capacity to reduce levels of reactive oxygen species (ROS) in vitro. Honey samples were tested in assays for inhibition of ROS production by activated human PMNs, antioxidant activity (scavenging of superoxide anion in a cell-free system) and inhibition of human complement (reducing levels of ROS by limiting formation of complement factors that attract and stimulate PMNs). For buckwheat honey (NewYork, US), moisture and free acid content were determined by refractive index measurement and potentiometric titration respectively. Honey constituents other than sugars were investigated by thin layer chromatography, using natural product reagent to detect phenolic compounds. Constituents with antioxidant properties were detected by spraying the chromatogram with DPPH. Although most honey samples were shown to be active, significant differences were observed, with the highly active honey exceeding the activities of samples with minor effects by factors of 4 to 30. Most pronounced activities were found for American buckwheat honey from the state of NewYork. Phenolic constituents of buckwheat honey were shown to have antioxidant activity. As buckwheat honey was most effective in reducing ROS levels, it was selected for use in wound-healing products. The major antioxidant properties in buckwheat honey derive from its phenolic constituents, which are present in relatively large amounts. Its phenolic compounds may also exert antibacterial activity, whereas its low pH and high free acid content may assist wound healing.

Experimental and Theoretical Basis for a Closed-Form Spectral BRDF Model

DTIC Science & Technology

2015-09-17

EXPERIMENTAL AND THEORETICAL BASIS FOR A CLOSED-FORM SPECTRAL BRDF MODEL DISSERTATION Samuel D. Butler, Major, USAF AFIT-ENP-DS-15-S-021 DEPARTMENT...SPECTRAL BRDF MODEL DISSERTATION Presented to the Faculty Graduate School of Engineering and Management Air Force Institute of Technology Air University Air...FOR A CLOSED-FORM SPECTRAL BRDF MODEL DISSERTATION Samuel D. Butler, BS, MS Major, USAF Committee Membership: Michael A. Marciniak, PhD Chairman Kevin

Mobile health: a synopsis and comment on "Increasing physical activity with mobile devices: a meta-analysis".

PubMed

Johnston, Winter; Hoffman, Sara; Thornton, Louise

2014-03-01

We offer a synopsis and commentary on J. Fanning and colleagues' article "Increasing Physical Activity with Mobile Devices: A Meta-Analysis" published in the Journal of Medical Internet Research. Although regular physical activity has a range of benefits, very few adults in the USA meet recommended guidelines for daily physical activity. The meta-analysis of Fanning et al. (2012) aimed to synthesize the results of research using mobile devices to increase physical activity. Their review identified 11 studies that used mobile technologies, including short message service (SMS), apps, or personal digital assistant (PDA) to improve physical activity behaviors among participants. Fanning et al. conclude that while literature in this area is limited to date, there is initial support for the efficacy of mobile-based interventions for improving physical activity. Included studies varied greatly, and the majority used only SMS to influence physical behaviors, meaning generalization of results to other forms of mobile technologies may be premature. This review does, however, provide a foundation for understanding how mobile-based interventions may be used efficaciously for the development of future interventions to improve health behaviors.

40 CFR 1508.18 - Major Federal action.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Major Federal action. Major Federal action includes actions with effects that may be major and which are... legislative proposals (§§ 1506.8, 1508.17). Actions do not include funding assistance solely in the form of...

Mechanical properties and leaching modeling of activated incinerator bottom ash in Portland cement blends

DOE Office of Scientific and Technical Information (OSTI.GOV)

Onori, Roberta, E-mail: Roberta.onori@uniroma1.it; Polettini, Alessandra; Pomi, Raffaella

2011-02-15

In the present study the evolution of mechanical strength and the leaching behavior of major and trace elements from activated incinerator bottom ash/Portland cement mixtures were investigated. Chemical and mechanical activation were applied with the purpose of improving the reactivity of bottom ash in cement blends. Chemical activation made use of NaOH, KOH, CaCl{sub 2} or CaSO{sub 4}, which were selected for the experimental campaign on the basis of the results from previous studies. The results indicated that CaCl{sub 2} exhibited by far the best effects on the evolution of the hydration process in the mixtures; a positive effect onmore » mechanical strength was also observed when CaSO{sub 4} was used as the activator, while the gain in strength produced by KOH and NaOH was irrelevant. Geochemical modeling of the leaching solutions provided information on the mineral phases responsible for the release of major elements from the hardened materials and also indicated the important role played by surface sorption onto amorphous Fe and Al minerals in dictating the leaching of Pb. The leaching of the other trace metal cations investigated (Cu, Ni and Zn) could not be explained by any pure mineral included in the thermodynamic database used, suggesting they were present in the materials in the form of complex minerals or phase assemblages for which no consistent thermodynamic data are presently available in the literature.« less

Functional interaction between Cerebratulus lacteus cytolysin A-III and phospholipase A/sub 2/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, J.; Blumenthal, K.M.

A study on the interaction between bee venom phospholipase A/sub 2/ and Cerebratulus lacteus cytolysin A-III, a major hemolysin secreted by this organism has been carried out. The hemolytic activity of A-III in phosphate-buffered saline is increased 5-fold in the presence of phospholipase A/sub 2/ from bee venom. Dansylphosphatidylethanolamine (DPE) labeled, phosphatidylcholine-containing liposomes and human erythrocyte membranes were employed to study the interaction between these two proteins. In DPE-liposomes, A-III alone had no effect on DPE fluorescence nor did it enhance either the phospholipase A/sub 2/-dependent fluorescence increase or blue shift in emission maximum, indicating that the cytolysis is notmore » a major phospholipase A/sub 2/-activator. However, when DPE was incorporated into erythrocyte membranes, A-III alone induced a 40% fluorescence increase and a 5 nm blue shift, implying a transient activation of an endogenous phospholipase A/sub 2/. Further studies using synthetic lysophosphatidylcholine and free fatty acids demonstrated that the hemolytic activity of A-III is potentiated by free fatty acids, a product of phospholipid degradation catalyzed by phospholipase A/sub 2/. Subsequent analysis of this phenomenon by gel filtration chromatography, analytical ultracentrifugation, chemical cross-linking, and measurement of (/sup 14/C)oleic acid binding by the cytolysin demonstrated that binding of oleic acid to A-III causes aggregation of the toxin molecules to a tetrameric form which has a higher ..cap alpha..-helix content and a greater activity than the monomer.« less

Destructin-1 is a collagen-degrading endopeptidase secreted by Pseudogymnoascus destructans, the causative agent of white-nose syndrome

PubMed Central

O’Donoghue, Anthony J.; Knudsen, Giselle M.; Beekman, Chapman; Perry, Jenna A.; Johnson, Alexander D.; DeRisi, Joseph L.; Craik, Charles S.; Bennett, Richard J.

2015-01-01

Pseudogymnoascus destructans is the causative agent of white-nose syndrome, a disease that has caused the deaths of millions of bats in North America. This psychrophilic fungus proliferates at low temperatures and targets hibernating bats, resulting in their premature arousal from stupor with catastrophic consequences. Despite the impact of white-nose syndrome, little is known about the fungus itself or how it infects its mammalian host. P. destructans is not amenable to genetic manipulation, and therefore understanding the proteins involved in infection requires alternative approaches. Here, we identify hydrolytic enzymes secreted by P. destructans, and use a novel and unbiased substrate profiling technique to define active peptidases. These experiments revealed that endopeptidases are the major proteolytic activities secreted by P. destructans, and that collagen, the major structural protein in mammals, is actively degraded by the secretome. A serine endopeptidase, hereby-named Destructin-1, was subsequently identified, and a recombinant form overexpressed and purified. Biochemical analysis of Destructin-1 showed that it mediated collagen degradation, and a potent inhibitor of peptidase activity was identified. Treatment of P. destructans-conditioned media with this antagonist blocked collagen degradation and facilitated the detection of additional secreted proteolytic activities, including aminopeptidases and carboxypeptidases. These results provide molecular insights into the secretome of P. destructans, and identify serine endopeptidases that have the clear potential to facilitate tissue invasion and pathogenesis in the mammalian host. PMID:25944934

The effect of major depression on participation in preventive health care activities

PubMed Central

Patten, Scott B; Williams, Jeanne VA; Lavorato, Dina H; Eliasziw, Michael

2009-01-01

Background The objective of this study was to determine whether major depressive episodes (MDE) contribute to a lower rate of participation in three prevention activities: blood pressure checks, mammograms and Pap tests. Methods The data source for this study was the Canadian National Population Health Survey (NPHS), a longitudinal study that started in 1994 and has subsequently re-interviewed its participants every two years. The NPHS included a short form version of the Composite International Diagnostic Interview (CIDI-SF) to assess past year MDE and also collected data on participation in preventive activities. Initially, we examined whether respondents with MDE in a particular year were less likely to participate in screening during that same year. In order to assess whether MDE negatively altered the pattern of participation, those successfully screened at the baseline interview in 1994 were identified and divided into cohorts depending on their MDE status. Proportional hazard models were used to quantify the effect of MDE on subsequent participation in screening. Results No effect of MDE on participation in the three preventive activities was identified either in the cross-sectional or longitudinal analysis. Adjustment for a set of relevant covariates did not alter this result. Conclusion Whereas MDE might be expected to reduce the frequency of participation in screening activities, no evidence for this was found in the current analysis. Since people with MDE may contact the health system more frequently, this may offset any tendency of the illness itself to reduce participation in screening. PMID:19320983

Mechanical properties and leaching modeling of activated incinerator bottom ash in Portland cement blends.

PubMed

Onori, Roberta; Polettini, Alessandra; Pomi, Raffaella

2011-02-01

In the present study the evolution of mechanical strength and the leaching behavior of major and trace elements from activated incinerator bottom ash/Portland cement mixtures were investigated. Chemical and mechanical activation were applied with the purpose of improving the reactivity of bottom ash in cement blends. Chemical activation made use of NaOH, KOH, CaCl(2) or CaSO(4), which were selected for the experimental campaign on the basis of the results from previous studies. The results indicated that CaCl(2) exhibited by far the best effects on the evolution of the hydration process in the mixtures; a positive effect on mechanical strength was also observed when CaSO(4) was used as the activator, while the gain in strength produced by KOH and NaOH was irrelevant. Geochemical modeling of the leaching solutions provided information on the mineral phases responsible for the release of major elements from the hardened materials and also indicated the important role played by surface sorption onto amorphous Fe and Al minerals in dictating the leaching of Pb. The leaching of the other trace metal cations investigated (Cu, Ni and Zn) could not be explained by any pure mineral included in the thermodynamic database used, suggesting they were present in the materials in the form of complex minerals or phase assemblages for which no consistent thermodynamic data are presently available in the literature. Copyright © 2010 Elsevier Ltd. All rights reserved.

Injuries to New Zealanders participating in adventure tourism and adventure sports: an analysis of Accident Compensation Corporation (ACC) claims.

PubMed

Bentley, Tim; Macky, Keith; Edwards, Jo

2006-12-15

The aim of this study was to examine the involvement of adventure tourism and adventure sports activity in injury claims made to the Accident Compensation Corporation (ACC). Epidemiological analysis of ACC claims for the period, July 2004 to June 2005, where adventure activities were involved in the injury. 18,697 adventure tourism and adventure sports injury claims were identified from the data, representing 28 activity sectors. Injuries were most common during the summer months, and were most frequently located in the major population centres. The majority of injuries were incurred by claimants in the 20-50 years age groups, although claimants over 50 years of age had highest claims costs. Males incurred 60% of all claims. Four activities (horse riding, mountain biking, tramping/hiking, and surfing) were responsible for approximately 60% of all adventure tourism and adventure sports-related injuries. Slips, trips, and falls were the most common injury initiating events, and injuries were most often to the back/spine, shoulder, and knee. These findings suggest the need to investigate whether regulatory intervention in the form of codes of practice for high injury count activities such as horse riding and mountain biking may be necessary. Health promotion messages and education programs should focus on these and other high-injury risk areas. Improved risk management practices are required for commercial adventure tourism and adventure sports operators in New Zealand if safety is to be improved across this sector.

Radon as a natural tracer for underwater cave exploration and hypogenic cave formation

NASA Astrophysics Data System (ADS)

Csondor, Katalin; Erőss, Anita; Horváth, Ákos; Szieberth, Dénes

2017-04-01

Using 222Rn as a natural tracer is a novel approach in underwater cave exploration and in the research of active hypogenic caves. The research area, the Molnár János cave is one of the largest caves of an unique hypogenic karst system, the Buda Thermal Karst (Budapest, Hungary). The cave system is mainly characterized by water-filled passages. The cave is located at one of the main discharge areas of the Buda Thermal Karst and the major outflow point of the waters of the cave system is the Boltív spring, which feeds the artificial Malom Lake. Previous complex hydrogeological studies and radon measurements in the cave system and in the spring established the highest radon concentration (71 Bq/L, where the average is 44 Bq/L) in the springwater. The origin of radon was identified in the form of iron-hydroxide containing biofilms, which form by mixing of waters and efficiently adsorb radium from the thermal water component and cause local radon anomalies. Since mixing of waters is responsible for the formation of the cave as well, these iron-hydroxide containing biofilms and consequently high radon concentrations mark the active cave forming zones. The aim of the study was to use the radon as a natural tracer to locate active mixing and cave forming zones. Based on previous radon measurements it is supposed that the active mixing and cave forming zone has to be close to the spring, since the highest radon concentration was measured there. Therefore, the radon activity concentration mapping was carried out with the help of divers and involving that part of the cave which closest to the spring. Based on our measurements the highest radon concentration (84 Bq/L) ever was achieved in the springwater. Based on the radon concentration distribution direct connection and active karst conduit was established between the spring and the deepest room of the researched part of the cave, which was verified by artificial tracer as well. However, the distribution of radon in the cave passages shows lower concentrations (18-46 Bq/L) compared to the spring, therefore an addition deep inflow from a hitherto unknown cave passages is assumed, from which waters with high radon content arrive to the spring. These passages are supposed to be in the active cave formation (mixing) zone. The Buda Thermal Karst research was funded by the Hungarian Scientific Research Fund under the grant agreement no. NK 101356.

Emerging indications for extracorporeal membrane oxygenation in adults with respiratory failure.

PubMed

Abrams, Darryl; Brodie, Daniel

2013-08-01

Recent advances in technology have spurred the increasing use of extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure. However, this accounts for only a small percentage of patients with respiratory failure. We envision the application of ECMO in many other forms of respiratory failure in the coming years. Patients with less severe forms of acute respiratory distress syndrome, for instance, may benefit from enhanced lung-protective ventilation with the very low tidal volumes made possible by direct carbon dioxide removal from the blood. For those in whom hypercapnia predominates, extracorporeal support will allow for the elimination of invasive mechanical ventilation in some cases. The potential benefits of ECMO may be further enhanced by improved techniques, which facilitate active mobilization. Although ECMO for these and other expanded applications is under active investigation, it has yet to be proven beneficial in these settings in rigorous controlled trials. Ultimately, with upcoming and future technological advances, there is the promise of true destination therapy, which could lead to a major paradigm shift in the management of respiratory failure.

A morphologic study of unfertilized oocytes and abnormal embryos in human in vitro fertilization.

PubMed

Bałakier, H; Casper, R F

1991-04-01

The morphology of human, unfertilized oocytes and abnormal embryos cultured in vitro for 48-72 hr was examined in an attempt to learn more about oocyte maturation and reproductive failure in in vitro fertilization (IVF). About 21% of the unfertilized oocytes were totally degenerated. The majority (56%) of the remaining oocytes was arrested at the metaphase II stage. They contained coherent chromosomal plates and had extruded the first polar body with nuclear material. About 13% of oocytes underwent spontaneous activation. In most of these cases the second polar body was retained and many subnuclei or one big nucleus was formed. Five percent of metaphase II oocytes penetrated by sperm were not activated, likely as a result of oocyte immaturity. The developmental ability of abnormal embryos was poor. Several one-cell-stage zygotes were arrested at the pronuclear stage or at mitosis of the first mitotic division. Polyspermic embryos, especially those which contained four or more pronuclei, did not divide or formed uneven, multinucleated blastomeres. However, some triploid and tetraploid embryos often appeared normal morphologically despite their lethal chromosomal abnormalities.

Determination of free, esterified, glycosylated and insoluble-bound phenolics composition in the edible part of araticum fruit (Annona crassiflora Mart.) and its by-products by HPLC-ESI-MS/MS.

PubMed

Arruda, Henrique Silvano; Pereira, Gustavo Araujo; de Morais, Damila Rodrigues; Eberlin, Marcos Nogueira; Pastore, Glaucia Maria

2018-04-15

Phenolics present in the free, esterified, glycosylated and insoluble-bound forms of araticum pulp, peel and seed were for the first time characterized and quantified using HPLC-ESI-MS/MS. Levels of total phenolics, flavonoids, condensed tannins and antioxidant activities from araticum fruit followed the order peel > pulp > seed. Overall, insoluble-bound and esterified phenolics were the dominant forms of phenolics from araticum fruit parts and the highest contributors to their antioxidant activities. Extracts were found to contain contrasting levels of phenolics that were specific to each fruit part. From 10 phenolics quantified in araticum fruit, catechin and epicatechin were the major ones from pulp and peel, whereas seed displayed caffeic acid, catechin and epicatechin as its main phenolics. Araticum fruit was found to provide a good source of phenolics, and the full exploitation of this fruit may find applications in the food, cosmetic and pharmaceutical industries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biological and Pathological Implications of an Alternative ATP-Powered Proteasomal Assembly With Cdc48 and the 20S Peptidase.

PubMed

Esaki, Masatoshi; Johjima-Murata, Ai; Islam, Md Tanvir; Ogura, Teru

2018-01-01

The ATP-powered protein degradation machinery plays essential roles in maintaining protein homeostasis in all organisms. Robust proteolytic activities are typically sequestered within protein complexes to avoid the fatal removal of essential proteins. Because the openings of proteolytic chambers are narrow, substrate proteins must undergo unfolding. AAA superfamily proteins (ATPases associated with diverse cellular activities) are mostly located at these openings and regulate protein degradation appropriately. The 26S proteasome, comprising 20S peptidase and 19S regulatory particles, is the major ATP-powered protein degradation machinery in eukaryotes. The 19S particles are composed of six AAA proteins and 13 regulatory proteins, and bind to both ends of a barrel-shaped proteolytic chamber formed by the 20S peptidase. Several recent studies have reported that another AAA protein, Cdc48, can replace the 19S particles to form an alternative ATP-powered proteasomal complex, i.e., the Cdc48-20S proteasome. This review focuses on our current knowledge of this alternative proteasome and its possible linkage to amyotrophic lateral sclerosis.

[The isolation and characteristics of mutants of the Saccharopolyspora erythraea strain resistant to thiostrepton].

PubMed

Nastasiak, I N; Fedorenko, V A; Danilenko, V N

1997-01-01

The formation of thiostreptone resistant spontaneous and nitrosoguanidine-induced mutants in the erythromycin-producing organism Saccharopolyspora erythraea was investigated. The investigated collection of the mutants was heterogeneous by the level of the thiostreptone resistance (2.5 to 20 micrograms/ml). The thiostreptone resistance mutations had a pleiotropic effect: 17 per cent of the mutants was characterized by the growth thermosensitivity and 26 and 5.8 per cent of the mutants were characterized by loss of the ability to form melanine and aerial mycelium respectively. Such phenotypes were most frequent in the mutants resistant to low concentrations of thiostreptone (2 to 5 micrograms/ml). The absolute majority of the isolated thiostreptone resistant mutants was unstable and formed both the antibiotic resistant and the antibiotic sensitive clones. The greatest portion of the strains with high antibiotic activity (20 per cent) was detected among the S. erythraea spontaneous mutants on the medium with 2.5 micrograms/ ml of thiostreptone. It was shown that the instability of the high antibiotic activity in the mutants was associated with loss of the thiostreptone resistance property.